Kim Zuber, PA-C

The question of when to treat liver transplant patients with chronic hepatitis C virus (HCV) infection is vital. HCV is the diagnosis most commonly leading to liver transplantation, and recurrence of HCV after transplant is nearly universal. An estimated 30% of HCV liver transplant recipients experience recurrence within five years of transplantation, resulting in death or loss of the allograft because of cirrhosis or graft failure.¹ Thus, if we knew when and how to treat HCV in this population, we could envision a world in which liver transplants would not be required—and certainly one in which retransplant because of HCV would never be needed.

In planning to treat HCV-positive patients who need a liver transplant, the question arises: Do we treat them preoperatively, perioperatively, or postoperatively? And if we select postoperative treatment, do we wait until the graft shows HCV recurrence, or do we treat prophylactically—knowing that recurrence is likely?  

Results from multiple small studies of interferon-free treatment of HCV, both prior to and following recurrence of HCV posttransplant, have been reported. The SOLAR trial, which used ribavirin plus sofosbuvir, demonstrated a sustained viral response (SVR) rate of 70%.² The SOLAR-1 trial of ledipasvir/sofosbuvir (Harvoni^®) plus ribavirin in patients with genotype 1 or 4 who were treated following posttransplant recurrence showed an average SVR rate of 96%.³ Duration of treatment varied, depending on genotype and presence of cirrhosis, and there was differing dosing and addition of ribavirin at multiple doses. A 10% mortality rate was reported, but deaths occurred mainly in patients with severe cirrhosis.

A small trial was also conducted of genotype 3 patients treated with ledipasvir/sofosbuvir, with or without ribavirin.⁴ The addition of ribavirin appeared to shorten treatment, but patients in both treatment groups had excellent rates of SVR. However, further study is needed before this combination of medications can be recommended and/or FDA approved. Full details are available at http://hcvguidelines.org.

Ombitasvir/paritaprevir/ ritonavir with dasabuvir (Viekira Pak^™) plus ribavirin for 24 weeks was evaluated in patients with HCV recurrence following liver transplant.⁵ This group of patients had very minimal fibrosis and essentially normal liver function. In this study group, an SVR rate exceeding 95% was achieved.

Continue for data on treatment of patients >>

The data on treatment of patients who need a transplant or who experience HCV recurrence posttransplant are very encouraging. If the SVR rates are maintained over time, it may be possible to significantly decrease the requirement for retransplantation—or even transplant in the first place. As transplant is not without significant morbidity and mortality, especially in the recurrence group, avoiding it would allow patients to live longer and healthier lives. More work is needed to understand the optimal time to treat and the best and safest regimens. Numerous trials evaluating these important management questions are ongoing.^6-9

In the not-too-distant future, the requirement for liver transplantation in patients with chronic HCV infection is likely to decrease substantially. A recent New England Journal of Medicine editorial discussing liver allocation concluded that transplant centers now treating significant numbers of patients with HCV cirrhosis may soon be idle.¹⁰

If only we could be so lucky ...

REFERENCES
1. Watt K, Veldt B, Charlton M. A practical guide to the management of HCV infection following liver transplantation. Am J Transplant. 2009;9(8):1707-1713.

2. Charlton M, Gane E, Manns MP, et al. Sofosbuvir and ribavirin for treatment of compensated recurrent hepatitis C virus infection after liver transplantation. Gastroenterology. 2015;148(1):108-117.

3. Reddy KR, Everson GT, Flamm SL, et al. Ledipasvir/sofosbuvir with ribavirin for the treatment of HCV in patients with post transplant recurrence: preliminary results of a prospective, multicenter study. Presented at: 65th Annual Meeting of the American Association for the Study of Liver Diseases; November 7-11, 2014; Boston, MA. Abstract 8.

4. Kohler JJ, Nettles JH, Amblard F, et al. Approaches to hepatitis C treatment and cure using NS5A inhibitors. Infect Drug Resist. 2014;7:41-56.

5. Curry MP, Forns X, Chung RT, et al. Sofosbuvir and ribavirin prevent recurrence of HCV infection after liver transplantation: an open-label study. Gastroenterology. 2015;148(1):100-107.

6. A Phase 2 open-label study in patients with recurrent genotype 1 hepatitis C post–orthotopic liver transplant to explore the safety and efficacy of simeprevir and sofosbuvir with and without ribavirin. https://clinicaltrials.gov/ct2/show/NCT02165189?term=%22olysio%22&rank=1. Accessed February 15, 2015.

7. Phase 2, open-label study to investigate the pharmacokinetics, efficacy, safety, and tolerability of the combination of simeprevir (TMC435), daclatasvir (BMS-790052) and ribavirin (RBV) in subjects with recurrent chronic hepatitis C genotype 1b infection after orthotopic liver transplantation. https://clinicaltrials.gov/ct2/show/NCT01938625?term=%22olysio%22&rank=4. Accessed February 15, 2015.

8. A Phase 3, multicenter, open-label, single-arm study to investigate the efficacy and safety of a 12-week regimen of simeprevir in combination with sofosbuvir in treatment-naïve or -experienced subjects with chronic genotype 4 hepatitis C virus infection. https://clinicaltrials.gov/ct2/show/NCT02250807?term=%22olysio%22&rank=7. Accessed February 15, 2015.

9. A Phase 2 open-label study in patients with recurrent genotype 1 hepatitis C post–orthotopic liver transplant to explore the safety and efficacy of simeprevir and sofosbuvir with and without ribavirin. https://clinicaltrials.gov/ct2/show/NCT02165189?term=%22sovaldi%22&rank=6. Accessed February 15, 2015.

10. Lamas D, Rosenbaum L. Very complicated math: reconfiguring organ allocation. N Engl J Med. 2014;371(26):2447-2450.

The question of when to treat liver transplant patients with chronic hepatitis C virus (HCV) infection is vital. HCV is the diagnosis most commonly leading to liver transplantation, and recurrence of HCV after transplant is nearly universal. An estimated 30% of HCV liver transplant recipients experience recurrence within five years of transplantation, resulting in death or loss of the allograft because of cirrhosis or graft failure.¹ Thus, if we knew when and how to treat HCV in this population, we could envision a world in which liver transplants would not be required—and certainly one in which retransplant because of HCV would never be needed.

In planning to treat HCV-positive patients who need a liver transplant, the question arises: Do we treat them preoperatively, perioperatively, or postoperatively? And if we select postoperative treatment, do we wait until the graft shows HCV recurrence, or do we treat prophylactically—knowing that recurrence is likely?  

Results from multiple small studies of interferon-free treatment of HCV, both prior to and following recurrence of HCV posttransplant, have been reported. The SOLAR trial, which used ribavirin plus sofosbuvir, demonstrated a sustained viral response (SVR) rate of 70%.² The SOLAR-1 trial of ledipasvir/sofosbuvir (Harvoni^®) plus ribavirin in patients with genotype 1 or 4 who were treated following posttransplant recurrence showed an average SVR rate of 96%.³ Duration of treatment varied, depending on genotype and presence of cirrhosis, and there was differing dosing and addition of ribavirin at multiple doses. A 10% mortality rate was reported, but deaths occurred mainly in patients with severe cirrhosis.

A small trial was also conducted of genotype 3 patients treated with ledipasvir/sofosbuvir, with or without ribavirin.⁴ The addition of ribavirin appeared to shorten treatment, but patients in both treatment groups had excellent rates of SVR. However, further study is needed before this combination of medications can be recommended and/or FDA approved. Full details are available at http://hcvguidelines.org.

Ombitasvir/paritaprevir/ ritonavir with dasabuvir (Viekira Pak^™) plus ribavirin for 24 weeks was evaluated in patients with HCV recurrence following liver transplant.⁵ This group of patients had very minimal fibrosis and essentially normal liver function. In this study group, an SVR rate exceeding 95% was achieved.

Continue for data on treatment of patients >>

The data on treatment of patients who need a transplant or who experience HCV recurrence posttransplant are very encouraging. If the SVR rates are maintained over time, it may be possible to significantly decrease the requirement for retransplantation—or even transplant in the first place. As transplant is not without significant morbidity and mortality, especially in the recurrence group, avoiding it would allow patients to live longer and healthier lives. More work is needed to understand the optimal time to treat and the best and safest regimens. Numerous trials evaluating these important management questions are ongoing.^6-9

In the not-too-distant future, the requirement for liver transplantation in patients with chronic HCV infection is likely to decrease substantially. A recent New England Journal of Medicine editorial discussing liver allocation concluded that transplant centers now treating significant numbers of patients with HCV cirrhosis may soon be idle.¹⁰

If only we could be so lucky ...

REFERENCES
1. Watt K, Veldt B, Charlton M. A practical guide to the management of HCV infection following liver transplantation. Am J Transplant. 2009;9(8):1707-1713.

2. Charlton M, Gane E, Manns MP, et al. Sofosbuvir and ribavirin for treatment of compensated recurrent hepatitis C virus infection after liver transplantation. Gastroenterology. 2015;148(1):108-117.

3. Reddy KR, Everson GT, Flamm SL, et al. Ledipasvir/sofosbuvir with ribavirin for the treatment of HCV in patients with post transplant recurrence: preliminary results of a prospective, multicenter study. Presented at: 65th Annual Meeting of the American Association for the Study of Liver Diseases; November 7-11, 2014; Boston, MA. Abstract 8.

4. Kohler JJ, Nettles JH, Amblard F, et al. Approaches to hepatitis C treatment and cure using NS5A inhibitors. Infect Drug Resist. 2014;7:41-56.

5. Curry MP, Forns X, Chung RT, et al. Sofosbuvir and ribavirin prevent recurrence of HCV infection after liver transplantation: an open-label study. Gastroenterology. 2015;148(1):100-107.

6. A Phase 2 open-label study in patients with recurrent genotype 1 hepatitis C post–orthotopic liver transplant to explore the safety and efficacy of simeprevir and sofosbuvir with and without ribavirin. https://clinicaltrials.gov/ct2/show/NCT02165189?term=%22olysio%22&rank=1. Accessed February 15, 2015.

7. Phase 2, open-label study to investigate the pharmacokinetics, efficacy, safety, and tolerability of the combination of simeprevir (TMC435), daclatasvir (BMS-790052) and ribavirin (RBV) in subjects with recurrent chronic hepatitis C genotype 1b infection after orthotopic liver transplantation. https://clinicaltrials.gov/ct2/show/NCT01938625?term=%22olysio%22&rank=4. Accessed February 15, 2015.

8. A Phase 3, multicenter, open-label, single-arm study to investigate the efficacy and safety of a 12-week regimen of simeprevir in combination with sofosbuvir in treatment-naïve or -experienced subjects with chronic genotype 4 hepatitis C virus infection. https://clinicaltrials.gov/ct2/show/NCT02250807?term=%22olysio%22&rank=7. Accessed February 15, 2015.

9. A Phase 2 open-label study in patients with recurrent genotype 1 hepatitis C post–orthotopic liver transplant to explore the safety and efficacy of simeprevir and sofosbuvir with and without ribavirin. https://clinicaltrials.gov/ct2/show/NCT02165189?term=%22sovaldi%22&rank=6. Accessed February 15, 2015.

10. Lamas D, Rosenbaum L. Very complicated math: reconfiguring organ allocation. N Engl J Med. 2014;371(26):2447-2450.

The question of when to treat liver transplant patients with chronic hepatitis C virus (HCV) infection is vital. HCV is the diagnosis most commonly leading to liver transplantation, and recurrence of HCV after transplant is nearly universal. An estimated 30% of HCV liver transplant recipients experience recurrence within five years of transplantation, resulting in death or loss of the allograft because of cirrhosis or graft failure.¹ Thus, if we knew when and how to treat HCV in this population, we could envision a world in which liver transplants would not be required—and certainly one in which retransplant because of HCV would never be needed.

In planning to treat HCV-positive patients who need a liver transplant, the question arises: Do we treat them preoperatively, perioperatively, or postoperatively? And if we select postoperative treatment, do we wait until the graft shows HCV recurrence, or do we treat prophylactically—knowing that recurrence is likely?  

Results from multiple small studies of interferon-free treatment of HCV, both prior to and following recurrence of HCV posttransplant, have been reported. The SOLAR trial, which used ribavirin plus sofosbuvir, demonstrated a sustained viral response (SVR) rate of 70%.² The SOLAR-1 trial of ledipasvir/sofosbuvir (Harvoni^®) plus ribavirin in patients with genotype 1 or 4 who were treated following posttransplant recurrence showed an average SVR rate of 96%.³ Duration of treatment varied, depending on genotype and presence of cirrhosis, and there was differing dosing and addition of ribavirin at multiple doses. A 10% mortality rate was reported, but deaths occurred mainly in patients with severe cirrhosis.

A small trial was also conducted of genotype 3 patients treated with ledipasvir/sofosbuvir, with or without ribavirin.⁴ The addition of ribavirin appeared to shorten treatment, but patients in both treatment groups had excellent rates of SVR. However, further study is needed before this combination of medications can be recommended and/or FDA approved. Full details are available at http://hcvguidelines.org.

Ombitasvir/paritaprevir/ ritonavir with dasabuvir (Viekira Pak^™) plus ribavirin for 24 weeks was evaluated in patients with HCV recurrence following liver transplant.⁵ This group of patients had very minimal fibrosis and essentially normal liver function. In this study group, an SVR rate exceeding 95% was achieved.

Continue for data on treatment of patients >>

The data on treatment of patients who need a transplant or who experience HCV recurrence posttransplant are very encouraging. If the SVR rates are maintained over time, it may be possible to significantly decrease the requirement for retransplantation—or even transplant in the first place. As transplant is not without significant morbidity and mortality, especially in the recurrence group, avoiding it would allow patients to live longer and healthier lives. More work is needed to understand the optimal time to treat and the best and safest regimens. Numerous trials evaluating these important management questions are ongoing.^6-9

In the not-too-distant future, the requirement for liver transplantation in patients with chronic HCV infection is likely to decrease substantially. A recent New England Journal of Medicine editorial discussing liver allocation concluded that transplant centers now treating significant numbers of patients with HCV cirrhosis may soon be idle.¹⁰

If only we could be so lucky ...

REFERENCES
1. Watt K, Veldt B, Charlton M. A practical guide to the management of HCV infection following liver transplantation. Am J Transplant. 2009;9(8):1707-1713.

2. Charlton M, Gane E, Manns MP, et al. Sofosbuvir and ribavirin for treatment of compensated recurrent hepatitis C virus infection after liver transplantation. Gastroenterology. 2015;148(1):108-117.

3. Reddy KR, Everson GT, Flamm SL, et al. Ledipasvir/sofosbuvir with ribavirin for the treatment of HCV in patients with post transplant recurrence: preliminary results of a prospective, multicenter study. Presented at: 65th Annual Meeting of the American Association for the Study of Liver Diseases; November 7-11, 2014; Boston, MA. Abstract 8.

4. Kohler JJ, Nettles JH, Amblard F, et al. Approaches to hepatitis C treatment and cure using NS5A inhibitors. Infect Drug Resist. 2014;7:41-56.

5. Curry MP, Forns X, Chung RT, et al. Sofosbuvir and ribavirin prevent recurrence of HCV infection after liver transplantation: an open-label study. Gastroenterology. 2015;148(1):100-107.

6. A Phase 2 open-label study in patients with recurrent genotype 1 hepatitis C post–orthotopic liver transplant to explore the safety and efficacy of simeprevir and sofosbuvir with and without ribavirin. https://clinicaltrials.gov/ct2/show/NCT02165189?term=%22olysio%22&rank=1. Accessed February 15, 2015.

7. Phase 2, open-label study to investigate the pharmacokinetics, efficacy, safety, and tolerability of the combination of simeprevir (TMC435), daclatasvir (BMS-790052) and ribavirin (RBV) in subjects with recurrent chronic hepatitis C genotype 1b infection after orthotopic liver transplantation. https://clinicaltrials.gov/ct2/show/NCT01938625?term=%22olysio%22&rank=4. Accessed February 15, 2015.

8. A Phase 3, multicenter, open-label, single-arm study to investigate the efficacy and safety of a 12-week regimen of simeprevir in combination with sofosbuvir in treatment-naïve or -experienced subjects with chronic genotype 4 hepatitis C virus infection. https://clinicaltrials.gov/ct2/show/NCT02250807?term=%22olysio%22&rank=7. Accessed February 15, 2015.

9. A Phase 2 open-label study in patients with recurrent genotype 1 hepatitis C post–orthotopic liver transplant to explore the safety and efficacy of simeprevir and sofosbuvir with and without ribavirin. https://clinicaltrials.gov/ct2/show/NCT02165189?term=%22sovaldi%22&rank=6. Accessed February 15, 2015.

10. Lamas D, Rosenbaum L. Very complicated math: reconfiguring organ allocation. N Engl J Med. 2014;371(26):2447-2450.

Oh what a tangled web it weaves, this virus called hepatitis C. HCV has evolved over several thousand years into seven genotypes and multiple subtypes, making identification and treatment extremely variable.¹ The genotypes are usually geographically specific, with 70% to 75% of HCV patients in the United States classed as genotype 1.² Genotypes 2 and 3 account for most of the rest.³

While genotype does not impact the course or severity of the disease, it does affect the response to treatment. With today’s newest treatments, success rates for sustained viral response (SVR) are as high as 90% in patients with genotype 1. However, the treatment is not without cost: About $100,000 for patients without cirrhosis and even more for those with it, due to the extended length of treatment.

Chronic kidney disease (CKD) and HCV overlap in 10% to nearly 59% of the population in some geographic areas.⁴ Those with CKD who have had a previous kidney transplant, been on dialysis, and/or been treated prior to the introduction of epoetin alfa (Epogen^®, when blood transfusions were common) are more likely to be HCV-positive.

Unfortunately, patients often convert to HCV while on hemodialysis.⁴ This largely represents a nosocomial infection related to parenteral exposure. In the dialysis patient, the course of HCV is more aggressive than in others, with high morbidity—often resulting from cirrhosis and/or hepatocellular carcinoma.

With new HCV drugs available, CKD patients would appear to be a prime population to treat. In order to gain marketing approval, the FDA requires testing of new drugs in patients with varying degrees of renal impairment. However, the requirement is for “moderate” CKD, defined by the FDA as a glomerular filtration rate (GFR) of at least 30 mL/min/1.73m². The FDA does not require testing for patients with a lower GFR, or what nephrology practices refer to as stage 4 or stage 5 CKD; thus, no data are available for this population. The available pharmacokinetic data for the recently approved regimens of sofosbuvir/ledipasvir (Harvoni^®) and of ombitasvir/paritaprevir/ritonavir with dasabuvir (Viekira Pak^™) suggest that no dosing modifications are necessary in the moderately impaired kidney population.

Continue for the newest HCV drugs >>

The recent approvals of Harvoni and Viekira Pak are considered game-changers in the treatment of chronic HCV infection: They demonstrate that interferon is no longer always necessary. Interferon, especially in combination with ribavirin, was especially toxic for patients in the kidney failure population, although the pegylated form of interferon was less problematic. FDA approvals for Harvoni and Viekira Pak were based on clinical data demonstrating SVR rates exceeding 90%, even in traditionally difficult-to-treat populations (ie, patients with genotype 1, African-Americans, those with high viral load levels), which include many CKD patients.

The lack of clinical data in the CKD stage 4/5 population at the time of drug approval raises significant management challenges for the HCV-positive CKD patient. It is encouraging, however, that the FDA is requiring that all new medications be tested in the renally impaired population, even if not in the severely impaired groups. In the interim, and based solely on renal impairment study results for patients with GFR at or exceeding 30 mL/min/1.73m², HCV guidelines issued jointly by the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America⁵ include the recommendation that these new HCV medications be considered for use in the CKD population. Furthermore, there are no dosing adjustments recommended for any of the new HCV medications in stage 4 or stage 5 CKD due to lack of data. However, until more data become available, CKD patients must be managed on a case-by-case basis after consultation with a renal expert, with close attention to changes in GFR and adverse events.

When these new HCV medications are used in the general population and those with significant CKD, postmarketing reports to the FDA will be vital. Practitioners are encouraged to report adverse outcomes to the FDA MedWatch system (https://www.accessdata.fda.gov/scripts/medwatch). As any nephrology practice will tell you, we are starting to get phone calls from our hepatology colleagues asking for guidance, and the next few years will be a fascinating time for all of us. The promise of virologic cure for our HCV-positive patients is tangible and on the horizon.

REFERENCES
1. Maeterns G, Stuyyver L. Genotypes and genetic variation of hepatitis C cirus. Hep C Review. Dec 1998;ed 23.

2. Spach DH, Kim HN. Treatment of HCV genotype 1 (2015). www.hepatitisc.uw.edu/go/treatment-infection/treatment-genotype-1/core-concept/all. Accessed February 15, 2015.

3. Hepatitis C Technical Advisory Group. Hepatitis C genotypes and quasispecies (2005). www.hepatitis.va.gov/provider/reviews/genotypes.asp. Accessed February 15, 2015.

4. Carvalho-Filho RJ, Feldner AC, Silva AE, Ferraz ML. Management of hepatitis C in patients with chronic kidney disease. World J Gastroenterol. 2015;21(2):408-422.

5. American Association for the Study of Liver Diseases, Infectious Diseases Society of America. Recommendations for testing, managing, and treating hepatitis C. http://hcvguidelines.org. Accessed February 15, 2015.

Oh what a tangled web it weaves, this virus called hepatitis C. HCV has evolved over several thousand years into seven genotypes and multiple subtypes, making identification and treatment extremely variable.¹ The genotypes are usually geographically specific, with 70% to 75% of HCV patients in the United States classed as genotype 1.² Genotypes 2 and 3 account for most of the rest.³

While genotype does not impact the course or severity of the disease, it does affect the response to treatment. With today’s newest treatments, success rates for sustained viral response (SVR) are as high as 90% in patients with genotype 1. However, the treatment is not without cost: About $100,000 for patients without cirrhosis and even more for those with it, due to the extended length of treatment.

Chronic kidney disease (CKD) and HCV overlap in 10% to nearly 59% of the population in some geographic areas.⁴ Those with CKD who have had a previous kidney transplant, been on dialysis, and/or been treated prior to the introduction of epoetin alfa (Epogen^®, when blood transfusions were common) are more likely to be HCV-positive.

Unfortunately, patients often convert to HCV while on hemodialysis.⁴ This largely represents a nosocomial infection related to parenteral exposure. In the dialysis patient, the course of HCV is more aggressive than in others, with high morbidity—often resulting from cirrhosis and/or hepatocellular carcinoma.

With new HCV drugs available, CKD patients would appear to be a prime population to treat. In order to gain marketing approval, the FDA requires testing of new drugs in patients with varying degrees of renal impairment. However, the requirement is for “moderate” CKD, defined by the FDA as a glomerular filtration rate (GFR) of at least 30 mL/min/1.73m². The FDA does not require testing for patients with a lower GFR, or what nephrology practices refer to as stage 4 or stage 5 CKD; thus, no data are available for this population. The available pharmacokinetic data for the recently approved regimens of sofosbuvir/ledipasvir (Harvoni^®) and of ombitasvir/paritaprevir/ritonavir with dasabuvir (Viekira Pak^™) suggest that no dosing modifications are necessary in the moderately impaired kidney population.

Continue for the newest HCV drugs >>

The recent approvals of Harvoni and Viekira Pak are considered game-changers in the treatment of chronic HCV infection: They demonstrate that interferon is no longer always necessary. Interferon, especially in combination with ribavirin, was especially toxic for patients in the kidney failure population, although the pegylated form of interferon was less problematic. FDA approvals for Harvoni and Viekira Pak were based on clinical data demonstrating SVR rates exceeding 90%, even in traditionally difficult-to-treat populations (ie, patients with genotype 1, African-Americans, those with high viral load levels), which include many CKD patients.

The lack of clinical data in the CKD stage 4/5 population at the time of drug approval raises significant management challenges for the HCV-positive CKD patient. It is encouraging, however, that the FDA is requiring that all new medications be tested in the renally impaired population, even if not in the severely impaired groups. In the interim, and based solely on renal impairment study results for patients with GFR at or exceeding 30 mL/min/1.73m², HCV guidelines issued jointly by the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America⁵ include the recommendation that these new HCV medications be considered for use in the CKD population. Furthermore, there are no dosing adjustments recommended for any of the new HCV medications in stage 4 or stage 5 CKD due to lack of data. However, until more data become available, CKD patients must be managed on a case-by-case basis after consultation with a renal expert, with close attention to changes in GFR and adverse events.

When these new HCV medications are used in the general population and those with significant CKD, postmarketing reports to the FDA will be vital. Practitioners are encouraged to report adverse outcomes to the FDA MedWatch system (https://www.accessdata.fda.gov/scripts/medwatch). As any nephrology practice will tell you, we are starting to get phone calls from our hepatology colleagues asking for guidance, and the next few years will be a fascinating time for all of us. The promise of virologic cure for our HCV-positive patients is tangible and on the horizon.

REFERENCES
1. Maeterns G, Stuyyver L. Genotypes and genetic variation of hepatitis C cirus. Hep C Review. Dec 1998;ed 23.

2. Spach DH, Kim HN. Treatment of HCV genotype 1 (2015). www.hepatitisc.uw.edu/go/treatment-infection/treatment-genotype-1/core-concept/all. Accessed February 15, 2015.

3. Hepatitis C Technical Advisory Group. Hepatitis C genotypes and quasispecies (2005). www.hepatitis.va.gov/provider/reviews/genotypes.asp. Accessed February 15, 2015.

4. Carvalho-Filho RJ, Feldner AC, Silva AE, Ferraz ML. Management of hepatitis C in patients with chronic kidney disease. World J Gastroenterol. 2015;21(2):408-422.

5. American Association for the Study of Liver Diseases, Infectious Diseases Society of America. Recommendations for testing, managing, and treating hepatitis C. http://hcvguidelines.org. Accessed February 15, 2015.

Oh what a tangled web it weaves, this virus called hepatitis C. HCV has evolved over several thousand years into seven genotypes and multiple subtypes, making identification and treatment extremely variable.¹ The genotypes are usually geographically specific, with 70% to 75% of HCV patients in the United States classed as genotype 1.² Genotypes 2 and 3 account for most of the rest.³

While genotype does not impact the course or severity of the disease, it does affect the response to treatment. With today’s newest treatments, success rates for sustained viral response (SVR) are as high as 90% in patients with genotype 1. However, the treatment is not without cost: About $100,000 for patients without cirrhosis and even more for those with it, due to the extended length of treatment.

Chronic kidney disease (CKD) and HCV overlap in 10% to nearly 59% of the population in some geographic areas.⁴ Those with CKD who have had a previous kidney transplant, been on dialysis, and/or been treated prior to the introduction of epoetin alfa (Epogen^®, when blood transfusions were common) are more likely to be HCV-positive.

Unfortunately, patients often convert to HCV while on hemodialysis.⁴ This largely represents a nosocomial infection related to parenteral exposure. In the dialysis patient, the course of HCV is more aggressive than in others, with high morbidity—often resulting from cirrhosis and/or hepatocellular carcinoma.

With new HCV drugs available, CKD patients would appear to be a prime population to treat. In order to gain marketing approval, the FDA requires testing of new drugs in patients with varying degrees of renal impairment. However, the requirement is for “moderate” CKD, defined by the FDA as a glomerular filtration rate (GFR) of at least 30 mL/min/1.73m². The FDA does not require testing for patients with a lower GFR, or what nephrology practices refer to as stage 4 or stage 5 CKD; thus, no data are available for this population. The available pharmacokinetic data for the recently approved regimens of sofosbuvir/ledipasvir (Harvoni^®) and of ombitasvir/paritaprevir/ritonavir with dasabuvir (Viekira Pak^™) suggest that no dosing modifications are necessary in the moderately impaired kidney population.

Continue for the newest HCV drugs >>

The recent approvals of Harvoni and Viekira Pak are considered game-changers in the treatment of chronic HCV infection: They demonstrate that interferon is no longer always necessary. Interferon, especially in combination with ribavirin, was especially toxic for patients in the kidney failure population, although the pegylated form of interferon was less problematic. FDA approvals for Harvoni and Viekira Pak were based on clinical data demonstrating SVR rates exceeding 90%, even in traditionally difficult-to-treat populations (ie, patients with genotype 1, African-Americans, those with high viral load levels), which include many CKD patients.

The lack of clinical data in the CKD stage 4/5 population at the time of drug approval raises significant management challenges for the HCV-positive CKD patient. It is encouraging, however, that the FDA is requiring that all new medications be tested in the renally impaired population, even if not in the severely impaired groups. In the interim, and based solely on renal impairment study results for patients with GFR at or exceeding 30 mL/min/1.73m², HCV guidelines issued jointly by the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America⁵ include the recommendation that these new HCV medications be considered for use in the CKD population. Furthermore, there are no dosing adjustments recommended for any of the new HCV medications in stage 4 or stage 5 CKD due to lack of data. However, until more data become available, CKD patients must be managed on a case-by-case basis after consultation with a renal expert, with close attention to changes in GFR and adverse events.

When these new HCV medications are used in the general population and those with significant CKD, postmarketing reports to the FDA will be vital. Practitioners are encouraged to report adverse outcomes to the FDA MedWatch system (https://www.accessdata.fda.gov/scripts/medwatch). As any nephrology practice will tell you, we are starting to get phone calls from our hepatology colleagues asking for guidance, and the next few years will be a fascinating time for all of us. The promise of virologic cure for our HCV-positive patients is tangible and on the horizon.

REFERENCES
1. Maeterns G, Stuyyver L. Genotypes and genetic variation of hepatitis C cirus. Hep C Review. Dec 1998;ed 23.

2. Spach DH, Kim HN. Treatment of HCV genotype 1 (2015). www.hepatitisc.uw.edu/go/treatment-infection/treatment-genotype-1/core-concept/all. Accessed February 15, 2015.

3. Hepatitis C Technical Advisory Group. Hepatitis C genotypes and quasispecies (2005). www.hepatitis.va.gov/provider/reviews/genotypes.asp. Accessed February 15, 2015.

4. Carvalho-Filho RJ, Feldner AC, Silva AE, Ferraz ML. Management of hepatitis C in patients with chronic kidney disease. World J Gastroenterol. 2015;21(2):408-422.

5. American Association for the Study of Liver Diseases, Infectious Diseases Society of America. Recommendations for testing, managing, and treating hepatitis C. http://hcvguidelines.org. Accessed February 15, 2015.

Since the 1940s, scientists have been stymied by the cause of the “sliding stones” in California’s Death Valley. How, without human intervention, does a 700-lb boulder move from one place to another, leaving a distinctive, meandering trail? Finally, in August 2014, recorded pictures showed that the power of water, freezing and melting, actually moves these boulders.¹ Those who treat kidney stones (nephrolithiasis) have always known the power of liquid to move “boulders.”

The Sliding Stones of Death Valley, California

The incidence of kidney stones in the United States has risen from 3.8% of the population in the 1970s to 8.8% of the population in the 2010s.^2,3 Stones are three times more common in whites than in nonwhites and twice as common in men as in women.⁴ The cost of kidney stones in the US, including hospitalizations, surgery, and time lost from work, is calculated at $5 billion per year.⁵

Next page: History of treatment >>

Until the early 1980s, the treatment of choice for a kidney stone was “watchful waiting,” with hydration and pain management. A patient would be given a piece of cheesecloth or a basket, and instructed to urinate through it in order to “catch” the stone. When a stone finally passed, its chemical composition was analyzed. In patients with stones that were too large to pass or found in a location that made passage unlikely, surgical attempts were made to retrieve the stones. These surgeries could be open or “closed” (endoscopic), but they often caused permanent damage to the ureters and/or renal pelvis. Not surprisingly, the introduction of extracorporeal shock wave lithotripsy (ESWL) in the 1980s caused an immediate sensation.⁶

Stones can remain asymptomatic for some time—only to be found incidentally on radiologic exam for another condition.² But when a patient presents with “classic” symptoms of kidney stones—colicky flank pain, hematuria, testicular pain (males only!), urinary frequency and urgency, nausea and vomiting—a helical CT is ordered to determine stone position; knowing this is vital to treatment. If the stone is non-obstructing and measures less than 10 mm, medical management is the first choice.^7,8 This consists of IV or oral fluids, accompanied by narcotic and/or non-narcotic pain medications, as kidney stone pain can be excruciating. NSAIDs alone are rarely strong enough, and their use incurs a risk for intrinsic kidney damage.

If conservative care does not allow the stone to pass, alpha-adrenergic blockers and/or calcium channel blockers are added.⁹ In the case of cysteine stones, alkalization of the urine will help dissolve the stone.² Only 20% of stones are found in the ureter; the vast majority (up to 70%) are lower urethral stones (LUS). Use of tamsulosin has been shown to move LUS stones at a faster rate, so long as they measure less than 10 mm.¹⁰

Before treating the stone patient with acute presentation, the urology practitioner may wait a couple of days to see whether the stone passes. The treatment choice then depends on the size of the stone and the position at presentation. If a stone measures less than 6 mm, medical management will be chosen.² In fact, for smaller, nonobstructing stones, fluids, pain control, and alpha-blockers have been shown in the literature to produce a better outcome than other treatment options.⁹

For stones larger than 6 mm, or those causing an obstruction or a complication (pyelonephritis or urosepsis), removal is imperative.⁴ Modality choice depends on the position of the stone and the size of the patient. ESWL, the least invasive means, is the treatment of choice.² However, as obesity becomes more prevalent (with its underlying metabolic abnormalities), the effectiveness of ESWL may be hindered by the obese patient’s body mass. That said, some manufacturers are increasing the reach of their lithotripsy machines for just this reason.¹¹

Continue for more treatment options >>

Stenting, another option to allow stone fragments to pass, can be uncomfortable, and it requires anesthesia; however, its use is associated with minimal damage to the ureter.² Percutaneous nephrolithotomy, with or without a basket or a nephrostomy tube, can also be used.¹² This method is often needed in patients with a large “stone burden.”² Open procedures to remove stones, though the gold standard in the early 1980s, are rarely required today.

Recurrence rates for stones can be as high as 50%.¹³ Depending on the type of stone, certain interventions are essential to reduce recurrence. The ROKS stone calculator can be used to identify patients at increased risk for stone recurrence.¹⁴

REFERENCES
1. Norris RD, Norris JM, Lorenz RD, et al. Sliding rocks on racetrack playa, Death Valley National Park: first observation of rocks in motion. PLoS One. 2014;9(8):e105948.

2. Curhan G. Nephrolithiasis. In: Gilbert SJ, Weiner DE, eds. National Kidney Foundation’s Primer on Kidney Diseases. 6th ed. Philadelphia, PA: Elsevier; 2013:405-411.

3. Trinchieri A. Epidemiology of urolithiasis: an update. Clin Cases Miner Bone Metab. 2008;5(2):101-106.

4. Worcester EM, Coe FL. Clinical practice: calcium kidney stones. N Engl J Med. 2010;363(10):954-963.

5. Saigal CS, Joyce G, Timilsina AR; Urologic Diseases in America Project. Direct and indirect costs of nephrolithiasis in an employed population: opportunity for disease management? Kidney Int. 2005;68(4):1808-1814.

6. Segura JW, Patterson DE, LeRoy AJ, et al. Percutaneous removal of kidney stones: review of 1,000 cases. J Urol. 1985;134(6):1077-1081.

7. Wells CG, Chandrashekar KB, Jyothirmayi GN, et al. Kidney stones: current diagnosis and management. Clinician Reviews. 2012;22(2):31-37.

8. Coll DM, Varanelli MJ, Smith RC. Relationship of spontaneous passage of ureteral calculi to stone size and location as revealed by unenhanced helical CT. AJR Am J Roentgenol. 2002;178(1):101-103.

9. Campschroer T, Zhu Y, Duijvesz D, et al. Alpha-blockers as medical expulsive therapy for ureteral stones. Cochrane Database Syst Rev. 2014;4:CD008509.

10. Erturhan S, Erbagci A, Yagci F, et al. Comparative evaluation of efficacy of use of tamsulosin and/or tolterodine for medical treatment of distal ureteral stones. Urology. 2007;69(4):633-636.

11. Mezentsev VA. Extracorporeal shock wave lithotripsy in the treatment of renal pelvicalyceal stones in morbidly obese patients. Int Braz J Urol. 2005;31(2):105-110.

12. Amer T, Ahmed K, Bultitude M, et al. Standard versus tubeless percutaneous nephrolithotomy: a systematic review. Urol Int. 2012;88(4):373-82.

13. Ljunghall S. Incidence of upper urinary tract stones. Miner Electrolyte Metab. 1987;13(4):220-227.

14. Rule AD, Lieske JC, Li X, et al. The ROKS Nomogram for Predicting a Second Symptomatic Stone Episode. J Am Soc Nephrol. 2014 Aug 7. [Epub ahead of print]

Since the 1940s, scientists have been stymied by the cause of the “sliding stones” in California’s Death Valley. How, without human intervention, does a 700-lb boulder move from one place to another, leaving a distinctive, meandering trail? Finally, in August 2014, recorded pictures showed that the power of water, freezing and melting, actually moves these boulders.¹ Those who treat kidney stones (nephrolithiasis) have always known the power of liquid to move “boulders.”

The Sliding Stones of Death Valley, California

The incidence of kidney stones in the United States has risen from 3.8% of the population in the 1970s to 8.8% of the population in the 2010s.^2,3 Stones are three times more common in whites than in nonwhites and twice as common in men as in women.⁴ The cost of kidney stones in the US, including hospitalizations, surgery, and time lost from work, is calculated at $5 billion per year.⁵

Next page: History of treatment >>

Until the early 1980s, the treatment of choice for a kidney stone was “watchful waiting,” with hydration and pain management. A patient would be given a piece of cheesecloth or a basket, and instructed to urinate through it in order to “catch” the stone. When a stone finally passed, its chemical composition was analyzed. In patients with stones that were too large to pass or found in a location that made passage unlikely, surgical attempts were made to retrieve the stones. These surgeries could be open or “closed” (endoscopic), but they often caused permanent damage to the ureters and/or renal pelvis. Not surprisingly, the introduction of extracorporeal shock wave lithotripsy (ESWL) in the 1980s caused an immediate sensation.⁶

Stones can remain asymptomatic for some time—only to be found incidentally on radiologic exam for another condition.² But when a patient presents with “classic” symptoms of kidney stones—colicky flank pain, hematuria, testicular pain (males only!), urinary frequency and urgency, nausea and vomiting—a helical CT is ordered to determine stone position; knowing this is vital to treatment. If the stone is non-obstructing and measures less than 10 mm, medical management is the first choice.^7,8 This consists of IV or oral fluids, accompanied by narcotic and/or non-narcotic pain medications, as kidney stone pain can be excruciating. NSAIDs alone are rarely strong enough, and their use incurs a risk for intrinsic kidney damage.

If conservative care does not allow the stone to pass, alpha-adrenergic blockers and/or calcium channel blockers are added.⁹ In the case of cysteine stones, alkalization of the urine will help dissolve the stone.² Only 20% of stones are found in the ureter; the vast majority (up to 70%) are lower urethral stones (LUS). Use of tamsulosin has been shown to move LUS stones at a faster rate, so long as they measure less than 10 mm.¹⁰

Before treating the stone patient with acute presentation, the urology practitioner may wait a couple of days to see whether the stone passes. The treatment choice then depends on the size of the stone and the position at presentation. If a stone measures less than 6 mm, medical management will be chosen.² In fact, for smaller, nonobstructing stones, fluids, pain control, and alpha-blockers have been shown in the literature to produce a better outcome than other treatment options.⁹

For stones larger than 6 mm, or those causing an obstruction or a complication (pyelonephritis or urosepsis), removal is imperative.⁴ Modality choice depends on the position of the stone and the size of the patient. ESWL, the least invasive means, is the treatment of choice.² However, as obesity becomes more prevalent (with its underlying metabolic abnormalities), the effectiveness of ESWL may be hindered by the obese patient’s body mass. That said, some manufacturers are increasing the reach of their lithotripsy machines for just this reason.¹¹

Continue for more treatment options >>

Stenting, another option to allow stone fragments to pass, can be uncomfortable, and it requires anesthesia; however, its use is associated with minimal damage to the ureter.² Percutaneous nephrolithotomy, with or without a basket or a nephrostomy tube, can also be used.¹² This method is often needed in patients with a large “stone burden.”² Open procedures to remove stones, though the gold standard in the early 1980s, are rarely required today.

Recurrence rates for stones can be as high as 50%.¹³ Depending on the type of stone, certain interventions are essential to reduce recurrence. The ROKS stone calculator can be used to identify patients at increased risk for stone recurrence.¹⁴

REFERENCES
1. Norris RD, Norris JM, Lorenz RD, et al. Sliding rocks on racetrack playa, Death Valley National Park: first observation of rocks in motion. PLoS One. 2014;9(8):e105948.

2. Curhan G. Nephrolithiasis. In: Gilbert SJ, Weiner DE, eds. National Kidney Foundation’s Primer on Kidney Diseases. 6th ed. Philadelphia, PA: Elsevier; 2013:405-411.

3. Trinchieri A. Epidemiology of urolithiasis: an update. Clin Cases Miner Bone Metab. 2008;5(2):101-106.

4. Worcester EM, Coe FL. Clinical practice: calcium kidney stones. N Engl J Med. 2010;363(10):954-963.

5. Saigal CS, Joyce G, Timilsina AR; Urologic Diseases in America Project. Direct and indirect costs of nephrolithiasis in an employed population: opportunity for disease management? Kidney Int. 2005;68(4):1808-1814.

6. Segura JW, Patterson DE, LeRoy AJ, et al. Percutaneous removal of kidney stones: review of 1,000 cases. J Urol. 1985;134(6):1077-1081.

7. Wells CG, Chandrashekar KB, Jyothirmayi GN, et al. Kidney stones: current diagnosis and management. Clinician Reviews. 2012;22(2):31-37.

8. Coll DM, Varanelli MJ, Smith RC. Relationship of spontaneous passage of ureteral calculi to stone size and location as revealed by unenhanced helical CT. AJR Am J Roentgenol. 2002;178(1):101-103.

9. Campschroer T, Zhu Y, Duijvesz D, et al. Alpha-blockers as medical expulsive therapy for ureteral stones. Cochrane Database Syst Rev. 2014;4:CD008509.

10. Erturhan S, Erbagci A, Yagci F, et al. Comparative evaluation of efficacy of use of tamsulosin and/or tolterodine for medical treatment of distal ureteral stones. Urology. 2007;69(4):633-636.

11. Mezentsev VA. Extracorporeal shock wave lithotripsy in the treatment of renal pelvicalyceal stones in morbidly obese patients. Int Braz J Urol. 2005;31(2):105-110.

12. Amer T, Ahmed K, Bultitude M, et al. Standard versus tubeless percutaneous nephrolithotomy: a systematic review. Urol Int. 2012;88(4):373-82.

13. Ljunghall S. Incidence of upper urinary tract stones. Miner Electrolyte Metab. 1987;13(4):220-227.

14. Rule AD, Lieske JC, Li X, et al. The ROKS Nomogram for Predicting a Second Symptomatic Stone Episode. J Am Soc Nephrol. 2014 Aug 7. [Epub ahead of print]

Since the 1940s, scientists have been stymied by the cause of the “sliding stones” in California’s Death Valley. How, without human intervention, does a 700-lb boulder move from one place to another, leaving a distinctive, meandering trail? Finally, in August 2014, recorded pictures showed that the power of water, freezing and melting, actually moves these boulders.¹ Those who treat kidney stones (nephrolithiasis) have always known the power of liquid to move “boulders.”

The Sliding Stones of Death Valley, California

The incidence of kidney stones in the United States has risen from 3.8% of the population in the 1970s to 8.8% of the population in the 2010s.^2,3 Stones are three times more common in whites than in nonwhites and twice as common in men as in women.⁴ The cost of kidney stones in the US, including hospitalizations, surgery, and time lost from work, is calculated at $5 billion per year.⁵

Next page: History of treatment >>

Until the early 1980s, the treatment of choice for a kidney stone was “watchful waiting,” with hydration and pain management. A patient would be given a piece of cheesecloth or a basket, and instructed to urinate through it in order to “catch” the stone. When a stone finally passed, its chemical composition was analyzed. In patients with stones that were too large to pass or found in a location that made passage unlikely, surgical attempts were made to retrieve the stones. These surgeries could be open or “closed” (endoscopic), but they often caused permanent damage to the ureters and/or renal pelvis. Not surprisingly, the introduction of extracorporeal shock wave lithotripsy (ESWL) in the 1980s caused an immediate sensation.⁶

Stones can remain asymptomatic for some time—only to be found incidentally on radiologic exam for another condition.² But when a patient presents with “classic” symptoms of kidney stones—colicky flank pain, hematuria, testicular pain (males only!), urinary frequency and urgency, nausea and vomiting—a helical CT is ordered to determine stone position; knowing this is vital to treatment. If the stone is non-obstructing and measures less than 10 mm, medical management is the first choice.^7,8 This consists of IV or oral fluids, accompanied by narcotic and/or non-narcotic pain medications, as kidney stone pain can be excruciating. NSAIDs alone are rarely strong enough, and their use incurs a risk for intrinsic kidney damage.

If conservative care does not allow the stone to pass, alpha-adrenergic blockers and/or calcium channel blockers are added.⁹ In the case of cysteine stones, alkalization of the urine will help dissolve the stone.² Only 20% of stones are found in the ureter; the vast majority (up to 70%) are lower urethral stones (LUS). Use of tamsulosin has been shown to move LUS stones at a faster rate, so long as they measure less than 10 mm.¹⁰

Before treating the stone patient with acute presentation, the urology practitioner may wait a couple of days to see whether the stone passes. The treatment choice then depends on the size of the stone and the position at presentation. If a stone measures less than 6 mm, medical management will be chosen.² In fact, for smaller, nonobstructing stones, fluids, pain control, and alpha-blockers have been shown in the literature to produce a better outcome than other treatment options.⁹

For stones larger than 6 mm, or those causing an obstruction or a complication (pyelonephritis or urosepsis), removal is imperative.⁴ Modality choice depends on the position of the stone and the size of the patient. ESWL, the least invasive means, is the treatment of choice.² However, as obesity becomes more prevalent (with its underlying metabolic abnormalities), the effectiveness of ESWL may be hindered by the obese patient’s body mass. That said, some manufacturers are increasing the reach of their lithotripsy machines for just this reason.¹¹

Continue for more treatment options >>

Stenting, another option to allow stone fragments to pass, can be uncomfortable, and it requires anesthesia; however, its use is associated with minimal damage to the ureter.² Percutaneous nephrolithotomy, with or without a basket or a nephrostomy tube, can also be used.¹² This method is often needed in patients with a large “stone burden.”² Open procedures to remove stones, though the gold standard in the early 1980s, are rarely required today.

Recurrence rates for stones can be as high as 50%.¹³ Depending on the type of stone, certain interventions are essential to reduce recurrence. The ROKS stone calculator can be used to identify patients at increased risk for stone recurrence.¹⁴

REFERENCES
1. Norris RD, Norris JM, Lorenz RD, et al. Sliding rocks on racetrack playa, Death Valley National Park: first observation of rocks in motion. PLoS One. 2014;9(8):e105948.

2. Curhan G. Nephrolithiasis. In: Gilbert SJ, Weiner DE, eds. National Kidney Foundation’s Primer on Kidney Diseases. 6th ed. Philadelphia, PA: Elsevier; 2013:405-411.

3. Trinchieri A. Epidemiology of urolithiasis: an update. Clin Cases Miner Bone Metab. 2008;5(2):101-106.

4. Worcester EM, Coe FL. Clinical practice: calcium kidney stones. N Engl J Med. 2010;363(10):954-963.

5. Saigal CS, Joyce G, Timilsina AR; Urologic Diseases in America Project. Direct and indirect costs of nephrolithiasis in an employed population: opportunity for disease management? Kidney Int. 2005;68(4):1808-1814.

6. Segura JW, Patterson DE, LeRoy AJ, et al. Percutaneous removal of kidney stones: review of 1,000 cases. J Urol. 1985;134(6):1077-1081.

7. Wells CG, Chandrashekar KB, Jyothirmayi GN, et al. Kidney stones: current diagnosis and management. Clinician Reviews. 2012;22(2):31-37.

8. Coll DM, Varanelli MJ, Smith RC. Relationship of spontaneous passage of ureteral calculi to stone size and location as revealed by unenhanced helical CT. AJR Am J Roentgenol. 2002;178(1):101-103.

9. Campschroer T, Zhu Y, Duijvesz D, et al. Alpha-blockers as medical expulsive therapy for ureteral stones. Cochrane Database Syst Rev. 2014;4:CD008509.

10. Erturhan S, Erbagci A, Yagci F, et al. Comparative evaluation of efficacy of use of tamsulosin and/or tolterodine for medical treatment of distal ureteral stones. Urology. 2007;69(4):633-636.

11. Mezentsev VA. Extracorporeal shock wave lithotripsy in the treatment of renal pelvicalyceal stones in morbidly obese patients. Int Braz J Urol. 2005;31(2):105-110.

12. Amer T, Ahmed K, Bultitude M, et al. Standard versus tubeless percutaneous nephrolithotomy: a systematic review. Urol Int. 2012;88(4):373-82.

13. Ljunghall S. Incidence of upper urinary tract stones. Miner Electrolyte Metab. 1987;13(4):220-227.

14. Rule AD, Lieske JC, Li X, et al. The ROKS Nomogram for Predicting a Second Symptomatic Stone Episode. J Am Soc Nephrol. 2014 Aug 7. [Epub ahead of print]

The incidence of kidney stones in the United States is as high as 11% among men and 6% among women.¹ This translates into a 1-in-11 risk nationwide, with white men being at greater risk than any other cohort. However, for those patients with high-risk medical issues, such as metabolic syndrome, chronic indwelling urinary catheters, frequent catheterization, and/or recurrent urinary tract infections (UTIs), kidney stones are even more common.² Often, the cause of the stones in at-risk patients is an infection. The most frequent source of UTIs is Escherichia coli, but more complicated infections are often caused by Proteus mirabilis.³ Seventy percent of the stones resulting from UTIs are attributed to P mirabilis.⁴

In 2008, a group of microbiology researchers led by Melanie Pearson, PhD, were able to isolate the genome sequence of P mirabilis.⁵Proteus is a gram-negative enteric bacterium that is often found in complicated UTIs. Proteus is more common among patients with the aforementioned high-risk medical issues and is a particularly common cause of UTIs in the nursing home population (particularly in residents with indwelling catheters).³ It is also a potential cause of kidney stones.

While calcium stones are the most common type of stones,¹ infections, though uncommon, are a secondary source. Stones resulting from infection are imminently treatable; the difficulty is in isolating the source of the infection. Proteus is a particularly toxic, difficult-to treat bacterium that can become resistant to antibiotics.³Proteus produces the enzyme urease, which can reduce the acidity of the urine, allowing stones to form. Once stone formation begins, bacteria can sequester within the stone, making them less susceptible to antibiotic treatment.

Proteus often seems to occur randomly. It has been found as a cause of kidney stones, for example, in a patient who four months earlier underwent transurethral resection of the prostate.⁷Proteus has been reported in a nursing home patient with dementia but no known risk factors.⁸Proteus can cause a pyelonephritis to coalesce into a stone; this complicates what is already an insult to the urinary tract and makes treatment all the more complicated.⁹

Pearson’s group from the University of Michigan has spent the past 10 years sequencing the Proteus bacterium in order to try to gain a foothold in the fight against the infection and the kidney stones it can produce. In 2014 they published their findings on the fimbriae of the Proteus organism.¹⁰ Fimbriae are small pili, or adherence factors, found on the surface of a bacterium (more often on gram-negative bacteria than on gram-positive bacteria), which allow the bacteria to attach to urinary tract tissue and prevent them from being easily dislodged.¹¹ Pearson’s group also found that the fimbriae of the Proteus bacterium are more numerous than those of other bacteria, allowing Proteus to more easily attach to tissue than, say, Salmonella enterica.⁵ Thus, Proteus is more likely than other uropathogenic agents to cause a kidney stone, in part because of the “stickiness” of its many fimbriae.

While stones with an infectious cause are less common than others, they are a danger to our most fragile patients. Thus, when an infectious kidney stone forms, it will require aggressive treatment and a hard-hitting plan to minimize recurrence. Proteus is an especially virulent organism that will require all our resources to overcome it.

REFERENCES
1. Scales CD Jr, Smith AC, Hanley JM, Saigal CS; Urologic Diseases in America Project. Prevalence of kidney stones in the United States. Eur Urol. 2012;62(1):160-165.

2. National Kidney Foundation. Diet and kidney stones. kidney.org/atoz/content/diet.cfm. Accessed October 1, 2104.

3. University of Michigan Health System. Bacterium that causes kidney stones and complicated urinary tract infections gives up its genetic secrets (2006). ScienceDaily. sciencedaily.com/releases/2006/05/060524125023.htm. Accessed October 1, 2014.

4. Torzewska A, Budzyńska A, Białczak-Kokot M, Różalski A. In vitro studies of epithelium-associated crystallization caused by uropathogens during urinary calculi development. Microb Pathog. 2014;71-72:25-31.

5. Pearson MM, Sebaihia M, Churcher C, et al. Complete genome sequence of uropathogenic Proteus mirabilis, a master of both adherence and motility. J Bacteriol. 2008;190(11):4027-4037.

6. Wells CG, Chandrashekar KB, Jyothirmayi GN, et al. Kidney stones: current diagnosis and management. Clinician Reviews. 2012;22(2):31-37.

7. Rowe CM, Ghei M, Adamska E. Moans, groans and renal stones: an interesting case of abdominal pain. BMJ Case Rep. 2013 Nov 4.

8. Chew R, Thomas S, Mantha ML, et al. Large urate cystolith associated with Proteus urinary tract infection. Kidney Int. 2012;81(8):802.

9. Shields J, Maxwell AP. Acute pyelonephritis can have serious complications. Practitioner. 2010;254(1728):19, 21, 23-24.

10. Kuan L, Schaffer JN, Zouzias CD, Pearson MM. Characterization of 17 chaperone-usher fimbriae encoded by Proteus mirabilis reveals strong conservation. J Med Microbiol. 2014;63(pt 7):911-922.

11. Proft T, Baker EN. Pili in Gram-negative and Gram-positive bacteria: structure, assembly and their role in disease. Cell Mol Life Sci. 2009;66(4):613-635.

The incidence of kidney stones in the United States is as high as 11% among men and 6% among women.¹ This translates into a 1-in-11 risk nationwide, with white men being at greater risk than any other cohort. However, for those patients with high-risk medical issues, such as metabolic syndrome, chronic indwelling urinary catheters, frequent catheterization, and/or recurrent urinary tract infections (UTIs), kidney stones are even more common.² Often, the cause of the stones in at-risk patients is an infection. The most frequent source of UTIs is Escherichia coli, but more complicated infections are often caused by Proteus mirabilis.³ Seventy percent of the stones resulting from UTIs are attributed to P mirabilis.⁴

In 2008, a group of microbiology researchers led by Melanie Pearson, PhD, were able to isolate the genome sequence of P mirabilis.⁵Proteus is a gram-negative enteric bacterium that is often found in complicated UTIs. Proteus is more common among patients with the aforementioned high-risk medical issues and is a particularly common cause of UTIs in the nursing home population (particularly in residents with indwelling catheters).³ It is also a potential cause of kidney stones.

While calcium stones are the most common type of stones,¹ infections, though uncommon, are a secondary source. Stones resulting from infection are imminently treatable; the difficulty is in isolating the source of the infection. Proteus is a particularly toxic, difficult-to treat bacterium that can become resistant to antibiotics.³Proteus produces the enzyme urease, which can reduce the acidity of the urine, allowing stones to form. Once stone formation begins, bacteria can sequester within the stone, making them less susceptible to antibiotic treatment.

Proteus often seems to occur randomly. It has been found as a cause of kidney stones, for example, in a patient who four months earlier underwent transurethral resection of the prostate.⁷Proteus has been reported in a nursing home patient with dementia but no known risk factors.⁸Proteus can cause a pyelonephritis to coalesce into a stone; this complicates what is already an insult to the urinary tract and makes treatment all the more complicated.⁹

Pearson’s group from the University of Michigan has spent the past 10 years sequencing the Proteus bacterium in order to try to gain a foothold in the fight against the infection and the kidney stones it can produce. In 2014 they published their findings on the fimbriae of the Proteus organism.¹⁰ Fimbriae are small pili, or adherence factors, found on the surface of a bacterium (more often on gram-negative bacteria than on gram-positive bacteria), which allow the bacteria to attach to urinary tract tissue and prevent them from being easily dislodged.¹¹ Pearson’s group also found that the fimbriae of the Proteus bacterium are more numerous than those of other bacteria, allowing Proteus to more easily attach to tissue than, say, Salmonella enterica.⁵ Thus, Proteus is more likely than other uropathogenic agents to cause a kidney stone, in part because of the “stickiness” of its many fimbriae.

While stones with an infectious cause are less common than others, they are a danger to our most fragile patients. Thus, when an infectious kidney stone forms, it will require aggressive treatment and a hard-hitting plan to minimize recurrence. Proteus is an especially virulent organism that will require all our resources to overcome it.

REFERENCES
1. Scales CD Jr, Smith AC, Hanley JM, Saigal CS; Urologic Diseases in America Project. Prevalence of kidney stones in the United States. Eur Urol. 2012;62(1):160-165.

2. National Kidney Foundation. Diet and kidney stones. kidney.org/atoz/content/diet.cfm. Accessed October 1, 2104.

3. University of Michigan Health System. Bacterium that causes kidney stones and complicated urinary tract infections gives up its genetic secrets (2006). ScienceDaily. sciencedaily.com/releases/2006/05/060524125023.htm. Accessed October 1, 2014.

4. Torzewska A, Budzyńska A, Białczak-Kokot M, Różalski A. In vitro studies of epithelium-associated crystallization caused by uropathogens during urinary calculi development. Microb Pathog. 2014;71-72:25-31.

5. Pearson MM, Sebaihia M, Churcher C, et al. Complete genome sequence of uropathogenic Proteus mirabilis, a master of both adherence and motility. J Bacteriol. 2008;190(11):4027-4037.

6. Wells CG, Chandrashekar KB, Jyothirmayi GN, et al. Kidney stones: current diagnosis and management. Clinician Reviews. 2012;22(2):31-37.

7. Rowe CM, Ghei M, Adamska E. Moans, groans and renal stones: an interesting case of abdominal pain. BMJ Case Rep. 2013 Nov 4.

8. Chew R, Thomas S, Mantha ML, et al. Large urate cystolith associated with Proteus urinary tract infection. Kidney Int. 2012;81(8):802.

9. Shields J, Maxwell AP. Acute pyelonephritis can have serious complications. Practitioner. 2010;254(1728):19, 21, 23-24.

10. Kuan L, Schaffer JN, Zouzias CD, Pearson MM. Characterization of 17 chaperone-usher fimbriae encoded by Proteus mirabilis reveals strong conservation. J Med Microbiol. 2014;63(pt 7):911-922.

11. Proft T, Baker EN. Pili in Gram-negative and Gram-positive bacteria: structure, assembly and their role in disease. Cell Mol Life Sci. 2009;66(4):613-635.

The incidence of kidney stones in the United States is as high as 11% among men and 6% among women.¹ This translates into a 1-in-11 risk nationwide, with white men being at greater risk than any other cohort. However, for those patients with high-risk medical issues, such as metabolic syndrome, chronic indwelling urinary catheters, frequent catheterization, and/or recurrent urinary tract infections (UTIs), kidney stones are even more common.² Often, the cause of the stones in at-risk patients is an infection. The most frequent source of UTIs is Escherichia coli, but more complicated infections are often caused by Proteus mirabilis.³ Seventy percent of the stones resulting from UTIs are attributed to P mirabilis.⁴

In 2008, a group of microbiology researchers led by Melanie Pearson, PhD, were able to isolate the genome sequence of P mirabilis.⁵Proteus is a gram-negative enteric bacterium that is often found in complicated UTIs. Proteus is more common among patients with the aforementioned high-risk medical issues and is a particularly common cause of UTIs in the nursing home population (particularly in residents with indwelling catheters).³ It is also a potential cause of kidney stones.

While calcium stones are the most common type of stones,¹ infections, though uncommon, are a secondary source. Stones resulting from infection are imminently treatable; the difficulty is in isolating the source of the infection. Proteus is a particularly toxic, difficult-to treat bacterium that can become resistant to antibiotics.³Proteus produces the enzyme urease, which can reduce the acidity of the urine, allowing stones to form. Once stone formation begins, bacteria can sequester within the stone, making them less susceptible to antibiotic treatment.

Proteus often seems to occur randomly. It has been found as a cause of kidney stones, for example, in a patient who four months earlier underwent transurethral resection of the prostate.⁷Proteus has been reported in a nursing home patient with dementia but no known risk factors.⁸Proteus can cause a pyelonephritis to coalesce into a stone; this complicates what is already an insult to the urinary tract and makes treatment all the more complicated.⁹

Pearson’s group from the University of Michigan has spent the past 10 years sequencing the Proteus bacterium in order to try to gain a foothold in the fight against the infection and the kidney stones it can produce. In 2014 they published their findings on the fimbriae of the Proteus organism.¹⁰ Fimbriae are small pili, or adherence factors, found on the surface of a bacterium (more often on gram-negative bacteria than on gram-positive bacteria), which allow the bacteria to attach to urinary tract tissue and prevent them from being easily dislodged.¹¹ Pearson’s group also found that the fimbriae of the Proteus bacterium are more numerous than those of other bacteria, allowing Proteus to more easily attach to tissue than, say, Salmonella enterica.⁵ Thus, Proteus is more likely than other uropathogenic agents to cause a kidney stone, in part because of the “stickiness” of its many fimbriae.

While stones with an infectious cause are less common than others, they are a danger to our most fragile patients. Thus, when an infectious kidney stone forms, it will require aggressive treatment and a hard-hitting plan to minimize recurrence. Proteus is an especially virulent organism that will require all our resources to overcome it.

REFERENCES
1. Scales CD Jr, Smith AC, Hanley JM, Saigal CS; Urologic Diseases in America Project. Prevalence of kidney stones in the United States. Eur Urol. 2012;62(1):160-165.

2. National Kidney Foundation. Diet and kidney stones. kidney.org/atoz/content/diet.cfm. Accessed October 1, 2104.

3. University of Michigan Health System. Bacterium that causes kidney stones and complicated urinary tract infections gives up its genetic secrets (2006). ScienceDaily. sciencedaily.com/releases/2006/05/060524125023.htm. Accessed October 1, 2014.

4. Torzewska A, Budzyńska A, Białczak-Kokot M, Różalski A. In vitro studies of epithelium-associated crystallization caused by uropathogens during urinary calculi development. Microb Pathog. 2014;71-72:25-31.

5. Pearson MM, Sebaihia M, Churcher C, et al. Complete genome sequence of uropathogenic Proteus mirabilis, a master of both adherence and motility. J Bacteriol. 2008;190(11):4027-4037.

6. Wells CG, Chandrashekar KB, Jyothirmayi GN, et al. Kidney stones: current diagnosis and management. Clinician Reviews. 2012;22(2):31-37.

7. Rowe CM, Ghei M, Adamska E. Moans, groans and renal stones: an interesting case of abdominal pain. BMJ Case Rep. 2013 Nov 4.

8. Chew R, Thomas S, Mantha ML, et al. Large urate cystolith associated with Proteus urinary tract infection. Kidney Int. 2012;81(8):802.

9. Shields J, Maxwell AP. Acute pyelonephritis can have serious complications. Practitioner. 2010;254(1728):19, 21, 23-24.

10. Kuan L, Schaffer JN, Zouzias CD, Pearson MM. Characterization of 17 chaperone-usher fimbriae encoded by Proteus mirabilis reveals strong conservation. J Med Microbiol. 2014;63(pt 7):911-922.

11. Proft T, Baker EN. Pili in Gram-negative and Gram-positive bacteria: structure, assembly and their role in disease. Cell Mol Life Sci. 2009;66(4):613-635.

Kidney stones are found in 11% of the population and are more than twice as common in men as in women.¹ Patients with underlying metabolic conditions (ie, obesity, diabetes, hypertension, hyperuricemia, hypercholesterolemia, hypertension, chronic kidney disease) are much more likely than others to have kidney stones. This is also a population at increased risk for cardiac disease. So if a patient has both kidney stones and heart disease, is kidney stone disease a cause or effect of heart disease? Or are the causes of heart disease also the causes of kidney stones?

For many years, professionals thought the population affected by kidney stones was also the group with risk factors for heart disease—that the metabolic conditions were found in both groups, but that the stones were not meaningful: The finding of kidney stones in the cardiac patient was an incidental, and slightly interesting, finding. Yet a study published recently in the American Journal of Kidney Disease has turned this concept on its head.² Liu and associates have done a meta-analysis of studies involving more than 3.5 million patients to explain exactly how kidney stones are related to cardiac disease.

In 1973, Westlund reported that patients who had kidney stones were just as likely to have had a myocardial infarction (MI).³ He was unable to identify an increased risk for MI in stone formers in his all-male cohort. In 1976, Elmfeldt and colleagues reported twice as many MIs in study subjects with kidney stones as in patients without stones.⁴ However, that same year, Ljunghall and Hedstrand were unable to find a correlation between kidney stones and heart disease in middle-aged men.⁵ Recently, Rule et al, using a 10,800-member study cohort of Minnesota residents, did show a 31% increased incidence of MI in patients with kidney stones.⁶

Liu and his group decided to try to answer this question once and for all. Using a graded system that examined studies of kidney stone patients who also showed signs of cardiac disease, they performed a meta-analysis comparing 50,000 patients with kidney stones and more than 3.5 million controls (patients without kidney stones). Controlling for the standard risk factors within this group (eg, age, gender, BMI, medication use, diabetes, smoking, alcohol use), the investigators identified kidney stones as a separate identifiable risk factor for cardiac disease.

In fact, Liu’s study team was able to quantify exactly how much greater a risk for cardiac disease exists in a kidney stone patient.² Using a multivariate outcomes data plot and defining cardiac disease using hard endpoints (fatal or nonfatal MI or coronary revascularization), the researchers found a 19% increase in cardiac disease among the kidney stone patients.⁷ When the endpoint used was cerebrovascular accident (CVA), patients with kidney stones had a 40% higher rate of stroke.

However, the real shock came when Liu and colleagues looked at the risk factors by gender. Quite simply, women with kidney stones had a higher rate of cardiac disease and stroke than men. In totality, the increased risk for cardiac disease and stroke for a male stone patient was not statistically significant. But in female stone patients, a 40% higher rate of stroke and a 31% higher rate of cardiac disease was discovered. This explains the huge disparity in previous studies. The increased risk for cardiac disease in the kidney stone patient is borne solely by the females of the population!²

Thus, we need to aggressively evaluate and treat our female patients for heart disease when they present with kidney stones. Just as the woman’s symptoms of MI are not “classic,” and one needs to consider gender when evaluating for MI, so do we need to consider gender in the kidney stone patient.⁸

Next time your patient is a woman with a kidney stone, remember to raise cardiac issues with her. The MI you prevent may be in my mother or my sister.

REFERENCES
1. Wells CG, Chandrashekar KB, Jyothirmayi GN, et al. Kidney stones: current diagnosis and management. Clinician Reviews. 2012;22(2):31-37.

2. Liu Y, Li S, Zeng Z, et al. Kidney stones and cardiovascular risk: a meta-analysis of cohort studies. Am J Kidney Dis. 2014;64(3):402-410.

3. Westlund K. Urolithiasis and coronary heart disease: a note on association. Am J Epidemiol. 1973;97(3):167-172.

4. Elmfeldt D, Vedin A, Wilhelmsson C, et al. Morbidity in representative male survivors of myocardial infarction compared to representative population samples. J Chronic Dis. 1976;29(4):221-231.

5. Ljunghall S, Hedstrand H. Renal stones and coronary heart disease. Acta Med Scand. 1976;199(6):481-485.

6. Rule AD, Roger VL, Melton LJ 3rd, et al. Kidney stones associate with increased risk for myocardial infarction. J Am Soc Nephrol. 2010;21(10):1641-1644.

7. Kidney stones linked to coronary heart disease, stroke [press release]. New York, NY: National Kidney Foundation; September 1, 2014. www.kidney.org/news/kidney-stones-linked-coronary-heart-disease-stroke. Accessed September 30, 2014.

8. McSweeney JC, Cody M, O’Sullivan P, et al. Women’s early warning symptoms of acute myocardial infarction. Circulation. 2003;108(21):2619-2623.

Kidney stones are found in 11% of the population and are more than twice as common in men as in women.¹ Patients with underlying metabolic conditions (ie, obesity, diabetes, hypertension, hyperuricemia, hypercholesterolemia, hypertension, chronic kidney disease) are much more likely than others to have kidney stones. This is also a population at increased risk for cardiac disease. So if a patient has both kidney stones and heart disease, is kidney stone disease a cause or effect of heart disease? Or are the causes of heart disease also the causes of kidney stones?

For many years, professionals thought the population affected by kidney stones was also the group with risk factors for heart disease—that the metabolic conditions were found in both groups, but that the stones were not meaningful: The finding of kidney stones in the cardiac patient was an incidental, and slightly interesting, finding. Yet a study published recently in the American Journal of Kidney Disease has turned this concept on its head.² Liu and associates have done a meta-analysis of studies involving more than 3.5 million patients to explain exactly how kidney stones are related to cardiac disease.

In 1973, Westlund reported that patients who had kidney stones were just as likely to have had a myocardial infarction (MI).³ He was unable to identify an increased risk for MI in stone formers in his all-male cohort. In 1976, Elmfeldt and colleagues reported twice as many MIs in study subjects with kidney stones as in patients without stones.⁴ However, that same year, Ljunghall and Hedstrand were unable to find a correlation between kidney stones and heart disease in middle-aged men.⁵ Recently, Rule et al, using a 10,800-member study cohort of Minnesota residents, did show a 31% increased incidence of MI in patients with kidney stones.⁶

Liu and his group decided to try to answer this question once and for all. Using a graded system that examined studies of kidney stone patients who also showed signs of cardiac disease, they performed a meta-analysis comparing 50,000 patients with kidney stones and more than 3.5 million controls (patients without kidney stones). Controlling for the standard risk factors within this group (eg, age, gender, BMI, medication use, diabetes, smoking, alcohol use), the investigators identified kidney stones as a separate identifiable risk factor for cardiac disease.

In fact, Liu’s study team was able to quantify exactly how much greater a risk for cardiac disease exists in a kidney stone patient.² Using a multivariate outcomes data plot and defining cardiac disease using hard endpoints (fatal or nonfatal MI or coronary revascularization), the researchers found a 19% increase in cardiac disease among the kidney stone patients.⁷ When the endpoint used was cerebrovascular accident (CVA), patients with kidney stones had a 40% higher rate of stroke.

However, the real shock came when Liu and colleagues looked at the risk factors by gender. Quite simply, women with kidney stones had a higher rate of cardiac disease and stroke than men. In totality, the increased risk for cardiac disease and stroke for a male stone patient was not statistically significant. But in female stone patients, a 40% higher rate of stroke and a 31% higher rate of cardiac disease was discovered. This explains the huge disparity in previous studies. The increased risk for cardiac disease in the kidney stone patient is borne solely by the females of the population!²

Thus, we need to aggressively evaluate and treat our female patients for heart disease when they present with kidney stones. Just as the woman’s symptoms of MI are not “classic,” and one needs to consider gender when evaluating for MI, so do we need to consider gender in the kidney stone patient.⁸

Next time your patient is a woman with a kidney stone, remember to raise cardiac issues with her. The MI you prevent may be in my mother or my sister.

REFERENCES
1. Wells CG, Chandrashekar KB, Jyothirmayi GN, et al. Kidney stones: current diagnosis and management. Clinician Reviews. 2012;22(2):31-37.

2. Liu Y, Li S, Zeng Z, et al. Kidney stones and cardiovascular risk: a meta-analysis of cohort studies. Am J Kidney Dis. 2014;64(3):402-410.

3. Westlund K. Urolithiasis and coronary heart disease: a note on association. Am J Epidemiol. 1973;97(3):167-172.

4. Elmfeldt D, Vedin A, Wilhelmsson C, et al. Morbidity in representative male survivors of myocardial infarction compared to representative population samples. J Chronic Dis. 1976;29(4):221-231.

5. Ljunghall S, Hedstrand H. Renal stones and coronary heart disease. Acta Med Scand. 1976;199(6):481-485.

6. Rule AD, Roger VL, Melton LJ 3rd, et al. Kidney stones associate with increased risk for myocardial infarction. J Am Soc Nephrol. 2010;21(10):1641-1644.

7. Kidney stones linked to coronary heart disease, stroke [press release]. New York, NY: National Kidney Foundation; September 1, 2014. www.kidney.org/news/kidney-stones-linked-coronary-heart-disease-stroke. Accessed September 30, 2014.

8. McSweeney JC, Cody M, O’Sullivan P, et al. Women’s early warning symptoms of acute myocardial infarction. Circulation. 2003;108(21):2619-2623.

Kidney stones are found in 11% of the population and are more than twice as common in men as in women.¹ Patients with underlying metabolic conditions (ie, obesity, diabetes, hypertension, hyperuricemia, hypercholesterolemia, hypertension, chronic kidney disease) are much more likely than others to have kidney stones. This is also a population at increased risk for cardiac disease. So if a patient has both kidney stones and heart disease, is kidney stone disease a cause or effect of heart disease? Or are the causes of heart disease also the causes of kidney stones?

For many years, professionals thought the population affected by kidney stones was also the group with risk factors for heart disease—that the metabolic conditions were found in both groups, but that the stones were not meaningful: The finding of kidney stones in the cardiac patient was an incidental, and slightly interesting, finding. Yet a study published recently in the American Journal of Kidney Disease has turned this concept on its head.² Liu and associates have done a meta-analysis of studies involving more than 3.5 million patients to explain exactly how kidney stones are related to cardiac disease.

In 1973, Westlund reported that patients who had kidney stones were just as likely to have had a myocardial infarction (MI).³ He was unable to identify an increased risk for MI in stone formers in his all-male cohort. In 1976, Elmfeldt and colleagues reported twice as many MIs in study subjects with kidney stones as in patients without stones.⁴ However, that same year, Ljunghall and Hedstrand were unable to find a correlation between kidney stones and heart disease in middle-aged men.⁵ Recently, Rule et al, using a 10,800-member study cohort of Minnesota residents, did show a 31% increased incidence of MI in patients with kidney stones.⁶

Liu and his group decided to try to answer this question once and for all. Using a graded system that examined studies of kidney stone patients who also showed signs of cardiac disease, they performed a meta-analysis comparing 50,000 patients with kidney stones and more than 3.5 million controls (patients without kidney stones). Controlling for the standard risk factors within this group (eg, age, gender, BMI, medication use, diabetes, smoking, alcohol use), the investigators identified kidney stones as a separate identifiable risk factor for cardiac disease.

In fact, Liu’s study team was able to quantify exactly how much greater a risk for cardiac disease exists in a kidney stone patient.² Using a multivariate outcomes data plot and defining cardiac disease using hard endpoints (fatal or nonfatal MI or coronary revascularization), the researchers found a 19% increase in cardiac disease among the kidney stone patients.⁷ When the endpoint used was cerebrovascular accident (CVA), patients with kidney stones had a 40% higher rate of stroke.

However, the real shock came when Liu and colleagues looked at the risk factors by gender. Quite simply, women with kidney stones had a higher rate of cardiac disease and stroke than men. In totality, the increased risk for cardiac disease and stroke for a male stone patient was not statistically significant. But in female stone patients, a 40% higher rate of stroke and a 31% higher rate of cardiac disease was discovered. This explains the huge disparity in previous studies. The increased risk for cardiac disease in the kidney stone patient is borne solely by the females of the population!²

Thus, we need to aggressively evaluate and treat our female patients for heart disease when they present with kidney stones. Just as the woman’s symptoms of MI are not “classic,” and one needs to consider gender when evaluating for MI, so do we need to consider gender in the kidney stone patient.⁸

Next time your patient is a woman with a kidney stone, remember to raise cardiac issues with her. The MI you prevent may be in my mother or my sister.

REFERENCES
1. Wells CG, Chandrashekar KB, Jyothirmayi GN, et al. Kidney stones: current diagnosis and management. Clinician Reviews. 2012;22(2):31-37.

2. Liu Y, Li S, Zeng Z, et al. Kidney stones and cardiovascular risk: a meta-analysis of cohort studies. Am J Kidney Dis. 2014;64(3):402-410.

3. Westlund K. Urolithiasis and coronary heart disease: a note on association. Am J Epidemiol. 1973;97(3):167-172.

4. Elmfeldt D, Vedin A, Wilhelmsson C, et al. Morbidity in representative male survivors of myocardial infarction compared to representative population samples. J Chronic Dis. 1976;29(4):221-231.

5. Ljunghall S, Hedstrand H. Renal stones and coronary heart disease. Acta Med Scand. 1976;199(6):481-485.

6. Rule AD, Roger VL, Melton LJ 3rd, et al. Kidney stones associate with increased risk for myocardial infarction. J Am Soc Nephrol. 2010;21(10):1641-1644.

7. Kidney stones linked to coronary heart disease, stroke [press release]. New York, NY: National Kidney Foundation; September 1, 2014. www.kidney.org/news/kidney-stones-linked-coronary-heart-disease-stroke. Accessed September 30, 2014.

8. McSweeney JC, Cody M, O’Sullivan P, et al. Women’s early warning symptoms of acute myocardial infarction. Circulation. 2003;108(21):2619-2623.

Each year in the United States alone, more than half a million patients are seen in emergency departments with kidney stones. This translates to a stone incidence of 9% of all males and 6% of all females over the lifespan, or 1 in 11 people.¹ Of these, 53% will have another stone during their lifetime.² Since kidney stones are extremely painful and can cause permanent kidney damage, the ability to predict which patients are likely to have a stone recurrence is extremely valuable. Recently, an online calculator has been developed that can help clinicians predict which first-time kidney stone patients are in the “worrisome” group and which are less likely to have a recurrence.³

Kidney stones (nephrolithiasis) are increasingly common in males, those between ages 30 and 50, and those with certain underlying medical conditions, such as hypertension, diabetes, and gout, as well as those with a history of bariatric surgery.⁴ A family history of stone formation is also predictive.

Since more than half of patients will have a second episode of kidney stones, the ability to identify and aggressively treat at-risk patients is vital. Using a data set of clinical characteristics from more than 2,000 first-time kidney stone patients from Olmsted County, Minnesota, and following these patients longitudinally for more than 20 years, Rule et al identified patients who had a second episode of kidney stones—as well as the characteristics associated with stone recurrence.⁵ They then developed a multivariate calculator, the ROKS nomogram, which can be used after a patient’s first episode of kidney stones to predict the likelihood of stone recurrence at 2, 5, and 10 years.³ The authors of the ROKS stone calculator were inspired by the World Health Organization’s FRAX calculator, which predicts 10-year fracture probability.^5,6

Rule et al identified 11 risk factors that they incorporated into the ROKS calculator. These include, but are not limited to, age, sex, race, family history, hematuria, presence of uric acid stones, and characteristics of the position of the initial stone in the pelvis. Not surprisingly, Rule et al found the kidney stone recurrence rate greatest in younger males who were white and had a family history of stones.

Minnesota, it should be noted, is an area of the country where summers are cooler; since people in warmer climates are at increased risk for kidney stones (particularly during the summer months), it is possible that the ROKS calculator would be even more useful in the South or Southwest than in the original study setting.⁵

A free, downloadable app of the ROKS calculator is available at the QxMD app “Calculate” (iOS: http://qx.md/qx, Android: http://qx.md/android, or web-based http://qxmd.com/ROKS).

Any episode of kidney stones increases the risk for chronic kidney disease and/or kidney failure.⁷ The absolute risk increase, though small, is present; any preventive measures one can offer at-risk patients is valuable. These range from increasing fluids and acidifying the urine to adding medications, including thiazide diuretics and allopurinol, to reduce stone formation. Unfortunately, only 3% of all first-time kidney stone patients are currently treated with medication to prevent a second episode.³ This creates an unnecessary risk for complications in a significant number of patients. By identifying members of the stone population who are likely to have a second event, clinicians can reduce the risk for recurrence.

Close monitoring of a patient with a significant stone history is vital. The ROKS calculator will allow practitioners to identify patients at increased risk for recurrent kidney stones and treat them aggressively—reducing the associated kidney damage and pain.

References
1. Scales CD Jr, Smith AC, Hanley JM, Saigal CS. Urologic Diseases in America Project: prevalence of kidney stones in the United States. Eur Urol. 2012;62:160-165.

2. Ljunghall S. Incidence of upper urinary tract stones. Miner Electrolyte Metab. 1987;13(4):220-227.

3. Rule AD, Lieske JC, Li X, et al. The ROKS Nomogram for Predicting a Second Symptomatic Stone Episode. J Am Soc Nephrol. 2014 Aug 7. [Epub ahead of print]

4. National Kidney Foundation. Kidney stones: how common are kidney stones? www.kidney.org/atoz/content/kidneystones.cfm. Accessed September 24, 2014.

5. Eisner BH, Goldfarb DS. A Nomogram for the Prediction of Kidney Stone Recurrence. J Am Soc Nephrol. 2014 Aug 7. [Epub ahead of print]

6. Kanis JA on behalf of the World Health Organization Scientific Group (2007). Assessment of osteoporosis at the primary healthcare level: report of a WHO Scientific Group. www.iofbonehealth.org/sites/default/files/WHO_Technical_Report-2007.pdf. Accessed September 26, 2014.

7. Alexander RT, Hemmelgarn BR, Wiebe N, et al. Kidney stones and kidney function loss: a cohort study. BMJ. 2012;345:e5287.

Each year in the United States alone, more than half a million patients are seen in emergency departments with kidney stones. This translates to a stone incidence of 9% of all males and 6% of all females over the lifespan, or 1 in 11 people.¹ Of these, 53% will have another stone during their lifetime.² Since kidney stones are extremely painful and can cause permanent kidney damage, the ability to predict which patients are likely to have a stone recurrence is extremely valuable. Recently, an online calculator has been developed that can help clinicians predict which first-time kidney stone patients are in the “worrisome” group and which are less likely to have a recurrence.³

Kidney stones (nephrolithiasis) are increasingly common in males, those between ages 30 and 50, and those with certain underlying medical conditions, such as hypertension, diabetes, and gout, as well as those with a history of bariatric surgery.⁴ A family history of stone formation is also predictive.

Since more than half of patients will have a second episode of kidney stones, the ability to identify and aggressively treat at-risk patients is vital. Using a data set of clinical characteristics from more than 2,000 first-time kidney stone patients from Olmsted County, Minnesota, and following these patients longitudinally for more than 20 years, Rule et al identified patients who had a second episode of kidney stones—as well as the characteristics associated with stone recurrence.⁵ They then developed a multivariate calculator, the ROKS nomogram, which can be used after a patient’s first episode of kidney stones to predict the likelihood of stone recurrence at 2, 5, and 10 years.³ The authors of the ROKS stone calculator were inspired by the World Health Organization’s FRAX calculator, which predicts 10-year fracture probability.^5,6

Rule et al identified 11 risk factors that they incorporated into the ROKS calculator. These include, but are not limited to, age, sex, race, family history, hematuria, presence of uric acid stones, and characteristics of the position of the initial stone in the pelvis. Not surprisingly, Rule et al found the kidney stone recurrence rate greatest in younger males who were white and had a family history of stones.

Minnesota, it should be noted, is an area of the country where summers are cooler; since people in warmer climates are at increased risk for kidney stones (particularly during the summer months), it is possible that the ROKS calculator would be even more useful in the South or Southwest than in the original study setting.⁵

A free, downloadable app of the ROKS calculator is available at the QxMD app “Calculate” (iOS: http://qx.md/qx, Android: http://qx.md/android, or web-based http://qxmd.com/ROKS).

Any episode of kidney stones increases the risk for chronic kidney disease and/or kidney failure.⁷ The absolute risk increase, though small, is present; any preventive measures one can offer at-risk patients is valuable. These range from increasing fluids and acidifying the urine to adding medications, including thiazide diuretics and allopurinol, to reduce stone formation. Unfortunately, only 3% of all first-time kidney stone patients are currently treated with medication to prevent a second episode.³ This creates an unnecessary risk for complications in a significant number of patients. By identifying members of the stone population who are likely to have a second event, clinicians can reduce the risk for recurrence.

Close monitoring of a patient with a significant stone history is vital. The ROKS calculator will allow practitioners to identify patients at increased risk for recurrent kidney stones and treat them aggressively—reducing the associated kidney damage and pain.

References
1. Scales CD Jr, Smith AC, Hanley JM, Saigal CS. Urologic Diseases in America Project: prevalence of kidney stones in the United States. Eur Urol. 2012;62:160-165.

2. Ljunghall S. Incidence of upper urinary tract stones. Miner Electrolyte Metab. 1987;13(4):220-227.

3. Rule AD, Lieske JC, Li X, et al. The ROKS Nomogram for Predicting a Second Symptomatic Stone Episode. J Am Soc Nephrol. 2014 Aug 7. [Epub ahead of print]

4. National Kidney Foundation. Kidney stones: how common are kidney stones? www.kidney.org/atoz/content/kidneystones.cfm. Accessed September 24, 2014.

5. Eisner BH, Goldfarb DS. A Nomogram for the Prediction of Kidney Stone Recurrence. J Am Soc Nephrol. 2014 Aug 7. [Epub ahead of print]

6. Kanis JA on behalf of the World Health Organization Scientific Group (2007). Assessment of osteoporosis at the primary healthcare level: report of a WHO Scientific Group. www.iofbonehealth.org/sites/default/files/WHO_Technical_Report-2007.pdf. Accessed September 26, 2014.

7. Alexander RT, Hemmelgarn BR, Wiebe N, et al. Kidney stones and kidney function loss: a cohort study. BMJ. 2012;345:e5287.

Each year in the United States alone, more than half a million patients are seen in emergency departments with kidney stones. This translates to a stone incidence of 9% of all males and 6% of all females over the lifespan, or 1 in 11 people.¹ Of these, 53% will have another stone during their lifetime.² Since kidney stones are extremely painful and can cause permanent kidney damage, the ability to predict which patients are likely to have a stone recurrence is extremely valuable. Recently, an online calculator has been developed that can help clinicians predict which first-time kidney stone patients are in the “worrisome” group and which are less likely to have a recurrence.³

Kidney stones (nephrolithiasis) are increasingly common in males, those between ages 30 and 50, and those with certain underlying medical conditions, such as hypertension, diabetes, and gout, as well as those with a history of bariatric surgery.⁴ A family history of stone formation is also predictive.

Since more than half of patients will have a second episode of kidney stones, the ability to identify and aggressively treat at-risk patients is vital. Using a data set of clinical characteristics from more than 2,000 first-time kidney stone patients from Olmsted County, Minnesota, and following these patients longitudinally for more than 20 years, Rule et al identified patients who had a second episode of kidney stones—as well as the characteristics associated with stone recurrence.⁵ They then developed a multivariate calculator, the ROKS nomogram, which can be used after a patient’s first episode of kidney stones to predict the likelihood of stone recurrence at 2, 5, and 10 years.³ The authors of the ROKS stone calculator were inspired by the World Health Organization’s FRAX calculator, which predicts 10-year fracture probability.^5,6

Rule et al identified 11 risk factors that they incorporated into the ROKS calculator. These include, but are not limited to, age, sex, race, family history, hematuria, presence of uric acid stones, and characteristics of the position of the initial stone in the pelvis. Not surprisingly, Rule et al found the kidney stone recurrence rate greatest in younger males who were white and had a family history of stones.

Minnesota, it should be noted, is an area of the country where summers are cooler; since people in warmer climates are at increased risk for kidney stones (particularly during the summer months), it is possible that the ROKS calculator would be even more useful in the South or Southwest than in the original study setting.⁵

A free, downloadable app of the ROKS calculator is available at the QxMD app “Calculate” (iOS: http://qx.md/qx, Android: http://qx.md/android, or web-based http://qxmd.com/ROKS).

Any episode of kidney stones increases the risk for chronic kidney disease and/or kidney failure.⁷ The absolute risk increase, though small, is present; any preventive measures one can offer at-risk patients is valuable. These range from increasing fluids and acidifying the urine to adding medications, including thiazide diuretics and allopurinol, to reduce stone formation. Unfortunately, only 3% of all first-time kidney stone patients are currently treated with medication to prevent a second episode.³ This creates an unnecessary risk for complications in a significant number of patients. By identifying members of the stone population who are likely to have a second event, clinicians can reduce the risk for recurrence.

Close monitoring of a patient with a significant stone history is vital. The ROKS calculator will allow practitioners to identify patients at increased risk for recurrent kidney stones and treat them aggressively—reducing the associated kidney damage and pain.

References
1. Scales CD Jr, Smith AC, Hanley JM, Saigal CS. Urologic Diseases in America Project: prevalence of kidney stones in the United States. Eur Urol. 2012;62:160-165.

2. Ljunghall S. Incidence of upper urinary tract stones. Miner Electrolyte Metab. 1987;13(4):220-227.

3. Rule AD, Lieske JC, Li X, et al. The ROKS Nomogram for Predicting a Second Symptomatic Stone Episode. J Am Soc Nephrol. 2014 Aug 7. [Epub ahead of print]

4. National Kidney Foundation. Kidney stones: how common are kidney stones? www.kidney.org/atoz/content/kidneystones.cfm. Accessed September 24, 2014.

5. Eisner BH, Goldfarb DS. A Nomogram for the Prediction of Kidney Stone Recurrence. J Am Soc Nephrol. 2014 Aug 7. [Epub ahead of print]

6. Kanis JA on behalf of the World Health Organization Scientific Group (2007). Assessment of osteoporosis at the primary healthcare level: report of a WHO Scientific Group. www.iofbonehealth.org/sites/default/files/WHO_Technical_Report-2007.pdf. Accessed September 26, 2014.

7. Alexander RT, Hemmelgarn BR, Wiebe N, et al. Kidney stones and kidney function loss: a cohort study. BMJ. 2012;345:e5287.

By age 70, 11% of men and 6% of women in the United States will have had at least one occurrence of kidney stones (nephrolithiasis).^1,2 This translates to a nationwide incidence rate of one in 11. More than 50% of those affected by kidney stones will experience a recurrence.³

Treatments for kidney stones, though available, are underutilized; only 3% of patients are treated after their first occurrence.³ Since treatment depends on the composition of the initial stone, identification is essential. Once the stone type is identified, treatment can be directed at the metabolic abnormality that caused the stone’s formation.

There are five types of stones: calcium-based, struvite, uric-acid, cystine, and the problematic “mixed.” The most common is the calcium-based stone, which accounts for nearly 80% of identified stones.^3,4 It is not the amount of calcium in the diet that usually causes a stone but rather the calcium excreted by the kidney collecting system.

One of the first recommendations for treatment of a calcium-based stone is a low-salt diet.⁴ Extra urinary sodium excretion (as a result of excess consumption) will increase calcium excretion in the urine. Decreasing salt in the diet will reduce sodium in the urine and, by extension, calcium as well. If conservative dietary changes are insufficient, a thiazide diuretic may be prescribed. (At present, a randomized clinical trial assessing treatment with oral potassium vs thiazides vs allopurinol for calcium-based stones is underway. Data from this trial will direct prevention strategies for calcium-based stones in the future.)

Uric acid stones can occur if the urine contains a high level of purine as a result of acidic foods in the diet. This usually means a diet rich in meats, shellfish, and high-purine foods (the same ones that can trigger gout).⁵ Control of the diet, alkalization of the urine, and/or treatment of the underlying high serum uric acid levels with allopurinol are the current recommended treatments.⁶

Struvite stones are caused by kidney infections. Many require long-term low-dose antibiotics in order to reduce reoccurrence.⁶ It is vital to know if a stone is struvite, since the treatment is significantly different from that for other types of stones. 

Cystine stones result from a genetic disorder (cystinuria) that affects an amino acid. Often, these types of stones are seen in younger patients, and any teen who presents with kidney stones should undergo a work-up for the genetic abnormality. (See Zuber K. Woman, 26, with kidney stones. Clinician Reviews. 2011;21(3):8-10.)

When a patient complains of severe, colicky abdominal pain, hematuria, or a sharp pain in the back or flank, the thought of kidney stones must be front and center. Evaluation incudes both serum testing and CT.^5,7 Abdominal plain films and/or an intravenous pyelogram were considered state of the art in the 1980s and 1990s, but helical CT has become the scan of choice since it allows for measurement of the size, position, and level of obstruction. Helical CTs are increasingly available nationwide—and a sensitivity of 95% to 100% makes them the preferred method of evalution.^5,8

REFERENCES
1. Scales CD Jr, Smith AC, Hanley JM, Saigal CS. Urologic Diseases in America Project: Prevalence of kidney stones in the United States. Eur Urol. 2012;62:160-165.

2. Worcester EM, Coe FL. Calcium kidney stones. N Engl J Med. 2010;363:954-963.

3. Rule A, Lieske JC, Li X, et al. The ROKS Nomogram for Predicting a Second Symptomatic Stone Episode. J Am Soc Nephrol. 2014 Aug 7; [Epub ahead of print].

4. National Kidney Foundation. Diet and kidney stones. www.kidney.org/atoz/content/diet.cfm. Accessed September 9, 2104.

5. Jackman SV, Potter SR, Regan F, Jarrett TW. Plain abdominal x-ray versus computerized tomography screening: sensitivity for stone localization after nonenhanced spiral computerized tomography. J Urol. 2000;164(2):308-310.

6. Lipkin ME, Preminger GM. Demystifying the medical management of nephrolithiasis. Rev Urol. 2011;13(1):34-38.

7. National Institute of Diabetes and Digestive and Kidney Diseases. Kidney stones in adults: what are the types of kidney stones?  http://kidney.niddk.nih.gov/KUDiseases/pubs/stonesadults/index.aspx#types. Accessed September 9, 2014.

8. Harrington K, Torreggiani W. CT analysis of renal stone composition: a novel and noninvasive method to analyse stones. Ir Med J. 2014;107(3):69.

By age 70, 11% of men and 6% of women in the United States will have had at least one occurrence of kidney stones (nephrolithiasis).^1,2 This translates to a nationwide incidence rate of one in 11. More than 50% of those affected by kidney stones will experience a recurrence.³

Treatments for kidney stones, though available, are underutilized; only 3% of patients are treated after their first occurrence.³ Since treatment depends on the composition of the initial stone, identification is essential. Once the stone type is identified, treatment can be directed at the metabolic abnormality that caused the stone’s formation.

There are five types of stones: calcium-based, struvite, uric-acid, cystine, and the problematic “mixed.” The most common is the calcium-based stone, which accounts for nearly 80% of identified stones.^3,4 It is not the amount of calcium in the diet that usually causes a stone but rather the calcium excreted by the kidney collecting system.

One of the first recommendations for treatment of a calcium-based stone is a low-salt diet.⁴ Extra urinary sodium excretion (as a result of excess consumption) will increase calcium excretion in the urine. Decreasing salt in the diet will reduce sodium in the urine and, by extension, calcium as well. If conservative dietary changes are insufficient, a thiazide diuretic may be prescribed. (At present, a randomized clinical trial assessing treatment with oral potassium vs thiazides vs allopurinol for calcium-based stones is underway. Data from this trial will direct prevention strategies for calcium-based stones in the future.)

Uric acid stones can occur if the urine contains a high level of purine as a result of acidic foods in the diet. This usually means a diet rich in meats, shellfish, and high-purine foods (the same ones that can trigger gout).⁵ Control of the diet, alkalization of the urine, and/or treatment of the underlying high serum uric acid levels with allopurinol are the current recommended treatments.⁶

Struvite stones are caused by kidney infections. Many require long-term low-dose antibiotics in order to reduce reoccurrence.⁶ It is vital to know if a stone is struvite, since the treatment is significantly different from that for other types of stones. 

Cystine stones result from a genetic disorder (cystinuria) that affects an amino acid. Often, these types of stones are seen in younger patients, and any teen who presents with kidney stones should undergo a work-up for the genetic abnormality. (See Zuber K. Woman, 26, with kidney stones. Clinician Reviews. 2011;21(3):8-10.)

When a patient complains of severe, colicky abdominal pain, hematuria, or a sharp pain in the back or flank, the thought of kidney stones must be front and center. Evaluation incudes both serum testing and CT.^5,7 Abdominal plain films and/or an intravenous pyelogram were considered state of the art in the 1980s and 1990s, but helical CT has become the scan of choice since it allows for measurement of the size, position, and level of obstruction. Helical CTs are increasingly available nationwide—and a sensitivity of 95% to 100% makes them the preferred method of evalution.^5,8

REFERENCES
1. Scales CD Jr, Smith AC, Hanley JM, Saigal CS. Urologic Diseases in America Project: Prevalence of kidney stones in the United States. Eur Urol. 2012;62:160-165.

2. Worcester EM, Coe FL. Calcium kidney stones. N Engl J Med. 2010;363:954-963.

3. Rule A, Lieske JC, Li X, et al. The ROKS Nomogram for Predicting a Second Symptomatic Stone Episode. J Am Soc Nephrol. 2014 Aug 7; [Epub ahead of print].

4. National Kidney Foundation. Diet and kidney stones. www.kidney.org/atoz/content/diet.cfm. Accessed September 9, 2104.

5. Jackman SV, Potter SR, Regan F, Jarrett TW. Plain abdominal x-ray versus computerized tomography screening: sensitivity for stone localization after nonenhanced spiral computerized tomography. J Urol. 2000;164(2):308-310.

6. Lipkin ME, Preminger GM. Demystifying the medical management of nephrolithiasis. Rev Urol. 2011;13(1):34-38.

7. National Institute of Diabetes and Digestive and Kidney Diseases. Kidney stones in adults: what are the types of kidney stones?  http://kidney.niddk.nih.gov/KUDiseases/pubs/stonesadults/index.aspx#types. Accessed September 9, 2014.

8. Harrington K, Torreggiani W. CT analysis of renal stone composition: a novel and noninvasive method to analyse stones. Ir Med J. 2014;107(3):69.

By age 70, 11% of men and 6% of women in the United States will have had at least one occurrence of kidney stones (nephrolithiasis).^1,2 This translates to a nationwide incidence rate of one in 11. More than 50% of those affected by kidney stones will experience a recurrence.³

Treatments for kidney stones, though available, are underutilized; only 3% of patients are treated after their first occurrence.³ Since treatment depends on the composition of the initial stone, identification is essential. Once the stone type is identified, treatment can be directed at the metabolic abnormality that caused the stone’s formation.

There are five types of stones: calcium-based, struvite, uric-acid, cystine, and the problematic “mixed.” The most common is the calcium-based stone, which accounts for nearly 80% of identified stones.^3,4 It is not the amount of calcium in the diet that usually causes a stone but rather the calcium excreted by the kidney collecting system.

One of the first recommendations for treatment of a calcium-based stone is a low-salt diet.⁴ Extra urinary sodium excretion (as a result of excess consumption) will increase calcium excretion in the urine. Decreasing salt in the diet will reduce sodium in the urine and, by extension, calcium as well. If conservative dietary changes are insufficient, a thiazide diuretic may be prescribed. (At present, a randomized clinical trial assessing treatment with oral potassium vs thiazides vs allopurinol for calcium-based stones is underway. Data from this trial will direct prevention strategies for calcium-based stones in the future.)

Uric acid stones can occur if the urine contains a high level of purine as a result of acidic foods in the diet. This usually means a diet rich in meats, shellfish, and high-purine foods (the same ones that can trigger gout).⁵ Control of the diet, alkalization of the urine, and/or treatment of the underlying high serum uric acid levels with allopurinol are the current recommended treatments.⁶

Struvite stones are caused by kidney infections. Many require long-term low-dose antibiotics in order to reduce reoccurrence.⁶ It is vital to know if a stone is struvite, since the treatment is significantly different from that for other types of stones. 

Cystine stones result from a genetic disorder (cystinuria) that affects an amino acid. Often, these types of stones are seen in younger patients, and any teen who presents with kidney stones should undergo a work-up for the genetic abnormality. (See Zuber K. Woman, 26, with kidney stones. Clinician Reviews. 2011;21(3):8-10.)

When a patient complains of severe, colicky abdominal pain, hematuria, or a sharp pain in the back or flank, the thought of kidney stones must be front and center. Evaluation incudes both serum testing and CT.^5,7 Abdominal plain films and/or an intravenous pyelogram were considered state of the art in the 1980s and 1990s, but helical CT has become the scan of choice since it allows for measurement of the size, position, and level of obstruction. Helical CTs are increasingly available nationwide—and a sensitivity of 95% to 100% makes them the preferred method of evalution.^5,8

REFERENCES
1. Scales CD Jr, Smith AC, Hanley JM, Saigal CS. Urologic Diseases in America Project: Prevalence of kidney stones in the United States. Eur Urol. 2012;62:160-165.

2. Worcester EM, Coe FL. Calcium kidney stones. N Engl J Med. 2010;363:954-963.

3. Rule A, Lieske JC, Li X, et al. The ROKS Nomogram for Predicting a Second Symptomatic Stone Episode. J Am Soc Nephrol. 2014 Aug 7; [Epub ahead of print].

4. National Kidney Foundation. Diet and kidney stones. www.kidney.org/atoz/content/diet.cfm. Accessed September 9, 2104.

5. Jackman SV, Potter SR, Regan F, Jarrett TW. Plain abdominal x-ray versus computerized tomography screening: sensitivity for stone localization after nonenhanced spiral computerized tomography. J Urol. 2000;164(2):308-310.

6. Lipkin ME, Preminger GM. Demystifying the medical management of nephrolithiasis. Rev Urol. 2011;13(1):34-38.

7. National Institute of Diabetes and Digestive and Kidney Diseases. Kidney stones in adults: what are the types of kidney stones?  http://kidney.niddk.nih.gov/KUDiseases/pubs/stonesadults/index.aspx#types. Accessed September 9, 2014.

8. Harrington K, Torreggiani W. CT analysis of renal stone composition: a novel and noninvasive method to analyse stones. Ir Med J. 2014;107(3):69.

Kidney stones (nephrolithiasis), seen in 11% of all Americans, may increase patients’ risk for chronic kidney disease (CKD), although current research findings are insufficient to support a well-established relationship.^1,2 Actually, CKD may have a protective effect against the formation of calcium-based stones (which account for about 80% of all stones), since the CKD-affected kidney may fail to concentrate and excrete calcium. However, this effect is often offset by metabolic syndrome, diabetes, and hypertension—all of which increase the risk for calcium-based stones.^4,5 Heredity is also a factor.

After calcium-based stones, the most common types are struvite, uric acid, cysteine, and “mixed” stones. Not so common are the hereditary stones associated with four relatively rare conditions: primary hyperoxaluria (PH), adenine phosphoribosyltransferase (APRT) deficiency, cystinuria, and Dent’s disease. According to the NIH Rare Diseases Clinical Research Network, only 524 patients with these conditions are enrolled in the Mayo Clinic–based Rare Kidney Stone Consortium, indicating the orphan status of these illnesses.⁶

Patients with PH are born with an autosomal recessive error of glyoxylate metabolism that results in an overproduction of calcium oxalate.⁷ The oxalate is deposited in various organs—most often the kidneys, in the form of kidney stones. PH can occur in infants; parents are often alerted by rust spots in diapers, caused by passage of small stones.

There are three types of PH: PH1, PH2, and PH3. PH1 and PH2 account for approximately 90% of cases.⁸ In PH1, the genetic error is linked to an insufficient or absent liver enzyme. About 50% of children with PH1 will develop end-stage renal disease by young adulthood.⁹ One of the suggested treatments is liver transplantation, because replacing the diseased kidney alone would not spare the newly transplanted kidney from the same fate: a shower of stones from the liver. For patients with PH2 (which is generally less severe than PH1), kidney transplantation alone is often effective.¹⁰ In patients with any type of PH, high fluid intake is recommended.

Like PH, APRT/2,8-DHA crystalluria is an autosomal recessive disorder, one that researchers consider underrecognized and underdiagnosed. The majority of cases have been reported from Japan, France, and Iceland.¹¹ Often the stones are misidentified as uric acid or xanthine stones. Patients with APRT deficiency present with a range of symptoms—from stone disease to full kidney failure.¹² Treatment components include administration of allopurinol (a purine analog), increased fluid intake, a mildly purine-restricted diet, and extracorporeal shock-wave lithotripsy, when indicated.¹³

Cystinuria is found in 1% to 2% of patients with kidney stones but about 5% of children with stones¹⁴; it most often presents in early childhood. Patients have impaired renal cysteine transport, which leads to stone formation.¹⁵ Before it became possible to identify the genes responsible for cystinuria, patients were classified according to cystine excretion levels. Treatment includes high fluid intake, mild restriction of protein and sodium, alkalinization of urine, and use of medications including penicillamine and captopril.^16,17

The rare stone-producing illness Dent’s disease is an X-linked recessive condition that can lead to hypercalciuria, stones, CKD, and rickets.¹⁸ It usually presents in childhood, often in children who fail to thrive, and is associated with mutations of at least two genes (accounting for different disease types). Low-molecular-weight proteinuria is almost always present, but renal failure is relatively uncommon. Thiazide therapy has been found effective in treating the hypercalciuria associated with Dent’s disease, and addition of an ACE inhibitor may be helpful in patients with cystinosis.¹⁹

Kidney stones should be suspected in children with a family history of stones and symptoms such as hematuria, flank or abdominal pain, and/or urinary symptoms (dysuria, urinary tract infection). Genetic testing and counseling is frequently advised for these children and their families, as the correct diagnosis guides appropriate treatment.

References
1. Scales CD Jr, Smith AC, Hanley JM, Saigal CS. Urologic Diseases in America Project: Prevalence of kidney stones in the United States. Eur Urol. 2012;62:160-165.

2. Worcester EM, Coe FL. Calcium kidney stones. N Engl J Med. 2010;363:954-963.

3. Rule AD, Krambeck AE, Lieske JC. Chronic kidney disease in kidney stone formers. Clin J Am Soc Nephrol. 2011;6(8):2069-2075.

4. Teichman JM. Clinical practice. Acute renal colic from ureteral calculus. N Engl J Med. 2004;350(7):684-693.

5. National Institute of Diabetes and Digestive and Kidney Diseases. Kidney stones in adults: what are the types of kidney stones? http://kidney.niddk.nih.gov/KUDiseases/pubs/stonesadults/index.aspx. Accessed September 29, 2014.

6. Nazzal L. Spotlight on RDCRN consortia: the Rare Kidney Stone Consortium. http://rarediseasesnetwork.org/spotlight/April2013/RKSC. Accessed September 26, 2014.

7. Hoppe B. An update on primary hyperoxaluria. Nat Rev Nephrol. 2012;8(8):467-475.

8. Hoppe B, Langman CB. A United States survey on diagnosis, treatment, and outcome of primary hyperoxaluria. Pediatr Nephrol. 2003;18(10):986-991.

9. Harambat J, Farque S, Acquaviva C. Genotype-phenotype correlation in primary hyperoxaluria type 1: the p.Gly170Arg AGXT mutation is associated with a better outcome. Kidney Int. 2010;77(5):443-449.

10. Bergstralh EJ, Monico CG, Lieske JC. Transplantation outcomes in primary hyperoxaluria. Am J Transplant. 2010;10(11):2493-2501. 

11. Rare Clinical Diseases Research Network. Diseases in depth: adenine phosphoribosyltransferase (APRT) deficiency. www.rarediseasesnetwork.org/RKSC/professional/APRT/index.htm. Accessed September 29, 2014.

12. Edvardsson V, Palsson R. Adenine phosphoribosyltransferase deficiency and 2,8-dihydroxyadeninuria. In: Moriwaki Y, ed. Genetic Errors Associated with Purine and Pyrimidine Metabolism in Humans: Diagnosis and Treatment. Kerala, India: Research Signpost; 2006:79-93.

13. Edvardsson V, Palsson R, Olafsson I, et al. Clinical features and genotype of adenine phosphoribosyltransferase deficiency in Iceland. Am J Kidney Dis. 2001;38(3):473-480.

14. Stapleton FB. Childhood stones. Endocrinol Metab Clin North Am. 2002;31(4):1001-1015.

15. Mattoo A, Goldfarb DS. Cystinuria. Semin Nephrol. 2008;28(2):181-191.

16. Goldfarb DS, Coe FL, Asplin JR. Urinary cystine excretion and capacity in patients with cystinuria. Kidney Int. 2006;69(6):1041-1047.

17. Perazella MA, Buller GK. Successful treatment of cystinuria with captopril. Am J Kidney Dis. 1993;21(5):504-507.

18. Devuyst O, Thakker RV. Dent’s disease. Orphanet J Rare Dis. 2010;5:28.

19. Ludwig M, Utsch B, Monnens LA. Recent advances in understanding the clinical and genetic heterogeneity of Dent’s disease. Nephrol Dial Transplant. 2006;21(10):2708-2717.

Kidney stones (nephrolithiasis), seen in 11% of all Americans, may increase patients’ risk for chronic kidney disease (CKD), although current research findings are insufficient to support a well-established relationship.^1,2 Actually, CKD may have a protective effect against the formation of calcium-based stones (which account for about 80% of all stones), since the CKD-affected kidney may fail to concentrate and excrete calcium. However, this effect is often offset by metabolic syndrome, diabetes, and hypertension—all of which increase the risk for calcium-based stones.^4,5 Heredity is also a factor.

After calcium-based stones, the most common types are struvite, uric acid, cysteine, and “mixed” stones. Not so common are the hereditary stones associated with four relatively rare conditions: primary hyperoxaluria (PH), adenine phosphoribosyltransferase (APRT) deficiency, cystinuria, and Dent’s disease. According to the NIH Rare Diseases Clinical Research Network, only 524 patients with these conditions are enrolled in the Mayo Clinic–based Rare Kidney Stone Consortium, indicating the orphan status of these illnesses.⁶

Patients with PH are born with an autosomal recessive error of glyoxylate metabolism that results in an overproduction of calcium oxalate.⁷ The oxalate is deposited in various organs—most often the kidneys, in the form of kidney stones. PH can occur in infants; parents are often alerted by rust spots in diapers, caused by passage of small stones.

There are three types of PH: PH1, PH2, and PH3. PH1 and PH2 account for approximately 90% of cases.⁸ In PH1, the genetic error is linked to an insufficient or absent liver enzyme. About 50% of children with PH1 will develop end-stage renal disease by young adulthood.⁹ One of the suggested treatments is liver transplantation, because replacing the diseased kidney alone would not spare the newly transplanted kidney from the same fate: a shower of stones from the liver. For patients with PH2 (which is generally less severe than PH1), kidney transplantation alone is often effective.¹⁰ In patients with any type of PH, high fluid intake is recommended.

Like PH, APRT/2,8-DHA crystalluria is an autosomal recessive disorder, one that researchers consider underrecognized and underdiagnosed. The majority of cases have been reported from Japan, France, and Iceland.¹¹ Often the stones are misidentified as uric acid or xanthine stones. Patients with APRT deficiency present with a range of symptoms—from stone disease to full kidney failure.¹² Treatment components include administration of allopurinol (a purine analog), increased fluid intake, a mildly purine-restricted diet, and extracorporeal shock-wave lithotripsy, when indicated.¹³

Cystinuria is found in 1% to 2% of patients with kidney stones but about 5% of children with stones¹⁴; it most often presents in early childhood. Patients have impaired renal cysteine transport, which leads to stone formation.¹⁵ Before it became possible to identify the genes responsible for cystinuria, patients were classified according to cystine excretion levels. Treatment includes high fluid intake, mild restriction of protein and sodium, alkalinization of urine, and use of medications including penicillamine and captopril.^16,17

The rare stone-producing illness Dent’s disease is an X-linked recessive condition that can lead to hypercalciuria, stones, CKD, and rickets.¹⁸ It usually presents in childhood, often in children who fail to thrive, and is associated with mutations of at least two genes (accounting for different disease types). Low-molecular-weight proteinuria is almost always present, but renal failure is relatively uncommon. Thiazide therapy has been found effective in treating the hypercalciuria associated with Dent’s disease, and addition of an ACE inhibitor may be helpful in patients with cystinosis.¹⁹

Kidney stones should be suspected in children with a family history of stones and symptoms such as hematuria, flank or abdominal pain, and/or urinary symptoms (dysuria, urinary tract infection). Genetic testing and counseling is frequently advised for these children and their families, as the correct diagnosis guides appropriate treatment.

References
1. Scales CD Jr, Smith AC, Hanley JM, Saigal CS. Urologic Diseases in America Project: Prevalence of kidney stones in the United States. Eur Urol. 2012;62:160-165.

2. Worcester EM, Coe FL. Calcium kidney stones. N Engl J Med. 2010;363:954-963.

3. Rule AD, Krambeck AE, Lieske JC. Chronic kidney disease in kidney stone formers. Clin J Am Soc Nephrol. 2011;6(8):2069-2075.

4. Teichman JM. Clinical practice. Acute renal colic from ureteral calculus. N Engl J Med. 2004;350(7):684-693.

5. National Institute of Diabetes and Digestive and Kidney Diseases. Kidney stones in adults: what are the types of kidney stones? http://kidney.niddk.nih.gov/KUDiseases/pubs/stonesadults/index.aspx. Accessed September 29, 2014.

6. Nazzal L. Spotlight on RDCRN consortia: the Rare Kidney Stone Consortium. http://rarediseasesnetwork.org/spotlight/April2013/RKSC. Accessed September 26, 2014.

7. Hoppe B. An update on primary hyperoxaluria. Nat Rev Nephrol. 2012;8(8):467-475.

8. Hoppe B, Langman CB. A United States survey on diagnosis, treatment, and outcome of primary hyperoxaluria. Pediatr Nephrol. 2003;18(10):986-991.

9. Harambat J, Farque S, Acquaviva C. Genotype-phenotype correlation in primary hyperoxaluria type 1: the p.Gly170Arg AGXT mutation is associated with a better outcome. Kidney Int. 2010;77(5):443-449.

10. Bergstralh EJ, Monico CG, Lieske JC. Transplantation outcomes in primary hyperoxaluria. Am J Transplant. 2010;10(11):2493-2501. 

11. Rare Clinical Diseases Research Network. Diseases in depth: adenine phosphoribosyltransferase (APRT) deficiency. www.rarediseasesnetwork.org/RKSC/professional/APRT/index.htm. Accessed September 29, 2014.

12. Edvardsson V, Palsson R. Adenine phosphoribosyltransferase deficiency and 2,8-dihydroxyadeninuria. In: Moriwaki Y, ed. Genetic Errors Associated with Purine and Pyrimidine Metabolism in Humans: Diagnosis and Treatment. Kerala, India: Research Signpost; 2006:79-93.

13. Edvardsson V, Palsson R, Olafsson I, et al. Clinical features and genotype of adenine phosphoribosyltransferase deficiency in Iceland. Am J Kidney Dis. 2001;38(3):473-480.

14. Stapleton FB. Childhood stones. Endocrinol Metab Clin North Am. 2002;31(4):1001-1015.

15. Mattoo A, Goldfarb DS. Cystinuria. Semin Nephrol. 2008;28(2):181-191.

16. Goldfarb DS, Coe FL, Asplin JR. Urinary cystine excretion and capacity in patients with cystinuria. Kidney Int. 2006;69(6):1041-1047.

17. Perazella MA, Buller GK. Successful treatment of cystinuria with captopril. Am J Kidney Dis. 1993;21(5):504-507.

18. Devuyst O, Thakker RV. Dent’s disease. Orphanet J Rare Dis. 2010;5:28.

19. Ludwig M, Utsch B, Monnens LA. Recent advances in understanding the clinical and genetic heterogeneity of Dent’s disease. Nephrol Dial Transplant. 2006;21(10):2708-2717.

Kidney stones (nephrolithiasis), seen in 11% of all Americans, may increase patients’ risk for chronic kidney disease (CKD), although current research findings are insufficient to support a well-established relationship.^1,2 Actually, CKD may have a protective effect against the formation of calcium-based stones (which account for about 80% of all stones), since the CKD-affected kidney may fail to concentrate and excrete calcium. However, this effect is often offset by metabolic syndrome, diabetes, and hypertension—all of which increase the risk for calcium-based stones.^4,5 Heredity is also a factor.

After calcium-based stones, the most common types are struvite, uric acid, cysteine, and “mixed” stones. Not so common are the hereditary stones associated with four relatively rare conditions: primary hyperoxaluria (PH), adenine phosphoribosyltransferase (APRT) deficiency, cystinuria, and Dent’s disease. According to the NIH Rare Diseases Clinical Research Network, only 524 patients with these conditions are enrolled in the Mayo Clinic–based Rare Kidney Stone Consortium, indicating the orphan status of these illnesses.⁶

Patients with PH are born with an autosomal recessive error of glyoxylate metabolism that results in an overproduction of calcium oxalate.⁷ The oxalate is deposited in various organs—most often the kidneys, in the form of kidney stones. PH can occur in infants; parents are often alerted by rust spots in diapers, caused by passage of small stones.

There are three types of PH: PH1, PH2, and PH3. PH1 and PH2 account for approximately 90% of cases.⁸ In PH1, the genetic error is linked to an insufficient or absent liver enzyme. About 50% of children with PH1 will develop end-stage renal disease by young adulthood.⁹ One of the suggested treatments is liver transplantation, because replacing the diseased kidney alone would not spare the newly transplanted kidney from the same fate: a shower of stones from the liver. For patients with PH2 (which is generally less severe than PH1), kidney transplantation alone is often effective.¹⁰ In patients with any type of PH, high fluid intake is recommended.

Like PH, APRT/2,8-DHA crystalluria is an autosomal recessive disorder, one that researchers consider underrecognized and underdiagnosed. The majority of cases have been reported from Japan, France, and Iceland.¹¹ Often the stones are misidentified as uric acid or xanthine stones. Patients with APRT deficiency present with a range of symptoms—from stone disease to full kidney failure.¹² Treatment components include administration of allopurinol (a purine analog), increased fluid intake, a mildly purine-restricted diet, and extracorporeal shock-wave lithotripsy, when indicated.¹³

Cystinuria is found in 1% to 2% of patients with kidney stones but about 5% of children with stones¹⁴; it most often presents in early childhood. Patients have impaired renal cysteine transport, which leads to stone formation.¹⁵ Before it became possible to identify the genes responsible for cystinuria, patients were classified according to cystine excretion levels. Treatment includes high fluid intake, mild restriction of protein and sodium, alkalinization of urine, and use of medications including penicillamine and captopril.^16,17

The rare stone-producing illness Dent’s disease is an X-linked recessive condition that can lead to hypercalciuria, stones, CKD, and rickets.¹⁸ It usually presents in childhood, often in children who fail to thrive, and is associated with mutations of at least two genes (accounting for different disease types). Low-molecular-weight proteinuria is almost always present, but renal failure is relatively uncommon. Thiazide therapy has been found effective in treating the hypercalciuria associated with Dent’s disease, and addition of an ACE inhibitor may be helpful in patients with cystinosis.¹⁹

Kidney stones should be suspected in children with a family history of stones and symptoms such as hematuria, flank or abdominal pain, and/or urinary symptoms (dysuria, urinary tract infection). Genetic testing and counseling is frequently advised for these children and their families, as the correct diagnosis guides appropriate treatment.

References
1. Scales CD Jr, Smith AC, Hanley JM, Saigal CS. Urologic Diseases in America Project: Prevalence of kidney stones in the United States. Eur Urol. 2012;62:160-165.

2. Worcester EM, Coe FL. Calcium kidney stones. N Engl J Med. 2010;363:954-963.

3. Rule AD, Krambeck AE, Lieske JC. Chronic kidney disease in kidney stone formers. Clin J Am Soc Nephrol. 2011;6(8):2069-2075.

4. Teichman JM. Clinical practice. Acute renal colic from ureteral calculus. N Engl J Med. 2004;350(7):684-693.

5. National Institute of Diabetes and Digestive and Kidney Diseases. Kidney stones in adults: what are the types of kidney stones? http://kidney.niddk.nih.gov/KUDiseases/pubs/stonesadults/index.aspx. Accessed September 29, 2014.

6. Nazzal L. Spotlight on RDCRN consortia: the Rare Kidney Stone Consortium. http://rarediseasesnetwork.org/spotlight/April2013/RKSC. Accessed September 26, 2014.

7. Hoppe B. An update on primary hyperoxaluria. Nat Rev Nephrol. 2012;8(8):467-475.

8. Hoppe B, Langman CB. A United States survey on diagnosis, treatment, and outcome of primary hyperoxaluria. Pediatr Nephrol. 2003;18(10):986-991.

9. Harambat J, Farque S, Acquaviva C. Genotype-phenotype correlation in primary hyperoxaluria type 1: the p.Gly170Arg AGXT mutation is associated with a better outcome. Kidney Int. 2010;77(5):443-449.

10. Bergstralh EJ, Monico CG, Lieske JC. Transplantation outcomes in primary hyperoxaluria. Am J Transplant. 2010;10(11):2493-2501. 

11. Rare Clinical Diseases Research Network. Diseases in depth: adenine phosphoribosyltransferase (APRT) deficiency. www.rarediseasesnetwork.org/RKSC/professional/APRT/index.htm. Accessed September 29, 2014.

12. Edvardsson V, Palsson R. Adenine phosphoribosyltransferase deficiency and 2,8-dihydroxyadeninuria. In: Moriwaki Y, ed. Genetic Errors Associated with Purine and Pyrimidine Metabolism in Humans: Diagnosis and Treatment. Kerala, India: Research Signpost; 2006:79-93.

13. Edvardsson V, Palsson R, Olafsson I, et al. Clinical features and genotype of adenine phosphoribosyltransferase deficiency in Iceland. Am J Kidney Dis. 2001;38(3):473-480.

14. Stapleton FB. Childhood stones. Endocrinol Metab Clin North Am. 2002;31(4):1001-1015.

15. Mattoo A, Goldfarb DS. Cystinuria. Semin Nephrol. 2008;28(2):181-191.

16. Goldfarb DS, Coe FL, Asplin JR. Urinary cystine excretion and capacity in patients with cystinuria. Kidney Int. 2006;69(6):1041-1047.

17. Perazella MA, Buller GK. Successful treatment of cystinuria with captopril. Am J Kidney Dis. 1993;21(5):504-507.

18. Devuyst O, Thakker RV. Dent’s disease. Orphanet J Rare Dis. 2010;5:28.

19. Ludwig M, Utsch B, Monnens LA. Recent advances in understanding the clinical and genetic heterogeneity of Dent’s disease. Nephrol Dial Transplant. 2006;21(10):2708-2717.

The long lazy days of summer are ending: The warm evenings, the iced tea, the sounds of kids playing at the pool being overshadowed by the loud moans of the patient with kidney stones ….

Kidney stones (nephrolithiasis) are collections of crystals that coalesce into a hard ball and can lodge in any location of the urinary collecting systems. More than half a million patients seen in US emergency departments each year will receive a diagnosis of nephrolithiasis.¹

But the problem is much more common in the summer, thanks to the double whammy of heat and humidity.^2-4 Research indicates that it is not geographic area but instead the effects of climate that impact stone incidence.⁵ As climate change occurs, it is expected that the incidence of kidney stones will rise.

There is a “stone belt” that covers the southern portion of the United States (see Figure). As reported in Kidney International, this area is growing due to climate change and is expected to reach as far north as Nebraska, Illinois, Pennsylvania, and Oregon by 2095. Thus, the incidence of stone formation will increase throughout the 21st century in many parts of the US.⁶

Kidney stones are more common in men than in women and in white than in nonwhite persons (by three to four times). Peak incidence occurs between ages 20 and 50.¹ Heat plays a greater role in the increased incidence of stone formation in men for unknown reasons.⁶

Stones that lodge in the ureter or the calyces of the kidney will often cause obstruction. When the flow of urine is obstructed, infection, loss of kidney function, and chronic permanent damage can result. Thus, decreasing the incidence of stones is vital at any time of the year—but most significant during the summer. 

All patients with a history of stones require fluid hydration, up to 2.5 L/d, with extra intake during the heat of summer.⁷ Patients who travel to hot, humid regions must be encouraged to increase fluid consumption. Often, foreign travel can be problematic due to a decrease in access to clean drinking water and/or lavatory facilities. It is incumbent upon the practitioner to review risk for kidney stones with patients who plan to travel to warm areas.

As the summer season closes and school starts, this is a perfect time to review the causes, treatment, and most importantly, the methods to decrease recurrent kidney stone formation with patients. Each incident of stone formation for our patients can translate to an increased incidence of chronic kidney disease and a 50% risk for another stone during their lifetime.¹

REFERENCES
1. National Kidney Foundation. Kidney stones. www.kidney.org/atoz/content/kidneystones.cfm. Accessed September 10, 2014.

2.Schade GR, Faerber GJ. Urinary tract stones. Prim Care. 2010;37(3):565-581, ix.

3. Pearle MS, Calhoun E, Curhan GC. Urolithiasis. In: Litwin MS, Saigal CS, eds. Urologic Diseases in America. National Institute of Diabetes and Digestive and Kidney Diseases. 2007:281-320. http://kidney.niddk.nih.gov/statistics/uda/Urologic_Diseases_in_America.pdf. Accessed September 10, 2014.

4. Romero V, Akpinar H, Assimos DG. Kidney stones: a global picture of prevalence, incidence and associated risk factors. Rev Urol. 2010;12(2-3):e86-e96.

5. Eisner BH, Sheth S, Herrick B, et al. The effects of ambient temperature, humidity and season of year on urine composition in patients with nephrolithiasis. BJU Int. 2012;110(11c):E1014–E1017.

6. Fakheri RJ, Goldfarb DS. Ambient temperature as a contributor to kidney stone formation: Implications of global warming. Kidney Int. 2011;79:1178–1185.

7. Lipkin ME, Preminger GM. Demystifying the medical management of nephrolithiasis. Rev Urol. 2011;13(1):34-38.

The long lazy days of summer are ending: The warm evenings, the iced tea, the sounds of kids playing at the pool being overshadowed by the loud moans of the patient with kidney stones ….

Kidney stones (nephrolithiasis) are collections of crystals that coalesce into a hard ball and can lodge in any location of the urinary collecting systems. More than half a million patients seen in US emergency departments each year will receive a diagnosis of nephrolithiasis.¹

But the problem is much more common in the summer, thanks to the double whammy of heat and humidity.^2-4 Research indicates that it is not geographic area but instead the effects of climate that impact stone incidence.⁵ As climate change occurs, it is expected that the incidence of kidney stones will rise.

There is a “stone belt” that covers the southern portion of the United States (see Figure). As reported in Kidney International, this area is growing due to climate change and is expected to reach as far north as Nebraska, Illinois, Pennsylvania, and Oregon by 2095. Thus, the incidence of stone formation will increase throughout the 21st century in many parts of the US.⁶

Kidney stones are more common in men than in women and in white than in nonwhite persons (by three to four times). Peak incidence occurs between ages 20 and 50.¹ Heat plays a greater role in the increased incidence of stone formation in men for unknown reasons.⁶

Stones that lodge in the ureter or the calyces of the kidney will often cause obstruction. When the flow of urine is obstructed, infection, loss of kidney function, and chronic permanent damage can result. Thus, decreasing the incidence of stones is vital at any time of the year—but most significant during the summer. 

All patients with a history of stones require fluid hydration, up to 2.5 L/d, with extra intake during the heat of summer.⁷ Patients who travel to hot, humid regions must be encouraged to increase fluid consumption. Often, foreign travel can be problematic due to a decrease in access to clean drinking water and/or lavatory facilities. It is incumbent upon the practitioner to review risk for kidney stones with patients who plan to travel to warm areas.

As the summer season closes and school starts, this is a perfect time to review the causes, treatment, and most importantly, the methods to decrease recurrent kidney stone formation with patients. Each incident of stone formation for our patients can translate to an increased incidence of chronic kidney disease and a 50% risk for another stone during their lifetime.¹

REFERENCES
1. National Kidney Foundation. Kidney stones. www.kidney.org/atoz/content/kidneystones.cfm. Accessed September 10, 2014.

2.Schade GR, Faerber GJ. Urinary tract stones. Prim Care. 2010;37(3):565-581, ix.

3. Pearle MS, Calhoun E, Curhan GC. Urolithiasis. In: Litwin MS, Saigal CS, eds. Urologic Diseases in America. National Institute of Diabetes and Digestive and Kidney Diseases. 2007:281-320. http://kidney.niddk.nih.gov/statistics/uda/Urologic_Diseases_in_America.pdf. Accessed September 10, 2014.

4. Romero V, Akpinar H, Assimos DG. Kidney stones: a global picture of prevalence, incidence and associated risk factors. Rev Urol. 2010;12(2-3):e86-e96.

5. Eisner BH, Sheth S, Herrick B, et al. The effects of ambient temperature, humidity and season of year on urine composition in patients with nephrolithiasis. BJU Int. 2012;110(11c):E1014–E1017.

6. Fakheri RJ, Goldfarb DS. Ambient temperature as a contributor to kidney stone formation: Implications of global warming. Kidney Int. 2011;79:1178–1185.

7. Lipkin ME, Preminger GM. Demystifying the medical management of nephrolithiasis. Rev Urol. 2011;13(1):34-38.

The long lazy days of summer are ending: The warm evenings, the iced tea, the sounds of kids playing at the pool being overshadowed by the loud moans of the patient with kidney stones ….

Kidney stones (nephrolithiasis) are collections of crystals that coalesce into a hard ball and can lodge in any location of the urinary collecting systems. More than half a million patients seen in US emergency departments each year will receive a diagnosis of nephrolithiasis.¹

But the problem is much more common in the summer, thanks to the double whammy of heat and humidity.^2-4 Research indicates that it is not geographic area but instead the effects of climate that impact stone incidence.⁵ As climate change occurs, it is expected that the incidence of kidney stones will rise.

There is a “stone belt” that covers the southern portion of the United States (see Figure). As reported in Kidney International, this area is growing due to climate change and is expected to reach as far north as Nebraska, Illinois, Pennsylvania, and Oregon by 2095. Thus, the incidence of stone formation will increase throughout the 21st century in many parts of the US.⁶

Kidney stones are more common in men than in women and in white than in nonwhite persons (by three to four times). Peak incidence occurs between ages 20 and 50.¹ Heat plays a greater role in the increased incidence of stone formation in men for unknown reasons.⁶

Stones that lodge in the ureter or the calyces of the kidney will often cause obstruction. When the flow of urine is obstructed, infection, loss of kidney function, and chronic permanent damage can result. Thus, decreasing the incidence of stones is vital at any time of the year—but most significant during the summer. 

All patients with a history of stones require fluid hydration, up to 2.5 L/d, with extra intake during the heat of summer.⁷ Patients who travel to hot, humid regions must be encouraged to increase fluid consumption. Often, foreign travel can be problematic due to a decrease in access to clean drinking water and/or lavatory facilities. It is incumbent upon the practitioner to review risk for kidney stones with patients who plan to travel to warm areas.

As the summer season closes and school starts, this is a perfect time to review the causes, treatment, and most importantly, the methods to decrease recurrent kidney stone formation with patients. Each incident of stone formation for our patients can translate to an increased incidence of chronic kidney disease and a 50% risk for another stone during their lifetime.¹

REFERENCES
1. National Kidney Foundation. Kidney stones. www.kidney.org/atoz/content/kidneystones.cfm. Accessed September 10, 2014.

2.Schade GR, Faerber GJ. Urinary tract stones. Prim Care. 2010;37(3):565-581, ix.

3. Pearle MS, Calhoun E, Curhan GC. Urolithiasis. In: Litwin MS, Saigal CS, eds. Urologic Diseases in America. National Institute of Diabetes and Digestive and Kidney Diseases. 2007:281-320. http://kidney.niddk.nih.gov/statistics/uda/Urologic_Diseases_in_America.pdf. Accessed September 10, 2014.

4. Romero V, Akpinar H, Assimos DG. Kidney stones: a global picture of prevalence, incidence and associated risk factors. Rev Urol. 2010;12(2-3):e86-e96.

5. Eisner BH, Sheth S, Herrick B, et al. The effects of ambient temperature, humidity and season of year on urine composition in patients with nephrolithiasis. BJU Int. 2012;110(11c):E1014–E1017.

6. Fakheri RJ, Goldfarb DS. Ambient temperature as a contributor to kidney stone formation: Implications of global warming. Kidney Int. 2011;79:1178–1185.

7. Lipkin ME, Preminger GM. Demystifying the medical management of nephrolithiasis. Rev Urol. 2011;13(1):34-38.

Q: We are trying to develop renal education classes in our hospital’s general medical clinic. Participating patients (pre-renal) will be those we hope can be managed by their primary care providers in coordination with our nephrology specialists before their initial renal clinic visits. Our team of educators will include an RN, an NP, a primary care physician, and a nephrologist. Any information, models, and/or links to educational resources would be much appreciated.

Everyone loses 1% of kidney function per year after age 40. If we lived long enough, all of us would need renal education!

As you try to develop classes, one of your first concerns will be whether you want to charge for them. If they are meant to be billed for, they will take a much different form than a free kidney disease education class would. Let’s explore both.

PAID CLASSES
Only Medicare pays for education classes, and patients must be at stage 4 kidney disease (ie, glomerular filtration rate [GFR], 15 to 30 mL/dL). The class can be taught in a group or an individualized format, and an RN, a dietician, or a social worker can assist—but the bulk of the class must be taught by a practitioner with a National Provider Identifier billing number (an NP, a PA, or a physician).

Medicare specifies the content of the classes and has set certain requirements regarding a class’s site and length. In addition, there must be preevaluation and postevaluation tools in place, and the number of classes over a patient’s lifetime is limited to six.

The best program available (one that contains all the needed tools, slide sets, and handouts) is Your Treatment, Your Choice⁸ from the National Kidney Foundation (www.kidney.org/profes sionals/KLS/YTYC.cfm). It is free, but you must be a PA, an NP, or an MD to request it.

NONPAID CLASSES AND PROGRAMS
These can be given by anybody, and the format is up to the teacher. Prevention always trumps a cure, and preventing advanced kidney disease (GFR < 60 mL/dL) fits in very well in general practice. Promoting good health habits is a common goal. To that end, instruction regarding diet, blood pressure control, blood sugar control, and smoking cessation all help slow kidney disease progression.

What’s best about offering classes like these is that you don’t have to reinvent the wheel. There are some fantastic free programs out there. Some of our favorites are available through the National Kidney Disease Education Program (NKDEP) Web site: http://nkdep.nih.gov/resources.shtml. This is a division of one of the National Institutes of Health, paid for by your tax dollars, and it offers free or very inexpensive handouts, videos, and slide sets, all written at an eighth-grade reading level.

Among the materials offered is a phenomenal tear-off sheet, “Explaining Your Kidney Test Results,” which is available in English, Spanish, Chinese, and Vietnamese (with the first five copies free, then $1 each). It illustrates the stages of kidney function using the traffic light scenario: green, yellow, or red (stage 5 CKD is the red zone) and explains what patients can do to “stay out of the red.” We consider this one of the most effective tools we can use.

NKDEP also offers free handouts listing foods high in potassium, phosphorus, protein, and sodium. Nothing is as good as a renal dietician, but these forms are an excellent alternative.

NKDEP allows you to download and reprint almost all of their information free, or you can request 50 copies of just about any item at no cost. Put your best shopper on the Web site. The amount of materials offered is truly wonderful, and you can’t beat the price.

Another program is called Kidney School (http://kidneyschool
.org), a nonprofit organization set up by the kidney community that offers all kinds of videos and slide sets at no charge.

Last, but certainly not least, is Seymour Jones and the Temple of CKD, a five-minute video put out by the Renal Support Network (RSN; www.rsnhope.org). You can request the video from RSN or find it on YouTube (www.youtube.com/watch?v=lDJZHIVTNzo). Though hilarious, it makes excellent points about the symptoms of chronic kidney disease.

As you can see, there are many wonderful and varied (and free!) programs out there.

With the double-whammy of an aging population and increasing obesity, the number of people with kidney disease is growing exponentially; the past 20 years have seen a 67% increase in the number of patients with CKD, which now affects more than 20 million Americans. Yet in that same 20-year period, effective treatments have been developed for CKD that “can delay and, in some cases, prevent ESRD.”⁹ Patients with CKD need not assume there will be dialysis in their future.

Most importantly of all, we need to get out there and talk up prevention.                         

Kim Zuber, PA-C; Jane S. Davis, DNP, CRNP

REFERENCES
1. K/DOQI [Kidney Disease Outcome Quality Initiative] clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004;43(5 suppl 1):S1-S290.

2. Reilly RF, Jackson EK. Ch 25. Regulation of renal function and vascular volume. In: Chabner BA, Brunton LL, Knollman BC, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 12th ed. New York: McGraw-Hill Professional; 2010.

3. Sica DA, Gehr TW. Diuretic use in stage 5 chronic kidney disease and end-stage renal disease. Curr Opin Nephrol Hypertens. 2003;12(5): 483-490.

4. Cohen DL, Townsend RR. Treatment of hypertension in patients with chronic kidney disease. US Cardiology. 2009;6(2):54-58.

5. Wickersham RM, ed. Drug Facts and Comparisons. St. Louis, MO: Wolters Kluwer Health; 2009.

6. Comparison of commonly used diuretics (Detail Document). Pharmacist’s Letter/Prescriber’s Letter. February 2012.

7. DRUGDEX® System [Internet database]. Greenwood Village, Colo: Thomson Reuters (Healthcare) Inc. Updated periodically.

8. National Kidney Foundation. MIPPA Kidney Disease Education Benefit. Your Treatment, Your Choice (2010). www.kidney.org/professionals/KLS/YTYC.cfm. Accessed September 19, 2012.

9. Turner JM, Bauer C, Abramowitz MK, et al. Treatment of chronic kidney disease. Kidney Int. 2012;81(4):351-362.

Q: We are trying to develop renal education classes in our hospital’s general medical clinic. Participating patients (pre-renal) will be those we hope can be managed by their primary care providers in coordination with our nephrology specialists before their initial renal clinic visits. Our team of educators will include an RN, an NP, a primary care physician, and a nephrologist. Any information, models, and/or links to educational resources would be much appreciated.

Everyone loses 1% of kidney function per year after age 40. If we lived long enough, all of us would need renal education!

As you try to develop classes, one of your first concerns will be whether you want to charge for them. If they are meant to be billed for, they will take a much different form than a free kidney disease education class would. Let’s explore both.

PAID CLASSES
Only Medicare pays for education classes, and patients must be at stage 4 kidney disease (ie, glomerular filtration rate [GFR], 15 to 30 mL/dL). The class can be taught in a group or an individualized format, and an RN, a dietician, or a social worker can assist—but the bulk of the class must be taught by a practitioner with a National Provider Identifier billing number (an NP, a PA, or a physician).

Medicare specifies the content of the classes and has set certain requirements regarding a class’s site and length. In addition, there must be preevaluation and postevaluation tools in place, and the number of classes over a patient’s lifetime is limited to six.

The best program available (one that contains all the needed tools, slide sets, and handouts) is Your Treatment, Your Choice⁸ from the National Kidney Foundation (www.kidney.org/profes sionals/KLS/YTYC.cfm). It is free, but you must be a PA, an NP, or an MD to request it.

NONPAID CLASSES AND PROGRAMS
These can be given by anybody, and the format is up to the teacher. Prevention always trumps a cure, and preventing advanced kidney disease (GFR < 60 mL/dL) fits in very well in general practice. Promoting good health habits is a common goal. To that end, instruction regarding diet, blood pressure control, blood sugar control, and smoking cessation all help slow kidney disease progression.

What’s best about offering classes like these is that you don’t have to reinvent the wheel. There are some fantastic free programs out there. Some of our favorites are available through the National Kidney Disease Education Program (NKDEP) Web site: http://nkdep.nih.gov/resources.shtml. This is a division of one of the National Institutes of Health, paid for by your tax dollars, and it offers free or very inexpensive handouts, videos, and slide sets, all written at an eighth-grade reading level.

Among the materials offered is a phenomenal tear-off sheet, “Explaining Your Kidney Test Results,” which is available in English, Spanish, Chinese, and Vietnamese (with the first five copies free, then $1 each). It illustrates the stages of kidney function using the traffic light scenario: green, yellow, or red (stage 5 CKD is the red zone) and explains what patients can do to “stay out of the red.” We consider this one of the most effective tools we can use.

NKDEP also offers free handouts listing foods high in potassium, phosphorus, protein, and sodium. Nothing is as good as a renal dietician, but these forms are an excellent alternative.

NKDEP allows you to download and reprint almost all of their information free, or you can request 50 copies of just about any item at no cost. Put your best shopper on the Web site. The amount of materials offered is truly wonderful, and you can’t beat the price.

Another program is called Kidney School (http://kidneyschool
.org), a nonprofit organization set up by the kidney community that offers all kinds of videos and slide sets at no charge.

Last, but certainly not least, is Seymour Jones and the Temple of CKD, a five-minute video put out by the Renal Support Network (RSN; www.rsnhope.org). You can request the video from RSN or find it on YouTube (www.youtube.com/watch?v=lDJZHIVTNzo). Though hilarious, it makes excellent points about the symptoms of chronic kidney disease.

As you can see, there are many wonderful and varied (and free!) programs out there.

With the double-whammy of an aging population and increasing obesity, the number of people with kidney disease is growing exponentially; the past 20 years have seen a 67% increase in the number of patients with CKD, which now affects more than 20 million Americans. Yet in that same 20-year period, effective treatments have been developed for CKD that “can delay and, in some cases, prevent ESRD.”⁹ Patients with CKD need not assume there will be dialysis in their future.

Most importantly of all, we need to get out there and talk up prevention.                         

Kim Zuber, PA-C; Jane S. Davis, DNP, CRNP

REFERENCES
1. K/DOQI [Kidney Disease Outcome Quality Initiative] clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004;43(5 suppl 1):S1-S290.

2. Reilly RF, Jackson EK. Ch 25. Regulation of renal function and vascular volume. In: Chabner BA, Brunton LL, Knollman BC, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 12th ed. New York: McGraw-Hill Professional; 2010.

3. Sica DA, Gehr TW. Diuretic use in stage 5 chronic kidney disease and end-stage renal disease. Curr Opin Nephrol Hypertens. 2003;12(5): 483-490.

4. Cohen DL, Townsend RR. Treatment of hypertension in patients with chronic kidney disease. US Cardiology. 2009;6(2):54-58.

5. Wickersham RM, ed. Drug Facts and Comparisons. St. Louis, MO: Wolters Kluwer Health; 2009.

6. Comparison of commonly used diuretics (Detail Document). Pharmacist’s Letter/Prescriber’s Letter. February 2012.

7. DRUGDEX® System [Internet database]. Greenwood Village, Colo: Thomson Reuters (Healthcare) Inc. Updated periodically.

8. National Kidney Foundation. MIPPA Kidney Disease Education Benefit. Your Treatment, Your Choice (2010). www.kidney.org/professionals/KLS/YTYC.cfm. Accessed September 19, 2012.

9. Turner JM, Bauer C, Abramowitz MK, et al. Treatment of chronic kidney disease. Kidney Int. 2012;81(4):351-362.

Q: We are trying to develop renal education classes in our hospital’s general medical clinic. Participating patients (pre-renal) will be those we hope can be managed by their primary care providers in coordination with our nephrology specialists before their initial renal clinic visits. Our team of educators will include an RN, an NP, a primary care physician, and a nephrologist. Any information, models, and/or links to educational resources would be much appreciated.

Everyone loses 1% of kidney function per year after age 40. If we lived long enough, all of us would need renal education!

As you try to develop classes, one of your first concerns will be whether you want to charge for them. If they are meant to be billed for, they will take a much different form than a free kidney disease education class would. Let’s explore both.

PAID CLASSES
Only Medicare pays for education classes, and patients must be at stage 4 kidney disease (ie, glomerular filtration rate [GFR], 15 to 30 mL/dL). The class can be taught in a group or an individualized format, and an RN, a dietician, or a social worker can assist—but the bulk of the class must be taught by a practitioner with a National Provider Identifier billing number (an NP, a PA, or a physician).

Medicare specifies the content of the classes and has set certain requirements regarding a class’s site and length. In addition, there must be preevaluation and postevaluation tools in place, and the number of classes over a patient’s lifetime is limited to six.

The best program available (one that contains all the needed tools, slide sets, and handouts) is Your Treatment, Your Choice⁸ from the National Kidney Foundation (www.kidney.org/profes sionals/KLS/YTYC.cfm). It is free, but you must be a PA, an NP, or an MD to request it.

NONPAID CLASSES AND PROGRAMS
These can be given by anybody, and the format is up to the teacher. Prevention always trumps a cure, and preventing advanced kidney disease (GFR < 60 mL/dL) fits in very well in general practice. Promoting good health habits is a common goal. To that end, instruction regarding diet, blood pressure control, blood sugar control, and smoking cessation all help slow kidney disease progression.

What’s best about offering classes like these is that you don’t have to reinvent the wheel. There are some fantastic free programs out there. Some of our favorites are available through the National Kidney Disease Education Program (NKDEP) Web site: http://nkdep.nih.gov/resources.shtml. This is a division of one of the National Institutes of Health, paid for by your tax dollars, and it offers free or very inexpensive handouts, videos, and slide sets, all written at an eighth-grade reading level.

Among the materials offered is a phenomenal tear-off sheet, “Explaining Your Kidney Test Results,” which is available in English, Spanish, Chinese, and Vietnamese (with the first five copies free, then $1 each). It illustrates the stages of kidney function using the traffic light scenario: green, yellow, or red (stage 5 CKD is the red zone) and explains what patients can do to “stay out of the red.” We consider this one of the most effective tools we can use.

NKDEP also offers free handouts listing foods high in potassium, phosphorus, protein, and sodium. Nothing is as good as a renal dietician, but these forms are an excellent alternative.

NKDEP allows you to download and reprint almost all of their information free, or you can request 50 copies of just about any item at no cost. Put your best shopper on the Web site. The amount of materials offered is truly wonderful, and you can’t beat the price.

Another program is called Kidney School (http://kidneyschool
.org), a nonprofit organization set up by the kidney community that offers all kinds of videos and slide sets at no charge.

Last, but certainly not least, is Seymour Jones and the Temple of CKD, a five-minute video put out by the Renal Support Network (RSN; www.rsnhope.org). You can request the video from RSN or find it on YouTube (www.youtube.com/watch?v=lDJZHIVTNzo). Though hilarious, it makes excellent points about the symptoms of chronic kidney disease.

As you can see, there are many wonderful and varied (and free!) programs out there.

With the double-whammy of an aging population and increasing obesity, the number of people with kidney disease is growing exponentially; the past 20 years have seen a 67% increase in the number of patients with CKD, which now affects more than 20 million Americans. Yet in that same 20-year period, effective treatments have been developed for CKD that “can delay and, in some cases, prevent ESRD.”⁹ Patients with CKD need not assume there will be dialysis in their future.

Most importantly of all, we need to get out there and talk up prevention.                         

Kim Zuber, PA-C; Jane S. Davis, DNP, CRNP

REFERENCES
1. K/DOQI [Kidney Disease Outcome Quality Initiative] clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004;43(5 suppl 1):S1-S290.

2. Reilly RF, Jackson EK. Ch 25. Regulation of renal function and vascular volume. In: Chabner BA, Brunton LL, Knollman BC, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 12th ed. New York: McGraw-Hill Professional; 2010.

3. Sica DA, Gehr TW. Diuretic use in stage 5 chronic kidney disease and end-stage renal disease. Curr Opin Nephrol Hypertens. 2003;12(5): 483-490.

4. Cohen DL, Townsend RR. Treatment of hypertension in patients with chronic kidney disease. US Cardiology. 2009;6(2):54-58.

5. Wickersham RM, ed. Drug Facts and Comparisons. St. Louis, MO: Wolters Kluwer Health; 2009.

6. Comparison of commonly used diuretics (Detail Document). Pharmacist’s Letter/Prescriber’s Letter. February 2012.

7. DRUGDEX® System [Internet database]. Greenwood Village, Colo: Thomson Reuters (Healthcare) Inc. Updated periodically.

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