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Kidney Donation & HIV
Q) Now that patients are living with HIV/AIDS, can they donate kidneys or receive a kidney transplant?
Kidney disease often has multiple causes, including hypertension, diabetes, inherited conditions, and viral illnesses. The latter include primarily HIV, hepatitis C, and hepatitis B. With advances in the treatment of viral illnesses, the question of whether patients with these viruses can donate or receive a kidney transplant is being discussed not only in the United States but also worldwide.
The most recent CDC figures estimate that more than 1.1 million people in the US are living with HIV, of whom one in six (or nearly 16%) are undiagnosed. There are approximately 50,000 new infections reported annually.2
The Organ Transplant Amendments Act of 1988 banned HIV-positive people from donating organs. However, with the introduction of highly active antiretroviral therapy (HAART, now often referred to as active antiretroviral therapy) and the effective prophylaxis and management of opportunistic infections, mortality has been reduced. HIV/AIDS is often seen as a chronic disease and not the death sentence it once was.3 Since the development of HAART, there have been successful transplants to HIV-positive recipients from non–HIV-infected donors.
In November 2013, President Obama signed the HIV Organ Policy Equity (HOPE) Act, which lifted the ban on using organs from HIV-infected donors. The legislation directs the Department of Health and Human Services and the Organ Procurement and Transplantation Network to develop standards to make these transplants possible.4
Although there have not been any documented cases of transplants from HIV-infected donors to HIV-infected recipients in this country, such transplants have been very successful in South Africa.5 There, to qualify for kidney transplant, all recipients must have proven adherence, virologic suppression, and immune constitution. Donor suitability is defined as HIV infection (confirmed with the use of enzyme-linked immunosorbent assay), absence of proteinuria, and a normal kidney as assessed with post hoc renal biopsy.5
One of the chief concerns has been the effect of further immunosuppression on the recipients and the possibility of disease progression. Although the sample size is limited (four transplants), data from the available cases indicate no evidence of organ rejection at 12 months post-transplantation. In addition, the recipients’ CD4 counts remained lower than baseline due to immunosuppressive therapy. All four patients maintained a viral load of less than 50 copies, which suggested that any virus transplanted along with the kidney had not affected control of HIV infection.5 However, it should be noted that many of the agents used for posttransplant maintenance immunosuppression (mycophenolate mofetil, cyclosporine, tacrolimus, and sirolimus) have antiretroviral properties.3
HIV patients in the US must meet the following criteria to be listed for a transplant:
• Diagnosis of ESRD with at least a five-year life-expectancy
• CD4 count of > 200 cells/ μL for at least six months
• Undetectable HIV viremia (< 50 HIV-1 RNA copies/mL)
• Demonstrated adherence to stable antiviral regimen for at least six months
• Absence of AIDS-defining illness following successful immune reconstitution6
A prospective trial of 150 patients in 19 US transplant centers who met the above criteria demonstrated patient survival and graft survival rates comparable to those in patients ages 65 and older.6
While awaiting the donation, HIV patients can continue hemodialysis and peritoneal dialysis. With the improved antiviral drugs, HIV patients have a survival rate similar to the non–HIV-infected population.
Transplantation is the goal and certainly the hope of many advanced-stage kidney patients, but in reality, the need far exceeds the resources. The HOPE Act opens the door for many patients who were previously excluded from the possibility of a life without dialysis. Taking care of these patients will be a team effort, encompassing HIV and infectious disease specialists, pharmacists, nephrologists, transplant surgeons and coordinators, and primary care providers—including, of course, advanced practitioners.
Shelly Levinstein, MSN, CRNP
Nephrology Associates of York
York, PA
REFERENCES
1. Muzaale AD, Massie AB, Wang MC, et al. Risk of end-stage renal disease following live kidney donation. JAMA. 2014;311(6):579-586.
2. CDC. HIV in the United States: at a glance (2013). www.cdc.gov/hiv/statistics/basics/ataglance.html. Accessed June 16, 2014.
3. Frassetto LA, Tan-Tam C, Stock PG. Renal transplantation in patients with HIV. Nat Rev Nephrol. 2009;5(10):582-589.
4. Malani PN. New law allows organ transplants from deceased HIV-infected donors to HIV-infected recipients. JAMA. 2013;310(23): 2492-2493.
5. Muller E, Kahn D, Mendelson M. Renal transplantation between HIV-positive donors and recipients. N Engl J Med. 2010;362(24):2336-2337.
6. Mariani LH, Berns JS. Viral nephropathies. In: Gilbert SJ, Weiner DE, eds. National Kidney Foundation’s Primer on Kidney Diseases. 6th ed. Elsevier; 2014:253-261.
| Clinician Reviews in partnership with |
 |
Renal Consult is edited by Jane S. Davis, CRNP, DNP, a member of the Clinician Reviews editorial board, who is a nurse practitioner in the Division of Nephrology at the University of Alabama at Birmingham and is the communications chairperson for the National Kidney Foundation’s Council of Advanced Practitioners (NKF-CAP); and Kim Zuber, PA-C, MSPS, DFAAPA, who is a physician assistant with Metropolitan Nephrology in Alexandria, Virginia, and Clinton, Maryland; she is also past chair of the NKF-CAP.
| Clinician Reviews in partnership with |
|
Renal Consult is edited by Jane S. Davis, CRNP, DNP, a member of the Clinician Reviews editorial board, who is a nurse practitioner in the Division of Nephrology at the University of Alabama at Birmingham and is the communications chairperson for the National Kidney Foundation’s Council of Advanced Practitioners (NKF-CAP); and Kim Zuber, PA-C, MSPS, DFAAPA, who is a physician assistant with Metropolitan Nephrology in Alexandria, Virginia, and Clinton, Maryland; she is also past chair of the NKF-CAP.
| Clinician Reviews in partnership with |
|
Renal Consult is edited by Jane S. Davis, CRNP, DNP, a member of the Clinician Reviews editorial board, who is a nurse practitioner in the Division of Nephrology at the University of Alabama at Birmingham and is the communications chairperson for the National Kidney Foundation’s Council of Advanced Practitioners (NKF-CAP); and Kim Zuber, PA-C, MSPS, DFAAPA, who is a physician assistant with Metropolitan Nephrology in Alexandria, Virginia, and Clinton, Maryland; she is also past chair of the NKF-CAP.
Q) Now that patients are living with HIV/AIDS, can they donate kidneys or receive a kidney transplant?
Kidney disease often has multiple causes, including hypertension, diabetes, inherited conditions, and viral illnesses. The latter include primarily HIV, hepatitis C, and hepatitis B. With advances in the treatment of viral illnesses, the question of whether patients with these viruses can donate or receive a kidney transplant is being discussed not only in the United States but also worldwide.
The most recent CDC figures estimate that more than 1.1 million people in the US are living with HIV, of whom one in six (or nearly 16%) are undiagnosed. There are approximately 50,000 new infections reported annually.2
The Organ Transplant Amendments Act of 1988 banned HIV-positive people from donating organs. However, with the introduction of highly active antiretroviral therapy (HAART, now often referred to as active antiretroviral therapy) and the effective prophylaxis and management of opportunistic infections, mortality has been reduced. HIV/AIDS is often seen as a chronic disease and not the death sentence it once was.3 Since the development of HAART, there have been successful transplants to HIV-positive recipients from non–HIV-infected donors.
In November 2013, President Obama signed the HIV Organ Policy Equity (HOPE) Act, which lifted the ban on using organs from HIV-infected donors. The legislation directs the Department of Health and Human Services and the Organ Procurement and Transplantation Network to develop standards to make these transplants possible.4
Although there have not been any documented cases of transplants from HIV-infected donors to HIV-infected recipients in this country, such transplants have been very successful in South Africa.5 There, to qualify for kidney transplant, all recipients must have proven adherence, virologic suppression, and immune constitution. Donor suitability is defined as HIV infection (confirmed with the use of enzyme-linked immunosorbent assay), absence of proteinuria, and a normal kidney as assessed with post hoc renal biopsy.5
One of the chief concerns has been the effect of further immunosuppression on the recipients and the possibility of disease progression. Although the sample size is limited (four transplants), data from the available cases indicate no evidence of organ rejection at 12 months post-transplantation. In addition, the recipients’ CD4 counts remained lower than baseline due to immunosuppressive therapy. All four patients maintained a viral load of less than 50 copies, which suggested that any virus transplanted along with the kidney had not affected control of HIV infection.5 However, it should be noted that many of the agents used for posttransplant maintenance immunosuppression (mycophenolate mofetil, cyclosporine, tacrolimus, and sirolimus) have antiretroviral properties.3
HIV patients in the US must meet the following criteria to be listed for a transplant:
• Diagnosis of ESRD with at least a five-year life-expectancy
• CD4 count of > 200 cells/ μL for at least six months
• Undetectable HIV viremia (< 50 HIV-1 RNA copies/mL)
• Demonstrated adherence to stable antiviral regimen for at least six months
• Absence of AIDS-defining illness following successful immune reconstitution6
A prospective trial of 150 patients in 19 US transplant centers who met the above criteria demonstrated patient survival and graft survival rates comparable to those in patients ages 65 and older.6
While awaiting the donation, HIV patients can continue hemodialysis and peritoneal dialysis. With the improved antiviral drugs, HIV patients have a survival rate similar to the non–HIV-infected population.
Transplantation is the goal and certainly the hope of many advanced-stage kidney patients, but in reality, the need far exceeds the resources. The HOPE Act opens the door for many patients who were previously excluded from the possibility of a life without dialysis. Taking care of these patients will be a team effort, encompassing HIV and infectious disease specialists, pharmacists, nephrologists, transplant surgeons and coordinators, and primary care providers—including, of course, advanced practitioners.
Shelly Levinstein, MSN, CRNP
Nephrology Associates of York
York, PA
REFERENCES
1. Muzaale AD, Massie AB, Wang MC, et al. Risk of end-stage renal disease following live kidney donation. JAMA. 2014;311(6):579-586.
2. CDC. HIV in the United States: at a glance (2013). www.cdc.gov/hiv/statistics/basics/ataglance.html. Accessed June 16, 2014.
3. Frassetto LA, Tan-Tam C, Stock PG. Renal transplantation in patients with HIV. Nat Rev Nephrol. 2009;5(10):582-589.
4. Malani PN. New law allows organ transplants from deceased HIV-infected donors to HIV-infected recipients. JAMA. 2013;310(23): 2492-2493.
5. Muller E, Kahn D, Mendelson M. Renal transplantation between HIV-positive donors and recipients. N Engl J Med. 2010;362(24):2336-2337.
6. Mariani LH, Berns JS. Viral nephropathies. In: Gilbert SJ, Weiner DE, eds. National Kidney Foundation’s Primer on Kidney Diseases. 6th ed. Elsevier; 2014:253-261.
Q) Now that patients are living with HIV/AIDS, can they donate kidneys or receive a kidney transplant?
Kidney disease often has multiple causes, including hypertension, diabetes, inherited conditions, and viral illnesses. The latter include primarily HIV, hepatitis C, and hepatitis B. With advances in the treatment of viral illnesses, the question of whether patients with these viruses can donate or receive a kidney transplant is being discussed not only in the United States but also worldwide.
The most recent CDC figures estimate that more than 1.1 million people in the US are living with HIV, of whom one in six (or nearly 16%) are undiagnosed. There are approximately 50,000 new infections reported annually.2
The Organ Transplant Amendments Act of 1988 banned HIV-positive people from donating organs. However, with the introduction of highly active antiretroviral therapy (HAART, now often referred to as active antiretroviral therapy) and the effective prophylaxis and management of opportunistic infections, mortality has been reduced. HIV/AIDS is often seen as a chronic disease and not the death sentence it once was.3 Since the development of HAART, there have been successful transplants to HIV-positive recipients from non–HIV-infected donors.
In November 2013, President Obama signed the HIV Organ Policy Equity (HOPE) Act, which lifted the ban on using organs from HIV-infected donors. The legislation directs the Department of Health and Human Services and the Organ Procurement and Transplantation Network to develop standards to make these transplants possible.4
Although there have not been any documented cases of transplants from HIV-infected donors to HIV-infected recipients in this country, such transplants have been very successful in South Africa.5 There, to qualify for kidney transplant, all recipients must have proven adherence, virologic suppression, and immune constitution. Donor suitability is defined as HIV infection (confirmed with the use of enzyme-linked immunosorbent assay), absence of proteinuria, and a normal kidney as assessed with post hoc renal biopsy.5
One of the chief concerns has been the effect of further immunosuppression on the recipients and the possibility of disease progression. Although the sample size is limited (four transplants), data from the available cases indicate no evidence of organ rejection at 12 months post-transplantation. In addition, the recipients’ CD4 counts remained lower than baseline due to immunosuppressive therapy. All four patients maintained a viral load of less than 50 copies, which suggested that any virus transplanted along with the kidney had not affected control of HIV infection.5 However, it should be noted that many of the agents used for posttransplant maintenance immunosuppression (mycophenolate mofetil, cyclosporine, tacrolimus, and sirolimus) have antiretroviral properties.3
HIV patients in the US must meet the following criteria to be listed for a transplant:
• Diagnosis of ESRD with at least a five-year life-expectancy
• CD4 count of > 200 cells/ μL for at least six months
• Undetectable HIV viremia (< 50 HIV-1 RNA copies/mL)
• Demonstrated adherence to stable antiviral regimen for at least six months
• Absence of AIDS-defining illness following successful immune reconstitution6
A prospective trial of 150 patients in 19 US transplant centers who met the above criteria demonstrated patient survival and graft survival rates comparable to those in patients ages 65 and older.6
While awaiting the donation, HIV patients can continue hemodialysis and peritoneal dialysis. With the improved antiviral drugs, HIV patients have a survival rate similar to the non–HIV-infected population.
Transplantation is the goal and certainly the hope of many advanced-stage kidney patients, but in reality, the need far exceeds the resources. The HOPE Act opens the door for many patients who were previously excluded from the possibility of a life without dialysis. Taking care of these patients will be a team effort, encompassing HIV and infectious disease specialists, pharmacists, nephrologists, transplant surgeons and coordinators, and primary care providers—including, of course, advanced practitioners.
Shelly Levinstein, MSN, CRNP
Nephrology Associates of York
York, PA
REFERENCES
1. Muzaale AD, Massie AB, Wang MC, et al. Risk of end-stage renal disease following live kidney donation. JAMA. 2014;311(6):579-586.
2. CDC. HIV in the United States: at a glance (2013). www.cdc.gov/hiv/statistics/basics/ataglance.html. Accessed June 16, 2014.
3. Frassetto LA, Tan-Tam C, Stock PG. Renal transplantation in patients with HIV. Nat Rev Nephrol. 2009;5(10):582-589.
4. Malani PN. New law allows organ transplants from deceased HIV-infected donors to HIV-infected recipients. JAMA. 2013;310(23): 2492-2493.
5. Muller E, Kahn D, Mendelson M. Renal transplantation between HIV-positive donors and recipients. N Engl J Med. 2010;362(24):2336-2337.
6. Mariani LH, Berns JS. Viral nephropathies. In: Gilbert SJ, Weiner DE, eds. National Kidney Foundation’s Primer on Kidney Diseases. 6th ed. Elsevier; 2014:253-261.
Anemia, A1C, and Rhabdomyolysis
Q) Does anemia in CKD patients affect their A1C? Is A1C accurate in CKD patients?
Tight glycemic control is imperative for patients with chronic kidney disease (CKD), but the management of diabetes in CKD can be complex due to factors including anemia and changes in glucose and insulin homeostasis.
A1C is directly proportionate to the ambient blood glucose concentration and in the general diabetic population has proven to be a reliable marker.1 However, it may not be valid in patients with diabetes and CKD. Reduced red blood cell (RBC) lifespan, rapid hemolysis, and iron deficiency may lead to falsely decreased results.2 Decreased RBC survival results from an increase in hemoglobin turnover, which decreases glycemic exposure time.1 This process then lowers the amount of nonenzymatic glucose binding to hemoglobin.1 Folate deficiency caused by impaired intestinal absorption in CKD also affects RBC survival.3 Falsely increased results may be related to carbamylation of the hemoglobin and acidosis, both of which are influenced by uremia.2
Special considerations should be made for dialysis patients with diabetes. In hemodialysis patients, A1C may be falsely decreased due to blood loss, RBC transfusion, and erythropoietin therapy.3 Observational studies have shown that erythropoietin therapy is associated with lower A1C due to the increased number of immature RBCs that have a decreased glycemic exposure time.1 In peritoneal dialysis patients, A1C may increase after the start of therapy as a result of dialysate absorption.3
Research suggests that glycated albumin (GA) provides a short-term index of glycemic control (typically two to three weeks) and is not influenced by albumin concentration, RBC lifespan, or erythropoietin administration.1 A clear consensus on optimal levels of GA has not been established, but GA may be a more reliable marker of glycemic control in patients with diabetes and CKD. Further research is needed to establish a target GA level that predicts the best prognosis for patients with both conditions.1
A1C is the most reliable marker at this time, but special considerations should be made for the patient with CKD. Rather than focus on a single measurement, clinicians need to consider the patient’s symptoms and results from all labwork, along with A1C, to best evaluate glycemic control.4 Further research is needed in patients with diabetes and CKD to explore other reliable markers to help maintain tight glycemic control.
Continued on next page >>
Q) One of my patients developed severe leg cramps while taking statins. I felt it was questionable rhabdomyolysis and stopped the medication; the leg pain went away. Is there a way to know if the rhabdomyolysis is progressive?
Rhabdomyolysis is a serious condition caused by the breakdown of muscle tissue that leads to the release of myoglobin into the bloodstream. This condition can lead to severe kidney failure and death.
Previously, there has been no easy method to predict progressive rhabdomyolysis. But researchers from Brigham and Women’s Hospital recently developed the Rhabdomyolysis Risk Calculator, a prediction score that can help determine whether a patient with rhabdomyolysis is at risk for severe kidney failure or death.
The researchers conducted a retrospective cohort study of 2,371 patients admitted between 2000 and 2011 and examined variables that may be associated with kidney failure and death.5 They identified independent predictors for these outcomes, including age; gender; initial levels of phosphate, calcium, creatinine, carbon dioxide, and creatine kinase; and etiology of rhabdomyolysis (myositis, exercise, statin use, or seizure).5
This tool can assist providers in developing a patient-specific treatment plan. However, further research is needed to validate the current variables, verify the risk prediction score in other populations, and examine its ability to guide individualized treatment plans.
The Rhabdomyolysis Risk Calculator is available at www.brighamandwomens.org/research/rhabdo/default.aspx
Kristy Washinger, MSN, CRNP
Nephrology Associates of Central PA
Camp Hill, PA
REFERENCES
1. Vos FE, Schollum JB, Walker RJ. Glycated albumin is the preferred marker for assessing glycaemic control in advanced chronic kidney disease. Nephrol Dial Transplant Plus. 2011; 4(6):368-375.
2. National Kidney Foundation Kidney Disease Outcomes Quality Initiative. Clinical practice guidelines and clinical practice recommendations for diabetes and chronic kidney disease. Guideline 2: management of hyperglycemia and general diabetes care in chronic kidney disease. www.kidney.org/professionals/kdoqi/guideline_diabetes/guide2.htm. Accessed April 15, 2014.
3. Sharif A, Baboolal K. Diagnostic application of the A1c assay in renal disease. J Am Soc Nephrol. 2010;21(3):383-385.
4. American Diabetes Association. Standards of medical care in diabetes—2013. Diabetes Care. 2013;36(suppl 1):S11-S66.
5. McMahon GM, Zeng X, Walker SS. A risk prediction score for kidney failure or mortality in rhabdomyolysis. JAMA Intern Med. 2013;173(19):1821-1828.
| Clinician Reviews in partnership with |
|
Renal Consult is edited by Jane S. Davis, CRNP, DNP, a member of the Clinician Reviews editorial board, who is a nurse practitioner in the Division of Nephrology at the University of Alabama at Birmingham and is the communications chairperson for the National Kidney Foundation’s Council of Advanced Practitioners (NKF-CAP); and Kim Zuber, PA-C, MSPS, DFAAPA, who is a physician assistant with Metropolitan Nephrology in Alexandria, Virginia, and Clinton, Maryland; she is also past chair of the NKF-CAP. This month’s responses were authored by Kristy Washinger, MSN, CRNP, who practices at Nephrology Associates of Central PA in Camp Hill, Pennsylvania.
| Clinician Reviews in partnership with |
|
Renal Consult is edited by Jane S. Davis, CRNP, DNP, a member of the Clinician Reviews editorial board, who is a nurse practitioner in the Division of Nephrology at the University of Alabama at Birmingham and is the communications chairperson for the National Kidney Foundation’s Council of Advanced Practitioners (NKF-CAP); and Kim Zuber, PA-C, MSPS, DFAAPA, who is a physician assistant with Metropolitan Nephrology in Alexandria, Virginia, and Clinton, Maryland; she is also past chair of the NKF-CAP. This month’s responses were authored by Kristy Washinger, MSN, CRNP, who practices at Nephrology Associates of Central PA in Camp Hill, Pennsylvania.
| Clinician Reviews in partnership with |
|
Renal Consult is edited by Jane S. Davis, CRNP, DNP, a member of the Clinician Reviews editorial board, who is a nurse practitioner in the Division of Nephrology at the University of Alabama at Birmingham and is the communications chairperson for the National Kidney Foundation’s Council of Advanced Practitioners (NKF-CAP); and Kim Zuber, PA-C, MSPS, DFAAPA, who is a physician assistant with Metropolitan Nephrology in Alexandria, Virginia, and Clinton, Maryland; she is also past chair of the NKF-CAP. This month’s responses were authored by Kristy Washinger, MSN, CRNP, who practices at Nephrology Associates of Central PA in Camp Hill, Pennsylvania.
Q) Does anemia in CKD patients affect their A1C? Is A1C accurate in CKD patients?
Tight glycemic control is imperative for patients with chronic kidney disease (CKD), but the management of diabetes in CKD can be complex due to factors including anemia and changes in glucose and insulin homeostasis.
A1C is directly proportionate to the ambient blood glucose concentration and in the general diabetic population has proven to be a reliable marker.1 However, it may not be valid in patients with diabetes and CKD. Reduced red blood cell (RBC) lifespan, rapid hemolysis, and iron deficiency may lead to falsely decreased results.2 Decreased RBC survival results from an increase in hemoglobin turnover, which decreases glycemic exposure time.1 This process then lowers the amount of nonenzymatic glucose binding to hemoglobin.1 Folate deficiency caused by impaired intestinal absorption in CKD also affects RBC survival.3 Falsely increased results may be related to carbamylation of the hemoglobin and acidosis, both of which are influenced by uremia.2
Special considerations should be made for dialysis patients with diabetes. In hemodialysis patients, A1C may be falsely decreased due to blood loss, RBC transfusion, and erythropoietin therapy.3 Observational studies have shown that erythropoietin therapy is associated with lower A1C due to the increased number of immature RBCs that have a decreased glycemic exposure time.1 In peritoneal dialysis patients, A1C may increase after the start of therapy as a result of dialysate absorption.3
Research suggests that glycated albumin (GA) provides a short-term index of glycemic control (typically two to three weeks) and is not influenced by albumin concentration, RBC lifespan, or erythropoietin administration.1 A clear consensus on optimal levels of GA has not been established, but GA may be a more reliable marker of glycemic control in patients with diabetes and CKD. Further research is needed to establish a target GA level that predicts the best prognosis for patients with both conditions.1
A1C is the most reliable marker at this time, but special considerations should be made for the patient with CKD. Rather than focus on a single measurement, clinicians need to consider the patient’s symptoms and results from all labwork, along with A1C, to best evaluate glycemic control.4 Further research is needed in patients with diabetes and CKD to explore other reliable markers to help maintain tight glycemic control.
Continued on next page >>
Q) One of my patients developed severe leg cramps while taking statins. I felt it was questionable rhabdomyolysis and stopped the medication; the leg pain went away. Is there a way to know if the rhabdomyolysis is progressive?
Rhabdomyolysis is a serious condition caused by the breakdown of muscle tissue that leads to the release of myoglobin into the bloodstream. This condition can lead to severe kidney failure and death.
Previously, there has been no easy method to predict progressive rhabdomyolysis. But researchers from Brigham and Women’s Hospital recently developed the Rhabdomyolysis Risk Calculator, a prediction score that can help determine whether a patient with rhabdomyolysis is at risk for severe kidney failure or death.
The researchers conducted a retrospective cohort study of 2,371 patients admitted between 2000 and 2011 and examined variables that may be associated with kidney failure and death.5 They identified independent predictors for these outcomes, including age; gender; initial levels of phosphate, calcium, creatinine, carbon dioxide, and creatine kinase; and etiology of rhabdomyolysis (myositis, exercise, statin use, or seizure).5
This tool can assist providers in developing a patient-specific treatment plan. However, further research is needed to validate the current variables, verify the risk prediction score in other populations, and examine its ability to guide individualized treatment plans.
The Rhabdomyolysis Risk Calculator is available at www.brighamandwomens.org/research/rhabdo/default.aspx
Kristy Washinger, MSN, CRNP
Nephrology Associates of Central PA
Camp Hill, PA
REFERENCES
1. Vos FE, Schollum JB, Walker RJ. Glycated albumin is the preferred marker for assessing glycaemic control in advanced chronic kidney disease. Nephrol Dial Transplant Plus. 2011; 4(6):368-375.
2. National Kidney Foundation Kidney Disease Outcomes Quality Initiative. Clinical practice guidelines and clinical practice recommendations for diabetes and chronic kidney disease. Guideline 2: management of hyperglycemia and general diabetes care in chronic kidney disease. www.kidney.org/professionals/kdoqi/guideline_diabetes/guide2.htm. Accessed April 15, 2014.
3. Sharif A, Baboolal K. Diagnostic application of the A1c assay in renal disease. J Am Soc Nephrol. 2010;21(3):383-385.
4. American Diabetes Association. Standards of medical care in diabetes—2013. Diabetes Care. 2013;36(suppl 1):S11-S66.
5. McMahon GM, Zeng X, Walker SS. A risk prediction score for kidney failure or mortality in rhabdomyolysis. JAMA Intern Med. 2013;173(19):1821-1828.
Q) Does anemia in CKD patients affect their A1C? Is A1C accurate in CKD patients?
Tight glycemic control is imperative for patients with chronic kidney disease (CKD), but the management of diabetes in CKD can be complex due to factors including anemia and changes in glucose and insulin homeostasis.
A1C is directly proportionate to the ambient blood glucose concentration and in the general diabetic population has proven to be a reliable marker.1 However, it may not be valid in patients with diabetes and CKD. Reduced red blood cell (RBC) lifespan, rapid hemolysis, and iron deficiency may lead to falsely decreased results.2 Decreased RBC survival results from an increase in hemoglobin turnover, which decreases glycemic exposure time.1 This process then lowers the amount of nonenzymatic glucose binding to hemoglobin.1 Folate deficiency caused by impaired intestinal absorption in CKD also affects RBC survival.3 Falsely increased results may be related to carbamylation of the hemoglobin and acidosis, both of which are influenced by uremia.2
Special considerations should be made for dialysis patients with diabetes. In hemodialysis patients, A1C may be falsely decreased due to blood loss, RBC transfusion, and erythropoietin therapy.3 Observational studies have shown that erythropoietin therapy is associated with lower A1C due to the increased number of immature RBCs that have a decreased glycemic exposure time.1 In peritoneal dialysis patients, A1C may increase after the start of therapy as a result of dialysate absorption.3
Research suggests that glycated albumin (GA) provides a short-term index of glycemic control (typically two to three weeks) and is not influenced by albumin concentration, RBC lifespan, or erythropoietin administration.1 A clear consensus on optimal levels of GA has not been established, but GA may be a more reliable marker of glycemic control in patients with diabetes and CKD. Further research is needed to establish a target GA level that predicts the best prognosis for patients with both conditions.1
A1C is the most reliable marker at this time, but special considerations should be made for the patient with CKD. Rather than focus on a single measurement, clinicians need to consider the patient’s symptoms and results from all labwork, along with A1C, to best evaluate glycemic control.4 Further research is needed in patients with diabetes and CKD to explore other reliable markers to help maintain tight glycemic control.
Continued on next page >>
Q) One of my patients developed severe leg cramps while taking statins. I felt it was questionable rhabdomyolysis and stopped the medication; the leg pain went away. Is there a way to know if the rhabdomyolysis is progressive?
Rhabdomyolysis is a serious condition caused by the breakdown of muscle tissue that leads to the release of myoglobin into the bloodstream. This condition can lead to severe kidney failure and death.
Previously, there has been no easy method to predict progressive rhabdomyolysis. But researchers from Brigham and Women’s Hospital recently developed the Rhabdomyolysis Risk Calculator, a prediction score that can help determine whether a patient with rhabdomyolysis is at risk for severe kidney failure or death.
The researchers conducted a retrospective cohort study of 2,371 patients admitted between 2000 and 2011 and examined variables that may be associated with kidney failure and death.5 They identified independent predictors for these outcomes, including age; gender; initial levels of phosphate, calcium, creatinine, carbon dioxide, and creatine kinase; and etiology of rhabdomyolysis (myositis, exercise, statin use, or seizure).5
This tool can assist providers in developing a patient-specific treatment plan. However, further research is needed to validate the current variables, verify the risk prediction score in other populations, and examine its ability to guide individualized treatment plans.
The Rhabdomyolysis Risk Calculator is available at www.brighamandwomens.org/research/rhabdo/default.aspx
Kristy Washinger, MSN, CRNP
Nephrology Associates of Central PA
Camp Hill, PA
REFERENCES
1. Vos FE, Schollum JB, Walker RJ. Glycated albumin is the preferred marker for assessing glycaemic control in advanced chronic kidney disease. Nephrol Dial Transplant Plus. 2011; 4(6):368-375.
2. National Kidney Foundation Kidney Disease Outcomes Quality Initiative. Clinical practice guidelines and clinical practice recommendations for diabetes and chronic kidney disease. Guideline 2: management of hyperglycemia and general diabetes care in chronic kidney disease. www.kidney.org/professionals/kdoqi/guideline_diabetes/guide2.htm. Accessed April 15, 2014.
3. Sharif A, Baboolal K. Diagnostic application of the A1c assay in renal disease. J Am Soc Nephrol. 2010;21(3):383-385.
4. American Diabetes Association. Standards of medical care in diabetes—2013. Diabetes Care. 2013;36(suppl 1):S11-S66.
5. McMahon GM, Zeng X, Walker SS. A risk prediction score for kidney failure or mortality in rhabdomyolysis. JAMA Intern Med. 2013;173(19):1821-1828.
Determining Renal Function: What Those Test Results Mean
Q: Even though you suggested a random urine ACR (albumin-to-creatinine ratio), the internal medicine group ordered a 24-hour urine test for protein. As you can see from the results (see Table 2), the PCR (protein-to-creatinine ratio) is high. What does this mean? Does my patient have more severe kidney disease than I thought for her age?
Advanced age is a risk factor for CKD, and the patient has also had weight loss that can affect her serum creatinine. Because of her femur fracture, she has likely been in pain and probably has been taking nephrotoxic analgesics, such as NSAIDs or a ketorolac injection, commonly given postoperatively.
The patient’s weight does not appear to be stable, and she may have a degree of malnutrition. Both malnutrition and reduced muscle mass are known to decrease serum creatinine, which can mask worsening kidney disease. Thus she may have a lower true GFR than predicted by CG, which tends to overestimate renal function in the case of lower levels of creatinine production.6
Looking at all of these factors, it is likely that she has some degree of renal disease; however, it is important to determine if this is an acute change or a chronic issue. Looking closely at the higher-than-normal urinary protein result requires some out-of-the-box thinking.
Proteinuria has four types; each indicates a particular disorder.5 Table 3 provides examples of causative factors for each type.
Based on the data provided (Table 2), you have a high urinary protein result and are unsure if it is albumin. It is important to determine if this is albumin—and therefore pathognomonic for progressive kidney disease—or if the protein is of a nonalbumin type that will require further evaluation. What started as just an elderly female with a femur fracture and decreased GFR can turn into a diagnosis of multiple myeloma (which is more common in this age-group), kidney damage from postoperative medications, or another form of kidney disease. Only by looking at urinary protein type can one “tease out” what this might be.
In conclusion, there are many different ways to determine renal function, either by creatinine clearance or by using an estimation formula. Each one, used correctly, can offer advantages in certain populations. It is extremely important to determine whether an individual has diminished kidney function in order to be able to delay the progression of CKD.
Catherine B. York, MSN, APRN-BC
Springfield Nephrology
Associates, Springfield, MO
References
1. CDC. National chronic kidney disease fact sheet: general information and national estimates on chronic kidney disease in the United States, 2010. Atlanta, GA: US Department of Health and Human Services, CDC; 2010.
2. US Renal Data System. USRDS 2012 annual data report: atlas of end-stage renal disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2012.
3. US Renal Data System. USRDS 2012 annual data report: atlas of end-stage renal disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2011.
4. Clarkson MR, Brenner BM. Clinical assessment of the patient with kidney disease. In: Clarkson MR, Brenner BM. Pocket Companion to Brenner & Rector’s The Kidney. 7th ed. Philadelphia, PA: Elsevier Saunders; 2005: 3-19.5.
5. Hsu C. Clinical evaluation of kidney function. In: Greenberg A, Cheung A, Coffman T, et al, eds. Primer on Kidney Diseases, 5th ed. Philadelphia, PA; Saunders Elsevier; 2009:19-237.
6. Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3:1-150.
7. National Kidney Foundation. Guideline 5: assessment of proteinuria. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification; 2000.
8. Stevens LA, Coresh J, Greene T, et al. Assessing kidney function-measured and estimated glomerular filtration rate. N Engl J Med. 2006;354:2473-2483.
Q: Even though you suggested a random urine ACR (albumin-to-creatinine ratio), the internal medicine group ordered a 24-hour urine test for protein. As you can see from the results (see Table 2), the PCR (protein-to-creatinine ratio) is high. What does this mean? Does my patient have more severe kidney disease than I thought for her age?
Advanced age is a risk factor for CKD, and the patient has also had weight loss that can affect her serum creatinine. Because of her femur fracture, she has likely been in pain and probably has been taking nephrotoxic analgesics, such as NSAIDs or a ketorolac injection, commonly given postoperatively.
The patient’s weight does not appear to be stable, and she may have a degree of malnutrition. Both malnutrition and reduced muscle mass are known to decrease serum creatinine, which can mask worsening kidney disease. Thus she may have a lower true GFR than predicted by CG, which tends to overestimate renal function in the case of lower levels of creatinine production.6
Looking at all of these factors, it is likely that she has some degree of renal disease; however, it is important to determine if this is an acute change or a chronic issue. Looking closely at the higher-than-normal urinary protein result requires some out-of-the-box thinking.
Proteinuria has four types; each indicates a particular disorder.5 Table 3 provides examples of causative factors for each type.
Based on the data provided (Table 2), you have a high urinary protein result and are unsure if it is albumin. It is important to determine if this is albumin—and therefore pathognomonic for progressive kidney disease—or if the protein is of a nonalbumin type that will require further evaluation. What started as just an elderly female with a femur fracture and decreased GFR can turn into a diagnosis of multiple myeloma (which is more common in this age-group), kidney damage from postoperative medications, or another form of kidney disease. Only by looking at urinary protein type can one “tease out” what this might be.
In conclusion, there are many different ways to determine renal function, either by creatinine clearance or by using an estimation formula. Each one, used correctly, can offer advantages in certain populations. It is extremely important to determine whether an individual has diminished kidney function in order to be able to delay the progression of CKD.
Catherine B. York, MSN, APRN-BC
Springfield Nephrology
Associates, Springfield, MO
References
1. CDC. National chronic kidney disease fact sheet: general information and national estimates on chronic kidney disease in the United States, 2010. Atlanta, GA: US Department of Health and Human Services, CDC; 2010.
2. US Renal Data System. USRDS 2012 annual data report: atlas of end-stage renal disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2012.
3. US Renal Data System. USRDS 2012 annual data report: atlas of end-stage renal disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2011.
4. Clarkson MR, Brenner BM. Clinical assessment of the patient with kidney disease. In: Clarkson MR, Brenner BM. Pocket Companion to Brenner & Rector’s The Kidney. 7th ed. Philadelphia, PA: Elsevier Saunders; 2005: 3-19.5.
5. Hsu C. Clinical evaluation of kidney function. In: Greenberg A, Cheung A, Coffman T, et al, eds. Primer on Kidney Diseases, 5th ed. Philadelphia, PA; Saunders Elsevier; 2009:19-237.
6. Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3:1-150.
7. National Kidney Foundation. Guideline 5: assessment of proteinuria. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification; 2000.
8. Stevens LA, Coresh J, Greene T, et al. Assessing kidney function-measured and estimated glomerular filtration rate. N Engl J Med. 2006;354:2473-2483.
Q: Even though you suggested a random urine ACR (albumin-to-creatinine ratio), the internal medicine group ordered a 24-hour urine test for protein. As you can see from the results (see Table 2), the PCR (protein-to-creatinine ratio) is high. What does this mean? Does my patient have more severe kidney disease than I thought for her age?
Advanced age is a risk factor for CKD, and the patient has also had weight loss that can affect her serum creatinine. Because of her femur fracture, she has likely been in pain and probably has been taking nephrotoxic analgesics, such as NSAIDs or a ketorolac injection, commonly given postoperatively.
The patient’s weight does not appear to be stable, and she may have a degree of malnutrition. Both malnutrition and reduced muscle mass are known to decrease serum creatinine, which can mask worsening kidney disease. Thus she may have a lower true GFR than predicted by CG, which tends to overestimate renal function in the case of lower levels of creatinine production.6
Looking at all of these factors, it is likely that she has some degree of renal disease; however, it is important to determine if this is an acute change or a chronic issue. Looking closely at the higher-than-normal urinary protein result requires some out-of-the-box thinking.
Proteinuria has four types; each indicates a particular disorder.5 Table 3 provides examples of causative factors for each type.
Based on the data provided (Table 2), you have a high urinary protein result and are unsure if it is albumin. It is important to determine if this is albumin—and therefore pathognomonic for progressive kidney disease—or if the protein is of a nonalbumin type that will require further evaluation. What started as just an elderly female with a femur fracture and decreased GFR can turn into a diagnosis of multiple myeloma (which is more common in this age-group), kidney damage from postoperative medications, or another form of kidney disease. Only by looking at urinary protein type can one “tease out” what this might be.
In conclusion, there are many different ways to determine renal function, either by creatinine clearance or by using an estimation formula. Each one, used correctly, can offer advantages in certain populations. It is extremely important to determine whether an individual has diminished kidney function in order to be able to delay the progression of CKD.
Catherine B. York, MSN, APRN-BC
Springfield Nephrology
Associates, Springfield, MO
References
1. CDC. National chronic kidney disease fact sheet: general information and national estimates on chronic kidney disease in the United States, 2010. Atlanta, GA: US Department of Health and Human Services, CDC; 2010.
2. US Renal Data System. USRDS 2012 annual data report: atlas of end-stage renal disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2012.
3. US Renal Data System. USRDS 2012 annual data report: atlas of end-stage renal disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2011.
4. Clarkson MR, Brenner BM. Clinical assessment of the patient with kidney disease. In: Clarkson MR, Brenner BM. Pocket Companion to Brenner & Rector’s The Kidney. 7th ed. Philadelphia, PA: Elsevier Saunders; 2005: 3-19.5.
5. Hsu C. Clinical evaluation of kidney function. In: Greenberg A, Cheung A, Coffman T, et al, eds. Primer on Kidney Diseases, 5th ed. Philadelphia, PA; Saunders Elsevier; 2009:19-237.
6. Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3:1-150.
7. National Kidney Foundation. Guideline 5: assessment of proteinuria. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification; 2000.
8. Stevens LA, Coresh J, Greene T, et al. Assessing kidney function-measured and estimated glomerular filtration rate. N Engl J Med. 2006;354:2473-2483.
Determining Renal Function: What’s the Best Way to Evaluate?
Q: One of my patients is a 72-year-old woman who weighs 59 kg. Her creatinine clearance by Cockcroft-Gault (CG) came back low (49 mL/min). Is this due to her age, gender, and weight loss during the past five months (subsequent to a femur fracture), or does she have underlying kidney disease? Would a 24-hour urine creatinine test be the best way to determine her level of kidney function—and would it be appropriate for someone her age? Is there a better way to evaluate her kidney function?
Accurate measurement of renal function is vital for any patient suspected of having chronic kidney disease (CKD). More than 20 million adults in the United States, or more than 10% of the adult population, have CKD.1 The 2012 US Renal Data System (USRDS) Annual Data Report states that the prevalence of chronic kidney disease in the Medicare population alone rose more than three-fold between 2000 and 2010, from 2.7% to 9.2%.2
CKD consumes a large proportion of Medicare dollars: more than $23,000 per person per year (PPPY) annually. For end-stage renal disease (ESRD) patients on hemodialysis, the cost is an astounding $88,000 PPPY.2 The cost of treating 871,000 ESRD patients was more than $40 billion in both public and private funds in 2009.3
Risk factors for CKD include but are not limited to: advancing age, male sex, race, hypertension, diabetes mellitus, smoking, family history of kidney disease, proteinuria, exposure to nephrotoxins, and atherosclerosis.4
In the US, the most common methods used to estimate renal function are the CG (Cockcroft-Gault) equation, Modification of Diet in Renal Disease (MDRD) study equations, and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. It is often difficult to determine which test is best suited for a patient, because there are pros and cons to each formula and no one test is perfectly suited for every clinical application.4
Since we know this patient’s renal function is low via CG (49 mL/min), the next important question to ask is, “Is it progressive?” I would recommend obtaining a urinalysis to look for hematuria and albuminuria. Proteinuria is an all-encompassing term. Albumin is only one type of protein and is the single most predictive risk factor for kidney disease progression. Persistent albuminuria alone is diagnostic of renal disease.5 The recommended test is a random urine albumin-to-creatinine ratio (ACR; see Table 1).6
You asked if a 24-hour urine creatinine clearance might evaluate her renal function better. Creatinine clearance can be determined by a 24-hour urine test and a serum blood sample in a steady state. However, this test should be interpreted with caution due to both collection errors and the fact that creatinine clearance overestimates true glomerular filtration rate (GFR) due to tubular secretion of creatinine.7,8 Thus, this test is no longer routinely recommended to determine kidney function.8
Catherine B. York, MSN, APRN-BC
Springfield Nephrology
Associates, Springfield, MO
References
1. CDC. National chronic kidney disease fact sheet: general information and national estimates on chronic kidney disease in the United States, 2010. Atlanta, GA: US Department of Health and Human Services, CDC; 2010.
2. US Renal Data System. USRDS 2012 annual data report: atlas of end-stage renal disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2012.
3. US Renal Data System. USRDS 2012 annual data report: atlas of end-stage renal disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2011.
4. Clarkson MR, Brenner BM. Clinical assessment of the patient with kidney disease. In: Clarkson MR, Brenner BM. Pocket Companion to Brenner & Rector’s The Kidney. 7th ed. Philadelphia, PA: Elsevier Saunders; 2005: 3-19.5.
5. Hsu C. Clinical evaluation of kidney function. In: Greenberg A, Cheung A, Coffman T, et al, eds. Primer on Kidney Diseases, 5th ed. Philadelphia, PA; Saunders Elsevier; 2009:19-237.
6. Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3:1-150.
7. National Kidney Foundation. Guideline 5: assessment of proteinuria. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification; 2000.
8. Stevens LA, Coresh J, Greene T, et al. Assessing kidney function-measured and estimated glomerular filtration rate. N Engl J Med. 2006;354:2473-2483.
Q: One of my patients is a 72-year-old woman who weighs 59 kg. Her creatinine clearance by Cockcroft-Gault (CG) came back low (49 mL/min). Is this due to her age, gender, and weight loss during the past five months (subsequent to a femur fracture), or does she have underlying kidney disease? Would a 24-hour urine creatinine test be the best way to determine her level of kidney function—and would it be appropriate for someone her age? Is there a better way to evaluate her kidney function?
Accurate measurement of renal function is vital for any patient suspected of having chronic kidney disease (CKD). More than 20 million adults in the United States, or more than 10% of the adult population, have CKD.1 The 2012 US Renal Data System (USRDS) Annual Data Report states that the prevalence of chronic kidney disease in the Medicare population alone rose more than three-fold between 2000 and 2010, from 2.7% to 9.2%.2
CKD consumes a large proportion of Medicare dollars: more than $23,000 per person per year (PPPY) annually. For end-stage renal disease (ESRD) patients on hemodialysis, the cost is an astounding $88,000 PPPY.2 The cost of treating 871,000 ESRD patients was more than $40 billion in both public and private funds in 2009.3
Risk factors for CKD include but are not limited to: advancing age, male sex, race, hypertension, diabetes mellitus, smoking, family history of kidney disease, proteinuria, exposure to nephrotoxins, and atherosclerosis.4
In the US, the most common methods used to estimate renal function are the CG (Cockcroft-Gault) equation, Modification of Diet in Renal Disease (MDRD) study equations, and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. It is often difficult to determine which test is best suited for a patient, because there are pros and cons to each formula and no one test is perfectly suited for every clinical application.4
Since we know this patient’s renal function is low via CG (49 mL/min), the next important question to ask is, “Is it progressive?” I would recommend obtaining a urinalysis to look for hematuria and albuminuria. Proteinuria is an all-encompassing term. Albumin is only one type of protein and is the single most predictive risk factor for kidney disease progression. Persistent albuminuria alone is diagnostic of renal disease.5 The recommended test is a random urine albumin-to-creatinine ratio (ACR; see Table 1).6
You asked if a 24-hour urine creatinine clearance might evaluate her renal function better. Creatinine clearance can be determined by a 24-hour urine test and a serum blood sample in a steady state. However, this test should be interpreted with caution due to both collection errors and the fact that creatinine clearance overestimates true glomerular filtration rate (GFR) due to tubular secretion of creatinine.7,8 Thus, this test is no longer routinely recommended to determine kidney function.8
Catherine B. York, MSN, APRN-BC
Springfield Nephrology
Associates, Springfield, MO
References
1. CDC. National chronic kidney disease fact sheet: general information and national estimates on chronic kidney disease in the United States, 2010. Atlanta, GA: US Department of Health and Human Services, CDC; 2010.
2. US Renal Data System. USRDS 2012 annual data report: atlas of end-stage renal disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2012.
3. US Renal Data System. USRDS 2012 annual data report: atlas of end-stage renal disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2011.
4. Clarkson MR, Brenner BM. Clinical assessment of the patient with kidney disease. In: Clarkson MR, Brenner BM. Pocket Companion to Brenner & Rector’s The Kidney. 7th ed. Philadelphia, PA: Elsevier Saunders; 2005: 3-19.5.
5. Hsu C. Clinical evaluation of kidney function. In: Greenberg A, Cheung A, Coffman T, et al, eds. Primer on Kidney Diseases, 5th ed. Philadelphia, PA; Saunders Elsevier; 2009:19-237.
6. Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3:1-150.
7. National Kidney Foundation. Guideline 5: assessment of proteinuria. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification; 2000.
8. Stevens LA, Coresh J, Greene T, et al. Assessing kidney function-measured and estimated glomerular filtration rate. N Engl J Med. 2006;354:2473-2483.
Q: One of my patients is a 72-year-old woman who weighs 59 kg. Her creatinine clearance by Cockcroft-Gault (CG) came back low (49 mL/min). Is this due to her age, gender, and weight loss during the past five months (subsequent to a femur fracture), or does she have underlying kidney disease? Would a 24-hour urine creatinine test be the best way to determine her level of kidney function—and would it be appropriate for someone her age? Is there a better way to evaluate her kidney function?
Accurate measurement of renal function is vital for any patient suspected of having chronic kidney disease (CKD). More than 20 million adults in the United States, or more than 10% of the adult population, have CKD.1 The 2012 US Renal Data System (USRDS) Annual Data Report states that the prevalence of chronic kidney disease in the Medicare population alone rose more than three-fold between 2000 and 2010, from 2.7% to 9.2%.2
CKD consumes a large proportion of Medicare dollars: more than $23,000 per person per year (PPPY) annually. For end-stage renal disease (ESRD) patients on hemodialysis, the cost is an astounding $88,000 PPPY.2 The cost of treating 871,000 ESRD patients was more than $40 billion in both public and private funds in 2009.3
Risk factors for CKD include but are not limited to: advancing age, male sex, race, hypertension, diabetes mellitus, smoking, family history of kidney disease, proteinuria, exposure to nephrotoxins, and atherosclerosis.4
In the US, the most common methods used to estimate renal function are the CG (Cockcroft-Gault) equation, Modification of Diet in Renal Disease (MDRD) study equations, and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. It is often difficult to determine which test is best suited for a patient, because there are pros and cons to each formula and no one test is perfectly suited for every clinical application.4
Since we know this patient’s renal function is low via CG (49 mL/min), the next important question to ask is, “Is it progressive?” I would recommend obtaining a urinalysis to look for hematuria and albuminuria. Proteinuria is an all-encompassing term. Albumin is only one type of protein and is the single most predictive risk factor for kidney disease progression. Persistent albuminuria alone is diagnostic of renal disease.5 The recommended test is a random urine albumin-to-creatinine ratio (ACR; see Table 1).6
You asked if a 24-hour urine creatinine clearance might evaluate her renal function better. Creatinine clearance can be determined by a 24-hour urine test and a serum blood sample in a steady state. However, this test should be interpreted with caution due to both collection errors and the fact that creatinine clearance overestimates true glomerular filtration rate (GFR) due to tubular secretion of creatinine.7,8 Thus, this test is no longer routinely recommended to determine kidney function.8
Catherine B. York, MSN, APRN-BC
Springfield Nephrology
Associates, Springfield, MO
References
1. CDC. National chronic kidney disease fact sheet: general information and national estimates on chronic kidney disease in the United States, 2010. Atlanta, GA: US Department of Health and Human Services, CDC; 2010.
2. US Renal Data System. USRDS 2012 annual data report: atlas of end-stage renal disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2012.
3. US Renal Data System. USRDS 2012 annual data report: atlas of end-stage renal disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2011.
4. Clarkson MR, Brenner BM. Clinical assessment of the patient with kidney disease. In: Clarkson MR, Brenner BM. Pocket Companion to Brenner & Rector’s The Kidney. 7th ed. Philadelphia, PA: Elsevier Saunders; 2005: 3-19.5.
5. Hsu C. Clinical evaluation of kidney function. In: Greenberg A, Cheung A, Coffman T, et al, eds. Primer on Kidney Diseases, 5th ed. Philadelphia, PA; Saunders Elsevier; 2009:19-237.
6. Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3:1-150.
7. National Kidney Foundation. Guideline 5: assessment of proteinuria. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification; 2000.
8. Stevens LA, Coresh J, Greene T, et al. Assessing kidney function-measured and estimated glomerular filtration rate. N Engl J Med. 2006;354:2473-2483.
Why Take This Patient Off Her ACEI?
Q: I sent a 68-year-old, hypertensive, diabetic woman with stage 4 kidney disease (estimated glomerular filtration rate [eGFR], 25 mL/min/1.73 m2; serum creatinine [SCr], 2 mg/mL) to a local nephrology group. Since she was diabetic, we had had her taking an angiotensin-converting enzyme inhibitor (ACEI) for years. The first thing the nephrology group did was take her off the ACEI. Why would they do that? I thought the hypertensive drug of choice for all diabetic patients is an ACEI or an angiotensin receptor blocker (ARB). Am I wrong?
A: The renin-angiotensin-aldosterone system (RAAS) plays an important role in the regulation of blood pressure and intravascular volume through its effects on renin, angiotensin, and aldosterone production. Activation of RAAS causes an increase in blood pressure through vasoconstriction (angiotensin II effects) and the fluid retention associated with reabsorption of sodium and water (aldosterone effects). As such, the physiologic effects of RAAS have been implicated in the pathophysiology of cardiovascular diseases, such as heart failure, kidney disease, and hypertension.1
The JNC 7 guidelines2 (Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) recommend the use of ACEIs or ARBs for the treatment of hypertension in patients with chronic kidney disease (CKD) or diabetes to slow progression of kidney disease. Given the benefits of ACEI or ARB therapy in reducing mortality in cardiovascular disease (for which patients with CKD are at increased risk3), these medications are indicated in patients with CKD.
Angiotensin II causes systemic vasoconstriction and also acts on the efferent arterioles of the glomerulus. ACEI/ARB therapy causes vasodilation of the efferent arterioles, thus lowering the intraglomerular capillary pressure.1 This mechanism accounts for the antiproteinuric effect and the subsequent decrease in GFR when these agents are initiated.
Proteinuria is a marker that may indicate nephropathy and may lead to further kidney damage.1 Slowing renal disease progression depends on controlling blood pressure and proteinuria.3
To date, a number of trials have been conducted to explore the benefit of the antiproteinuric effects of ACEI/ARB therapy. The antiproteinuric effect is more pronounced in patients with more severe proteinuria. Studies of these agents in patients with diabetic and nondiabetic nephropathy have shown that besides reducing proteinuria, they slow progression to end-stage renal disease (ESRD), thus delaying the need for renal replacement therapy.4 As such, ACEI/ARB therapy is widely used to reduce proteinuria, independent of the blood pressure–lowering effects.
Initiation of ACEI/ARB therapy is associated with an increase in SCr due to the drugs’ effects on the efferent arterioles, resulting in a decrease in intraglomerular pressure.3 However, discontinuing therapy is not warranted unless the SCr rises to more than 30% above baseline. According to findings from one meta-analysis, the degree of loss in renal function when ACEI therapy was initiated was inversely related to the rate of annual decline in renal function.5 Thus, patients with higher SCr levels at the start of therapy had poorer renal function initially, but they received the greatest benefit in long-term renal preservation.
The rise in SCr typically occurs within a few days of therapy initiation; thus, SCr should be measured within the first seven days of therapy.3 The SCr level is expected to stabilize within six to eight weeks of therapy. Patients whose SCr level continues to rise more than 30% to 35% above baseline may need to discontinue ACEI/ARB therapy; this rise may be attributed to kidney hypoperfusion. Kidney hypoperfusion can also occur when diuretics are initiated or their dosage increased, when NSAIDs are used, or in patients with bilateral renal artery stenosis or volume depletion resulting from gastroenteritis.3
Hyperkalemia due to decreased urinary excretion of potassium (K+) may present yet another reason to discontinue ACEI/ARB therapy in patients with CKD. Incidence of hyperkalemia in those with CKD stages 3 through 5 who receive either an ACEI or an ARB ranges from 5% to 50%.3 Hyperkalemia can occur when a long-acting ACEI is prescribed or when ACEI/ARB therapy is used concurrently with NSAIDs or potassium-sparing diuretics; thiazides or loop diuretics, by contrast, can reduce the risk for hyperkalemia.
Risk factors for moderate hyperkalemia (serum K+ ≥ 5.6 mmol/L) include age older than 65, congestive heart failure, SCr level greater than 1.6 mg/dL, and a blood urea nitrogen level exceeding 18 mg/dL.5
A dosing reduction or discontinuation of ACEI/ARB therapy should be considered when serum K+ levels are 5.6 mmol/L or greater.3 Patients who are older than 70 or whose serum urea nitrogen level exceeds 25 mg/dL are at increased risk for severe hyperkalemia (K+ > 6.0 mmol/L). Termination of an ACEI or an ARB may be warranted in patients with a serum K+ level exceeding 6.0 mmol/L or in those considered at increased risk for severe hyperkalemia.3
Other patients may also benefit from discontinuing ACEI/ARB therapy. Few data exist to support their use in patients with kidney function at 25% or less, or those with a GFR below 30 mL/min/1.73 m2.3 Onuigbo6 suggests that ESRD in patients with CKD can either progress gradually and steadily or rapidly as a result of acute kidney injury (AKI). Patients with CKD who are at risk for ESRD because of AKI include those currently taking an ACEI or an ARB, older patients, and those who experience unexplained decreases in GFR.
To avoid any worsening of renal function, Onuigbo6 suggests temporarily discontinuing ACEI/ARB therapy in the following patients:
• Those older than 65 who are scheduled for colonoscopy, administration of IV radiocontrast, or surgery (especially cardiovascular surgery); or
• Patients hospitalized for an acute ailment.
Discontinuing these agents may prevent progression to ESRD in such patients.
In summary, use of ACEIs or ARBs to delay progression of renal disease may be continued if a clear therapeutic benefit exists. However, discontinuation should be considered if a patient with CKD is at risk for hyperkalemia or if the K+ level remains higher than 5.6 mmol/L, if SCr levels increase more than 30% above baseline, or if patients (especially those older than 65) are at risk for AKI.
References
1. Remuzzi G, Perico N, Macia M, Ruggenenti P. The role of renin-angiotensin-aldosterone system in the progression of chronic kidney disease. Kidney Int Suppl. 2005;99:S57-S65.
2. Chobanian AV, Bakris GL, Black HR, et al; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289:2560-2572.
3. Mangrum AJ, Bakris GL. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in chronic renal disease: safety issues. Semin Nephrol. 2004;24:168-175.
4. St Peter WL, Odum LE, Whaley-Connell AT. To RAS or not to RAS? The evidence for and cautions with renin-angiotensin system inhibition in patients with diabetic kidney disease. Pharmacotherapy. 2013 Apr 9.
5. Bakris GL, Weir MR. Angiotensin-converting enzyme inhibitor–associated elevations in serum creatinine: is this a cause for concern? Arch Intern Med. 2000;160:685-693.
6. Onuigbo MA. Is renoprotection with RAAS blockade a failed paradigm? Have we learnt any lessons so far? Int J Clin Pract. 2010;64:1341-1346.
Q: I sent a 68-year-old, hypertensive, diabetic woman with stage 4 kidney disease (estimated glomerular filtration rate [eGFR], 25 mL/min/1.73 m2; serum creatinine [SCr], 2 mg/mL) to a local nephrology group. Since she was diabetic, we had had her taking an angiotensin-converting enzyme inhibitor (ACEI) for years. The first thing the nephrology group did was take her off the ACEI. Why would they do that? I thought the hypertensive drug of choice for all diabetic patients is an ACEI or an angiotensin receptor blocker (ARB). Am I wrong?
A: The renin-angiotensin-aldosterone system (RAAS) plays an important role in the regulation of blood pressure and intravascular volume through its effects on renin, angiotensin, and aldosterone production. Activation of RAAS causes an increase in blood pressure through vasoconstriction (angiotensin II effects) and the fluid retention associated with reabsorption of sodium and water (aldosterone effects). As such, the physiologic effects of RAAS have been implicated in the pathophysiology of cardiovascular diseases, such as heart failure, kidney disease, and hypertension.1
The JNC 7 guidelines2 (Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) recommend the use of ACEIs or ARBs for the treatment of hypertension in patients with chronic kidney disease (CKD) or diabetes to slow progression of kidney disease. Given the benefits of ACEI or ARB therapy in reducing mortality in cardiovascular disease (for which patients with CKD are at increased risk3), these medications are indicated in patients with CKD.
Angiotensin II causes systemic vasoconstriction and also acts on the efferent arterioles of the glomerulus. ACEI/ARB therapy causes vasodilation of the efferent arterioles, thus lowering the intraglomerular capillary pressure.1 This mechanism accounts for the antiproteinuric effect and the subsequent decrease in GFR when these agents are initiated.
Proteinuria is a marker that may indicate nephropathy and may lead to further kidney damage.1 Slowing renal disease progression depends on controlling blood pressure and proteinuria.3
To date, a number of trials have been conducted to explore the benefit of the antiproteinuric effects of ACEI/ARB therapy. The antiproteinuric effect is more pronounced in patients with more severe proteinuria. Studies of these agents in patients with diabetic and nondiabetic nephropathy have shown that besides reducing proteinuria, they slow progression to end-stage renal disease (ESRD), thus delaying the need for renal replacement therapy.4 As such, ACEI/ARB therapy is widely used to reduce proteinuria, independent of the blood pressure–lowering effects.
Initiation of ACEI/ARB therapy is associated with an increase in SCr due to the drugs’ effects on the efferent arterioles, resulting in a decrease in intraglomerular pressure.3 However, discontinuing therapy is not warranted unless the SCr rises to more than 30% above baseline. According to findings from one meta-analysis, the degree of loss in renal function when ACEI therapy was initiated was inversely related to the rate of annual decline in renal function.5 Thus, patients with higher SCr levels at the start of therapy had poorer renal function initially, but they received the greatest benefit in long-term renal preservation.
The rise in SCr typically occurs within a few days of therapy initiation; thus, SCr should be measured within the first seven days of therapy.3 The SCr level is expected to stabilize within six to eight weeks of therapy. Patients whose SCr level continues to rise more than 30% to 35% above baseline may need to discontinue ACEI/ARB therapy; this rise may be attributed to kidney hypoperfusion. Kidney hypoperfusion can also occur when diuretics are initiated or their dosage increased, when NSAIDs are used, or in patients with bilateral renal artery stenosis or volume depletion resulting from gastroenteritis.3
Hyperkalemia due to decreased urinary excretion of potassium (K+) may present yet another reason to discontinue ACEI/ARB therapy in patients with CKD. Incidence of hyperkalemia in those with CKD stages 3 through 5 who receive either an ACEI or an ARB ranges from 5% to 50%.3 Hyperkalemia can occur when a long-acting ACEI is prescribed or when ACEI/ARB therapy is used concurrently with NSAIDs or potassium-sparing diuretics; thiazides or loop diuretics, by contrast, can reduce the risk for hyperkalemia.
Risk factors for moderate hyperkalemia (serum K+ ≥ 5.6 mmol/L) include age older than 65, congestive heart failure, SCr level greater than 1.6 mg/dL, and a blood urea nitrogen level exceeding 18 mg/dL.5
A dosing reduction or discontinuation of ACEI/ARB therapy should be considered when serum K+ levels are 5.6 mmol/L or greater.3 Patients who are older than 70 or whose serum urea nitrogen level exceeds 25 mg/dL are at increased risk for severe hyperkalemia (K+ > 6.0 mmol/L). Termination of an ACEI or an ARB may be warranted in patients with a serum K+ level exceeding 6.0 mmol/L or in those considered at increased risk for severe hyperkalemia.3
Other patients may also benefit from discontinuing ACEI/ARB therapy. Few data exist to support their use in patients with kidney function at 25% or less, or those with a GFR below 30 mL/min/1.73 m2.3 Onuigbo6 suggests that ESRD in patients with CKD can either progress gradually and steadily or rapidly as a result of acute kidney injury (AKI). Patients with CKD who are at risk for ESRD because of AKI include those currently taking an ACEI or an ARB, older patients, and those who experience unexplained decreases in GFR.
To avoid any worsening of renal function, Onuigbo6 suggests temporarily discontinuing ACEI/ARB therapy in the following patients:
• Those older than 65 who are scheduled for colonoscopy, administration of IV radiocontrast, or surgery (especially cardiovascular surgery); or
• Patients hospitalized for an acute ailment.
Discontinuing these agents may prevent progression to ESRD in such patients.
In summary, use of ACEIs or ARBs to delay progression of renal disease may be continued if a clear therapeutic benefit exists. However, discontinuation should be considered if a patient with CKD is at risk for hyperkalemia or if the K+ level remains higher than 5.6 mmol/L, if SCr levels increase more than 30% above baseline, or if patients (especially those older than 65) are at risk for AKI.
References
1. Remuzzi G, Perico N, Macia M, Ruggenenti P. The role of renin-angiotensin-aldosterone system in the progression of chronic kidney disease. Kidney Int Suppl. 2005;99:S57-S65.
2. Chobanian AV, Bakris GL, Black HR, et al; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289:2560-2572.
3. Mangrum AJ, Bakris GL. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in chronic renal disease: safety issues. Semin Nephrol. 2004;24:168-175.
4. St Peter WL, Odum LE, Whaley-Connell AT. To RAS or not to RAS? The evidence for and cautions with renin-angiotensin system inhibition in patients with diabetic kidney disease. Pharmacotherapy. 2013 Apr 9.
5. Bakris GL, Weir MR. Angiotensin-converting enzyme inhibitor–associated elevations in serum creatinine: is this a cause for concern? Arch Intern Med. 2000;160:685-693.
6. Onuigbo MA. Is renoprotection with RAAS blockade a failed paradigm? Have we learnt any lessons so far? Int J Clin Pract. 2010;64:1341-1346.
Q: I sent a 68-year-old, hypertensive, diabetic woman with stage 4 kidney disease (estimated glomerular filtration rate [eGFR], 25 mL/min/1.73 m2; serum creatinine [SCr], 2 mg/mL) to a local nephrology group. Since she was diabetic, we had had her taking an angiotensin-converting enzyme inhibitor (ACEI) for years. The first thing the nephrology group did was take her off the ACEI. Why would they do that? I thought the hypertensive drug of choice for all diabetic patients is an ACEI or an angiotensin receptor blocker (ARB). Am I wrong?
A: The renin-angiotensin-aldosterone system (RAAS) plays an important role in the regulation of blood pressure and intravascular volume through its effects on renin, angiotensin, and aldosterone production. Activation of RAAS causes an increase in blood pressure through vasoconstriction (angiotensin II effects) and the fluid retention associated with reabsorption of sodium and water (aldosterone effects). As such, the physiologic effects of RAAS have been implicated in the pathophysiology of cardiovascular diseases, such as heart failure, kidney disease, and hypertension.1
The JNC 7 guidelines2 (Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) recommend the use of ACEIs or ARBs for the treatment of hypertension in patients with chronic kidney disease (CKD) or diabetes to slow progression of kidney disease. Given the benefits of ACEI or ARB therapy in reducing mortality in cardiovascular disease (for which patients with CKD are at increased risk3), these medications are indicated in patients with CKD.
Angiotensin II causes systemic vasoconstriction and also acts on the efferent arterioles of the glomerulus. ACEI/ARB therapy causes vasodilation of the efferent arterioles, thus lowering the intraglomerular capillary pressure.1 This mechanism accounts for the antiproteinuric effect and the subsequent decrease in GFR when these agents are initiated.
Proteinuria is a marker that may indicate nephropathy and may lead to further kidney damage.1 Slowing renal disease progression depends on controlling blood pressure and proteinuria.3
To date, a number of trials have been conducted to explore the benefit of the antiproteinuric effects of ACEI/ARB therapy. The antiproteinuric effect is more pronounced in patients with more severe proteinuria. Studies of these agents in patients with diabetic and nondiabetic nephropathy have shown that besides reducing proteinuria, they slow progression to end-stage renal disease (ESRD), thus delaying the need for renal replacement therapy.4 As such, ACEI/ARB therapy is widely used to reduce proteinuria, independent of the blood pressure–lowering effects.
Initiation of ACEI/ARB therapy is associated with an increase in SCr due to the drugs’ effects on the efferent arterioles, resulting in a decrease in intraglomerular pressure.3 However, discontinuing therapy is not warranted unless the SCr rises to more than 30% above baseline. According to findings from one meta-analysis, the degree of loss in renal function when ACEI therapy was initiated was inversely related to the rate of annual decline in renal function.5 Thus, patients with higher SCr levels at the start of therapy had poorer renal function initially, but they received the greatest benefit in long-term renal preservation.
The rise in SCr typically occurs within a few days of therapy initiation; thus, SCr should be measured within the first seven days of therapy.3 The SCr level is expected to stabilize within six to eight weeks of therapy. Patients whose SCr level continues to rise more than 30% to 35% above baseline may need to discontinue ACEI/ARB therapy; this rise may be attributed to kidney hypoperfusion. Kidney hypoperfusion can also occur when diuretics are initiated or their dosage increased, when NSAIDs are used, or in patients with bilateral renal artery stenosis or volume depletion resulting from gastroenteritis.3
Hyperkalemia due to decreased urinary excretion of potassium (K+) may present yet another reason to discontinue ACEI/ARB therapy in patients with CKD. Incidence of hyperkalemia in those with CKD stages 3 through 5 who receive either an ACEI or an ARB ranges from 5% to 50%.3 Hyperkalemia can occur when a long-acting ACEI is prescribed or when ACEI/ARB therapy is used concurrently with NSAIDs or potassium-sparing diuretics; thiazides or loop diuretics, by contrast, can reduce the risk for hyperkalemia.
Risk factors for moderate hyperkalemia (serum K+ ≥ 5.6 mmol/L) include age older than 65, congestive heart failure, SCr level greater than 1.6 mg/dL, and a blood urea nitrogen level exceeding 18 mg/dL.5
A dosing reduction or discontinuation of ACEI/ARB therapy should be considered when serum K+ levels are 5.6 mmol/L or greater.3 Patients who are older than 70 or whose serum urea nitrogen level exceeds 25 mg/dL are at increased risk for severe hyperkalemia (K+ > 6.0 mmol/L). Termination of an ACEI or an ARB may be warranted in patients with a serum K+ level exceeding 6.0 mmol/L or in those considered at increased risk for severe hyperkalemia.3
Other patients may also benefit from discontinuing ACEI/ARB therapy. Few data exist to support their use in patients with kidney function at 25% or less, or those with a GFR below 30 mL/min/1.73 m2.3 Onuigbo6 suggests that ESRD in patients with CKD can either progress gradually and steadily or rapidly as a result of acute kidney injury (AKI). Patients with CKD who are at risk for ESRD because of AKI include those currently taking an ACEI or an ARB, older patients, and those who experience unexplained decreases in GFR.
To avoid any worsening of renal function, Onuigbo6 suggests temporarily discontinuing ACEI/ARB therapy in the following patients:
• Those older than 65 who are scheduled for colonoscopy, administration of IV radiocontrast, or surgery (especially cardiovascular surgery); or
• Patients hospitalized for an acute ailment.
Discontinuing these agents may prevent progression to ESRD in such patients.
In summary, use of ACEIs or ARBs to delay progression of renal disease may be continued if a clear therapeutic benefit exists. However, discontinuation should be considered if a patient with CKD is at risk for hyperkalemia or if the K+ level remains higher than 5.6 mmol/L, if SCr levels increase more than 30% above baseline, or if patients (especially those older than 65) are at risk for AKI.
References
1. Remuzzi G, Perico N, Macia M, Ruggenenti P. The role of renin-angiotensin-aldosterone system in the progression of chronic kidney disease. Kidney Int Suppl. 2005;99:S57-S65.
2. Chobanian AV, Bakris GL, Black HR, et al; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289:2560-2572.
3. Mangrum AJ, Bakris GL. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in chronic renal disease: safety issues. Semin Nephrol. 2004;24:168-175.
4. St Peter WL, Odum LE, Whaley-Connell AT. To RAS or not to RAS? The evidence for and cautions with renin-angiotensin system inhibition in patients with diabetic kidney disease. Pharmacotherapy. 2013 Apr 9.
5. Bakris GL, Weir MR. Angiotensin-converting enzyme inhibitor–associated elevations in serum creatinine: is this a cause for concern? Arch Intern Med. 2000;160:685-693.
6. Onuigbo MA. Is renoprotection with RAAS blockade a failed paradigm? Have we learnt any lessons so far? Int J Clin Pract. 2010;64:1341-1346.
Does Combination ACEi/ARB Therapy Benefit Patients With Proteinuria?
Q: I have a diabetic patient with microscopic proteinuria. I put her on an ACE inhibitor, but she still has the same albumin–creatinine ratio. My supervising physician suggested I add an ARB to her regimen, but I seem to remember reading that this does not work. Is that true? Or should I prescribe an ACE inhibitor/ARB combination?
This is a common question, but there is no consensus regarding the correct answer. The question should be: Are two drugs better than one when it comes to reducing proteinuria and progression to end-stage renal disease? Researchers have demonstrated a decrease in proteinuria in patients given combination ACE inhibitor/angiotension receptor blocker (ARB) therapy; however, the studies involved were found to have flaws, including small sample sizes and relatively short follow-up, once treatment was initiated.1,2
A larger study, known as Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET),3,4 is a multiyear study with more than 25,000 patients enrolled. ONTARGET (which excludes patients with heart failure) addresses the question of whether an ACE inhibitor in combination with an ARB, or either agent alone, is more effective in the reduction of proteinuria. In ONTARGET, combination therapy was associated with a decrease in proteinuria; however, the incidence of renal impairment was much higher.3
ONTARGET was the first trial to cast doubt on the belief that proteinuria is an accurate marker for progressive renal dysfunction. Combination treatment led to an advanced risk for increased serum creatinine and need for dialysis, despite the reduction in proteinuria. Further, combination therapy was more likely than either agent alone to cause adverse effects, including hypotension and hyperkalemia.3,4
Finally, the study also demonstrated that ACE inhibitors are not superior to ARBs. Both drugs reduce proteinuria, and each one taken alone decreases progression to end-stage renal disease. Therefore, the conclusion is that either an ACE inhibitor or an ARB alone is more efficacious than the two drugs combined.
Tricia A. Howard, MHS, PA-C, South University PA Program, Tampa, FL
References
1. Misra S, Stevermer JJ. ACE inhibitors and ARBs: one or the other—not both—for high-risk patients. J Fam Pract. 2009;58:24-26.
2. Jennings DL, Kalus JS, Coleman CI, et al. Combination therapy with an ACE inhibitor and an angiotensin receptor blocker for diabetic nephropathy: a meta-analysis. Diabet Med. 2007;24:486-493.
3. Mann JF, Schmieder RE, McQueen M, et al; ONTARGET investigators. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet. 2008;372:547-553.
4. Yusuf S, Teo KK, Pogue J, et al; ONTARGET Investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358:1547-1559.
Q: I have a diabetic patient with microscopic proteinuria. I put her on an ACE inhibitor, but she still has the same albumin–creatinine ratio. My supervising physician suggested I add an ARB to her regimen, but I seem to remember reading that this does not work. Is that true? Or should I prescribe an ACE inhibitor/ARB combination?
This is a common question, but there is no consensus regarding the correct answer. The question should be: Are two drugs better than one when it comes to reducing proteinuria and progression to end-stage renal disease? Researchers have demonstrated a decrease in proteinuria in patients given combination ACE inhibitor/angiotension receptor blocker (ARB) therapy; however, the studies involved were found to have flaws, including small sample sizes and relatively short follow-up, once treatment was initiated.1,2
A larger study, known as Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET),3,4 is a multiyear study with more than 25,000 patients enrolled. ONTARGET (which excludes patients with heart failure) addresses the question of whether an ACE inhibitor in combination with an ARB, or either agent alone, is more effective in the reduction of proteinuria. In ONTARGET, combination therapy was associated with a decrease in proteinuria; however, the incidence of renal impairment was much higher.3
ONTARGET was the first trial to cast doubt on the belief that proteinuria is an accurate marker for progressive renal dysfunction. Combination treatment led to an advanced risk for increased serum creatinine and need for dialysis, despite the reduction in proteinuria. Further, combination therapy was more likely than either agent alone to cause adverse effects, including hypotension and hyperkalemia.3,4
Finally, the study also demonstrated that ACE inhibitors are not superior to ARBs. Both drugs reduce proteinuria, and each one taken alone decreases progression to end-stage renal disease. Therefore, the conclusion is that either an ACE inhibitor or an ARB alone is more efficacious than the two drugs combined.
Tricia A. Howard, MHS, PA-C, South University PA Program, Tampa, FL
References
1. Misra S, Stevermer JJ. ACE inhibitors and ARBs: one or the other—not both—for high-risk patients. J Fam Pract. 2009;58:24-26.
2. Jennings DL, Kalus JS, Coleman CI, et al. Combination therapy with an ACE inhibitor and an angiotensin receptor blocker for diabetic nephropathy: a meta-analysis. Diabet Med. 2007;24:486-493.
3. Mann JF, Schmieder RE, McQueen M, et al; ONTARGET investigators. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet. 2008;372:547-553.
4. Yusuf S, Teo KK, Pogue J, et al; ONTARGET Investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358:1547-1559.
Q: I have a diabetic patient with microscopic proteinuria. I put her on an ACE inhibitor, but she still has the same albumin–creatinine ratio. My supervising physician suggested I add an ARB to her regimen, but I seem to remember reading that this does not work. Is that true? Or should I prescribe an ACE inhibitor/ARB combination?
This is a common question, but there is no consensus regarding the correct answer. The question should be: Are two drugs better than one when it comes to reducing proteinuria and progression to end-stage renal disease? Researchers have demonstrated a decrease in proteinuria in patients given combination ACE inhibitor/angiotension receptor blocker (ARB) therapy; however, the studies involved were found to have flaws, including small sample sizes and relatively short follow-up, once treatment was initiated.1,2
A larger study, known as Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET),3,4 is a multiyear study with more than 25,000 patients enrolled. ONTARGET (which excludes patients with heart failure) addresses the question of whether an ACE inhibitor in combination with an ARB, or either agent alone, is more effective in the reduction of proteinuria. In ONTARGET, combination therapy was associated with a decrease in proteinuria; however, the incidence of renal impairment was much higher.3
ONTARGET was the first trial to cast doubt on the belief that proteinuria is an accurate marker for progressive renal dysfunction. Combination treatment led to an advanced risk for increased serum creatinine and need for dialysis, despite the reduction in proteinuria. Further, combination therapy was more likely than either agent alone to cause adverse effects, including hypotension and hyperkalemia.3,4
Finally, the study also demonstrated that ACE inhibitors are not superior to ARBs. Both drugs reduce proteinuria, and each one taken alone decreases progression to end-stage renal disease. Therefore, the conclusion is that either an ACE inhibitor or an ARB alone is more efficacious than the two drugs combined.
Tricia A. Howard, MHS, PA-C, South University PA Program, Tampa, FL
References
1. Misra S, Stevermer JJ. ACE inhibitors and ARBs: one or the other—not both—for high-risk patients. J Fam Pract. 2009;58:24-26.
2. Jennings DL, Kalus JS, Coleman CI, et al. Combination therapy with an ACE inhibitor and an angiotensin receptor blocker for diabetic nephropathy: a meta-analysis. Diabet Med. 2007;24:486-493.
3. Mann JF, Schmieder RE, McQueen M, et al; ONTARGET investigators. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet. 2008;372:547-553.
4. Yusuf S, Teo KK, Pogue J, et al; ONTARGET Investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358:1547-1559.
A Reader Asks About Wild Ginger
Q: A friend of my teenage daughter was telling her about a new, “natural” weight-loss medication that contains wild ginger. Besides the obvious (a teen should not be taking “drugs” to lose weight), I seem to remember a problem with wild ginger. Is this substance dangerous?
A source of the herbal drug aristolochic acid (AA), wild ginger is a plant in the birthwort family. Its common name may be explained by the fact that it smells and tastes somewhat like ginger. However, wild ginger is not related to the common herb, ginger, that is found in the grocery store.
After multiple incidents of acute kidney failure in Europe, China, India, and the Balkans were linked to AA, the FDA sent out warning letters in 2001.5 However, as the saying goes, what goes around, comes around. A new wave of “natural” weight-loss remedies containing AA has become available for sale to unsuspecting consumers over the Internet.
Wild ginger plants grow in temperate regions, with a kidney-shaped leaf—ironic, since ingesting this substance can induce kidney failure. In an article published in 2012, researchers reported that a Chinese company had replaced Stephania tetrandra with Aristolochia fangchi in their weight-loss formula, resulting in multiple incidents of kidney failure.6 In 2013, investigators from London and Germany showed that products containing AA were commonly available online.7
Symptoms of AA ingestion include acute kidney failure with normal blood pressure; a normochromic, normocytic anemia with a moderate amount of urine protein excretion (< 1.5 g/d); and urine sediment with a few red blood cells. The serum creatininehas been reported anywhere from 1.4 to 12.7 mg/dL on presentation,7 but due to AA-associated reductions in fluid and food intake (ie, its “weight-loss” component), this can quickly progress to kidney failure.
Discontinuing use of the herbal remedy does not appear to stop users’ progression to kidney failure, as damage to the interstitial cells is already done by the time of presentation.
AA use is also associated with an increased incidence of both kidney cancer and urinary cancer. Quite a high-risk “natural” herbal remedy!
Kim Zuber, PA-C, MSPS, DFAAPA,Department Co-editor
References
5. Boyle B. FDA warns consumers to discontinue use of botanical products that contain aristolochic acid (2001). www.hcvadvocate.org/news/NewsUpdates_pdf/2.1.1.2_News_Review_Archive_2001/aristocholic.pdf. Accessed April 5, 2013.
6. Asif M. A brief study of toxic effects of some medicinal herbs on kidney. Adv Biomed Res. 2012;1:44.
7. Gökmen MR, Cosyns JP, Arlt VM, et al. The epidemiology, diagnosis, and management of aristolochic acid nephropathy: a narrative review. Ann Intern Med. 2013;158:469-477.
Q: A friend of my teenage daughter was telling her about a new, “natural” weight-loss medication that contains wild ginger. Besides the obvious (a teen should not be taking “drugs” to lose weight), I seem to remember a problem with wild ginger. Is this substance dangerous?
A source of the herbal drug aristolochic acid (AA), wild ginger is a plant in the birthwort family. Its common name may be explained by the fact that it smells and tastes somewhat like ginger. However, wild ginger is not related to the common herb, ginger, that is found in the grocery store.
After multiple incidents of acute kidney failure in Europe, China, India, and the Balkans were linked to AA, the FDA sent out warning letters in 2001.5 However, as the saying goes, what goes around, comes around. A new wave of “natural” weight-loss remedies containing AA has become available for sale to unsuspecting consumers over the Internet.
Wild ginger plants grow in temperate regions, with a kidney-shaped leaf—ironic, since ingesting this substance can induce kidney failure. In an article published in 2012, researchers reported that a Chinese company had replaced Stephania tetrandra with Aristolochia fangchi in their weight-loss formula, resulting in multiple incidents of kidney failure.6 In 2013, investigators from London and Germany showed that products containing AA were commonly available online.7
Symptoms of AA ingestion include acute kidney failure with normal blood pressure; a normochromic, normocytic anemia with a moderate amount of urine protein excretion (< 1.5 g/d); and urine sediment with a few red blood cells. The serum creatininehas been reported anywhere from 1.4 to 12.7 mg/dL on presentation,7 but due to AA-associated reductions in fluid and food intake (ie, its “weight-loss” component), this can quickly progress to kidney failure.
Discontinuing use of the herbal remedy does not appear to stop users’ progression to kidney failure, as damage to the interstitial cells is already done by the time of presentation.
AA use is also associated with an increased incidence of both kidney cancer and urinary cancer. Quite a high-risk “natural” herbal remedy!
Kim Zuber, PA-C, MSPS, DFAAPA,Department Co-editor
References
5. Boyle B. FDA warns consumers to discontinue use of botanical products that contain aristolochic acid (2001). www.hcvadvocate.org/news/NewsUpdates_pdf/2.1.1.2_News_Review_Archive_2001/aristocholic.pdf. Accessed April 5, 2013.
6. Asif M. A brief study of toxic effects of some medicinal herbs on kidney. Adv Biomed Res. 2012;1:44.
7. Gökmen MR, Cosyns JP, Arlt VM, et al. The epidemiology, diagnosis, and management of aristolochic acid nephropathy: a narrative review. Ann Intern Med. 2013;158:469-477.
Q: A friend of my teenage daughter was telling her about a new, “natural” weight-loss medication that contains wild ginger. Besides the obvious (a teen should not be taking “drugs” to lose weight), I seem to remember a problem with wild ginger. Is this substance dangerous?
A source of the herbal drug aristolochic acid (AA), wild ginger is a plant in the birthwort family. Its common name may be explained by the fact that it smells and tastes somewhat like ginger. However, wild ginger is not related to the common herb, ginger, that is found in the grocery store.
After multiple incidents of acute kidney failure in Europe, China, India, and the Balkans were linked to AA, the FDA sent out warning letters in 2001.5 However, as the saying goes, what goes around, comes around. A new wave of “natural” weight-loss remedies containing AA has become available for sale to unsuspecting consumers over the Internet.
Wild ginger plants grow in temperate regions, with a kidney-shaped leaf—ironic, since ingesting this substance can induce kidney failure. In an article published in 2012, researchers reported that a Chinese company had replaced Stephania tetrandra with Aristolochia fangchi in their weight-loss formula, resulting in multiple incidents of kidney failure.6 In 2013, investigators from London and Germany showed that products containing AA were commonly available online.7
Symptoms of AA ingestion include acute kidney failure with normal blood pressure; a normochromic, normocytic anemia with a moderate amount of urine protein excretion (< 1.5 g/d); and urine sediment with a few red blood cells. The serum creatininehas been reported anywhere from 1.4 to 12.7 mg/dL on presentation,7 but due to AA-associated reductions in fluid and food intake (ie, its “weight-loss” component), this can quickly progress to kidney failure.
Discontinuing use of the herbal remedy does not appear to stop users’ progression to kidney failure, as damage to the interstitial cells is already done by the time of presentation.
AA use is also associated with an increased incidence of both kidney cancer and urinary cancer. Quite a high-risk “natural” herbal remedy!
Kim Zuber, PA-C, MSPS, DFAAPA,Department Co-editor
References
5. Boyle B. FDA warns consumers to discontinue use of botanical products that contain aristolochic acid (2001). www.hcvadvocate.org/news/NewsUpdates_pdf/2.1.1.2_News_Review_Archive_2001/aristocholic.pdf. Accessed April 5, 2013.
6. Asif M. A brief study of toxic effects of some medicinal herbs on kidney. Adv Biomed Res. 2012;1:44.
7. Gökmen MR, Cosyns JP, Arlt VM, et al. The epidemiology, diagnosis, and management of aristolochic acid nephropathy: a narrative review. Ann Intern Med. 2013;158:469-477.
Acute Kidney Injury in the ICU: Medication Dosing
Q: As a hospitalist, I often see patients in our ICU develop AKI. Our pharmacist helps us with medication dosing, but sometimes I feel as if we're pulling a dose out of the air. Are there any studies or guidelines we can refer to?
Standard medication dosing adjustments for patients with impaired renal function are generally based on estimated glomerular filtration rate (eGFR). Because SCr is a lagging indicator of AKI, all methods of deriving eGFR from SCr are valid only when the patient is in a steady state.10
SCr has yet to be replaced by a real-time biomarker for AKI; this has left clinicians in the ICU setting with no simple or concise method for real-time assessment of renal function. In response to this common clinical conundrum, the RIFLE criteria,8 mentioned above, incorporates urinary output and relative increase in SCr as assessment criteria (see table for definitions).
This revised classification system may help the clinician define the severity of AKI in the acute setting. However, no medication dosing guidelines currently correspond with RIFLE staging. To further complicate the picture, there is evidence to suggest that AKI may affect drug metabolism through nonrenal pathways, such as hepatic clearance and transport functions.11 Add to this the potential for impaired drug absorption, distribution, and/or clearance due to variance in intravascular volume status, hepatic hypoperfusion, hypoxia, decreased protein synthesis, and competitive inhibition from concomitant medications—in short, the variables become too complex for calculating therapeutic drug dosing to be possible.
In the absence of definitive guidelines, the clinician plays a critical role in medication dosing adjustment for the ICU patient with AKI. The clinician must use astute clinical judgment to assess and prioritize the unique constellation of factors in any given case. Some of the factors that should be carefully considered when estimating medication dose adjustments in this context include RIFLE staging, trend in SCr, baseline SCr, nephrotoxicity of the medication to be administered, the drug's volume of distribution, the metabolic pathways of drug excretion, and the patient's weight.
A serum drug level, when available, is generally the best guide for dosing adjustment.10 The RIFLE staging does offer some clinical pearls that may be helpful. Though not evidence-based recommendations, these guides are commonly used in the clinical environment.
When patients are in the Failure stage, for example (see specifics in the table), they are generally considered to have an eGFR of less than 15 mL/min for purposes of drug dose adjustment (personal communication, Gideon Kayanan, PharmD, February 2013). However, patients in this category are much more likely than others to be undergoing dialysis, in which case the pharmacokinetics and pharmacodynamics are further complicated. In some cases, it may be appropriate to order creatinine clearance studies with a 6- or 12-hour urine collection and extrapolate a 24-hour creatinine clearance from this value.
The dearth of literature addressing this topic (despite the prevalence of AKI in the acute care setting) is a clear indication of the complexity of creating guidelines to address such a dynamic, multivariate pharmacokinetic process. Review of the literature clearly demonstrates that medical science in this area is not yet sufficiently developed to produce a standardized, data-driven guideline for dose adjustment calculation in patients with AKI.10 Until biomarkers are detected that offer real-time assessment of renal function and that can be used in the clinical setting, there will continue to be a component of estimation, analysis of trends, and reliance on clinical judgment in adjusting medication doses for inpatients with AKI. —AC
References
1. National Institute of Diabetes and Digestive and Kidney Diseases, NIH. US Renal Data System, 2010 Annual Data Report. www.usrds.org/2010/view/default.asp. Accessed March 5, 2013.
2. National Institute of Diabetes and Digestive and Kidney Diseases, NIH. US Renal Data System, 2011 Annual Data Report. www.usrds.org/2011/view/v2_00_appx.asp. Accessed March 5, 2013.
3. Waikar SS, Liu KD, Chertow GM. Diagnosis, epidemiology and outcomes of acute kidney injury. Clin J Am Soc Nephrol. 2008;3:844-861.
4. Chertow GM, Burdick E, Honour M, et al. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol. 2005;16:3365-3370.
5. Hsu RK, McCulloch CE, Dudley RA, et al. Temporal changes in incidence of dialysis-requiring AKI. J Am Soc Nephrol. 2012;24:37-42.
6. Wang HE, Muntner P, Chertow GM, Warnock DG. Acute kidney injury and mortality in hospitalized patients. Am J Nephrol. 2012;35:349-355.
7. Nisula S, Kaukonen KM, Vaara ST, et al. Incidence, risk factors and 90-day mortality of patients with acute kidney injury in Finnish intensive care units: the FINNAKI study. Intensive Care Med. 2013;39:420-428.
8. Hoste EA, Clermont G, Kersten A, et al. RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: a cohort analysis. Crit Care. 2006;10:R73.
9. Coca SG, Yusuf B, Shlipak MG, et al. Long-term risk of mortality and other adverse outcomes after acute kidney injury: a systematic review and meta-analysis. Am J Kidney Dis. 2009;53:961-973.
10. Matzke GR, Aronoff GR, Atkinson AJ Jr, et al. Drug dosing consideration in patients with acute and chronic kidney disease: a clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 2011;80:1122-1137.
11. Vilay AM, Churchwell MD, Mueller BA. Clinical review: drug metabolism and nonrenal clearance in acute kidney injury. Crit Care. 2008;12:235.
Q: As a hospitalist, I often see patients in our ICU develop AKI. Our pharmacist helps us with medication dosing, but sometimes I feel as if we're pulling a dose out of the air. Are there any studies or guidelines we can refer to?
Standard medication dosing adjustments for patients with impaired renal function are generally based on estimated glomerular filtration rate (eGFR). Because SCr is a lagging indicator of AKI, all methods of deriving eGFR from SCr are valid only when the patient is in a steady state.10
SCr has yet to be replaced by a real-time biomarker for AKI; this has left clinicians in the ICU setting with no simple or concise method for real-time assessment of renal function. In response to this common clinical conundrum, the RIFLE criteria,8 mentioned above, incorporates urinary output and relative increase in SCr as assessment criteria (see table for definitions).
This revised classification system may help the clinician define the severity of AKI in the acute setting. However, no medication dosing guidelines currently correspond with RIFLE staging. To further complicate the picture, there is evidence to suggest that AKI may affect drug metabolism through nonrenal pathways, such as hepatic clearance and transport functions.11 Add to this the potential for impaired drug absorption, distribution, and/or clearance due to variance in intravascular volume status, hepatic hypoperfusion, hypoxia, decreased protein synthesis, and competitive inhibition from concomitant medications—in short, the variables become too complex for calculating therapeutic drug dosing to be possible.
In the absence of definitive guidelines, the clinician plays a critical role in medication dosing adjustment for the ICU patient with AKI. The clinician must use astute clinical judgment to assess and prioritize the unique constellation of factors in any given case. Some of the factors that should be carefully considered when estimating medication dose adjustments in this context include RIFLE staging, trend in SCr, baseline SCr, nephrotoxicity of the medication to be administered, the drug's volume of distribution, the metabolic pathways of drug excretion, and the patient's weight.
A serum drug level, when available, is generally the best guide for dosing adjustment.10 The RIFLE staging does offer some clinical pearls that may be helpful. Though not evidence-based recommendations, these guides are commonly used in the clinical environment.
When patients are in the Failure stage, for example (see specifics in the table), they are generally considered to have an eGFR of less than 15 mL/min for purposes of drug dose adjustment (personal communication, Gideon Kayanan, PharmD, February 2013). However, patients in this category are much more likely than others to be undergoing dialysis, in which case the pharmacokinetics and pharmacodynamics are further complicated. In some cases, it may be appropriate to order creatinine clearance studies with a 6- or 12-hour urine collection and extrapolate a 24-hour creatinine clearance from this value.
The dearth of literature addressing this topic (despite the prevalence of AKI in the acute care setting) is a clear indication of the complexity of creating guidelines to address such a dynamic, multivariate pharmacokinetic process. Review of the literature clearly demonstrates that medical science in this area is not yet sufficiently developed to produce a standardized, data-driven guideline for dose adjustment calculation in patients with AKI.10 Until biomarkers are detected that offer real-time assessment of renal function and that can be used in the clinical setting, there will continue to be a component of estimation, analysis of trends, and reliance on clinical judgment in adjusting medication doses for inpatients with AKI. —AC
References
1. National Institute of Diabetes and Digestive and Kidney Diseases, NIH. US Renal Data System, 2010 Annual Data Report. www.usrds.org/2010/view/default.asp. Accessed March 5, 2013.
2. National Institute of Diabetes and Digestive and Kidney Diseases, NIH. US Renal Data System, 2011 Annual Data Report. www.usrds.org/2011/view/v2_00_appx.asp. Accessed March 5, 2013.
3. Waikar SS, Liu KD, Chertow GM. Diagnosis, epidemiology and outcomes of acute kidney injury. Clin J Am Soc Nephrol. 2008;3:844-861.
4. Chertow GM, Burdick E, Honour M, et al. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol. 2005;16:3365-3370.
5. Hsu RK, McCulloch CE, Dudley RA, et al. Temporal changes in incidence of dialysis-requiring AKI. J Am Soc Nephrol. 2012;24:37-42.
6. Wang HE, Muntner P, Chertow GM, Warnock DG. Acute kidney injury and mortality in hospitalized patients. Am J Nephrol. 2012;35:349-355.
7. Nisula S, Kaukonen KM, Vaara ST, et al. Incidence, risk factors and 90-day mortality of patients with acute kidney injury in Finnish intensive care units: the FINNAKI study. Intensive Care Med. 2013;39:420-428.
8. Hoste EA, Clermont G, Kersten A, et al. RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: a cohort analysis. Crit Care. 2006;10:R73.
9. Coca SG, Yusuf B, Shlipak MG, et al. Long-term risk of mortality and other adverse outcomes after acute kidney injury: a systematic review and meta-analysis. Am J Kidney Dis. 2009;53:961-973.
10. Matzke GR, Aronoff GR, Atkinson AJ Jr, et al. Drug dosing consideration in patients with acute and chronic kidney disease: a clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 2011;80:1122-1137.
11. Vilay AM, Churchwell MD, Mueller BA. Clinical review: drug metabolism and nonrenal clearance in acute kidney injury. Crit Care. 2008;12:235.
Q: As a hospitalist, I often see patients in our ICU develop AKI. Our pharmacist helps us with medication dosing, but sometimes I feel as if we're pulling a dose out of the air. Are there any studies or guidelines we can refer to?
Standard medication dosing adjustments for patients with impaired renal function are generally based on estimated glomerular filtration rate (eGFR). Because SCr is a lagging indicator of AKI, all methods of deriving eGFR from SCr are valid only when the patient is in a steady state.10
SCr has yet to be replaced by a real-time biomarker for AKI; this has left clinicians in the ICU setting with no simple or concise method for real-time assessment of renal function. In response to this common clinical conundrum, the RIFLE criteria,8 mentioned above, incorporates urinary output and relative increase in SCr as assessment criteria (see table for definitions).
This revised classification system may help the clinician define the severity of AKI in the acute setting. However, no medication dosing guidelines currently correspond with RIFLE staging. To further complicate the picture, there is evidence to suggest that AKI may affect drug metabolism through nonrenal pathways, such as hepatic clearance and transport functions.11 Add to this the potential for impaired drug absorption, distribution, and/or clearance due to variance in intravascular volume status, hepatic hypoperfusion, hypoxia, decreased protein synthesis, and competitive inhibition from concomitant medications—in short, the variables become too complex for calculating therapeutic drug dosing to be possible.
In the absence of definitive guidelines, the clinician plays a critical role in medication dosing adjustment for the ICU patient with AKI. The clinician must use astute clinical judgment to assess and prioritize the unique constellation of factors in any given case. Some of the factors that should be carefully considered when estimating medication dose adjustments in this context include RIFLE staging, trend in SCr, baseline SCr, nephrotoxicity of the medication to be administered, the drug's volume of distribution, the metabolic pathways of drug excretion, and the patient's weight.
A serum drug level, when available, is generally the best guide for dosing adjustment.10 The RIFLE staging does offer some clinical pearls that may be helpful. Though not evidence-based recommendations, these guides are commonly used in the clinical environment.
When patients are in the Failure stage, for example (see specifics in the table), they are generally considered to have an eGFR of less than 15 mL/min for purposes of drug dose adjustment (personal communication, Gideon Kayanan, PharmD, February 2013). However, patients in this category are much more likely than others to be undergoing dialysis, in which case the pharmacokinetics and pharmacodynamics are further complicated. In some cases, it may be appropriate to order creatinine clearance studies with a 6- or 12-hour urine collection and extrapolate a 24-hour creatinine clearance from this value.
The dearth of literature addressing this topic (despite the prevalence of AKI in the acute care setting) is a clear indication of the complexity of creating guidelines to address such a dynamic, multivariate pharmacokinetic process. Review of the literature clearly demonstrates that medical science in this area is not yet sufficiently developed to produce a standardized, data-driven guideline for dose adjustment calculation in patients with AKI.10 Until biomarkers are detected that offer real-time assessment of renal function and that can be used in the clinical setting, there will continue to be a component of estimation, analysis of trends, and reliance on clinical judgment in adjusting medication doses for inpatients with AKI. —AC
References
1. National Institute of Diabetes and Digestive and Kidney Diseases, NIH. US Renal Data System, 2010 Annual Data Report. www.usrds.org/2010/view/default.asp. Accessed March 5, 2013.
2. National Institute of Diabetes and Digestive and Kidney Diseases, NIH. US Renal Data System, 2011 Annual Data Report. www.usrds.org/2011/view/v2_00_appx.asp. Accessed March 5, 2013.
3. Waikar SS, Liu KD, Chertow GM. Diagnosis, epidemiology and outcomes of acute kidney injury. Clin J Am Soc Nephrol. 2008;3:844-861.
4. Chertow GM, Burdick E, Honour M, et al. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol. 2005;16:3365-3370.
5. Hsu RK, McCulloch CE, Dudley RA, et al. Temporal changes in incidence of dialysis-requiring AKI. J Am Soc Nephrol. 2012;24:37-42.
6. Wang HE, Muntner P, Chertow GM, Warnock DG. Acute kidney injury and mortality in hospitalized patients. Am J Nephrol. 2012;35:349-355.
7. Nisula S, Kaukonen KM, Vaara ST, et al. Incidence, risk factors and 90-day mortality of patients with acute kidney injury in Finnish intensive care units: the FINNAKI study. Intensive Care Med. 2013;39:420-428.
8. Hoste EA, Clermont G, Kersten A, et al. RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: a cohort analysis. Crit Care. 2006;10:R73.
9. Coca SG, Yusuf B, Shlipak MG, et al. Long-term risk of mortality and other adverse outcomes after acute kidney injury: a systematic review and meta-analysis. Am J Kidney Dis. 2009;53:961-973.
10. Matzke GR, Aronoff GR, Atkinson AJ Jr, et al. Drug dosing consideration in patients with acute and chronic kidney disease: a clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 2011;80:1122-1137.
11. Vilay AM, Churchwell MD, Mueller BA. Clinical review: drug metabolism and nonrenal clearance in acute kidney injury. Crit Care. 2008;12:235.
Acute Kidney Injury in the ICU: Increasing Prevalence
Q: In 10 years as a hospitalist advanced practitioner, I've been seeing more and more AKI in our ICU. Is this true everywhere, or are we doing something wrong?
AKI is on the rise nationwide (see hospitalization data in figure), and it carries grim implications for patient outcomes.1-3 AKI with a rise in serum creatinine (SCr) as modest as 0.3 mg/dL is associated with a 70% increase in mortality risk. A rise in SCr exceeding 0.5 mg/dL has been associated with a 6.5-fold rise in the risk for death, even when adjusted for age and gender.4 This is higher than the mortality rate for inpatients admitted with cardiovascular disease or cancer, and just slightly more favorable than the mortality risk associated with sepsis (odds ratios, 6.6 and 7.5, respectively). AKI management in the non-ICU setting incurs the third highest median direct hospital cost, after acute MI and stroke.3
A recent retrospective analysis of hospital admissions nationwide from 2000 to 2009 shows a 10% annual increase in the incidence of AKI requiring dialysis, with at least doubling of the incidence and the number of deaths during that 10-year time period.5 Analyzing the incidence of AKI not requiring dialysis over time is more challenging because the criteria to define AKI have not been static; however, the rise in AKI requiring dialysis has mirrored the rise in AKI not requiring dialysis—suggesting that there is in fact an increased incidence of AKI, independent of variability in the defining criteria.3
Researchers reported in 2012 that during the previous year, the incidence of AKI among all hospitalized patients was 1 in 5.6 In the ICU, incidence of AKI has been reported at 39%, with a mortality rate of 25%.7 Based on the RIFLE criteria (a recently revised classification system whose name refers to Risk, Injury, Failure; Loss and End-stage kidney disease),8 as many as two-thirds of patients admitted to the ICU meet criteria for a diagnosis of AKI.
Predictors for AKI include advancing age, baseline SCr below 1.2 mg/dL, the presence of diabetes, use of IV contrast, acute coronary syndromes, sepsis, liver or heart failure, and use of nephrotoxic medications.3
It is important for clinicians to recognize the implications of AKI, even when it manifests as a relatively minor rise in SCr. In addition to its association with poor outcomes in hospitalized patients, AKI increases the risk for chronic kidney disease and for readmissions within six months after hospital discharge.9 Unfortunately, our increased awareness of the implications of AKI in the inpatient setting has yet to translate into significant improvement in outcomes.
The evolution and availability of epidemiologic and outcome data, we can only hope, will serve to direct more resources and further study toward this issue. Clinicians' efforts to prevent and treat AKI can have profound implications for many of our nation's most chronically and critically ill patients. —AC
REFERENCES
1. National Institute of Diabetes and Digestive and Kidney Diseases, NIH. US Renal Data System, 2010 Annual Data Report. www.usrds.org/2010/view/default.asp. Accessed March 5, 2013.
2. National Institute of Diabetes and Digestive and Kidney Diseases, NIH. US Renal Data System, 2011 Annual Data Report. www.usrds.org/2011/view/v2_00_appx.asp. Accessed March 5, 2013.
3. Waikar SS, Liu KD, Chertow GM. Diagnosis, epidemiology and outcomes of acute kidney injury. Clin J Am Soc Nephrol. 2008;3:844-861.
4. Chertow GM, Burdick E, Honour M, et al. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol. 2005;16:3365-3370.
5. Hsu RK, McCulloch CE, Dudley RA, et al. Temporal changes in incidence of dialysis-requiring AKI. J Am Soc Nephrol. 2012;24:37-42.
6. Wang HE, Muntner P, Chertow GM, Warnock DG. Acute kidney injury and mortality in hospitalized patients. Am J Nephrol. 2012;35:349-355.
7. Nisula S, Kaukonen KM, Vaara ST, et al. Incidence, risk factors and 90-day mortality of patients with acute kidney injury in Finnish intensive care units: the FINNAKI study. Intensive Care Med. 2013;39:420-428.
8. Hoste EA, Clermont G, Kersten A, et al. RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: a cohort analysis. Crit Care. 2006;10:R73.
9. Coca SG, Yusuf B, Shlipak MG, et al. Long-term risk of mortality and other adverse outcomes after acute kidney injury: a systematic review and meta-analysis. Am J Kidney Dis. 2009;53:961-973.
10. Matzke GR, Aronoff GR, Atkinson AJ Jr, et al. Drug dosing consideration in patients with acute and chronic kidney disease: a clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 2011;80:1122-1137.
11. Vilay AM, Churchwell MD, Mueller BA. Clinical review: drug metabolism and nonrenal clearance in acute kidney injury. Crit Care. 2008;12:235.
Q: In 10 years as a hospitalist advanced practitioner, I've been seeing more and more AKI in our ICU. Is this true everywhere, or are we doing something wrong?
AKI is on the rise nationwide (see hospitalization data in figure), and it carries grim implications for patient outcomes.1-3 AKI with a rise in serum creatinine (SCr) as modest as 0.3 mg/dL is associated with a 70% increase in mortality risk. A rise in SCr exceeding 0.5 mg/dL has been associated with a 6.5-fold rise in the risk for death, even when adjusted for age and gender.4 This is higher than the mortality rate for inpatients admitted with cardiovascular disease or cancer, and just slightly more favorable than the mortality risk associated with sepsis (odds ratios, 6.6 and 7.5, respectively). AKI management in the non-ICU setting incurs the third highest median direct hospital cost, after acute MI and stroke.3
A recent retrospective analysis of hospital admissions nationwide from 2000 to 2009 shows a 10% annual increase in the incidence of AKI requiring dialysis, with at least doubling of the incidence and the number of deaths during that 10-year time period.5 Analyzing the incidence of AKI not requiring dialysis over time is more challenging because the criteria to define AKI have not been static; however, the rise in AKI requiring dialysis has mirrored the rise in AKI not requiring dialysis—suggesting that there is in fact an increased incidence of AKI, independent of variability in the defining criteria.3
Researchers reported in 2012 that during the previous year, the incidence of AKI among all hospitalized patients was 1 in 5.6 In the ICU, incidence of AKI has been reported at 39%, with a mortality rate of 25%.7 Based on the RIFLE criteria (a recently revised classification system whose name refers to Risk, Injury, Failure; Loss and End-stage kidney disease),8 as many as two-thirds of patients admitted to the ICU meet criteria for a diagnosis of AKI.
Predictors for AKI include advancing age, baseline SCr below 1.2 mg/dL, the presence of diabetes, use of IV contrast, acute coronary syndromes, sepsis, liver or heart failure, and use of nephrotoxic medications.3
It is important for clinicians to recognize the implications of AKI, even when it manifests as a relatively minor rise in SCr. In addition to its association with poor outcomes in hospitalized patients, AKI increases the risk for chronic kidney disease and for readmissions within six months after hospital discharge.9 Unfortunately, our increased awareness of the implications of AKI in the inpatient setting has yet to translate into significant improvement in outcomes.
The evolution and availability of epidemiologic and outcome data, we can only hope, will serve to direct more resources and further study toward this issue. Clinicians' efforts to prevent and treat AKI can have profound implications for many of our nation's most chronically and critically ill patients. —AC
REFERENCES
1. National Institute of Diabetes and Digestive and Kidney Diseases, NIH. US Renal Data System, 2010 Annual Data Report. www.usrds.org/2010/view/default.asp. Accessed March 5, 2013.
2. National Institute of Diabetes and Digestive and Kidney Diseases, NIH. US Renal Data System, 2011 Annual Data Report. www.usrds.org/2011/view/v2_00_appx.asp. Accessed March 5, 2013.
3. Waikar SS, Liu KD, Chertow GM. Diagnosis, epidemiology and outcomes of acute kidney injury. Clin J Am Soc Nephrol. 2008;3:844-861.
4. Chertow GM, Burdick E, Honour M, et al. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol. 2005;16:3365-3370.
5. Hsu RK, McCulloch CE, Dudley RA, et al. Temporal changes in incidence of dialysis-requiring AKI. J Am Soc Nephrol. 2012;24:37-42.
6. Wang HE, Muntner P, Chertow GM, Warnock DG. Acute kidney injury and mortality in hospitalized patients. Am J Nephrol. 2012;35:349-355.
7. Nisula S, Kaukonen KM, Vaara ST, et al. Incidence, risk factors and 90-day mortality of patients with acute kidney injury in Finnish intensive care units: the FINNAKI study. Intensive Care Med. 2013;39:420-428.
8. Hoste EA, Clermont G, Kersten A, et al. RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: a cohort analysis. Crit Care. 2006;10:R73.
9. Coca SG, Yusuf B, Shlipak MG, et al. Long-term risk of mortality and other adverse outcomes after acute kidney injury: a systematic review and meta-analysis. Am J Kidney Dis. 2009;53:961-973.
10. Matzke GR, Aronoff GR, Atkinson AJ Jr, et al. Drug dosing consideration in patients with acute and chronic kidney disease: a clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 2011;80:1122-1137.
11. Vilay AM, Churchwell MD, Mueller BA. Clinical review: drug metabolism and nonrenal clearance in acute kidney injury. Crit Care. 2008;12:235.
Q: In 10 years as a hospitalist advanced practitioner, I've been seeing more and more AKI in our ICU. Is this true everywhere, or are we doing something wrong?
AKI is on the rise nationwide (see hospitalization data in figure), and it carries grim implications for patient outcomes.1-3 AKI with a rise in serum creatinine (SCr) as modest as 0.3 mg/dL is associated with a 70% increase in mortality risk. A rise in SCr exceeding 0.5 mg/dL has been associated with a 6.5-fold rise in the risk for death, even when adjusted for age and gender.4 This is higher than the mortality rate for inpatients admitted with cardiovascular disease or cancer, and just slightly more favorable than the mortality risk associated with sepsis (odds ratios, 6.6 and 7.5, respectively). AKI management in the non-ICU setting incurs the third highest median direct hospital cost, after acute MI and stroke.3
A recent retrospective analysis of hospital admissions nationwide from 2000 to 2009 shows a 10% annual increase in the incidence of AKI requiring dialysis, with at least doubling of the incidence and the number of deaths during that 10-year time period.5 Analyzing the incidence of AKI not requiring dialysis over time is more challenging because the criteria to define AKI have not been static; however, the rise in AKI requiring dialysis has mirrored the rise in AKI not requiring dialysis—suggesting that there is in fact an increased incidence of AKI, independent of variability in the defining criteria.3
Researchers reported in 2012 that during the previous year, the incidence of AKI among all hospitalized patients was 1 in 5.6 In the ICU, incidence of AKI has been reported at 39%, with a mortality rate of 25%.7 Based on the RIFLE criteria (a recently revised classification system whose name refers to Risk, Injury, Failure; Loss and End-stage kidney disease),8 as many as two-thirds of patients admitted to the ICU meet criteria for a diagnosis of AKI.
Predictors for AKI include advancing age, baseline SCr below 1.2 mg/dL, the presence of diabetes, use of IV contrast, acute coronary syndromes, sepsis, liver or heart failure, and use of nephrotoxic medications.3
It is important for clinicians to recognize the implications of AKI, even when it manifests as a relatively minor rise in SCr. In addition to its association with poor outcomes in hospitalized patients, AKI increases the risk for chronic kidney disease and for readmissions within six months after hospital discharge.9 Unfortunately, our increased awareness of the implications of AKI in the inpatient setting has yet to translate into significant improvement in outcomes.
The evolution and availability of epidemiologic and outcome data, we can only hope, will serve to direct more resources and further study toward this issue. Clinicians' efforts to prevent and treat AKI can have profound implications for many of our nation's most chronically and critically ill patients. —AC
REFERENCES
1. National Institute of Diabetes and Digestive and Kidney Diseases, NIH. US Renal Data System, 2010 Annual Data Report. www.usrds.org/2010/view/default.asp. Accessed March 5, 2013.
2. National Institute of Diabetes and Digestive and Kidney Diseases, NIH. US Renal Data System, 2011 Annual Data Report. www.usrds.org/2011/view/v2_00_appx.asp. Accessed March 5, 2013.
3. Waikar SS, Liu KD, Chertow GM. Diagnosis, epidemiology and outcomes of acute kidney injury. Clin J Am Soc Nephrol. 2008;3:844-861.
4. Chertow GM, Burdick E, Honour M, et al. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol. 2005;16:3365-3370.
5. Hsu RK, McCulloch CE, Dudley RA, et al. Temporal changes in incidence of dialysis-requiring AKI. J Am Soc Nephrol. 2012;24:37-42.
6. Wang HE, Muntner P, Chertow GM, Warnock DG. Acute kidney injury and mortality in hospitalized patients. Am J Nephrol. 2012;35:349-355.
7. Nisula S, Kaukonen KM, Vaara ST, et al. Incidence, risk factors and 90-day mortality of patients with acute kidney injury in Finnish intensive care units: the FINNAKI study. Intensive Care Med. 2013;39:420-428.
8. Hoste EA, Clermont G, Kersten A, et al. RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: a cohort analysis. Crit Care. 2006;10:R73.
9. Coca SG, Yusuf B, Shlipak MG, et al. Long-term risk of mortality and other adverse outcomes after acute kidney injury: a systematic review and meta-analysis. Am J Kidney Dis. 2009;53:961-973.
10. Matzke GR, Aronoff GR, Atkinson AJ Jr, et al. Drug dosing consideration in patients with acute and chronic kidney disease: a clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 2011;80:1122-1137.
11. Vilay AM, Churchwell MD, Mueller BA. Clinical review: drug metabolism and nonrenal clearance in acute kidney injury. Crit Care. 2008;12:235.
Guidelines on Hematuria: Determing the Cause
The American Urological Association (AUA) published guidelines for asymptomatic microhematuria. The document includes 19 guidelines with recommendation levels ranging from A to C (high to low) and some expert opinion recommendations included. The full guidelines can be accessed at http://www.auanet.org/common/pdf/education/clinical-guidance/Asymptomatic-Microhematuria.pdf.
Q: A 45-year-old man came into my office complaining that he had seen “pink” in his urine. I dipped the urine in the office, and it was positive for blood. What should I do now? Should I send him directly to nephrology or urology? Or should I do a work-up myself? And if I do the work-up, what tests should I order?
When treating the patient with hematuria, it is important to keep in mind both the most common benign causes and the more serious causes of hematuria. The most common benign causes, according to the AUA guideline 6,1 include infection, menstruation, vigorous exercise, trauma, anticoagulant use, and a recent urologic procedure. The potentially serious causes include glomerulonephritis (which can be rapidly progressive) and malignancy.
The AUA (guidelines 1 to 4, based on expert opinion)1 recommends confirming hematuria with a microscopic exam rather than relying on a urine dipstick.
The common benign causes of hematuria can usually be identified in the course of a thorough history and physical. Because hematuria can be a harbinger of renal disease, however, serum creatinine and blood urea nitrogen (BUN) should be ordered at the initial evaluation in the primary care setting.
If a benign cause of hematuria is identified and renal function is normal, the patient should be treated by the primary care provider and re-evaluated as indicated, based on the underlying diagnosis. If there is a rise in serum creatinine or a reduction in estimated glomerular filtration rate (eGFR) in conjunction with the hematuria, the patient should be referred to nephrology for further evaluation.
If no benign cause of hematuria is identified and renal function is unaffected, the patient should be referred to urology for urologic evaluation.1
Alexis Chettiar, ACNP, East Bay Nephrology Medical Group, Oakland, CA
References
1. Davis R, Jones JS, Barocas DA, et al; American Urological Association. Diagnosis, Evaluation, and Follow-up of Asymptomatic Microhematuria (AMH) in Adults: AUA Guideline. Linthicum, MD: American Urological Association Education and Research, Inc; 2012. http://www.auanet.org/common/pdf/education/clinical-guidance/Asymptomatic-Microhematuria.pdf. Accessed January 24, 2013.
2. National Kidney and Urologic Diseases Information Clearinghouse. Hematuria: blood in the urine (2012). http://kidney.niddk.nih.gov/kudiseases/pubs/hematuria. Accessed January 17, 2013.
3. Geavlete B, Jecu M, Multescu R, et al. HAL blue-light cystoscopy in high-risk nonmuscle-invasive bladder cancer: re-TURBT recurrence rates in a prospective, randomized study. Urology. 2010;76(3):664-669.
Suggested Reading
Feldman AS, Hsu C-Y, Kurtz M, Cho KC. Etiology and evaluation of hematuria in adults (2012). www.uptodate.com/contents/etiology-and-evaluation-of-hematuria-in-adults. Accessed January 17, 2013.
Jayne D. Hematuria and proteinuria. In: Greenberg A, ed; National Kidney Foundation. Primer on Kidney Diseases. 5th ed. Saunders; 2009:33-42.
The American Urological Association (AUA) published guidelines for asymptomatic microhematuria. The document includes 19 guidelines with recommendation levels ranging from A to C (high to low) and some expert opinion recommendations included. The full guidelines can be accessed at http://www.auanet.org/common/pdf/education/clinical-guidance/Asymptomatic-Microhematuria.pdf.
Q: A 45-year-old man came into my office complaining that he had seen “pink” in his urine. I dipped the urine in the office, and it was positive for blood. What should I do now? Should I send him directly to nephrology or urology? Or should I do a work-up myself? And if I do the work-up, what tests should I order?
When treating the patient with hematuria, it is important to keep in mind both the most common benign causes and the more serious causes of hematuria. The most common benign causes, according to the AUA guideline 6,1 include infection, menstruation, vigorous exercise, trauma, anticoagulant use, and a recent urologic procedure. The potentially serious causes include glomerulonephritis (which can be rapidly progressive) and malignancy.
The AUA (guidelines 1 to 4, based on expert opinion)1 recommends confirming hematuria with a microscopic exam rather than relying on a urine dipstick.
The common benign causes of hematuria can usually be identified in the course of a thorough history and physical. Because hematuria can be a harbinger of renal disease, however, serum creatinine and blood urea nitrogen (BUN) should be ordered at the initial evaluation in the primary care setting.
If a benign cause of hematuria is identified and renal function is normal, the patient should be treated by the primary care provider and re-evaluated as indicated, based on the underlying diagnosis. If there is a rise in serum creatinine or a reduction in estimated glomerular filtration rate (eGFR) in conjunction with the hematuria, the patient should be referred to nephrology for further evaluation.
If no benign cause of hematuria is identified and renal function is unaffected, the patient should be referred to urology for urologic evaluation.1
Alexis Chettiar, ACNP, East Bay Nephrology Medical Group, Oakland, CA
References
1. Davis R, Jones JS, Barocas DA, et al; American Urological Association. Diagnosis, Evaluation, and Follow-up of Asymptomatic Microhematuria (AMH) in Adults: AUA Guideline. Linthicum, MD: American Urological Association Education and Research, Inc; 2012. http://www.auanet.org/common/pdf/education/clinical-guidance/Asymptomatic-Microhematuria.pdf. Accessed January 24, 2013.
2. National Kidney and Urologic Diseases Information Clearinghouse. Hematuria: blood in the urine (2012). http://kidney.niddk.nih.gov/kudiseases/pubs/hematuria. Accessed January 17, 2013.
3. Geavlete B, Jecu M, Multescu R, et al. HAL blue-light cystoscopy in high-risk nonmuscle-invasive bladder cancer: re-TURBT recurrence rates in a prospective, randomized study. Urology. 2010;76(3):664-669.
Suggested Reading
Feldman AS, Hsu C-Y, Kurtz M, Cho KC. Etiology and evaluation of hematuria in adults (2012). www.uptodate.com/contents/etiology-and-evaluation-of-hematuria-in-adults. Accessed January 17, 2013.
Jayne D. Hematuria and proteinuria. In: Greenberg A, ed; National Kidney Foundation. Primer on Kidney Diseases. 5th ed. Saunders; 2009:33-42.
The American Urological Association (AUA) published guidelines for asymptomatic microhematuria. The document includes 19 guidelines with recommendation levels ranging from A to C (high to low) and some expert opinion recommendations included. The full guidelines can be accessed at http://www.auanet.org/common/pdf/education/clinical-guidance/Asymptomatic-Microhematuria.pdf.
Q: A 45-year-old man came into my office complaining that he had seen “pink” in his urine. I dipped the urine in the office, and it was positive for blood. What should I do now? Should I send him directly to nephrology or urology? Or should I do a work-up myself? And if I do the work-up, what tests should I order?
When treating the patient with hematuria, it is important to keep in mind both the most common benign causes and the more serious causes of hematuria. The most common benign causes, according to the AUA guideline 6,1 include infection, menstruation, vigorous exercise, trauma, anticoagulant use, and a recent urologic procedure. The potentially serious causes include glomerulonephritis (which can be rapidly progressive) and malignancy.
The AUA (guidelines 1 to 4, based on expert opinion)1 recommends confirming hematuria with a microscopic exam rather than relying on a urine dipstick.
The common benign causes of hematuria can usually be identified in the course of a thorough history and physical. Because hematuria can be a harbinger of renal disease, however, serum creatinine and blood urea nitrogen (BUN) should be ordered at the initial evaluation in the primary care setting.
If a benign cause of hematuria is identified and renal function is normal, the patient should be treated by the primary care provider and re-evaluated as indicated, based on the underlying diagnosis. If there is a rise in serum creatinine or a reduction in estimated glomerular filtration rate (eGFR) in conjunction with the hematuria, the patient should be referred to nephrology for further evaluation.
If no benign cause of hematuria is identified and renal function is unaffected, the patient should be referred to urology for urologic evaluation.1
Alexis Chettiar, ACNP, East Bay Nephrology Medical Group, Oakland, CA
References
1. Davis R, Jones JS, Barocas DA, et al; American Urological Association. Diagnosis, Evaluation, and Follow-up of Asymptomatic Microhematuria (AMH) in Adults: AUA Guideline. Linthicum, MD: American Urological Association Education and Research, Inc; 2012. http://www.auanet.org/common/pdf/education/clinical-guidance/Asymptomatic-Microhematuria.pdf. Accessed January 24, 2013.
2. National Kidney and Urologic Diseases Information Clearinghouse. Hematuria: blood in the urine (2012). http://kidney.niddk.nih.gov/kudiseases/pubs/hematuria. Accessed January 17, 2013.
3. Geavlete B, Jecu M, Multescu R, et al. HAL blue-light cystoscopy in high-risk nonmuscle-invasive bladder cancer: re-TURBT recurrence rates in a prospective, randomized study. Urology. 2010;76(3):664-669.
Suggested Reading
Feldman AS, Hsu C-Y, Kurtz M, Cho KC. Etiology and evaluation of hematuria in adults (2012). www.uptodate.com/contents/etiology-and-evaluation-of-hematuria-in-adults. Accessed January 17, 2013.
Jayne D. Hematuria and proteinuria. In: Greenberg A, ed; National Kidney Foundation. Primer on Kidney Diseases. 5th ed. Saunders; 2009:33-42.