Management Specifics in Kidney Disease: Fluid Prep for Cardiac Catheterizations

Q: Is there any science behind the use of acetylcysteine/fluid prep for cardiac catheterizations, or is that just “voodoo” medicine?

Contrast-induced nephropathy (CIN) is the third most common cause of hospital-acquired acute kidney injury. In recent years, the use of iodinated radiocontrast medium has increased significantly, due to increased use of both percutaneous coronary interventions and CT scanning. The radiocontrast medium causes vasoconstriction, which leads to a reduction in renal blood flow, with a resulting decrease in GFR. Preexisting impaired kidney function results in increased risk due to slower clearance of the contrast materials, and the resulting prolonged exposure increases the risk for further renal injury.¹⁰

A GFR below 60 mL/min/1.73m², volume depletion, and diabetes all increase the risk for CIN. Among patients who experience an acute kidney injury due to contrast medium, the risk for adverse outcomes increases, including early or late cardiovascular events, prolonged hospitalizations, and death. As no FDA-approved treatment yet exists for CIN, the best medicine is to try to prevent it.¹¹

Several interventions can reduce the patient’s risk for CIN. These include IV hydration, acetylcysteine/fluid prep, selection of the safest possible type and volume of radiocontrast medium, and avoidance of nephrotoxic medications immediately before the patient’s exposure to contrast medium.

In multiple randomized clinical trials, the efficacy of IV hydration in reducing the risk for CIN has been examined. Most notably, the REMEDIAL trial¹² demonstrated that IV hydration with sodium bicarbonate was superior to 0.9% hydration with normal saline. However, the largest trial to date did not show any benefit in using sodium bicarbonate, compared with normal saline.¹³ There is no consensus regarding the optimal hydration solution or timing, rate, or total volume of fluid administered, although the current literature does show that IV hydration in some form appears to decrease the risk for CIN.¹¹

The recently released Kidney Disease Improving Global Outcomes (K/DIGO) Clinical Practice Guidelines for Acute Kidney Injury¹⁴ recommend IV volume expansion with normal saline or sodium bicarbonate solution. No particular regimen is recommended.

Acetylcysteine is an antioxidant with vasodilatory properties. A number of clinical trials and meta-analyses have been conducted to examine its efficacy. For instance, Kelly et al¹⁵ have suggested the benefit of acetylcysteine in the prevention of CIN, but several studies included in their meta-analysis were criticized for being of low quality. While the findings among these studies vary, none of the research teams reported any negative outcomes from the use of acetylcysteine. Although there is no definitive proof of its benefit, acetylcysteine is well tolerated, economical, and easily accessible; the general consensus is to use it.¹¹ The K/DIGO Clinical Practice Guidelines for Acute Kidney Injury¹⁴ recommend using acetylcysteine in conjunction with isotonic solution in patients at increased risk for acute kidney injury.¹⁵

Other interventions include careful consideration of the type of radiocontrast agent to be used. Use of a low-osmolality agent such as iohexol (Omnipaque™ 350) or an iso-osmolar agent such as iodixanol (Visipaque™ 320) incurs much lower risk than do older, higher-osmolarity agents.¹⁶ In addition, although there are no scientific data to support this, withholding all potentially nephrotoxic medications (eg, ACE inhibitors, ARBs, NSAIDs, aminoglycosides, high-dose loop diuretics) prior to exposure to contrast medium is a prudent measure to reduce a patient’s risk profile.¹⁰

In summary, there are considerable conflicting data from multiple clinical studies regarding the use of acetylcysteine or IV hydration to minimize the risk for CIN. In fact, new guidelines are due to be published soon that may take a more definitive stand. Nevertheless, categorization as “voodoo” medicine seems inappropriate when an intervention appears to offer positive impact on patient care.
Kimberley Brinkman, MS, CNN, GNP-BC, Nephrology, Hypertension, and

Internal Medicine, Lawrence, MA

REFERENCES

1. Greene JH. Restricting dietary sodium and potassium intake: a dietitian’s perspective. In: Daugirdas JT. Handbook of Chronic Kidney Disease Management. Philadelphia, PA: Lippincott Williams & Wilkins; 2011:81-96.

2. National Kidney Foundation. K/DOQI Clinical Practice Guidelines on Hypertension and Antihypertensive Agents in Chronic Kidney Disease. Guideline 6: Dietary and other therapeutic lifestyle changes in adults. www.kidney .org/professionals/kdoqi/guidelines_bp/guide_6.htm. Accessed November 21, 2012.

3. National Kidney Foundation. K/DOQI Clinical Practice Guidelines on Hypertension and Antihypertensive Agents in Chronic Kidney Disease. Guideline 11: Use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in CKD. www.kidney.org/professionals/kdoqi/guidelines_bp/guide_11 .htm. Accessed November 21, 2012.

4. Nutrition 411. Renal diet preparation in-service for kitchen staff: leaching potassium from vegetables. www.rd411.com/renalcenter/ article1.php?ID=8pro. Accessed November 21, 2012.

5. Burrowes JD, Ramer NJ. Removal of potassium from tuberous root vegetables by leaching. J Ren Nutr. 2006;16(4):304-311.

6. Bargman JM, Skorecki K. Chapter 280. Chronic kidney disease. In: Longo D, Fauci A, Kasper E, et al, eds. Harrison’s Principles of Internal Medicine. 18th ed. New York, NY: McGraw-Hill; 2012. www.accesspharmacy

.com/content.aspx?aid=9130075. Accessed November 21, 2012.

7. Ryan MJ, Tuttle KR. Elevations in serum creatinine with RAAS blockade: why isn’t it a sign of kidney injury? Curr Opin Nephrol Hypertens. 2008;17(5):443–449.

8. Schoolwerth AC, Sica DA, Ballermann BJ, Wilcox CS. Renal considerations in angiotensin converting enzyme inhibitor therapy: a statement for healthcare professionals from the Council on the Kidney in Cardiovascular Disease and the Council for High Blood Pressure Research of the American Heart Association. Circulation. 2001;104(16):1985-1991.

9. Bakris GL, Weir MR. Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine: Is this a cause for concern? Arch Intern Med. 2000;160(5):685-693.

10. Coca SG, Perazella MA. Use of iodinated and gadolinium-containing contrast media. In: Gaudiras JT. Handbook of Chronic Kidney Disease Management. Philadelphia, PA: Lippincott Williams & Wilkins: 2011:363-375.

11. Rudnick MR, Tumlin JA. Prevention of contrast-induced nephropathy (2012). www .uptodate.com/contents/prevention-of-

contrast-induced-nephropathy. Accessed November 21, 2012.

12. Briguori C, Airoldi F, D’Andrea D, et al. Renal Insufficiency Following Contrast Media Administration Trial (REMEDIAL): a randomized comparison of 3 preventive strategies. Circulation. 2007;115(10):1211-1217.

13. Brar SS, Shen AY, Jorgensen MB, et al. Sodium bicarbonate vs sodium chloride for the prevention of contrast medium–induced nephropathy in patients undergoing coronary angiography: a randomized trial. JAMA. 2008;300(9):1038-1046.

14. National Kidney Foundation. K/DIGO Clinical Practice Guideline for Acute Kidney Injury. www.kdigo.org/clinical_practice_guidelines/pdf/KDIGO%20AKI%20Guideline

.pdf. Accessed November 21, 2012.

15. Kelly AM, Dwamena B, Cronin P, et al. Meta-analysis: effectiveness of drugs for preventing radiocontrast-induced nephropathy. Ann Intern Med. 2008;148(4):284-294.

16. Rudnick M, Feldman H. Contrast-induced nephropathy: what are the true clinical consequences? Clin J Am Soc Nephrol. 2008; 3(1):263-272.

Q: Is there any science behind the use of acetylcysteine/fluid prep for cardiac catheterizations, or is that just “voodoo” medicine?

Contrast-induced nephropathy (CIN) is the third most common cause of hospital-acquired acute kidney injury. In recent years, the use of iodinated radiocontrast medium has increased significantly, due to increased use of both percutaneous coronary interventions and CT scanning. The radiocontrast medium causes vasoconstriction, which leads to a reduction in renal blood flow, with a resulting decrease in GFR. Preexisting impaired kidney function results in increased risk due to slower clearance of the contrast materials, and the resulting prolonged exposure increases the risk for further renal injury.¹⁰

A GFR below 60 mL/min/1.73m², volume depletion, and diabetes all increase the risk for CIN. Among patients who experience an acute kidney injury due to contrast medium, the risk for adverse outcomes increases, including early or late cardiovascular events, prolonged hospitalizations, and death. As no FDA-approved treatment yet exists for CIN, the best medicine is to try to prevent it.¹¹

Several interventions can reduce the patient’s risk for CIN. These include IV hydration, acetylcysteine/fluid prep, selection of the safest possible type and volume of radiocontrast medium, and avoidance of nephrotoxic medications immediately before the patient’s exposure to contrast medium.

In multiple randomized clinical trials, the efficacy of IV hydration in reducing the risk for CIN has been examined. Most notably, the REMEDIAL trial¹² demonstrated that IV hydration with sodium bicarbonate was superior to 0.9% hydration with normal saline. However, the largest trial to date did not show any benefit in using sodium bicarbonate, compared with normal saline.¹³ There is no consensus regarding the optimal hydration solution or timing, rate, or total volume of fluid administered, although the current literature does show that IV hydration in some form appears to decrease the risk for CIN.¹¹

The recently released Kidney Disease Improving Global Outcomes (K/DIGO) Clinical Practice Guidelines for Acute Kidney Injury¹⁴ recommend IV volume expansion with normal saline or sodium bicarbonate solution. No particular regimen is recommended.

Acetylcysteine is an antioxidant with vasodilatory properties. A number of clinical trials and meta-analyses have been conducted to examine its efficacy. For instance, Kelly et al¹⁵ have suggested the benefit of acetylcysteine in the prevention of CIN, but several studies included in their meta-analysis were criticized for being of low quality. While the findings among these studies vary, none of the research teams reported any negative outcomes from the use of acetylcysteine. Although there is no definitive proof of its benefit, acetylcysteine is well tolerated, economical, and easily accessible; the general consensus is to use it.¹¹ The K/DIGO Clinical Practice Guidelines for Acute Kidney Injury¹⁴ recommend using acetylcysteine in conjunction with isotonic solution in patients at increased risk for acute kidney injury.¹⁵

Other interventions include careful consideration of the type of radiocontrast agent to be used. Use of a low-osmolality agent such as iohexol (Omnipaque™ 350) or an iso-osmolar agent such as iodixanol (Visipaque™ 320) incurs much lower risk than do older, higher-osmolarity agents.¹⁶ In addition, although there are no scientific data to support this, withholding all potentially nephrotoxic medications (eg, ACE inhibitors, ARBs, NSAIDs, aminoglycosides, high-dose loop diuretics) prior to exposure to contrast medium is a prudent measure to reduce a patient’s risk profile.¹⁰

In summary, there are considerable conflicting data from multiple clinical studies regarding the use of acetylcysteine or IV hydration to minimize the risk for CIN. In fact, new guidelines are due to be published soon that may take a more definitive stand. Nevertheless, categorization as “voodoo” medicine seems inappropriate when an intervention appears to offer positive impact on patient care.
Kimberley Brinkman, MS, CNN, GNP-BC, Nephrology, Hypertension, and

Internal Medicine, Lawrence, MA

REFERENCES

1. Greene JH. Restricting dietary sodium and potassium intake: a dietitian’s perspective. In: Daugirdas JT. Handbook of Chronic Kidney Disease Management. Philadelphia, PA: Lippincott Williams & Wilkins; 2011:81-96.

2. National Kidney Foundation. K/DOQI Clinical Practice Guidelines on Hypertension and Antihypertensive Agents in Chronic Kidney Disease. Guideline 6: Dietary and other therapeutic lifestyle changes in adults. www.kidney .org/professionals/kdoqi/guidelines_bp/guide_6.htm. Accessed November 21, 2012.

3. National Kidney Foundation. K/DOQI Clinical Practice Guidelines on Hypertension and Antihypertensive Agents in Chronic Kidney Disease. Guideline 11: Use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in CKD. www.kidney.org/professionals/kdoqi/guidelines_bp/guide_11 .htm. Accessed November 21, 2012.

4. Nutrition 411. Renal diet preparation in-service for kitchen staff: leaching potassium from vegetables. www.rd411.com/renalcenter/ article1.php?ID=8pro. Accessed November 21, 2012.

5. Burrowes JD, Ramer NJ. Removal of potassium from tuberous root vegetables by leaching. J Ren Nutr. 2006;16(4):304-311.

6. Bargman JM, Skorecki K. Chapter 280. Chronic kidney disease. In: Longo D, Fauci A, Kasper E, et al, eds. Harrison’s Principles of Internal Medicine. 18th ed. New York, NY: McGraw-Hill; 2012. www.accesspharmacy

.com/content.aspx?aid=9130075. Accessed November 21, 2012.

7. Ryan MJ, Tuttle KR. Elevations in serum creatinine with RAAS blockade: why isn’t it a sign of kidney injury? Curr Opin Nephrol Hypertens. 2008;17(5):443–449.

8. Schoolwerth AC, Sica DA, Ballermann BJ, Wilcox CS. Renal considerations in angiotensin converting enzyme inhibitor therapy: a statement for healthcare professionals from the Council on the Kidney in Cardiovascular Disease and the Council for High Blood Pressure Research of the American Heart Association. Circulation. 2001;104(16):1985-1991.

9. Bakris GL, Weir MR. Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine: Is this a cause for concern? Arch Intern Med. 2000;160(5):685-693.

10. Coca SG, Perazella MA. Use of iodinated and gadolinium-containing contrast media. In: Gaudiras JT. Handbook of Chronic Kidney Disease Management. Philadelphia, PA: Lippincott Williams & Wilkins: 2011:363-375.

11. Rudnick MR, Tumlin JA. Prevention of contrast-induced nephropathy (2012). www .uptodate.com/contents/prevention-of-

contrast-induced-nephropathy. Accessed November 21, 2012.

12. Briguori C, Airoldi F, D’Andrea D, et al. Renal Insufficiency Following Contrast Media Administration Trial (REMEDIAL): a randomized comparison of 3 preventive strategies. Circulation. 2007;115(10):1211-1217.

13. Brar SS, Shen AY, Jorgensen MB, et al. Sodium bicarbonate vs sodium chloride for the prevention of contrast medium–induced nephropathy in patients undergoing coronary angiography: a randomized trial. JAMA. 2008;300(9):1038-1046.

14. National Kidney Foundation. K/DIGO Clinical Practice Guideline for Acute Kidney Injury. www.kdigo.org/clinical_practice_guidelines/pdf/KDIGO%20AKI%20Guideline

.pdf. Accessed November 21, 2012.

15. Kelly AM, Dwamena B, Cronin P, et al. Meta-analysis: effectiveness of drugs for preventing radiocontrast-induced nephropathy. Ann Intern Med. 2008;148(4):284-294.

16. Rudnick M, Feldman H. Contrast-induced nephropathy: what are the true clinical consequences? Clin J Am Soc Nephrol. 2008; 3(1):263-272.

Q: Is there any science behind the use of acetylcysteine/fluid prep for cardiac catheterizations, or is that just “voodoo” medicine?

Contrast-induced nephropathy (CIN) is the third most common cause of hospital-acquired acute kidney injury. In recent years, the use of iodinated radiocontrast medium has increased significantly, due to increased use of both percutaneous coronary interventions and CT scanning. The radiocontrast medium causes vasoconstriction, which leads to a reduction in renal blood flow, with a resulting decrease in GFR. Preexisting impaired kidney function results in increased risk due to slower clearance of the contrast materials, and the resulting prolonged exposure increases the risk for further renal injury.¹⁰

A GFR below 60 mL/min/1.73m², volume depletion, and diabetes all increase the risk for CIN. Among patients who experience an acute kidney injury due to contrast medium, the risk for adverse outcomes increases, including early or late cardiovascular events, prolonged hospitalizations, and death. As no FDA-approved treatment yet exists for CIN, the best medicine is to try to prevent it.¹¹

Several interventions can reduce the patient’s risk for CIN. These include IV hydration, acetylcysteine/fluid prep, selection of the safest possible type and volume of radiocontrast medium, and avoidance of nephrotoxic medications immediately before the patient’s exposure to contrast medium.

In multiple randomized clinical trials, the efficacy of IV hydration in reducing the risk for CIN has been examined. Most notably, the REMEDIAL trial¹² demonstrated that IV hydration with sodium bicarbonate was superior to 0.9% hydration with normal saline. However, the largest trial to date did not show any benefit in using sodium bicarbonate, compared with normal saline.¹³ There is no consensus regarding the optimal hydration solution or timing, rate, or total volume of fluid administered, although the current literature does show that IV hydration in some form appears to decrease the risk for CIN.¹¹

The recently released Kidney Disease Improving Global Outcomes (K/DIGO) Clinical Practice Guidelines for Acute Kidney Injury¹⁴ recommend IV volume expansion with normal saline or sodium bicarbonate solution. No particular regimen is recommended.

Acetylcysteine is an antioxidant with vasodilatory properties. A number of clinical trials and meta-analyses have been conducted to examine its efficacy. For instance, Kelly et al¹⁵ have suggested the benefit of acetylcysteine in the prevention of CIN, but several studies included in their meta-analysis were criticized for being of low quality. While the findings among these studies vary, none of the research teams reported any negative outcomes from the use of acetylcysteine. Although there is no definitive proof of its benefit, acetylcysteine is well tolerated, economical, and easily accessible; the general consensus is to use it.¹¹ The K/DIGO Clinical Practice Guidelines for Acute Kidney Injury¹⁴ recommend using acetylcysteine in conjunction with isotonic solution in patients at increased risk for acute kidney injury.¹⁵

Other interventions include careful consideration of the type of radiocontrast agent to be used. Use of a low-osmolality agent such as iohexol (Omnipaque™ 350) or an iso-osmolar agent such as iodixanol (Visipaque™ 320) incurs much lower risk than do older, higher-osmolarity agents.¹⁶ In addition, although there are no scientific data to support this, withholding all potentially nephrotoxic medications (eg, ACE inhibitors, ARBs, NSAIDs, aminoglycosides, high-dose loop diuretics) prior to exposure to contrast medium is a prudent measure to reduce a patient’s risk profile.¹⁰

In summary, there are considerable conflicting data from multiple clinical studies regarding the use of acetylcysteine or IV hydration to minimize the risk for CIN. In fact, new guidelines are due to be published soon that may take a more definitive stand. Nevertheless, categorization as “voodoo” medicine seems inappropriate when an intervention appears to offer positive impact on patient care.
Kimberley Brinkman, MS, CNN, GNP-BC, Nephrology, Hypertension, and

Internal Medicine, Lawrence, MA

REFERENCES

1. Greene JH. Restricting dietary sodium and potassium intake: a dietitian’s perspective. In: Daugirdas JT. Handbook of Chronic Kidney Disease Management. Philadelphia, PA: Lippincott Williams & Wilkins; 2011:81-96.

2. National Kidney Foundation. K/DOQI Clinical Practice Guidelines on Hypertension and Antihypertensive Agents in Chronic Kidney Disease. Guideline 6: Dietary and other therapeutic lifestyle changes in adults. www.kidney .org/professionals/kdoqi/guidelines_bp/guide_6.htm. Accessed November 21, 2012.

3. National Kidney Foundation. K/DOQI Clinical Practice Guidelines on Hypertension and Antihypertensive Agents in Chronic Kidney Disease. Guideline 11: Use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in CKD. www.kidney.org/professionals/kdoqi/guidelines_bp/guide_11 .htm. Accessed November 21, 2012.

4. Nutrition 411. Renal diet preparation in-service for kitchen staff: leaching potassium from vegetables. www.rd411.com/renalcenter/ article1.php?ID=8pro. Accessed November 21, 2012.

5. Burrowes JD, Ramer NJ. Removal of potassium from tuberous root vegetables by leaching. J Ren Nutr. 2006;16(4):304-311.

6. Bargman JM, Skorecki K. Chapter 280. Chronic kidney disease. In: Longo D, Fauci A, Kasper E, et al, eds. Harrison’s Principles of Internal Medicine. 18th ed. New York, NY: McGraw-Hill; 2012. www.accesspharmacy

.com/content.aspx?aid=9130075. Accessed November 21, 2012.

7. Ryan MJ, Tuttle KR. Elevations in serum creatinine with RAAS blockade: why isn’t it a sign of kidney injury? Curr Opin Nephrol Hypertens. 2008;17(5):443–449.

8. Schoolwerth AC, Sica DA, Ballermann BJ, Wilcox CS. Renal considerations in angiotensin converting enzyme inhibitor therapy: a statement for healthcare professionals from the Council on the Kidney in Cardiovascular Disease and the Council for High Blood Pressure Research of the American Heart Association. Circulation. 2001;104(16):1985-1991.

9. Bakris GL, Weir MR. Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine: Is this a cause for concern? Arch Intern Med. 2000;160(5):685-693.

10. Coca SG, Perazella MA. Use of iodinated and gadolinium-containing contrast media. In: Gaudiras JT. Handbook of Chronic Kidney Disease Management. Philadelphia, PA: Lippincott Williams & Wilkins: 2011:363-375.

11. Rudnick MR, Tumlin JA. Prevention of contrast-induced nephropathy (2012). www .uptodate.com/contents/prevention-of-

contrast-induced-nephropathy. Accessed November 21, 2012.

12. Briguori C, Airoldi F, D’Andrea D, et al. Renal Insufficiency Following Contrast Media Administration Trial (REMEDIAL): a randomized comparison of 3 preventive strategies. Circulation. 2007;115(10):1211-1217.

13. Brar SS, Shen AY, Jorgensen MB, et al. Sodium bicarbonate vs sodium chloride for the prevention of contrast medium–induced nephropathy in patients undergoing coronary angiography: a randomized trial. JAMA. 2008;300(9):1038-1046.

14. National Kidney Foundation. K/DIGO Clinical Practice Guideline for Acute Kidney Injury. www.kdigo.org/clinical_practice_guidelines/pdf/KDIGO%20AKI%20Guideline

.pdf. Accessed November 21, 2012.

15. Kelly AM, Dwamena B, Cronin P, et al. Meta-analysis: effectiveness of drugs for preventing radiocontrast-induced nephropathy. Ann Intern Med. 2008;148(4):284-294.

16. Rudnick M, Feldman H. Contrast-induced nephropathy: what are the true clinical consequences? Clin J Am Soc Nephrol. 2008; 3(1):263-272.