Management Specifics in Kidney Disease: Rise in SCr

Q:  How much of a bump in serum creatinine (SCr) can I expect after I start a patient on an ACE inhibitor or an angiotensin II receptor blocker (ARB)? How often should I check the patient’s SCr?

ACE inhibitors and ARBs inhibit the angiotensin-induced vasoconstriction of the efferent arterioles of the glomerular microcirculation. Inhibition of the renin-angiotensin-aldosterone system (RAAS) by these medications reduces both intraglomerular filtration pressure and proteinuria, delaying the progression of kidney disease.⁶ In response to RAAS inhibition, the GFR is slightly decreased and SCr is increased, reflecting the beneficial effects of the ACE inhibitor or the ARB on renal hemodynamics.^7,8 SCr may rise 10% to 30% from baseline within the first two weeks and generally stabilizes within two to four weeks.⁸

Patients with normal renal function initiated on an ACE inhibitor or an ARB experience a rise in SCr of about 0.2 mg/dL over a two- to three-week period, returning to baseline during week 4. Patients with abnormal renal function will have an increase in SCr of approximately 0.5 mg/dL over a four-week period.⁹ A progressive increase in SCr as great as 2.0 mg/dL may be seen in patients with bilateral renal artery stenosis, extensive atherosclerotic cardiovascular disease, or dehydration. In these instances, treatment with the ACE inhibitor or the ARB should be discontinued.⁹ 

Close monitoring is recommended in patients with chronic kidney disease Stage 3 through Stage 5 who are started on an ACE inhibitor or an ARB. SCr and K should be evaluated before and four weeks after initiating or titrating therapy.⁹ If SCr has increased by less than 0.5 mg/dL from a baseline measurement of 2.5 mg/dL or less; or if the rise in SCr is 1.0 mg/dL or less when the baseline SCr exceeds 2.5 mg/dL and K is 5.5 mEq/L or less, continue to titrate the agents, rechecking blood pressure (BP) and levels of SCr and K every four weeks until BP is at goal.⁸ Once SCr, K, and BP are stable, they should be rechecked annually.⁹

The adverse effects of ACE inhibitor/ARB use include angioedema and hyperkalemia, while only ACE inhibitors cause patients to cough. 

Afix Kehinde, PharmD, College of Pharmacy, University of Illinois at Chicago; Cheryl L. Gilmartin, PharmD, Clinical Assistant Professor, Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago; Clinical Pharmacist, Ambulatory Pharmacy Services, University of Illinois Hospital & Health Sciences System, Chicago

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:  How much of a bump in serum creatinine (SCr) can I expect after I start a patient on an ACE inhibitor or an angiotensin II receptor blocker (ARB)? How often should I check the patient’s SCr?

ACE inhibitors and ARBs inhibit the angiotensin-induced vasoconstriction of the efferent arterioles of the glomerular microcirculation. Inhibition of the renin-angiotensin-aldosterone system (RAAS) by these medications reduces both intraglomerular filtration pressure and proteinuria, delaying the progression of kidney disease.⁶ In response to RAAS inhibition, the GFR is slightly decreased and SCr is increased, reflecting the beneficial effects of the ACE inhibitor or the ARB on renal hemodynamics.^7,8 SCr may rise 10% to 30% from baseline within the first two weeks and generally stabilizes within two to four weeks.⁸

Patients with normal renal function initiated on an ACE inhibitor or an ARB experience a rise in SCr of about 0.2 mg/dL over a two- to three-week period, returning to baseline during week 4. Patients with abnormal renal function will have an increase in SCr of approximately 0.5 mg/dL over a four-week period.⁹ A progressive increase in SCr as great as 2.0 mg/dL may be seen in patients with bilateral renal artery stenosis, extensive atherosclerotic cardiovascular disease, or dehydration. In these instances, treatment with the ACE inhibitor or the ARB should be discontinued.⁹ 

Close monitoring is recommended in patients with chronic kidney disease Stage 3 through Stage 5 who are started on an ACE inhibitor or an ARB. SCr and K should be evaluated before and four weeks after initiating or titrating therapy.⁹ If SCr has increased by less than 0.5 mg/dL from a baseline measurement of 2.5 mg/dL or less; or if the rise in SCr is 1.0 mg/dL or less when the baseline SCr exceeds 2.5 mg/dL and K is 5.5 mEq/L or less, continue to titrate the agents, rechecking blood pressure (BP) and levels of SCr and K every four weeks until BP is at goal.⁸ Once SCr, K, and BP are stable, they should be rechecked annually.⁹

The adverse effects of ACE inhibitor/ARB use include angioedema and hyperkalemia, while only ACE inhibitors cause patients to cough. 

Afix Kehinde, PharmD, College of Pharmacy, University of Illinois at Chicago; Cheryl L. Gilmartin, PharmD, Clinical Assistant Professor, Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago; Clinical Pharmacist, Ambulatory Pharmacy Services, University of Illinois Hospital & Health Sciences System, Chicago

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:  How much of a bump in serum creatinine (SCr) can I expect after I start a patient on an ACE inhibitor or an angiotensin II receptor blocker (ARB)? How often should I check the patient’s SCr?

ACE inhibitors and ARBs inhibit the angiotensin-induced vasoconstriction of the efferent arterioles of the glomerular microcirculation. Inhibition of the renin-angiotensin-aldosterone system (RAAS) by these medications reduces both intraglomerular filtration pressure and proteinuria, delaying the progression of kidney disease.⁶ In response to RAAS inhibition, the GFR is slightly decreased and SCr is increased, reflecting the beneficial effects of the ACE inhibitor or the ARB on renal hemodynamics.^7,8 SCr may rise 10% to 30% from baseline within the first two weeks and generally stabilizes within two to four weeks.⁸

Patients with normal renal function initiated on an ACE inhibitor or an ARB experience a rise in SCr of about 0.2 mg/dL over a two- to three-week period, returning to baseline during week 4. Patients with abnormal renal function will have an increase in SCr of approximately 0.5 mg/dL over a four-week period.⁹ A progressive increase in SCr as great as 2.0 mg/dL may be seen in patients with bilateral renal artery stenosis, extensive atherosclerotic cardiovascular disease, or dehydration. In these instances, treatment with the ACE inhibitor or the ARB should be discontinued.⁹ 

Close monitoring is recommended in patients with chronic kidney disease Stage 3 through Stage 5 who are started on an ACE inhibitor or an ARB. SCr and K should be evaluated before and four weeks after initiating or titrating therapy.⁹ If SCr has increased by less than 0.5 mg/dL from a baseline measurement of 2.5 mg/dL or less; or if the rise in SCr is 1.0 mg/dL or less when the baseline SCr exceeds 2.5 mg/dL and K is 5.5 mEq/L or less, continue to titrate the agents, rechecking blood pressure (BP) and levels of SCr and K every four weeks until BP is at goal.⁸ Once SCr, K, and BP are stable, they should be rechecked annually.⁹

The adverse effects of ACE inhibitor/ARB use include angioedema and hyperkalemia, while only ACE inhibitors cause patients to cough. 

Afix Kehinde, PharmD, College of Pharmacy, University of Illinois at Chicago; Cheryl L. Gilmartin, PharmD, Clinical Assistant Professor, Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago; Clinical Pharmacist, Ambulatory Pharmacy Services, University of Illinois Hospital & Health Sciences System, Chicago

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.