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Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine: is this a cause for concern?
Arch Intern Med. 2000 Mar 13; 160(5):685-93.AI

Abstract

BACKGROUND

Reducing the actions of the renin-angiotensin-aldosterone system with angiotensin-converting enzyme inhibitors (ACEIs) slows nephropathy progression in patients with or without diabetes. Post hoc analyses of many ACEI-based clinical trials demonstrate the greatest slowing of renal disease progression in patients with the greatest degree of renal insufficiency at study initiation. However, many physicians fail to use ACEIs or angiotensin receptor blockers in patients with renal insufficiency for fear that either serum creatinine or potassium levels will rise.

OBJECTIVE

To determine if limited initial reduction in either glomerular filtration rate (GFR) or elevation in serum creatinine levels, associated with ACEI or angiotensin receptor blocker use, results in long-term protection against decline in renal function in patients with renal insufficiency.

METHODS

We reviewed 12 randomized clinical trials that evaluated renal disease progression among patients with preexisting renal insufficiency. Six of these studies were multicenter, double-blinded, and placebo controlled, with the remainder being smaller randomized studies with a minimum 2-year follow-up on renal function. These investigations evaluated patients with and without diabetes or systolic heart failure. Average duration of follow-up for all studies was 3 years. Trials were examined in the context of changes in either serum creatinine levels or GFR in the group randomized to an ACEI (N = 1,102). Sixty-four percent of these individuals (705/1,102) had renal function data at both less than 6 months and at the end of the study.

RESULTS

Most trials demonstrated that patients with preexisting renal insufficiency manifested an acute fall in GFR, a rise in serum creatinine, or both. Those randomized to an ACEI with a serum creatinine level of 124 pmol/L or greater (> or =1.4 mg/dL) demonstrated a 55% to 75% risk reduction in renal disease progression compared with those with normal renal function randomized to an ACEI. An inverse correlation was observed between the amount of renal function loss at baseline and the subsequent rate of annual decline in renal function following randomization to an antihypertensive regimen that contained an ACEI.

CONCLUSIONS

A strong association exists between acute increases in serum creatinine of up to 30% that stabilize within the first 2 months of ACEI therapy and long-term preservation of renal function. This relationship holds for persons with creatinine values of greater than 124 pmol/L (>1.4 mg/dL). Thus, withdrawal of an ACEI in such patients should occur only when the rise in creatinine exceeds 30% above baseline within the first 2 months of ACEI initiation, or hyperkalemia develops, ie, serum potassium level of 5.6 mmol/L or greater.

Authors+Show Affiliations

Rush University Hypertension/Clinical Research Center, Department of Preventive Medicine, Rush Presbyterian-St Luke's Medical Center, Chicago, Ill 60612, USA. gbakris@rush.eduNo affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis

Language

eng

PubMed ID

10724055

Citation

Bakris, G L., and M R. Weir. "Angiotensin-converting Enzyme Inhibitor-associated Elevations in Serum Creatinine: Is This a Cause for Concern?" Archives of Internal Medicine, vol. 160, no. 5, 2000, pp. 685-93.
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):685-93.
Bakris, G. L., & Weir, M. R. (2000). Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine: is this a cause for concern? Archives of Internal Medicine, 160(5), 685-93.
Bakris GL, Weir MR. Angiotensin-converting Enzyme Inhibitor-associated Elevations in Serum Creatinine: Is This a Cause for Concern. Arch Intern Med. 2000 Mar 13;160(5):685-93. PubMed PMID: 10724055.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine: is this a cause for concern? AU - Bakris,G L, AU - Weir,M R, PY - 2000/3/21/pubmed PY - 2000/4/1/medline PY - 2000/3/21/entrez SP - 685 EP - 93 JF - Archives of internal medicine JO - Arch Intern Med VL - 160 IS - 5 N2 - BACKGROUND: Reducing the actions of the renin-angiotensin-aldosterone system with angiotensin-converting enzyme inhibitors (ACEIs) slows nephropathy progression in patients with or without diabetes. Post hoc analyses of many ACEI-based clinical trials demonstrate the greatest slowing of renal disease progression in patients with the greatest degree of renal insufficiency at study initiation. However, many physicians fail to use ACEIs or angiotensin receptor blockers in patients with renal insufficiency for fear that either serum creatinine or potassium levels will rise. OBJECTIVE: To determine if limited initial reduction in either glomerular filtration rate (GFR) or elevation in serum creatinine levels, associated with ACEI or angiotensin receptor blocker use, results in long-term protection against decline in renal function in patients with renal insufficiency. METHODS: We reviewed 12 randomized clinical trials that evaluated renal disease progression among patients with preexisting renal insufficiency. Six of these studies were multicenter, double-blinded, and placebo controlled, with the remainder being smaller randomized studies with a minimum 2-year follow-up on renal function. These investigations evaluated patients with and without diabetes or systolic heart failure. Average duration of follow-up for all studies was 3 years. Trials were examined in the context of changes in either serum creatinine levels or GFR in the group randomized to an ACEI (N = 1,102). Sixty-four percent of these individuals (705/1,102) had renal function data at both less than 6 months and at the end of the study. RESULTS: Most trials demonstrated that patients with preexisting renal insufficiency manifested an acute fall in GFR, a rise in serum creatinine, or both. Those randomized to an ACEI with a serum creatinine level of 124 pmol/L or greater (> or =1.4 mg/dL) demonstrated a 55% to 75% risk reduction in renal disease progression compared with those with normal renal function randomized to an ACEI. An inverse correlation was observed between the amount of renal function loss at baseline and the subsequent rate of annual decline in renal function following randomization to an antihypertensive regimen that contained an ACEI. CONCLUSIONS: A strong association exists between acute increases in serum creatinine of up to 30% that stabilize within the first 2 months of ACEI therapy and long-term preservation of renal function. This relationship holds for persons with creatinine values of greater than 124 pmol/L (>1.4 mg/dL). Thus, withdrawal of an ACEI in such patients should occur only when the rise in creatinine exceeds 30% above baseline within the first 2 months of ACEI initiation, or hyperkalemia develops, ie, serum potassium level of 5.6 mmol/L or greater. SN - 0003-9926 UR - https://www.unboundmedicine.com/medline/citation/10724055/Angiotensin_converting_enzyme_inhibitor_associated_elevations_in_serum_creatinine:_is_this_a_cause_for_concern L2 - https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/vol/160/pg/685 DB - PRIME DP - Unbound Medicine ER -