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Renin-Angiotensin System Inhibition in Advanced Chronic Kidney Disease.
N Engl J Med. 2022 12 01; 387(22):2021-2032.NEJM

Abstract

BACKGROUND

Renin-angiotensin system (RAS) inhibitors - including angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) - slow the progression of mild or moderate chronic kidney disease. However, the results of some studies have suggested that the discontinuation of RAS inhibitors in patients with advanced chronic kidney disease may increase the estimated glomerular filtration rate (eGFR) or slow its decline.

METHODS

In this multicenter, open-label trial, we randomly assigned patients with advanced and progressive chronic kidney disease (eGFR, <30 ml per minute per 1.73 m2 of body-surface area) either to discontinue or to continue therapy with RAS inhibitors. The primary outcome was the eGFR at 3 years; eGFR values that were obtained after the initiation of renal-replacement therapy were excluded. Secondary outcomes included the development of end-stage kidney disease (ESKD); a composite of a decrease of more than 50% in the eGFR or the initiation of renal-replacement therapy, including ESKD; hospitalization; blood pressure; exercise capacity; and quality of life. Prespecified subgroups were defined according to age, eGFR, type of diabetes, mean arterial pressure, and proteinuria.

RESULTS

At 3 years, among the 411 patients who were enrolled, the least-squares mean (±SE) eGFR was 12.6±0.7 ml per minute per 1.73 m2 in the discontinuation group and 13.3±0.6 ml per minute per 1.73 m2 in the continuation group (difference, -0.7; 95% confidence interval [CI], -2.5 to 1.0; P = 0.42), with a negative value favoring the outcome in the continuation group. No heterogeneity in outcome according to the prespecified subgroups was observed. ESKD or the initiation of renal-replacement therapy occurred in 128 patients (62%) in the discontinuation group and in 115 patients (56%) in the continuation group (hazard ratio, 1.28; 95% CI, 0.99 to 1.65). Adverse events were similar in the discontinuation group and continuation group with respect to cardiovascular events (108 vs. 88) and deaths (20 vs. 22).

CONCLUSIONS

Among patients with advanced and progressive chronic kidney disease, the discontinuation of RAS inhibitors was not associated with a significant between-group difference in the long-term rate of decrease in the eGFR. (Funded by the National Institute for Health Research and the Medical Research Council; STOP ACEi EudraCT number, 2013-003798-82; ISRCTN number, 62869767.).

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Publisher Full Text (DOI)

Authors+Show Affiliations

Bhandari S
From the Department of Renal Medicine, Hull University Teaching Hospitals NHS Trust, and Hull York Medical School, Hull (S.B.), the Birmingham Clinical Trials Unit, Institute of Applied Health Research (S.M., N.I., E.B., M.C.), and the Institute of Inflammation and Aging (P.C.), University of Birmingham, and the Department of Renal Medicine, Queen Elizabeth Hospital, University Hospitals Birmingham (P.C.), Birmingham, the Sheffield Kidney Institute, Sheffield (A.K.), and the British Heart Foundation Centre for Research Excellence, School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (J.G.F.C.) - all in the United Kingdom.
Mehta S
From the Department of Renal Medicine, Hull University Teaching Hospitals NHS Trust, and Hull York Medical School, Hull (S.B.), the Birmingham Clinical Trials Unit, Institute of Applied Health Research (S.M., N.I., E.B., M.C.), and the Institute of Inflammation and Aging (P.C.), University of Birmingham, and the Department of Renal Medicine, Queen Elizabeth Hospital, University Hospitals Birmingham (P.C.), Birmingham, the Sheffield Kidney Institute, Sheffield (A.K.), and the British Heart Foundation Centre for Research Excellence, School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (J.G.F.C.) - all in the United Kingdom.
Khwaja A
From the Department of Renal Medicine, Hull University Teaching Hospitals NHS Trust, and Hull York Medical School, Hull (S.B.), the Birmingham Clinical Trials Unit, Institute of Applied Health Research (S.M., N.I., E.B., M.C.), and the Institute of Inflammation and Aging (P.C.), University of Birmingham, and the Department of Renal Medicine, Queen Elizabeth Hospital, University Hospitals Birmingham (P.C.), Birmingham, the Sheffield Kidney Institute, Sheffield (A.K.), and the British Heart Foundation Centre for Research Excellence, School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (J.G.F.C.) - all in the United Kingdom.
Cleland JGF
From the Department of Renal Medicine, Hull University Teaching Hospitals NHS Trust, and Hull York Medical School, Hull (S.B.), the Birmingham Clinical Trials Unit, Institute of Applied Health Research (S.M., N.I., E.B., M.C.), and the Institute of Inflammation and Aging (P.C.), University of Birmingham, and the Department of Renal Medicine, Queen Elizabeth Hospital, University Hospitals Birmingham (P.C.), Birmingham, the Sheffield Kidney Institute, Sheffield (A.K.), and the British Heart Foundation Centre for Research Excellence, School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (J.G.F.C.) - all in the United Kingdom.
Ives N
From the Department of Renal Medicine, Hull University Teaching Hospitals NHS Trust, and Hull York Medical School, Hull (S.B.), the Birmingham Clinical Trials Unit, Institute of Applied Health Research (S.M., N.I., E.B., M.C.), and the Institute of Inflammation and Aging (P.C.), University of Birmingham, and the Department of Renal Medicine, Queen Elizabeth Hospital, University Hospitals Birmingham (P.C.), Birmingham, the Sheffield Kidney Institute, Sheffield (A.K.), and the British Heart Foundation Centre for Research Excellence, School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (J.G.F.C.) - all in the United Kingdom.
Brettell E
From the Department of Renal Medicine, Hull University Teaching Hospitals NHS Trust, and Hull York Medical School, Hull (S.B.), the Birmingham Clinical Trials Unit, Institute of Applied Health Research (S.M., N.I., E.B., M.C.), and the Institute of Inflammation and Aging (P.C.), University of Birmingham, and the Department of Renal Medicine, Queen Elizabeth Hospital, University Hospitals Birmingham (P.C.), Birmingham, the Sheffield Kidney Institute, Sheffield (A.K.), and the British Heart Foundation Centre for Research Excellence, School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (J.G.F.C.) - all in the United Kingdom.
Chadburn M
From the Department of Renal Medicine, Hull University Teaching Hospitals NHS Trust, and Hull York Medical School, Hull (S.B.), the Birmingham Clinical Trials Unit, Institute of Applied Health Research (S.M., N.I., E.B., M.C.), and the Institute of Inflammation and Aging (P.C.), University of Birmingham, and the Department of Renal Medicine, Queen Elizabeth Hospital, University Hospitals Birmingham (P.C.), Birmingham, the Sheffield Kidney Institute, Sheffield (A.K.), and the British Heart Foundation Centre for Research Excellence, School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (J.G.F.C.) - all in the United Kingdom.
Cockwell P
From the Department of Renal Medicine, Hull University Teaching Hospitals NHS Trust, and Hull York Medical School, Hull (S.B.), the Birmingham Clinical Trials Unit, Institute of Applied Health Research (S.M., N.I., E.B., M.C.), and the Institute of Inflammation and Aging (P.C.), University of Birmingham, and the Department of Renal Medicine, Queen Elizabeth Hospital, University Hospitals Birmingham (P.C.), Birmingham, the Sheffield Kidney Institute, Sheffield (A.K.), and the British Heart Foundation Centre for Research Excellence, School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (J.G.F.C.) - all in the United Kingdom.
STOP ACEi Trial Investigators
No affiliation info available

MeSH

HumansAngiotensin Receptor AntagonistsAngiotensin-Converting Enzyme InhibitorsAngiotensinsAntihypertensive AgentsGlomerular Filtration RateKidney Failure, ChronicQuality of LifeRenal Insufficiency, ChronicRenin-Angiotensin System

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

36326117

Citation

Bhandari, Sunil, et al. "Renin-Angiotensin System Inhibition in Advanced Chronic Kidney Disease." The New England Journal of Medicine, vol. 387, no. 22, 2022, pp. 2021-2032.
Bhandari S, Mehta S, Khwaja A, et al. Renin-Angiotensin System Inhibition in Advanced Chronic Kidney Disease. N Engl J Med. 2022;387(22):2021-2032.
Bhandari, S., Mehta, S., Khwaja, A., Cleland, J. G. F., Ives, N., Brettell, E., Chadburn, M., & Cockwell, P. (2022). Renin-Angiotensin System Inhibition in Advanced Chronic Kidney Disease. The New England Journal of Medicine, 387(22), 2021-2032. https://doi.org/10.1056/NEJMoa2210639
Bhandari S, et al. Renin-Angiotensin System Inhibition in Advanced Chronic Kidney Disease. N Engl J Med. 2022 12 1;387(22):2021-2032. PubMed PMID: 36326117.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Renin-Angiotensin System Inhibition in Advanced Chronic Kidney Disease. AU - Bhandari,Sunil, AU - Mehta,Samir, AU - Khwaja,Arif, AU - Cleland,John G F, AU - Ives,Natalie, AU - Brettell,Elizabeth, AU - Chadburn,Marie, AU - Cockwell,Paul, AU - ,, Y1 - 2022/11/03/ PY - 2022/11/4/pubmed PY - 2022/12/3/medline PY - 2022/11/3/entrez SP - 2021 EP - 2032 JF - The New England journal of medicine JO - N Engl J Med VL - 387 IS - 22 N2 - BACKGROUND: Renin-angiotensin system (RAS) inhibitors - including angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) - slow the progression of mild or moderate chronic kidney disease. However, the results of some studies have suggested that the discontinuation of RAS inhibitors in patients with advanced chronic kidney disease may increase the estimated glomerular filtration rate (eGFR) or slow its decline. METHODS: In this multicenter, open-label trial, we randomly assigned patients with advanced and progressive chronic kidney disease (eGFR, <30 ml per minute per 1.73 m2 of body-surface area) either to discontinue or to continue therapy with RAS inhibitors. The primary outcome was the eGFR at 3 years; eGFR values that were obtained after the initiation of renal-replacement therapy were excluded. Secondary outcomes included the development of end-stage kidney disease (ESKD); a composite of a decrease of more than 50% in the eGFR or the initiation of renal-replacement therapy, including ESKD; hospitalization; blood pressure; exercise capacity; and quality of life. Prespecified subgroups were defined according to age, eGFR, type of diabetes, mean arterial pressure, and proteinuria. RESULTS: At 3 years, among the 411 patients who were enrolled, the least-squares mean (±SE) eGFR was 12.6±0.7 ml per minute per 1.73 m2 in the discontinuation group and 13.3±0.6 ml per minute per 1.73 m2 in the continuation group (difference, -0.7; 95% confidence interval [CI], -2.5 to 1.0; P = 0.42), with a negative value favoring the outcome in the continuation group. No heterogeneity in outcome according to the prespecified subgroups was observed. ESKD or the initiation of renal-replacement therapy occurred in 128 patients (62%) in the discontinuation group and in 115 patients (56%) in the continuation group (hazard ratio, 1.28; 95% CI, 0.99 to 1.65). Adverse events were similar in the discontinuation group and continuation group with respect to cardiovascular events (108 vs. 88) and deaths (20 vs. 22). CONCLUSIONS: Among patients with advanced and progressive chronic kidney disease, the discontinuation of RAS inhibitors was not associated with a significant between-group difference in the long-term rate of decrease in the eGFR. (Funded by the National Institute for Health Research and the Medical Research Council; STOP ACEi EudraCT number, 2013-003798-82; ISRCTN number, 62869767.). SN - 1533-4406 UR - https://www.unboundmedicine.com/medline/citation/36326117/Renin_Angiotensin_System_Inhibition_in_Advanced_Chronic_Kidney_Disease_ DB - PRIME DP - Unbound Medicine ER -