• Elaine Ku, Lesley A Inker, Hocine Tighiouart, Charles E McCulloch, Ogechi M Adingwupu, Tom Greene, Raymond O Estacio, Mark Woodward, Dick de Zeeuw, Julia B Lewis, Thierry Hannedouche, Tazeen H Jafar, Enyu Imai, Giuseppe Remuzzi, Hiddo J L Heerspink, Fan Fan Hou, Robert D Toto, Philip K Li, and Mark J Sarnak.
• Departments of Medicine and Pediatrics, Division of Nephrology, and Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California (E.K.).
• Ann. Intern. Med. 2024 Jul 1; 177 (7): 953963953-963.

BackgroundIn patients with advanced chronic kidney disease (CKD), the effects of initiating treatment with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin-receptor blocker (ARB) on the risk for kidney failure with replacement therapy (KFRT) and death remain unclear.PurposeTo examine the association of ACEi or ARB treatment initiation, relative to a non-ACEi or ARB comparator, with rates of KFRT and death.Data SourcesOvid Medline and the Chronic Kidney Disease Epidemiology Collaboration Clinical Trials Consortium from 1946 through 31 December 2023.Study SelectionCompleted randomized controlled trials testing either an ACEi or an ARB versus a comparator (placebo or antihypertensive drugs other than ACEi or ARB) that included patients with a baseline estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m2.Data ExtractionThe primary outcome was KFRT, and the secondary outcome was death before KFRT. Analyses were done using Cox proportional hazards models according to the intention-to-treat principle. Prespecified subgroup analyses were done according to baseline age (<65 vs. ≥65 years), eGFR (<20 vs. ≥20 mL/min/1.73 m2), albuminuria (urine albumin-creatinine ratio <300 vs. ≥300 mg/g), and history of diabetes.Data SynthesisA total of 1739 participants from 18 trials were included, with a mean age of 54.9 years and mean eGFR of 22.2 mL/min/1.73 m2, of whom 624 (35.9%) developed KFRT and 133 (7.6%) died during a median follow-up of 34 months (IQR, 19 to 40 months). Overall, ACEi or ARB treatment initiation led to lower risk for KFRT (adjusted hazard ratio, 0.66 [95% CI, 0.55 to 0.79]) but not death (hazard ratio, 0.86 [CI, 0.58 to 1.28]). There was no statistically significant interaction between ACEi or ARB treatment and age, eGFR, albuminuria, or diabetes (P for interaction > 0.05 for all).LimitationIndividual participant-level data for hyperkalemia or acute kidney injury were not available.ConclusionInitiation of ACEi or ARB therapy protects against KFRT, but not death, in people with advanced CKD.Primary Funding SourceNational Institutes of Health. (PROSPERO: CRD42022307589).

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