Skip to main content
. Author manuscript; available in PMC: 2022 Jun 1.
Published in final edited form as: Am J Kidney Dis. 2021 Apr 21;77(6):969–983. doi: 10.1053/j.ajkd.2020.12.022

Table 3:

Summary of major clinical trials on ACEI and ARB therapy on kidney function decline.

REIN, Stratum 2 (n=166) RENAAL (n=1,513) AASK (n=1,094) IDNT (n=1,715) VA NEPHRON-D (n=1,448)
Kidney-related inclusion criteria CLcr 20–70 ml/min/1.73 m2; proteinuria ≥3 g/d Scr 1.3–3.0 mg/dL; UACR ≥300 mg/g GFR 20–65 ml/min/1.73 m2; UPCR ≤2.5 g/d Scr 1.0 (F) or 1.2 (M) 3.0 mg/dL; proteinuria ≥900 mg/d eGFR 30-<90 ml/min/1.73 m2; UACR ≥300 mg/g
Follow-up Mean: ~1.3 y Mean: 3.4 y Range: 3.0–6.4 y Mean: 2.6 y Median: 2.2 y
% with diabetes 0%* 100% 0% 100% 100%
% with HTN 87% 93%c 100% 100% n/a
Intervention Ramipril vs Placebo Losartan vs Placebo Ramipril vs Metoprolol vs Amlodipine Irbesartan vs Placebo vs Amlodipine Losartan + Lisinopril vs Losartan + Placebo
Mean baseline eGFR, GFR, or Scr GFR 37.4–40.2 ml/min/1.73 m2 Scr ~1.9b mg/dL GFR 45.6 ml/min/1.73 m2 Scr ~1.7b mg/dL eGFR ~53.6–53.7 ml/min/1.73 m2
Baseline UPCR or UPE Mean: 5.1–5.6 g/d n/a Median: 0.08 g/g Median: ~2.9 g/d Median: ~1.6–2.1 g/g
Baseline UACR or UAE n/a Median: ~1,237–1,261 mg/g n/a Median: ~1.9 g/d Median: 847 mg/g
Kidney function decline** 0.53 vs 0.88 ml/min/mo; p=0.03a HR: 0.84 (0.72–0.98) Risk Reduction for ramipril: 22% (1%−38%) vs. Metoprolol, 38% (14%−56%) vs. Amlodipine RR for Irbesartan: 0.81 (0.67–0.99) vs. Placebo, 0.76 (0.63–0.92) vs. Amlodipine HR: 0.88 (0.70–1.12)
a

Analysis among 117 participants with at least 3 GFR measurements;

b

eGFR or GFR not available;

c

Percent receiving anti-HTN drugs at baseline;

*

None with “insulin-dependent diabetes mellitus”

Abbreviations: ACEI=angiotensin-converting-enzyme inhibitor; ARB= angiotensin-receptor blocker; GFR=glomerular filtration rate; eGFR=estimated glomerular filtration rate; UPCR=urinary protein-creatinine ratio; UPE=urine protein excretion; UACR=urinary albumin-creatinine ratio; UAE=urine albumin excretion; RR=relative risk; Scr= serum creatinine; RENAAL, Reduction in End Points in Non-Insulin-Dependent Diabetes With the Angiotensin II Antagonist Losartan; VA NEPHRON-D, Veterans Affairs Nephropathy in Diabetes Study; CLcr, creatinine clearance; IDNT, Irbesartan Diabetic Nephropathy Trial; HTN, hypertension; REIN, Ramipril Efficacy in Nephropathy; F, female; M, male; n/a=not available.

**

defined in each study as follows: RENAAL (HR for SCr doubling, KFRT, or death); IDNT (RR for SCr doubling, SCr≥6.0 mg/dL, KFRT, or death); AASK (GFR decline ≥50% or ≥25 ml/min/1.73 m2 from baseline, KFRT, or death); VA NEPHRON-D (HR first occurrence of absolute decline in eGFR ≥30 ml/min/1.73 m2 if eGFR at randomization ≥60 ml/min/1.73 m2, relative decline in eGFR ≥50% if eGFR at randomization <60 ml/min/1.73 m2; eGFR <15 ml/min/1.73 m2, KFRT; or death).

Based on information in The GISEN Group 1997 (Lancet, https://doi.org/10.1016/S0140-6736(96)11445-8), Brenner et al 2001 (NEJM, https://doi.org/10.1056/nejmoa011161), Wright et al 2002 (JAMA, https://doi.org/10.1001/jama.288.19.2421), Lewis et al 2001 (NEJM, https://doi.org/10.1056/nejmoa011303), Fried et al 2013 (NEJM, https://doi.org/10.1056/nejmoa1303154).