Antiproteinuric and Renoprotective Effects of ACE Inhibitors and Angiotensin II Receptor Blockers

A meta-analysis 3 included 26 RCTs (20 for ACEi and 6 for ARB) comprising 10 378 participants with diabetes and albuminuria. Compared to placebo, treatment with ACEi or ARB did not reduce all-cause mortality or cardiovascular mortality. For renal outcomes, ARB significantly reduced the risk of end-stage renal disease (ESRD) by 23% (odds ratio 0.77, 95% CI 0.65 to 0.92), while ACE inhibitors were not associated with a decreased risk of ESRD (0.69, 0.43 to 1.10). Both ACEi and ARB reduced the risk of doubling of the serum creatinine level (0.60, 0.39 to 0.91 for ACEi; 0.75, 0.64 to 0.88 for ARB), and subgroup analyses for patients with macroalbuminuria or microalbuminuria showed similar results.

Another meta-analysis 4 included 8 RCTs with 25 647 patients, assessing renoprotective effect of ACEi or ARB or dihydropyridine CCB. ESRD showed significantly higher frequency with CCB therapy compared with ACEi or ARB, though blood pressure was decreased similarly in both groups in every trial (OR 1.25; 95% CI, 1.05 to1.48; p = 0.01). In contrast, there was no significant difference in the incidence of all-cause mortality between these two groups, though ACEi or ARB exhibited better renoprotective effect compared to CCB (OR, 0.96; 95% CI 0.89 to 1.03; p = 0.24).

A netwotk meta-analysis 5 included 119 RCTs with 64 768 CKD-patiens. ACEi and ARB reduced the odds of kidney failure by 39% and 30% (ORs of 0.61, 95% credible interval 0.47 to 0.79 and 0.70, 95% credible interval 0.52 to 0.89), respectively, compared to placebo, and by 35% and 25% (ORs of 0.65, 95% credible interval 0.51 to 0.80 and 0.75, 95% credible interval 0.54to 0.97), respectively, compared with other active controls, whereas other active controls did not show evidence of a significant effect on kidney failure. Both ACEi and ARB produced odds reductions for major cardiovascular events (ORs of 0.82, 95% credible interval 0.71 to 0.92 and 0.76, 95% credible interval 0.62 to 0.89, respectively) versus placebo. Comparisons did not show significant effects on risk for cardiovascular death. ACEi but not ARB significantly reduced the odds of all-cause death versus active controls (OR 0.72, 95% credible interval 0.53 to 0.92). Compared with ARB, ACEi were consistently associated with higher probabilities of reducing kidney failure, cardiovascular death, or all-cause death.

A Cochrane review [Abstract] 6 included 6 trials with a total of 9379 participants with CKD stages 1 to 3, without diabetes. There was insufficient evidence to determine the effectiveness of ACEi or ARB (death, cardiovascular events, or kidney failure progression) compared to placebo. The certainty of the evidence was very low.

References

• Wang K, Hu J, Luo T et al. Effects of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers on All-Cause Mortality and Renal Outcomes in Patients with Diabetes and Albuminuria: a Systematic Review and Meta-Analysis. Kidney Blood Press Res 2018;43(3):768-779. [PubMed]
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• Xie X, Liu Y, Perkovic V et al. Renin-Angiotensin System Inhibitors and Kidney and Cardiovascular Outcomes in Patients With CKD: A Bayesian Network Meta-analysis of Randomized Clinical Trials. Am J Kidney Dis 2016;67(5):728-41. [PubMed]
• Cooper TE, Teng C, Tunnicliffe DJ, ym. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for adults with early (stage 1 to 3) non-diabetic chronic kidney disease. Cochrane Database Syst Rev 2023;7(7):CD007751 [PubMed]