January/February 2023
Should we continue ACE inhibitors and ARBs in patients with advanced kidney disease?

A randomised trial suggests that continuing them is safe in patients who are followed carefully.

ACE inhibitors and angiotensin­ receptor blockers (ARBs) can slow progression of mild-­to-moderate chronic kidney disease (CKD). But are they beneficial, harmful or neutral in patients with advanced CKD? To address this question, UK researchers identified 411 adults with estimated glomerular filtration rate (GFR) below 30 mL/minute/1.73 m2 who had been receiving ACE inhibitors or ARBs and randomised them to discontinue or continue these drugs. At baseline, median serum creatinine was 260 mcmol/L and median GFR was 18 mL/minute. Patients on dialysis were excluded.

At median follow up of three years, these outcomes were noted:

• mean GFR was about 13 mL/minute in both groups; however, the proportion of patients progressing to renal replacement therapy or terminal palliative care was 62%

• with discontinuation and 56% with continuation; this difference just missed statistical significance (hazard ratio, 1.28;95% confidence interval, 0.99–1.65) 

• mortality was about 10% in both groups

• proteinuria and blood pressure increased transiently in the discontinuation group, but later, no differences were noted between groups

• incidences of myocardial infarction, stroke and heart failure hospitalisations were similar in the two groups.

Comment: Continuing ACE inhibitors or ARBs was not harmful in patients with estimated GFR lower than 30 mL/minute. The big question – not quite resolved here – is whether continuing these drugs confers any benefit. The six percentage­ point difference in progression to end­-stage renal disease, favouring the continuation group, would have been significant in a slightly larger study. In my view, these results support continuing ACE inhibitors and ARBs in patients with advanced CKD unless substantial hyperkalaemia or otherwise unexplained sudden deterioration in renal function occurs.

Clinical Professor of Medicine, University of Colorado School of Medicine, Aurora, USA.

Bhandari S, et al. Renin-angiotensin system inhibition in advanced chronic kidney disease. N Engl J Med 2022; 387: 2021-2032.

This summary is taken from the following Journal Watch title: General Medicine

N Engl J Med