https://orcid.org/0000-0002-9642-8380
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Massimo Volpe, Carlo Patrono, Discontinuation of renin–angiotensin system inhibitors brings no benefits in severe chronic kidney disease, European Heart Journal, Volume 45, Issue 26, 7 July 2024, Pages 2279–2280, https://doi.org/10.1093/eurheartj/ehae248
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Comment on ‘Renin–Angiotensin System Inhibition in Advanced Chronic Kidney Disease’, which was published in the New England Journal of Medicine, https://doi.org/10.1056/NEJMoa2210639.
Comment
A large body of evidence has demonstrated that RAS inhibitors have beneficial effects in patients at risk of developing CKD, such as those with hypertension and diabetes, slowing the progression of renal disease and the reduction of eGFR.2 Consistently, guidelines from the Kidney Disease: Improving Global Outcomes Work Group recommend the prescription of ACE inhibitors and ARBs in hypertensive patients with and without diabetes and urine protein excretion > 300 mg/day and suggest these pharmacological classes as the first-line strategy in patients with non-dialysis-dependent diabetic CKD and urine albumin excretion of 30–300 mg/day, even in the absence of high BP.3
However, most clinical trials excluded participants with eGFR < 30 mL/min/1.73 m2, generating a lack of evidence-based recommendations about the initiation and continuation of these drugs in an important subset of advanced renal disease, with no indication of eGFR threshold(s) below which the discontinuation of RAS inhibitors is required or treatment initiation is contraindicated. Controversial findings, mostly from observational studies, have been produced in the last decades raising a warning on RAS inhibitors potentially compromising the residual kidney function and accelerating eGFR reduction in patients with CKD. A small observational study demonstrated that in subjects with advanced CKD who were treated with RAS inhibitors, the withdrawal of this treatment was associated with a slowing of eGFR decline.4 In another observational study, patients with advanced CKD treated with ACE inhibitors or ARBs had a 25% increase in serum creatinine levels whereas those who discontinued RAS inhibitors experienced an improvement in kidney function.5 The analysis of a large observational registry also suggested that the discontinuation of RAS inhibitors may reduce the risk of progression to ESKD.6 As a result of these reports, physicians are often reluctant about the use of RAS inhibitors in patients with advanced chronic CKD, even when these compounds would be recommended for other concomitant indications, such as resistant hypertension, diabetes, heart failure, or post-myocardial infarction left ventricular dysfunction.
