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Objective: Hypertension is a major problem in chronic kidney disease (CKD) with a prevalence approaching 100%, contributing to the risk of CKD progression, cardiovascular events and all-cause mortality. Renin-angiotensin system inhibitors (RASi) are the first-line therapy for antihypertensive treatment in patients with CKD, due to its protective effects. However, it is common practice stopping RASi in advanced CKD to attempt to delay kidney replacement therapy (KRT) initiation and/or to prevent drug-related acute kidney injury. Design and method: From the CKD-Rein prospective cohort, which included 3033 outpatients from nephrology clinics in France, we selected participants with an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 and who were treated with RASi for at least 3 months. We used the G-formula to deal with time-fixed (age, sex, diabetes, heart failure, lung diseases) and time-varying confounding (eGFR, systolic blood pressure, serum sodium and potassium, diuretic prescription) to compare two treatment strategies: to discontinue or to continue RASi. The outcome, MACE, was the composite of cardiovascular death, myocardial infarction, stroke or hospitalization for heart failure. Competing risks were initiation of KRT and non-cardiovascular death. Results: From the 1,472 patients included (median age 69 years, median eGFR 25mL/min/1.73m2, 34% women), 27% discontinued RASi over a median follow-up of 35 17-51 months. The crude rate of RASi discontinuation was higher in the presence of cardiovascular comorbidities and more severe CKD. The number of reported serious adverse reactions over the follow-up (such as acute kidney injury or hyperkalemia) was low, but higher in the discontinuation than in the continuation group (47 versus 23 per 1,000 person-years). After taking the afore-mentioned potential confounders into account, the 36-month risk of MACE was twice as high in the discontinuation group as that in the continuation group (RR 2.13, 95%CI 1.60-2.85). Conclusions: RASi discontinuation was significantly associated with MACE risk, the leading cause of morbidity and mortality in advanced CKD. Our results, along with other published data, suggest that the risk-benefit balance favors continued use of RASi in this population.
Valentin et al. (Wed,) studied this question.