Estimated Effect of Restarting Renin-Angiotensin System Inhibitors after Discontinuation on Kidney Outcomes and Mortality

Key Points Restarting renin-angiotensin system inhibitor after discontinuation was associated with a lower risk of kidney outcomes and mortality but not related to hyperkalemia. Our findings support a proactive approach to restarting renin-angiotensin system inhibitor among patients with CKD. Background While renin-angiotensin system inhibitors (RASi) have been the mainstream treatment for patients with CKD, they are often discontinued because of adverse effects such as hyperkalemia and AKI. It is unknown whether restarting RASi after discontinuation improves clinical outcomes. Methods Using the Osaka Consortium for Kidney disease Research database, we performed a target trial emulation study including 6065 patients with an eGFR of 10–60 ml/min per 1.73 m 2 who were followed up by nephrologists and discontinued RASi between 2005 and 2021. With a clone-censor-weight approach, we compared a treatment strategy for restarting RASi within a year after discontinuation with that for not restarting RASi. Patients were followed up for 5 years at maximum after RASi discontinuation. The primary outcome was a composite kidney outcome (initiation of KRT, a ≥50% decline in eGFR, or kidney failure [eGFR <5 ml/min per 1.73 m 2 ]). Secondary outcomes were all-cause death and incidence of hyperkalemia (serum potassium levels ≥5.5 mEq/L). Results Among those who discontinued RASi (mean [SD] age 66 [15] years, 62% male, mean [SD] eGFR 40 [26] ml/min per 1.73 m 2 ), 2262 (37%) restarted RASi within a year. Restarting RASi was associated with a lower hazard of the composite kidney outcome (hazard ratio [HR], 0.85; 95% confidence intervals [CIs], 0.78 to 0.93]) and all-cause death (HR, 0.70; 95% CI, 0.61 to 0.80) compared with not restarting RASi. The incidence of hyperkalemia did not differ significantly between the two strategies (HR, 1.11; 95% CI, 0.96 to 1.27). Conclusions Restarting RASi after discontinuation was associated with a lower risk of kidney outcomes and mortality but not related to the incidence of hyperkalemia.