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

BACKGROUND:While renin-angiotensin system inhibitors (RASi) have been the mainstream treatment for patients with CKD, they are often discontinued due to adverse effects such as hyperkalemia and acute kidney injury. It is unknown whether restarting RASi after discontinuation improves clinical outcomes. METHODS:Using the OCKR (Osaka Consortium for Kidney disease Research) database, we performed a target trial emulation study including 6,065 patients with an eGFR of 10-60 mL/min/1.73m2 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 five years at maximum after RASi discontinuation. The primary outcome was a composite kidney outcome (initiation of kidney replacement therapy, a ≥50% decline in eGFR, or kidney failure [eGFR <5 mL/min/1.73m2]). Secondary outcomes were all-cause death and incidence of hyperkalemia (serum potassium levels ≥5.5 mEq/L). RESULTS:Among those who discontinued RASi (mean [standard deviation (SD)] age 66 [15] years, 62% male, mean [SD] eGFR 40 [26] ml/min/1.73m2), 2,262 (37%) restarted RASi within a year. Restarting RASi was associated with a lower hazard of the composite kidney outcome (hazard ratio 0.85 [95% confidence intervals (CIs) 0.78 to 0.93]) and all-cause death (hazard ratio 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 (hazard ratio 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.