Effects of Restarting RASi Therapy After Discontinuation

Renin-angiotensin system inhibitors (RASi) are a common treatment for CKD but are often discontinued due to hyperkalemia and AKI. To determine whether restarting RASi after discontinuation would improve clinical outcomes, Koki Hattori and colleagues performed a target trial emulation study using the Osaka Consortium for Kidney Disease Research database.  

The study cohort comprised 6,065 patients with an eGFR of 10-60 mL/min/1.73 m2 who discontinued RASi between 2005 and 2021. The researchers used a clone-censor-weight approach to compare a treatment strategy for restarting RASi within a year after discontinuation with not restarting RASi. The study’s primary outcome was a composite kidney outcome (initiation of kidney replacement therapy, a ≥50% decline in eGFR, or kidney failure [eGFR <5 mL/min/1.73 m²]). Secondary outcomes included all-cause death and incidence of hyperkalemia (serum potassium levels ≥5.5 mEq/L). Patient follow-up was 5 years maximum after RASi discontinuation.  

Mean age was 66 (SD 15) years, 62% of subjects were male, and mean eGFR was 40 (SD 26) mL/min/1.73 m². In total, 2,262 patients (37%) restarted RASi within a year. Restarting RASi was associated with a lower risk of the composite kidney outcome (HR, 0.85; 95% CI, 0.78-0.93) and all-cause death (HR, 0.70; 95% CI, 0.61-0.80) compared to not restarting RASi. There was no significant difference in hyperkalemia incidence between the two strategies (HR, 1.11; 95% CI, 0.96-1.27). 

The findings support a proactive approach to restarting RASi among patients with CKD. 

Source: Journal of the American Society of Nephrology