Findings: Stopping RAS Inhibitors Does Not Alter eGFR Outcome in Advanced CKD

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In patients with advanced chronic kidney disease (CKD), discontinuation of renin-angiotensin system (RAS) inhibitor therapy does not affect the long-term rate of decline in kidney function, according to a report in The New England Journal of Medicine.

The randomized, open-label STOP-ACEi trial included 411 patients with advanced, progressive CKD, with an estimated glomerular filtration rate (eGFR) of less than 30 mL/min/1.73 m2. Patients were assigned to either continue or discontinue RAS inhibitor therapy. For those in the discontinuation group, any other type of guideline-recommended anti-hypertensive agent could be used; RAS inhibitors could be restarted only as a “last resort.” Change in eGFR at 3 years was assessed, along with secondary outcomes.

The least-squares mean change in eGFR was not significantly different between groups: 12.6 mL/min/1.73 m2 in patients who discontinued RAS inhibitors and 13.3 mL/min/1.73 m2 in those who continued therapy. Three-year rates of end stage kidney disease or renal replacement therapy were similar as well: 62% and 56%, respectively. There was no significant difference in serious adverse cardiovascular, vascular, or heart failure events.

Patients in the discontinuation group initially had higher blood pressure values, but this was corrected over time. Other secondary outcomes were also similar, including a 6-minute walk test and protein level.

In patients with mild to moderate CKD, RAS inhibitors slow the decline in eGFR and progression to advanced kidney diseases. However, there is limited evidence showing any benefit of RAS inhibitors in patients with advanced CKD. One observational study reported increases in eGFR after RAS inhibitor discontinuation in this group of patients.

Within its limitations, the STOP-ACEi trial shows no clinically relevant change in eGFR and no increase in the rate of long-term eGFR decline, after stopping RAS inhibitor therapy in patients with advanced, progressive CKD. The findings “do not support the hypothesis that the discontinuation of RAS inhibitors in patients with advanced and progressive chronic kidney disease would improve kidney function, quality of life, or exercise capacity,” the researchers concluded [Bhandari S, et al. Renin-angiotensin system inhibition in advanced chronic kidney disease. N Engl J Med, published online ahead of print November 3, 2022. doi: 10.1056/NEJMoa2210639;].