Stopping renin-angiotensin system inhibitors in advanced CKD did not appear to affect eGFR

Stopping renin-angiotensin system (RAS) inhibitors in patients with advanced chronic kidney disease (CKD) does not appear to affect the rate of decline of estimated glomerular filtration rate (eGFR), a recent study found.

In a multicenter, open-label trial, researchers in the United Kingdom randomly assigned patients with advanced, progressive CKD (eGFR <30 mL/min/1.73 m²) to discontinue or continue therapy with RAS inhibitors, including angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers. The study's primary outcome was eGFR at three years, excluding values obtained after renal replacement therapy was started. Secondary outcomes included end-stage kidney disease (ESKD), a composite of a decrease of more than 50% in eGFR or the initiation of renal replacement therapy, hospitalization, blood pressure, exercise capacity, and quality of life. The study results were published Nov. 3 by the New England Journal of Medicine.

Four hundred eleven patients were enrolled in the trial, 206 in the discontinuation group and 205 in the continuation group, with follow-up until June 19, 2021. Patients' median age was 63 years, 68% were men, and 15% were non-White. Median eGFR at baseline was 18 mL/min/1.73 m², and 29% of patients had an eGFR below 15 mL/min/1.73 m². At three years, the least-squares mean (±SE) eGFR was 12.6±0.7 mL/min/1.73 m² in those who discontinued RAS inhibitors and 13.3±0.6 mL/min/1.73 m² in those who did not (difference, −0.7 mL/min/1.73 m² [95% CI, −2.5 to 1.0 mL/min/1.73 m²]; P=0.42). No heterogeneity in outcomes was seen according to prespecified subgroups of age, eGFR, type of diabetes, mean arterial pressure, and proteinuria. One hundred twenty-eight patients in the discontinuation group and 115 patients in the continuation group developed ESKD or began renal replacement therapy (62% vs. 56%; hazard ratio, 1.28 [95% CI, 0.99 to 1.65]). Cardiovascular events and deaths were similar between groups (108 vs. 88 and 20 vs. 22, respectively).

The trial did not include many non-White patients or patients with higher levels of proteinuria, the researchers noted. The results may also be affected by the trial's open-label design, among other limitations, they said. They concluded that discontinuation of RAS inhibitors in patients with advanced and progressive CKD in this trial did not lead to a clinically relevant change in eGFR or a between-group difference in the long-term rate of eGFR decline.

“Our 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 authors wrote. They also noted that while their trial was not powered to examine the effect of discontinuing RAS inhibitors on cardiovascular risk in this population and data on this question have been lacking, “because our findings are consistent with a lack of advantage for such discontinuation with respect to kidney function, there is little rationale to conduct a larger randomized trial to investigate cardiovascular safety.”