Renin-angiotensin system inhibitors initiation and mortality in non-proteinuric chronic kidney disease: a target trial emulation
Fan Luo, Luhua Jin, Shiyu Zhou, Ruixuan Chen, Mingzhen Pang, Yuxin Lin, Yanqin Li, Licong Su, Xin Xu, Sheng Nie, Fan Fan HouAbstract
Background
Treatment options for nonproteinuric chronic kidney disease (CKD) are limited. While renin-angiotensin system inhibitors (RASIs) are cornerstone therapies for proteinuric CKD, evidence supporting the clinical benefit of RASIs initiation in nonproteinuric CKD is lacking.
Methods
We emulated sequential target trials using a retrospective cohort from the China Renal Data System (CRDS). Adults with nonproteinuric CKD (urine albumin-to-creatinine ratio <30 mg/g) were included to assess the intention-to-treat effect of initiating RASIs on all-cause and cardiovascular mortality. The primary estimate was the three-year risk difference. A composite kidney outcome (>25% eGFR decline with stage deterioration or kidney replacement therapy) was also explored.
Results
A total of 17 382 eligible person-trials (10 101 unique persons) were included. The three-year cumulative incidence of all-cause mortality was 14.88% (95% confidence interval [CI], 13.65% to 16.51%) and 18.26% (95% CI, 17.67% to 19.42%) in the RASIs initiation group and the control group, respectively, corresponding to a risk difference of − 3.39% (95% CI, −4.71% to − 2.07%). A significant association favoring RASIs initiation was also observed in terms of cardiovascular mortality, with a three-year risk difference of -1.46% (95%CI, -2.57% to -0.52%). Estimates from the subgroup and the sensitivity analyses were consistent with the primary analysis. A similar trend of association was observed for composite kidney outcomes, though the three-year cumulative risk difference between groups did not reach statistical significance (risk difference, −0.88%; 95% CI, −2.42% to 1.40%).
Conclusions
Initiation of RASIs may be associated with lower risks of all-cause and cardiovascular mortality in patients with nonproteinuric CKD.