Kidney and Mortality Outcomes on Renin-Angiotensin System Inhibitors in Nonproteinuric CKD: Findings from the CRIC Study

Background: The kidney benefits of renin angiotensin system inhibitors (RASIs) in patients with absent or minimal proteinuria in CKD is not known. We evaluated the long-term kidney outcomes and survival in those with non-proteinuric CKD treated with RASIs vs. other antihypertensive drugs. Methods: Among participants with CKD and less than 0.5 g/day of proteinuria in the Chronic Renal Insufficiency Cohort Study, we evaluated baseline RASI use vs other antihypertensive medications (i.e. intention-to-treat approach) with inverse probability of treatment weighting (IPTW) and Cox proportional hazards modeling to determine the association of RASIs with (1) CKD progression (halving of eGFR, dialysis, or transplant) and (2) all-cause mortality. Secondary analyses included censoring with drug discontinuation (i.e. per-protocol) and a new user, time-updated RASI use approach (i.e. cumulative exposure) to evaluate the association of RASI use with CKD progression. Results: A total of 2664 participants with non-proteinuric CKD met inclusion criteria. In the baseline RASI use approaches, use of RASIs was not significantly associated with CKD progression. The time-updated approach was underpowered but showed a higher risk of CKD progression among low level RASI users (RASI use during 0-25% of follow-up) vs. non-users but no higher risk of CKD progression among higher level RASI users (RASI use during >25% of follow-up) vs. non-users. RASI users had a lower mortality risk vs. non-users in the per-protocol analysis (adjusted HR 0.63, 95% CI 0.49-0.80) and a non-significantly lower mortality risk among higher level RASI users (>25%) vs. non-users. Conclusion: Among people with non-proteinuric CKD, RASI use is not associated with CKD progression but may be associated with lower mortality risk compared to other antihypertensive medications. For people with non-proteinuric CKD, RASIs may not provide a kidney benefit, but may still confer a mortality benefit for hypertension management. Funding: NIDDK Support