Renin-Angiotensin System Inhibitors in Patients With Nonproteinuric Chronic Kidney Disease and Kidney Outcomes: Findings From the CRIC Study.

RATIONALE &

OBJECTIVE

The kidney-protective benefits of renin-angiotensin system inhibitors (RASIs; ie, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers) in nonproteinuric chronic kidney disease (CKD) are unclear. We aimed to evaluate kidney outcomes in adults with nonproteinuric CKD treated with RASIs versus other antihypertensive medications.

STUDY

DESIGN

Using data from the Chronic Renal Insufficiency Cohort study, a prospective cohort study, we evaluated the association of RASI use with kidney outcomes and survival. Secondary analyses included censoring with drug discontinuation and a time-updated RASI approach (ie, cumulative exposure).

SETTING &

PARTICIPANTS

Individuals with <0.5 g/d of proteinuria (via 24-hour urine collection or spot test) on ≥1 antihypertensive medication. Participants with heart failure were excluded.

EXPOSURE: Patient-reported use of RASIs versus non-RASI antihypertensive medication.

OUTCOMES: (1) CKD progression (halving of estimated glomerular filtration rate, dialysis, or transplant) and (2) all-cause mortality.

ANALYTICAL APPROACH: Inverse probability of treatment weighting and Cox proportional hazards modeling; marginal structural models.

RESULTS

Among the 2,664 participants, the mean age was 62 years, 46% were female, and the mean estimated glomerular filtration rate was 50 mL/min/1.73 m2. There were 457 kidney events (29/1,000 person-years) in RASI users versus 129 (23/1,000 person-years) in the comparator. Treatment with RASIs was not associated with CKD progression in the baseline analysis (adjusted hazard ratio [HR], 1.01; 95% CI, 0.81-1.25) and drug discontinuation analysis (adjusted HR, 0.92; 95% CI, 0.68-1.25). The cumulative exposure approach showed a higher risk of CKD progression for low RASI users (<50% of follow-up) versus nonusers but no higher risk of CKD progression among high RASI users (≥50% of follow-up) versus nonusers. RASI users had a lower mortality risk in the drug discontinuation analysis (adjusted HR, 0.64; 95% CI, 0.50-0.82) and a nonsignificantly lower risk among participants receiving treatment with RASIs ≥75% of follow-up versus nonusers.

LIMITATIONS: Residual confounding cannot be ruled out. Medication use was patient-reported, increasing the potential for misclassification.

CONCLUSIONS

For people with nonproteinuric CKD, RASIs may not be kidney-protective but may still confer a mortality benefit for hypertension management.