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Renin-Angiotensin System Inhibitors in Patients With Nonproteinuric Chronic Kidney Disease and Kidney Outcomes:
Insights
Renin-angiotensin system inhibitors (RASIs) do not appear to protect kidneys in nonproteinuric chronic kidney disease (CKD). However, RASIs may reduce mortality risk in these patients, suggesting a role in hypertension management.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Pharmacology
Background:
- Chronic kidney disease (CKD) affects millions globally, with nonproteinuric CKD representing a significant subgroup.
- Renin-angiotensin system inhibitors (RASIs), including ACE inhibitors and ARBs, are widely used for hypertension and CKD management.
- The specific benefits of RASIs in nonproteinuric CKD patients regarding kidney protection remain incompletely understood.
Purpose of the Study:
- To investigate the association between RASI use and kidney outcomes in adults with nonproteinuric CKD.
- To evaluate the impact of RASIs on all-cause mortality in this patient population.
- To compare kidney and survival outcomes between RASI users and non-RASI antihypertensive medication users.
Main Methods:
- Analysis of data from the prospective Chronic Renal Insufficiency Cohort study.
- Inclusion of adult participants with nonproteinuric CKD (proteinuria <0.5 g/d) on antihypertensive medication, excluding those with heart failure.
- Utilized inverse probability of treatment weighting and Cox proportional hazards models, including marginal structural models for cumulative exposure analysis.
Main Results:
- RASI use was not associated with a reduced risk of CKD progression (eGFR halving, dialysis, or transplant) in baseline or drug discontinuation analyses.
- Cumulative exposure analysis indicated a higher risk of CKD progression with lower RASI exposure, but not with high exposure (≥50% follow-up).
- RASI users demonstrated a significantly lower risk of all-cause mortality, particularly in analyses accounting for drug discontinuation.
Conclusions:
- RASIs may not offer direct kidney protection in patients with nonproteinuric CKD.
- RASIs might provide a mortality benefit in hypertensive patients with nonproteinuric CKD.
- Further research is warranted to clarify the role of RASIs in managing nonproteinuric CKD and associated cardiovascular risks.
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.
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