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Kidney Week

Abstract: FR-PO175

Kidney Function Outcomes Following RAAS Inhibition in Patients with Heart Failure

Session Information

Category: CKD (Non-Dialysis)

  • 1901 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention


  • McCallum, Wendy I., Tufts Medical Center, Boston, Massachusetts, United States
  • Tighiouart, Hocine, Tufts Medical Center, Boston, Massachusetts, United States
  • Ku, Elaine, University of California San Francisco Medical Center, San Francisco, California, United States
  • Salem, Deeb N., Tufts Medical Center, Boston, Massachusetts, United States
  • Sarnak, Mark J., Tufts Medical Center, Boston, Massachusetts, United States

Blockade of the renin-angiotensin-aldosterone system (RAAS) is beneficial for cardiovascular outcomes in patients with heart failure with reduced ejection fraction (HFrEF), but is also associated with decline in estimated glomerular filtration rate (eGFR). Long-term kidney outcomes after RAAS inhibition remain unclear in HFrEF.


We performed a retrospective analysis of the Studies Of Left Ventricular Dysfunction (SOLVD) trials, in which participants with HFrEF were randomized to enalapril vs placebo in the Treatment Trial (n=2423) if symptomatic, and in the Prevention Trial (n=4094) if asymptomatic. Joint models were used to estimate rate of decline in eGFR. Multivariable Cox models were used to evaluate the association of enalapril vs placebo for the following 3 outcomes at any timepoint: 1) ≥0.3 mg/dl increase in serum creatinine, 2) ≥30% decline in eGFR, and 2) incident CKD Stage 4 or 5 as defined by new eGFR ≤30 ml/min/1.73m2.


A total of 6,517 participants randomized to enalapril (n=3254) or placebo (n=3263) were included in this analysis. Mean baseline eGFR was higher in Prevention vs Treatment (76.2±18.6 vs 69.5±19.8 ml/min/1.73m2, p<0.01). Over a median follow-up of 24 months, mean eGFR declined at similar rates, -1.6 (95% CI -1.8,-1.4) for Prevention vs -1.7 ml/min/1.73m2/year (95% CI -2.0, -1.5) for Treatment (p=0.51) (Figure). Only 1.4% in Prevention Trial and 4.5% in Treatment Trial reached CKD stage 4 or 5. In adjusted analyses, randomization to enalapril was associated with a higher hazard of increase in creatinine by ≥0.3 mg/dl (HR of 1.32, 95% CI 1.18, 1.47), decline in eGFR by ≥30% (HR 1.33, 95% CI 1.18, 1.50) and CKD Stage 4 or 5 (HR 1.43, 95% CI 1.05, 1.95).


GFR decline on average was slow in both trials and only a small percentage of patients with HFrEF reached incident CKD Stage 4 or 5 over a median of 2 years. Randomization to enalapril carried a higher risk of reaching all kidney function endpoints but it remains to be determined whether these differences are of clinical importance.


  • Other NIH Support