Chronic kidney disease (CKD), anemia, and declining kidney function are recognized as risk factors for adverse outcomes in patients with heart failure. This analysis was conducted to evaluate whether anemia is a risk factor for kidney function decrease in patients with heart failure. Data from the Studies of Left Ventricular Dysfunction (SOLVD), a randomized trial of enalapril versus placebo in patients with ejection fractions <or=35%, were analyzed. After randomization, creatinine measurements were taken at 2 weeks, 6 weeks, 4 months, and every 4 months thereafter. The glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease Study (MDRD) equation, and GFR slope was calculated. "Rapid decrease" was defined as a decrease in the GFR of >or=6 ml/min/1.73 m(2)/year. Anemia was defined as baseline hematocrit <36%. Multivariate logistic regression weighted by the number of GFR assessments was used to test the relation between anemia and rapid decrease. We also evaluated whether CKD (baseline GFR </=60 ml/min/1.73 m(2)) modified the relation between anemia and rapid decrease. In the 6,360 subjects, the mean age was 59 years, 31% had CKD, and 6% had anemia. Median follow-up was 2 years. In multivariate analysis, anemia was associated with a 1.30 increased odds (95% confidence interval 1.18 to 1.45) of rapid decrease in GFR. In subjects with CKD, anemia was associated with a 1.71 increased odds (95% confidence interval 1.43 to 2.05) of rapid decrease, while in subjects without CKD, anemia was associated with a 1.16 increased odds (95% confidence interval 1.03 to 1.31) of rapid decrease (p for interaction <0.001). In conclusion, anemia is associated with a rapid decrease in kidney function in patients with heart failure, particularly in those with underlying CKD.