Residual renal function modulates response to erythropoietin in chronic renal insufficiency

Background. It is not known whether factors other than iron availability affect response to recombinant erythropoietin (Epoetin) in progressive chronic renal failure. Because uremic inhibitors of erythropoiesis accumulate with declining renal function, we theorized that residual renal function modulates responsiveness to Epoetin. Methods. We retrospectively studied 59 stable patients with progressive chronic renal failure (serum creatinine concentration ≥1.4 mg/dl) and anemia (hematocrit [Hct] <34%) who received Epoetin injections between January 1995 and December 1998 to determine whether creatinine clearance predicts responsiveness to Epoetin. We documented Hct, serum albumin concentration, serum creatinine concentration, blood urea nitrogen concentration, transferrin saturation, and body weight immediately before Epoetin therapy was started. Dose of Epoetin, length of treatment with Epoetin, maximum Hct achieved, and length of time to maximum Hct were noted, as was creatinine clearance at baseline. The study subjects consisted of 38 females and 21 males, with a mean age at baseline of 58 ± 15 yr. Twenty-four (41%) had diabetes mellitus. The mean weekly dose of Epoetin administered subcutaneously was 8,959 ± 3,355 U per patient. Consistent dosing criteria for Epoetin among patients with progressive chronic renal failure in our clinic were not employed; the prescribed dose of Epoetin was not based on the patient's weight, Hct, or serum creatinine concentration. Results. The mean duration of treatment with Epoetin was 10.3 ± 4.8 wk, and the mean maximum Hct achieved was 34 ± 6%. Following initiation of treatment with Epoetin, Hct rose in 53 of 59 subjects (90%), but was unchanged or dropped in the remaining 6. The mean rate of change of Hct in all the study subjects was 0.68 ± 0.56 percentage points per week. There was a direct correlation between baseline creatinine clearance and the rate of change in Hct after adjustment for dose of Epoetin (r = 0.37, p = 0.01). Linear regression analysis showed that baseline creatinine clearance and baseline Hct predicted the rate of change in Hct. Baseline creatinine clearance and the duration of treatment with Epoetin were the key determinants of maximum Hct achieved by each subject. Conclusions. We conclude that there are no established consistent dosing Criteria for Epoetin in patients with progressive chronic renal failure. In progressive chronic renal failure, response to Epoetin diminishes as renal failure progresses.