Recombinant human erythropoietin (r-HuEPO) therapy for anemia in chronic renal failure patients could have unfavorable renal effects since reversal of anemia can raise blood pressure and accelerate experimental glomerular injury. Thus, the effects of r-HuEPO on renal and systemic hemodynamics and the progression of renal disease were studied in predialysis chronic renal failure patients. The clearances of inulin and p-aminohippurate, fractional excretions of albumin and immunoglobulin G, cardiac output, plasma renin activity and aldosterone concentration were assessed at baseline, after short-term r-HuEPO (n = 4) or placebo (n = 4) therapy, and after long-term r-HuEPO for all patients (n = 8). In addition, the slope of l/serum creatinine with time was determined before and during continued r-HuEPO therapy. In contrast to placebo therapy, hematocrit increased with r-HuEPO from 32 to 37% after 7.6 +/- 2.7 weeks (mean +/- SD). Antihypertensive drug therapy was increased in 2 patients in each group. Renal function, cardiac output, plasma renin activity and aldosterone did not change significantly in either group. After 18 +/- 9 weeks of therapy for all patients, hematocrit increased from 31 to 39%. Antihypertensive drug therapy was increased in 5 patients and decreased in 1. Renal function decreased while proteinuria tended to increase. Cardiac output, plasma renin activity and aldosterone did not change. During 37 +/- 22 weeks of r-HuEPO therapy, the slope of l/serum creatinine did not worsen in any patient.(ABSTRACT TRUNCATED AT 250 WORDS)