Erythropoietin deficiency in hyporeninemia

The association of anemia and hyporeninemic hypoaldosteronism (HRHA) in type 1 diabetes has been described, and erythropoietin deficiency has been proposed as the cause. Subjects with type 1 diabetes with (n = 8) and without HRHA (n = 11) were studied, as were subjects taking angiotensin-converting enzyme inhibitors (ACEIs; n = 10). Renal function and sodium excretion were estimated with a 24-hour urine collection. Values for hemoglobin, hematocrit, serum erythropoietin, and red blood cell volume were determined. HRHA subjects were anemic (hemoglobin, 99 +/- 8 g/L ), and ACEI subjects had lower hemoglobin concentrations (120 +/- 4 g/L) compared with controls (134 +/- 3 g/L; P < 0.001 and P = 0.01, respectively). Also, the red cell mass in patients with HRHA was significantly less than that in controls (14.8 +/- 1.4 v 20.8 +/- 1.1 mL/kg; P = 0.004), indicating that the lower hemoglobin level in HRHA is not attributable to an expansion of extracellular volume. Erythropoietin levels in the HRHA (27% +/- 11% of predicted) and ACEI groups (43% +/- 9% of predicted) were low compared with controls (94% +/- 13% of predicted; P = 0.001 and P = 0.005, respectively). Renal function was greater than the levels at which anemia becomes a clinical feature in all groups, but creatinine clearance was less in the HRHA (63 +/- 12 mL/min/1.73 m2) and ACEI groups (76 +/- 11 mL/min/1.73 m2) compared with controls (123 +/- 9 mL/min/1.73 m2; P < 0.001 and P = 0.004, respectively). The fractional sodium reabsorption was decreased in HRHA (98.7% +/- 0.3%) and ACEI groups (98.7% +/- 0.3%) versus controls (99.4% +/- 0.1%; P = 0.007 and P = 0.01, respectively). Subjects with type 1 diabetes with HRHA had low hemoglobin concentrations that were caused, at least in part, by inappropriately low serum erythropoietin levels.