Insulin-like growth factor I plays a role in regulating erythropoiesis in patients with end-stage renal disease and erythrocytosis

Erythroid progenitor growth, the serum hormones that regulate erythropoiesi s, and the effect of patient's serum on the growth of normal erythroid prog enitors were assessed in eight patients with end-stage renal disease (ESRD) and erythrocytosis, All patients were male and had been on maintenance dia lysis, they had a hematocrit >50% and/or a red blood cell count >6 x 10(12) /L and an arterial oxygen saturation >95%. Four had acquired cystic disease of the kidney (ACDK), and four other non-ACDK patients did not have known causes of secondary erythrocytosis after appropriate investigations and lon g-term follow-up. The methylcellulose culture technique was used to assay t he erythroid progenitor (BFU-E/CFU-E) growth. Serum erythropoietin (EPO) an d insulin-like growth factor I (IGF-I) levels were measured by RIA. Paired experiments were performed to determine the effects of 10% sera from ESRD p atients and control subjects on normal marrow CFU-E growth. The numbers of EPO-dependent BFU-E in marrow and/or blood of patients with ESRD and erythr ocytosis were higher than those of normal controls. No EPO-independent eryt hroid colonies were found. Serum EPO levels were constantly normal in one p atient and elevated in three patients with ACDK; for non-ACDK patients, EPO levels were normal or low in two patients and persistently increased in on e, but fluctuated in the remaining one on serial assays. There was no corre lation between serum EPO levels and hematocrit values. The serum IGF-I leve ls in patients with ESRD and erythrocytosis were significantly increased co mpared with normal subjects or ESRD patients with anemia. We found an inver se correlation between serum EPO and IGF-1 levels. Sera from patients with ESRD and erythrocytosis exhibited a stimulating effect on normal marrow CFU -E growth. The stimulating effect of sera from patients who had a normal se rum EPO level and an elevated IGF-I level could be partially blocked by ant i-IGF-I. The present study suggests that IGF-I plays an important role in t he regulation of erythropoiesis in patients with ESRD and erythrocytosis wh o did not have an increased EPO production.