Increased immunoreactive erythropoietin in serum and kidney extracts

Radioimmunoassay of erythropoietin (epo) was performed upon serum samples and kidney extracts from rats that received intrarenal injections of nickel subsulfide (Ni3S2, 20 mg/rat). Serum epo concentrations were significantly increased from 1 to 4 weeks after Ni3S2 injection; the highest values occurred at 3 weeks, when serum epo in 5 Ni3S2-treated rats averaged 230 mU/ml (range = 94 - 370 mU/ml); for comparison, serum epo in 21 vehicle-treated controls averaged 19 mU/ml (range = less than 14 - 56 mU/ml, P less than 0.01). In kidney extracts of 5 rats killed 3 weeks after Ni3S2 injection, epo concentrations averaged 970 mU/g (range = 210 - 1880 mU/g); for comparison, epo in kidney extracts of 6 controls averaged 99 mU/g (range = 40 - 140 mU/g, P less than 0.005). These radioimmunoassays confirm previous bioassays findings that serum epo concentrations are significantly increased in rats with Ni3S2-induced erythrocytosis. Contrary to bioassay findings, this study demonstrates increased immunoreactive epo concentrations in kidney extracts of Ni3S2-treated rats, suggesting that renal epo in Ni3S2-treated rats occurs in a form that lacks biological activity in vivo.