Erythropoiesis after kidney transplantation: the role of erythropoietin, burst promoting activity and early erythroid progenitor cells.
Successful kidney transplantation is followed by the anemia correction due to re-establishment of normal erythropoietin secretion. The possible role of growth factors and cytokines regulating hematopoiesis in this anemia correction are not completely understood. The aim of this study was to investigate the role of erythropoietin and other stimulators in the regulation of erythropoiesis after kidney transplantation. Thirty-six kidney graft recipients with stable graft function for more than 12 months were studied. According to the hemoglobin levels they were divided into: group 1 (12 patients) with normal graft function (sCr = 145.2 +/- 15.8 micromol/l) and normal hemoglobin (12.7+/-0.3 g/dl), group 2 (11 patients) with normal graft function (sCr = 135 +/- 6.5 miromol/l) and posttransplant erythrocytosis (Hb = 18.1 +/- 0.2 g/dl) and group 3 (13 patients) with chronic graft failure (sCr = 223.7 +/- 28.9 micromol/l, range 181-294) and anemia (Hb = 9.0 +/- 0.8 g/dl). Early erythroid progenitors (BFU-E) from peripheral blood, serum immunoreactive Epo and burst promoting activity (BPA) in PHA-LCM prepared from patients' peripheral blood mononuclear cells were measured in all studied patients. The expected Epo for Hb was found normal in patients with normal graft function, 10 times higher in patients with PTE and low in patients with anemia. BPA in PHA-LCM prepared from PTE was increased in 4/6 patients, normal in 4/6 anemic patients, but it was decreased in 5 patients with normal Hb. The mean values were 20.8 +/- 6.3 in PTE group and 16.2 +/- 6.8 in anemic group, and 4.1 +/- 1.8 (at the level of normal controls) in group 1. The number of BFU-E derived colonies was low in most patients with normal hemoglobin and anemia, and increased in most patients with PTE. Spontaneous BFU-E colonies i.e. without Epo added to the cultures were found in 7 of 12 patients with PTE. The mean values of BFU-E showed significant differences between patients with PTE (17.43 +/- 7.3), and patients with normal hemoglobin and anemia (4.39 +/- 1.2 vs. 6.5 +/- 1.1). The results presented suggest that inappropriate Epo secretion depends on the graft function and is the primarily important regulator that caused PTE or anemia after kidney transplantation. Synergistic action of BPA with Epo as well as increased sensitivity of early erythroid precursors to these stimulators could explained sustained erythropoiesis in PTE patients. The high BPA levels in anemic transplant patients with moderate chronic graft failure could be beneficial if rHuEpo treatment is applied in this patient group.
Lezaic
V
V
Department of Nephrology, University Clinical Center, School of Medicine, Beograd, Yugoslavia. visnjal@eunet.yu
Biljanovic-Paunovic
L
L
Pavlovic-Kentera
V
V
Djukanovic
L
L
D000328:Adult; D000740:Anemia / Q000503:physiopathology*; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000097:blood; D015672:Erythroid Precursor Cells / Q000502:physiology*; D004920:Erythropoiesis / Q000502:physiology*; D004921:Erythropoietin / Q000378:metabolism*; D005260:Female; D005293:Ferritins / Q000097:blood; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood; D007501:Iron / Q000097:blood; D016030:Kidney Transplantation; D008297:Male; D011086:Polycythemia / Q000378:metabolism
D006454:Hemoglobins; D007166:Immunosuppressive Agents; D004921:Erythropoietin; D016572:Cyclosporine; D005293:Ferritins; D003404:Creatinine; D007501:Iron