Increased Serum Erythropoietin Level during Azathioprine Treatment in Renal Transplant Recipients

Abstract

One hundred and six renal transplant patients were studied. During the first 12 months after renal transplantation all patients were treated with cyclosporine (Cy) and prednisone. At 12 months after transplantation the patients were randomly allocated to either conventional treatment with azathioprine (Az) and prednisone (group Az) or to continued treatment with Cy and prednisone (group Cy). Serum erythropoietin (s-EPO), glomerular filtration rate (GFR) and hematocrit (Hct) were measured at 12,18 and 24 months after transplantation. s-EPO rose in the group Az from 19 U/l (mean) at 12 months to 28 U/l (p < 0.01) at 18 months and remained elevated at 24 months at 29 U/l compared with baseline level and with healthy subjects without anemia 18 U/l (p < 0.01). There was no significant change in s-EPO in group Cy during the study. The Hct in the two groups was not significantly different. GFR was the same in the two groups at 12 months and after 24 months. In conclusion, a switch from Cy to Az 1 year after renal transplantation results in a sustained rise in s-EPO which may in part represent a compensatory phenomenon to bone marrow suppression.

Thiopurine S-Methyltransferase Genotype Predicts Azathioprine-Induced Myelotoxicity in Kidney Transplant Recipients

“…Previous in vitro investigations involving cyclosporine have demonstrated concentrationdependent inhibition of erythropoietin release and proliferation of hematopoietic stem and progenitor cells (35,38). Azathioprine has been postulated to interfere with erythroid proliferation and erythropoietin receptor expression or interaction resulting in alterations to erythropoietin sensitivity (37). This study identified azathioprine-treated renal transplant patients possessing a nonfunctional TPMT mutant allele with significantly elevated cyclosporine whole blood trough concentrations.…”

“…Cyclosporine has been associated with stimulatory effects on bone marrow and early erythroid progenitors and has shown an inhibitory effect on erythroid progenitors and epoietin secretion (34)(35)(36)(37)(38). Previous in vitro investigations involving cyclosporine have demonstrated concentrationdependent inhibition of erythropoietin release and proliferation of hematopoietic stem and progenitor cells (35,38).…”

Does Erythropoietin Production after Renal Transplantation Depend on the Type of Immunosuppression?

“…After kidney transplantation, red-cell production is related to the ability of the graft to release EPO and the potential of bone marrow progenitor cells to respond to the circulating hormone. Immunosuppres sive drugs used in renal transplantation may affect both processes: azathioprine (Aza) possesses a well-known suppressive effect on the bone marrow and in a recently published paper, Jensen et al [2] suggested that this might cause a compensatory increase in EPO production. Clinical observations as well as in vivo and in vitro experimental studies showed that cyclosporine (CsA) impaired EPO response to hypoxia [3][4][5], On the other side.…”

Use of Recombinant Erythropoietin in a Pregnant Renal Transplant Recipient

“…Studies of serial erythropoietin levels have shown that levels fall during periods of graft rejection, though it is not clear whether the severity of graft rejection correlates with the decrease in level [19]. Some patients prove resistant to rHuEPO therapy following rejection of a graft, with the underlying mechanism possibly involving inflammation in the retained graft, although the precise pathophysiology is not understood [20].…”