New Approaches in TransplantationExperimental transplantationDoes Renal Tubular Injury-Induced Local Tissue Hypoxia Involve Post-Transplantation Erythrocytosis?

•The pathogenesis of PTE is not well understood and appears to be multifactorial.•Local tissue hypoxia in peritubular interstitium, which is the place of production of EPO, can induce the development of PTE by increasing renal erythrocytosis production.•HIF-α subunits are oxygen sensitive and increase in hypoxic conditions.•HIF-2α levels did not increase in renal transplant recipients with PTE.•Local tissue hypoxia in renal allograft does not seem to play an important role in the development of PTE.

BackgroundThe pathogenesis of post-transplantation erythrocytosis (PTE) is not well understood and appears to be multifactorial. Our hypothesis in this study was that several factors, including toxicity of calcineurin inhibitor, immunologic factors, and chronic allograft nephropathy, can trigger local tissue hypoxia in peritubular interstitium, which is where production of erythropoietin (EPO) takes place. This local interstitial tissue hypoxia can cause an increase in renal EPO production, which induces the development of PTE.MethodsThis cross-sectional study included 15 renal transplant recipients, in whom polycythemia developed after kidney transplantation, with elevated hematocrit level to >51%. Forty-eight age- and gender-matched renal transplant recipients with normal hematocrit level were included as the renal transplant control group. In addition, 13 age- and gender-matched healthy subjects were also included as the healthy control group. We used urine hypoxia-inducible factor-2 alpha (HIF-2α) levels to evaluate whether there is local tissue hypoxia in renal allograft. HIF-2α levels were measured by double antibody sandwich enzyme-linked immunosorbent assay (ELISA). Serum EPO and insulin-like growth factor-1 (IGF-1) levels were also measured.ResultsHIF-2α levels were significantly lower in the polycythemia group than the other two groups, but there was no significant difference between the healthy control group and the renal transplant control group with regard to HIF-2α levels. There was no significant difference among the 3 study groups in terms of levels of serum EPO and IGF-1.ConclusionLocal tissue hypoxia in renal allograft does not seem to play an important role in the development of PTE.