A Mutation of the Erythropoietin Receptor Correlates with Improved Function of Deceased-Donor Renal Transplants.

M. Fischereder,¹ S. Friedrich,¹ U. Klingmüller,² T. Kauke,³ T. Breidenbach,⁴ D. Boesebeck,⁵ E. Angelika,⁵ C. Cohen,¹ B. Banas,⁶ M. Guba,⁷ M. Stangl,⁸ B. Krämer,⁹ C. Hugo,¹⁰ K. Lopau,¹¹ M. Stadtler,¹² T. Mone.¹²

¹Medizinische Klinik IV, Klinikum der LMU, Munich, Germany
²DKFZ, Heidelberg, Germany
³Klinikum der LMU, Munich, Germany
⁴Chirurgische Klinik, Klinikum Augsburg, Augsburg, Germany
⁵DSO Bayern, Munich, Germany
⁶Nephrologie, Universitätsklinikum, Regensburg, Germany
⁷Surgery, Klinikum der LMU, Munich, Germany
⁸Surgery, Klinikum der TU, Munich, Germany
⁹Innere Medizin IV, Universitätsklinikum, Mannheim, Germany
¹⁰Innere Medizin, Universität Erlangen, Erlangen, Germany
¹¹Innere Medizin 2, Universitätsklinikum, Würzburg, Germany
¹²OneLegacy, Los Angeles

Meeting: 2017 American Transplant Congress

Abstract number: 437

Keywords: Gene polymorphism, Graft function, Kidney transplantation

Session Information

Session Name: Concurrent Session: Kidney Optimizing Donor/Recipient Selection and Matching

Session Type: Concurrent Session

Date: Tuesday, May 2, 2017

Session Time: 2:30pm-4:00pm

Presentation Time: 3:30pm-3:42pm

Location: E450a

Erythropoietin (Epo) protects renal tubular cells from ischemia/reperfusion injury in experimental transplantation, suggesting a relevant effect of erythropoietin receptor (EPOR) mediated signalling. Previously 6 mutations have been reported within the highly conserved EPOR. We hypothesized, that EPOR mutations modulate delayed graft function (DGF) after renal transplantation.

EDTA blood was collected from deceased organ donors. Demographic data were extracted from the medical record, donor Epo levels analyzed with a commercial assay and EPOR expression quantified in renal transplant biopsies with RT-PCR. EPOR sequencing of selected organ donors with unexpected good ischemia tolerance identified a variation in exon 2. DGF incidence, dialysis treatment post transplantation and transplant function on day 28 were analyzed in 853 deceased organ donors genotyped for this EPOR variant.

DGF incidence was significantly lower for kidneys from organ donors with Epo levels > 70 mU/ml (p=0.038). Transplant biopsies with acute tubular necrosis after renal transplantation exhibited significantly higher expression of EPOR than biopsies from living kidney donors and deceased kidney donors. EPOR sequencing revealed a gene variant G46E in exon 2 of the human EPOR. BaF3 cells stably expressing HA-taged wild-type hEpoR or hEpoR-G46E demonstrated significantly different EPOR phosphorylation after stimulation with Epo. The hEpoR-G46E correlated with fewer dialysis treatments after transplantation (2.42 ± 4.8 vs. 1.1 ± 1.8) and better transplant eGFR on day 28 after transplantation (39.5 ± 22.7 vs. 53.8 ± 23.0 ml/min; p=0.03).

DGF is associated with Epo signalling. Increased donor erythropoietin levels or a novel EPOR mutation correlate with less severe DGF.

CITATION INFORMATION: Fischereder M, Friedrich S, Klingmüller U, Kauke T, Breidenbach T, Boesebeck D, Angelika E, Cohen C, Banas B, Guba M, Stangl M, Krämer B, Hugo C, Lopau K, Stadtler M, Mone T. A Mutation of the Erythropoietin Receptor Correlates with Improved Function of Deceased-Donor Renal Transplants. Am J Transplant. 2017;17 (suppl 3).

To cite this abstract in AMA style:

Fischereder M, Friedrich S, Klingmüller U, Kauke T, Breidenbach T, Boesebeck D, Angelika E, Cohen C, Banas B, Guba M, Stangl M, Krämer B, Hugo C, Lopau K, Stadtler M, Mone T. A Mutation of the Erythropoietin Receptor Correlates with Improved Function of Deceased-Donor Renal Transplants. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/a-mutation-of-the-erythropoietin-receptor-correlates-with-improved-function-of-deceased-donor-renal-transplants/. Accessed November 21, 2024.

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