Erythropoietin resistance as surrogate marker of graft and patient survival in renal transplantation: 3-year prospective multicenter study

Background: Some transplant recipients demonstrate an inadequate response to erythropoiesis-stimulating agents, or so-called erythropoietin (Epo) resistance. The cause is multifactorial. Resistance to EPO may entail a poor prognosis for the graft and the patient, although results in the literature are inconsistent, and long-term follow-up is lacking.

Objective: To evaluate whether the presence of Epo resistance at the beginning of the study was a predictive factor for graft and patient survival.

Materials and methods: From 482 renal transplant recipients (Kidney Disease Outcomes Quality Initiative stage 3-4T) receiving Epo-stimulating agents in the Anemia and Renal Transplantation in Spain study, 101 were selected for the present study. Erythropoietin resistance was defined as a ratio of weekly Epo dosage/hemoglobin concentration>486,94 U/g/dL with a hemoglobin/<11 g/dL. Darbepoetin dosage was calculated in Epo equivalent units, with a 1:200 conversion factor. Patients were grouped as Epo-resistant (ER+) or not Epo-resistant (ER-), to assess whether Epo resistance was predictive of patient and graft survival.

Results: There were no differences in demographic data between the 2 groups except for a higher incidence of vascular, interstitial, and diabetes-related causes of chronic renal failure in the ER+ group. At 3 years posttransplantation, graft survival was 33% in the ER+ group vs 58% in the ER- group (P=.06), and patient survival was 52% in the ER+ group vs 88% in the ER- group (P=.008). Using a Cox regression model, at 3 years, the relative risk of graft failure was 1.96 in the ER+ group (95% CI, 0.93-3.12; P=.07), and of patient death was 3.9 (95% confidence interval, 1.30-11.63; P=.01).

Conclusion: Erythropoietin resistance is an independent risk factor for death after renal transplantation.