Background: The correction of anemia has been associated with improved kidney allograft outcomes. Recently, erythropoietin was shown to directly suppress alloreactive human T-cells by inhibiting the biochemical signaling pathway of the T-cell receptor, and IL-2 receptor. To examine the potential immunosuppressive role of erythropoietin, we evaluated the incidence of acute cellular rejection in relation to darbepoetin administration in kidney transplant recipients.

Methods: We performed a retrospective review of kidney transplant recipients at our transplant center from 2010 to 2013. All renal transplant recipients over a 36 month period were included. Data involving the administration and dosage of darbepoetin was included in the analysis.

Results: A total of 395 transplant recipients were included in this review. Patient characteristics included: median age 53 (range 18-80); 54% male; 46% Caucasian, 27% African American, 24% Hispanic; 46% received induction therapy. Median post transplant follow up was 3 years (range 1 -5 years). 169 patients received 1 or more doses of darbepoetin. 61 patients received only one dose, 68 patients received 2 to 4 doses, 29 patients received 5 to 9 doses, and 11 patients required 10 or more doses. Requirement of 5 or more doses of darbepoetin was significantly associated with acute cellular rejection (p = 0.003) and occurred more frequently in females (p = 0.004) and African Americans (p < 0.001).

In multivariate logistic regression analysis, patients who received 5 or more dosages of darbepoetin were more likely to develop acute cellular rejection with an odds ratio of 2.44, (95% CI 1.17 – 5.08, p = 0.017). This increased risk was independent of patient age, gender, race, whether they received induction therapy, or type of induction agent used.

Conclusion: Persistent anemia, requiring 5 or more doses of darbepoetin, is an independent predictor of acute cellular rejection in kidney transplant recipients.

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