Jefferies R1, Puttagunta H1, Olynyk J1,2, Krishnan A3, Irish A1, Swaminathan R1
1Fiona Stanley Hospital, Murdoch, Australia, 2Edith Cowan University, Joondalup, Australia, 3Sir Charles Gairdner Hospital, Nedlands, Australia
Aim: To elucidate the role of mTOR inhibitors on iron, hepcidin and erythropoietin-mediated regulation of hemopoiesis in stable renal transplant recipients (RTR).
Background: Impaired hemopoiesis is common following renal transplantation managed using mTOR inhibitors. The mechanisms responsible are uncertain but include direct effects on iron, hepcidin or erythropoietin-mediated hemopoiesis.
Methods: We conducted a single centre prospective case-control study of 26 adult RTR with stable allograft function. RTR received stable mTOR dosing (cases, 11/26[42%]) or stable tacrolimus dosing (controls, 15/26[58%]). Baseline demographics, full blood count, renal function, iron studies, hepcidin-25, Interleukin-6 (IL-6) and erythropoietin (EPO) levels were determined.
Results: There were no differences in age, gender or allograft function. Mean daily sirolimus dose for cases was 1.72mg, with mean trough level of 8.46ng/mL. Mean daily tacrolimus dose for controls was 4.3mg, with mean trough level of 5.8ng/mL. There were no differences in mean hemoglobin (143 vs 147 g/L; p=0.59), MCV (88 vs 90 fL; p=0.35), serum ferritin (150 vs 85.7 μg/L; p=0.06), transferrin saturation (26 vs 23.3%;p=0.46), IL-6 (11 vs 7.02 pg/ml; p=0.14) or hepcidin-25 (3.62 vs 3.26 nM; p=0.76) between the groups. EPO levels were significantly higher in the group receiving mTOR therapy compared with controls (16.8 vs 8.49 IU/L; mean difference 95% CI 0.97 – 15.7, p=0.028).
Conclusion: Higher levels of EPO in the absence of deranged iron biochemistry or hepcidin-25 levels suggest that EPO resistance rather than impaired iron metabolism may contribute to the impaired haemopoiesis previously demonstrated in RTR on mTOR therapy.
Biography:
Reece Jefferies is currently in his final year of basic physician training at Fiona Stanley Hospital in Perth with a keen interest in transplant medicine. He is applying for advanced training in respiratory medicine with the aim of pursuing a career in the field of advanced lung disease, pulmonary hypertension and lung transplant.