MTOR INHIBITORS AND MICROCYTIC ANEMIA: EFFECT ON IRON UTILIZATION AND INFLAMMATION AS COMPARED TO TACROLIMUS IN STABLE RENAL TRANSPLANT RECIPIENTS

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 anaemia, iron homeostasis and hepcidin production in stable renal transplant recipients (RTR).

Background: Anaemia is common following renal transplant and mTOR inhibitors have been shown to cause microcytosis in previous studies. Different theorised mechanisms for mTOR inhibitor induced anaemia include the development of a chronic inflammatory state and direct effects on iron homeostasis. There is currently no conclusive evidence for the mechanism behind this common problem.

Methods: A single centre prospective case-control study of 27 adult RTRs with stable allograft function at least one year post transplant was conducted between 2016-2019. RTRs were on stable mTOR dosing (cases, 12/27[44%]) or stable tacrolimus dosing (controls, 15/27[56%]). Baseline demographics, full blood count, renal function, iron studies, hepcidin-25, Interleukin-6 (IL-6) and erythropoietin (EPO) levels were performed.

Results: There were no differences in baseline characteristics (age, gender and allograft function), mean haemoglobin (142 vs 147g/L; p=0.52), mean cell volume (MCV) (88 vs 90fL; p=0.31), transferrin saturations (26 vs 23%;p=0.45), IL-6 (515 vs 315pg/ml;  p=0.21) or hepcidin-25 (4.2 vs 3.3nM; p=0.44) between the groups. Significant differences in mean ferritin (162 vs 86μg/L; p=0.03, mean difference 95%CI 7.95 – 145.5, p=0.03) and EPO (15.9 vs 8.5IU/L; mean difference 95% CI 0.21 – 14.66, p=0.04) were found, with both higher in the mTOR inhibitor group.

Conclusion: Haemoglobin, MCV, IL-6 and hepcidin did not differ between patients treated with mTOR inhibitors or tacrolimus. Higher EPO and ferritin independent of hepcidin-25 in patients with mTOR suggests EPO resistance as an explanation for the anaemia previously demonstrated in patients on mTOR inhibitors.


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.

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