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BACKGROUND: Sirolimus (SRL) has been implicated in the causation of post-transplantation anaemia (PTA). It also induces profound red blood cell (RBC) microcytosis, which is poorly understood. METHODS: We conducted a retrospective study of SRL-induced anaemia and microcytosis mean corpuscular volume (MCV) <80 fl with specific reference to iron homeostasis in 93 renal transplant patients treated with SRL for at least 3 months. RESULTS: While mean haemoglobin (Hb) and use of erythropoiesis-stimulating agents increased on SRL, RBC MCV underwent a significant decline throughout the whole study period of 24 months (P < 0.001) with the percentage of microcytosis rising from 2.2% at the start of SRL therapy to 40.7% after 24 months of therapy. An association between dMCV (MCV change on SRL) and SRL levels was shown at 3, 6, 12 and 24 months post-SRL (P = 0.015, P = 0.037, P = 0.002 and P = 0.001, respectively). Intravenous (IV) iron administration was an independent predictor of dMCV at 12 and 24 months on SRL (P = 0.031 and P = 0.048, respectively). All patients who, after starting SRL and seeing a fall in MCV, then went on to receive IV iron therapy, showed a marked increase in MCV; this did not happen to patients given oral iron therapy. CONCLUSIONS: SRL is associated with mild anaemia, but marked RBC microcytosis-these phenomena are correlated with SRL levels and the use of IV iron. Functional iron deficiency and impaired gastrointestinal absorption of iron seem likely explanations.
Sofroniadou et al. (Wed,) studied this question.