Anemia after late introduction of sirolimus may correlate with biochemical evidence of a chronic inflammatory state

Background. The responsibility of sirolimus (SRL) for postrenal transplant anemia has never been proven, because SRL is usually combined with myelotoxic drugs, and because of the high incidence of anemia in the posttransplant period. Methods. We retrospectively analyzed anemia in 46 renal transplant recipients, who had been switched from calcineurin inhibitors to SRL for biopsy-proven chronic allograft nephropathy. Results. The mean decrease in hemoglobin (Hb) after SRL introduction was 2.8 g/dl. The 24 patients, whose Hb fell by 2 g/dl, displayed microcytic aregenerative anemia with low serum iron despite high ferritinemia, consistent with anemia of chronic inflammatory states. Fibrinogen and CRP levels increased in these patients after sirolimus introduction. We subsequently focused our study on eight patients without confounding factors of anemia. Anemia improved in all eight after SRL withdrawal. IL6 and TNF alpha at the nadir of anemia were significantly higher than before SRL introduction and after its withdrawal. Decreases in Hb correlated with increases in proinflammatory cytokine levels in a linear regression model. Unchanged serum IL10 levels measured at the nadir of anemia were discordant with the inflammatory state. Conclusions. Late introduction of SRL may induce anemia and correlates with biochemical evidence of a chronic inflammatory state possibly due to defective IL10-dependent inflammatory autoregulation.