Effect of mycophenolate mofetil on erythropoiesis in stable renal transplant patients is correlated with mycophenolic acid trough levels

Background. Both mycophenolate mofetil (MMF) and azathioprine (AZA) are imm unosuppressive drugs that inhibit purine synthesis. In theory, MMF selectiv ely inhibits lymphocyte proliferation, while AZA has well-known effects on red blood cells and thrombocytes as well. In renal transplant recipients we replaced CsA therapy by MMF in an attempt to reduce the immunosuppressive load 1 year after kidney transplantation. During this study we observed the effect of MMF on haematological parameters such as haemoglobin (Hb), leuko cytes. and thrombocytes. Methods. One year after kidney transplantation 26 stable patients were conv erted from cyclosporin A (CsA) to MMF (2 g/day). Thereafter, these patients were tapered twice in their MMF dose from 2 g to 1.5 g (4 months after con version) and from 1.5 to 1 g (8 months after conversion) per day. The Hb le vels, leukocyte and thrombocyte counts, and mycophenolic acid (MPA) trough levels were routinely measured. Results. After conversion from CsA to MMF not only creatinine levels and th e number of leukocytes, but also the haemoglobin (Hb) level significantly d ecreased in 21/26 patients (P=0.0004). In eight patients the Hb level dropp ed more than 1 mmol/l (=1.61 g/dl). Only in two of eight patients was an ex planation for blood loss found. The effect on Hb level did not ameliorate a fter the first MMF dose reduction to 1.5 g/day. After tapering the MMF dose to 1 g/day, the Hb approached the pre-conversion level. Not only the MMF d ose but also the mycophenolic acid (MPA) trough level correlated with the H b level. Conclusions. After conversion from CsA to MMF 1 year after kidney transplan tation, a decrease in Hb level and leukocyte count was observed. The MPA tr ough level correlated also with the Hb level. The effect on the Hb level wa s reversible after dose reduction. This finding suggests that MMF exerts a negative effect on erythropoietic cells.