Department of Nephrology, Clinical Center, Skopje, R. Macedonia, Email: maknefpo{at}mt.net.mk
Sir,
Initial reports of treatment of patients with various glomerular diseases with mycophenolate mofetil (MMF) showed that partial or complete remissions of nephrotic proteinuria could be achieved in patients with relapsing minimal change disease, membranous nephropathy and lupus nephritis [1,2]. Since that time, several additional reports have been published about the clinical efficacy of MMF in the treatment of lupus nephritis [3]. In addition, an increasing number of publications have reported favourable responses to MMF in various experimental models of glomerular diseases [4]. All clinical studies published previously comprise only a small number of patients, but they are of particular interest because usually the patients treated with MMF have been resistant to conventional treatment.
We gave MMF 2 g/day for 9 months to eight patients with idiopathic membranous nephropathy, stages IIIIV, as documented by percutaneous renal biopsy and standard histopathological procedures. Three patients were male, five female. They were aged 48.5±3 years, median 50 years. Previous treatment had failed in five of eight patients (three patients had received cyclosporine+steroids, one cyclosporine+steroids+cyclophosphamide and one an alternative use of steroids and chlorambucil). The wash out period was at least 3 months. MMF was the first choice drug in the other three patients with membranous nephropathy and who were type 2 diabetes, only on diet. All patients were nephrotic, and three of eight of them had a slight elevation of serum urea and creatinine levels.
Proteinuria decreased significantly during the treatment (P<0.05), from 4.44±0.74 g/daily at start, to 1.99±0.29 g/day after 3 months, 1.9±0.44 g/day after 6 months and after 9 months. A significant decrease was noted thus after the first 3 months, and proteinuria remained stable after. Plasmaprotein levels increased significantly (P<0.05), at start 42±13.2 g/l, after 3 months 48±10.7 g/l, after 6 months 53±11.8 g/l and after 9 months 59±6.7 g/l. Renal function improved slightly, but not significantly (P>0.05). Serum creatinine levels decreased, at start 107.9±15 µmol/l, after 3 months 99.9±14, after 6 months 97.6±14.5 and after 9 months 86.6±11.6 µmol/l. Serum levels of urea also decreased, at start 9±1.7 mmol/l, after 3 months 7.6±1.2 mmol/l, after 6 months 8.4±1.5 mmol/l, and after 9 months 7.6±1 mmol/l. According to the adverse effects of the drug, we noted joint and muscle aches in one patient, a 58-year-old.
MMF is a specific inhibitor of inosine monophosphate dehydrogenase, which is involved in de novo purine synthesis [1]. It is a suppressor of both T and B cell lymphocyte proliferation and has an antiproliferative action on vascular smooth muscle cells; therefore, MMF is used in acute and chronic graft dysfunction. In experimental models MMF attenuates renal injury by interfering with the accumulation and proliferation of inflammatory cells [1,5]. It also decreases myofibroblast formation and collagen III deposition. The ability of MMF to suppress not only the immune response, but also smooth muscle cell proliferation makes the drug a good candidate for preventing renal fibrosis, as myofibroblasts share many features with vascular smooth muscle cells. Proliferation of tubular cells is also reduced by MMF. This a very important renoprotective effect of the drug because tubular cells play a role in the genesis of renal fibrosis. Preliminary results, including ours, suggest that MMF is effective in several types of glomerulonephritis after conventional therapy had failed. MMF combines two actions: as an immunosuppressive agent it reduces the inflammatory process and interferes with the genesis of fibrosis. MMF is generally well tolerated with few serious side effects; it is a steroid-sparing drug, without nephrotoxicity and adverse haemodynamic and metabolic effects. Future randomized studies including large number of patients will document long-term effectiveness and possible adverse effects [6].
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