NDT Advance Access originally published online on June 2, 2007
Nephrology Dialysis Transplantation 2007 22(9):2726-2727; doi:10.1093/ndt/gfm340
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Effective treatment of four consecutive idiopathic membranous nephropathy patients
Email: matsumoto16{at}aol.comSir,
Idiopathic membranous nephropathy (IMN) is a common cause of nephrotic syndrome in adults. The course of this disorder is often benign; however, the disease progresses to end-stage renal failure at 10 years, in approximately one-third of untreated patients [1]. Although several therapeutic regimens, including corticosteroids and other immunosuppressive drugs, have been studied, their efficacy is highly debated. Thus, new drugs or regimens with a higher efficacy and fewer side effects are urgently required for treating high-risk IMN patients [2], such as those with persistent high-grade proteinuria. We previously reported the effects of treatment with mizoribine followed by low-dose prednisone in four IMN and nephrotic syndrome patients [3]. Mizoribine inhibits purine nucleoside synthesis [4], and it is administered to patients after kidney transplantation in Japan, because of its fewer side effects.
Unfortunately, this regimen has not been popular, and additional reports have not been published. To draw attention to the true efficacy of our regimen, we report here four consecutive patients with newly diagnosed IMN and nephrotic syndrome.
From 2004 to 2005, four patients visited our Nephrology Department with lower extremity oedema. Each patient exhibited nephrotic syndrome without elevated creatinine concentrations; renal biopsy revealed IMN. These patients neither had any systemic illness nor had they received any immunosuppressive therapy. Hypertension was treated with a calcium channel blocker and/or an angiotensin receptor blocker, and furosemide was administered to control the oedema. After 2 months of observation without any other treatment, their serum albumin levels were 2.8–3.0 mg/dl and the urinary protein-to-creatinine ratio (P/C), which is closely correlated to daily protein excretion [5], ranged from 4.1 to 8.0 g/g. Mizoribine was started at a dose of 150 mg/day. After 2 months of mizoribine monotherapy, urinary protein excretion did not decrease in any patient. Therefore, 20 mg/day prednisone was combined with 150 mg/day mizoribine. The P/C ratio in each patient dropped dramatically within 1 month and decreased to 
0.4 g/g within 1 year of this combination therapy (Table 1); during this period, both the agents were tapered gradually. Hypoalbuminaemia was also restored to normal levels (>4.0 mg/dl) at 2–8 months after the combination therapy. We would like to emphasize that in IMN treatment, low-dose prednisone can have a beneficial effect after an initial isolated mizoribine treatment, which may form the base for prednisone therapy. The benefit of this combination therapy appear to outweigh the risks of immunotherapy.
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Conflict of interest statement. None declared.
Department of Nephrology
Shizuoka City Hospital
References
- Schieppati A, Mosconi L, Perna A, et al. Prognosis of untreated patients with idiopathic membranous nephropathy. N Engl J Med (1993) 329:85–89.
[Abstract/Free Full Text] - Pei Y, Cattran D, Greenwood C. Predicting chronic renal insufficiency in idiopathic membranous glomerulonephritis. Kidney Int (1992) 42:960–966.[Web of Science][Medline]
- Matsumoto Y, Amano I. Effective treatment of idiopathic membranous nephropathy. Nephron (2000) 86:507–508.[CrossRef][Web of Science][Medline]
- Mizuno K, Tsujino M, Takada M, et al. Studies on bredinin. I. Isolation, characterization and biological properties. J Antibiot (1974) 27:775–782.[Medline]
- Ginsberg JM, Chang BS, Matarese RA, et al. Use of single voided urine samples to estimate quantitative proteinuria. N Engl J Med (1983) 309:1543–1546.[Abstract]
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