NDT Advance Access originally published online on March 17, 2006
Nephrology Dialysis Transplantation 2006 21(8):2337-2338; doi:10.1093/ndt/gfl108
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Changing mizoribine administration from three divided doses to one single dose induced remission of relapsed membranous nephropathy
Email: rinzaruchan{at}yahoo.co.jpSir,
We describe a 75-year-old female with membranous nephropathy who was administered 150 mg of mizoribine in three separate doses of 50 mg. At this time, urinalysis was negative for protein. Membranous nephropathy relapsed in January 2005, and urinalysis was positive for protein. In addition to mizoribine, prednisolone 5 mg/day was started on February 28, and urinalysis was negative for protein once again on and after April 19. However in November, membranous nephropathy relapsed again, and her urine gave a 3+ result for protein on November 8. We advised an increased dosage of prednisolone, but she refused to comply because of the risk of side effects. We, therefore, changed the 150 mg of mizoribine administration from three divided doses to one without increasing the dosage of prednisolone on November 8. By December 6, the membranous nephropathy was in remission and her urine was again negative for protein.
Mizoribine is a novel immunosuppressive agent that selectively inhibits inosine monophosphate dehydrogenase and guanosine monophosphate synthetase, which inhibits T-cell and B-cell proliferation [1]. Mizoribine in the range of 0.1–5 µg/ml inhibits the human mixed-lymphocyte reaction at rates ranging from 36.4 to 62.2%, with 50% inhibition at about 1.0 µg/ml [2], and we previously reported that a blood mizoribine concentration above 1.0 µg/ml is necessary to treat relapsed renal vasculitis [3]. The peak blood mizoribine concentration in our patient was 2.95 µg/ml when the mizoribine (150 mg/day) was consumed in one dose. The peak blood concentration of mizoribine during regular use (two or three smaller doses/day) was <0.8 µg/ml [4]. However, we did not measure this value in our patient under this circumstance. We speculated that the higher optimal blood mizoribine concentration was achieved in our patient by changing the administration protocol, from three divided doses to one dose, thus inducing remission of relapsed membranous nephropathy.
Conflict of interest statement. None declared.
1 Department of Internal Medicine Nagasaki Municipal Medical Center2 Second Department of Internal Medicine3 Division of Renal Care Unit Nagasaki University School of Medicine Nagasaki, Japan
References
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- Sonda K, Takahashi K, Tanabe S, et al. Clinical pharmacokinetic study of mizoribine in renal transplantation patients. Transplant Proc 1996; 28: 3643–3648[Web of Science][Medline]
- Nishioka Y, Horita Y, Tadokoro M, et al. Mizoribine induces remission of relapsed ANCA-associated renal vasculitis. Nephrol Dial Transplant 2005; [Epub ahead of print]
- Kawasaki Y, Hosoya M, Kobayashi S, et al. Oral mizoribine pulse therapy for patients with steroid-resistant and frequently relapsing steroid-dependent nephritic syndrome. Nephrol Dial Transplant 2005; 20: 2243–2247
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