Study of mizoribine therapy in elderly patients with membranous nephropathy: comparison with patients not receiving mizoribine

Ito, Takafumi; Mochizuki, Kaori; Oka, Tomohiro; Hanada, Ken-ichi; Tanabe, Kazuaki

doi:10.1007/s11255-014-0850-7

Cited by 4 publications

(5 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, no marked liver dysfunction was recorded. Thus, in agreement with other studies [ 4 – 7 ], our results indicate that MZR is a safe immunosuppressant for long-term use.…”

Section: Discussionsupporting

confidence: 93%

“…However, CyA also has serious adverse effects such as nephrotoxicity and hypertension, and is not suitable for long-term therapy. From this viewpoint, MZR is known not to have serious adverse events and to be beneficial when administered over a long period [ 4 – 7 ].…”

Section: Discussionmentioning

confidence: 99%

“…Although a combination of steroids and immunosuppressants, e.g., alkylating agents [ 2 ] and calcineurin inhibitors [ 3 ], has been recommended by some guidelines for this purpose, the harmful side effects preclude long-term use of these medicines. On the other hand, several studies have shown that a combination of steroids and mizoribine (MZR), one of the purine metabolism inhibitors, is effective in patients with nephrotic syndrome [ 4 – 7 ] as well as transplant recipients without any serious adverse reactions [ 8 ]. MZR is an imidazole nucleotide that exerts selective inhibitory effects on inosine-5-monophosphate dehydrogenase, an enzyme in the de-novo purine nucleoside synthesis system [ 9 , 10 ], which are very similar to those of mycophenolate mofetil (MMF) and result in suppression of T and B lymphocyte proliferation.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Mizoribine therapy combined with steroids and mizoribine blood concentration monitoring for idiopathic membranous nephropathy with steroid-resistant nephrotic syndrome

et al. 2016

View full text Add to dashboard Cite

BackgroundWe designed a prospective and randomized trial of mizoribine (MZR) therapy combined with prednisolone (PSL) for idiopathic membranous nephropathy (IMN) with steroid-resistant nephrotic syndrome (SRNS).MethodsPatients with IMN were divided into 2 groups, and MZR combined with PSL was administered for 2 years. PSL was initially prescribed at 40 mg/day and tapered. MZR was given once-a-day at 150 mg and 3-times-a-day at 50 mg each to groups 1 and 2. Serum MZR concentrations from 0 to 4 h after administration were examined within one month of treatment. The concentration curve and peak serum level (C max) of MZR were estimated by the population pharmacokinetic (PPK) parameters of MZR.ResultsAt 2 years, 10 of 19 patients (52.6 %) in group 1 and 7 of 18 patients (38.9 %) in group 2 achieved complete remission (CR). The time-to-remission curve using the Kaplan–Meier technique revealed an increase in the cumulative CR rate in group 1, but no significant difference between the groups. Meanwhile, there was a significant difference in C max between groups 1 and 2 (mean ± SD: 1.20 ± 0.52 vs. 0.76 ± 0.39 μg/mL, p = 0.04), and C max levels in CR cases were significantly higher than those in non-CR cases. Receiver operating characteristic analysis showed that C max more than 1.1 µg/mL was necessary for CR in once-a-day administration.ConclusionAdministration of MZR once a day is useful when combined with PSL for treatment of IMN with SRNS. In addition, it is important to assay the serum concentration of MZR and to determine C max, and more than 1.1 µg/mL of C max is necessary for CR.

show abstract

“…Moreover, no marked liver dysfunction was recorded. Thus, in agreement with other studies [ 4 – 7 ], our results indicate that MZR is a safe immunosuppressant for long-term use.…”

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Mizoribine therapy combined with steroids and mizoribine blood concentration monitoring for idiopathic membranous nephropathy with steroid-resistant nephrotic syndrome

et al. 2016

View full text Add to dashboard Cite

show abstract

“…It is known that because MZR has a selective inhibitory effect on proliferation of lymphocytes, the rate of side effects is lower than that of other immunosuppressive drugs [ 32 ]. Because MZR in this study was combined, the methylprednisolone pulse was conducted only once, and the total dose of steroids could be reduced considerably without diminishing the treatment effect.…”

Section: Discussionmentioning

confidence: 99%

Comparison of immunosuppressive therapies for IgA nephropathy after tonsillectomy: three-course versus one-course steroid pulse combined with mizoribine

et al. 2015

View full text Add to dashboard Cite

Purpose It has been reported that steroid pulse therapy for IgA nephropathy improves renal prognosis. However, because of the side effects, steroid dose must be restricted to some cases. Treatment effects of steroid on cases already presenting with reduced renal function are unknown. In this study, we performed tonsillectomy in patients with IgA nephropathy and conducted a comparative study about subsequent immunosuppressive therapy. Methods Subjects were patients younger than 70 years of age diagnosed with IgA nephropathy by renal biopsy. Treatment protocols were a single-course steroid pulse combined with mizoribine during a period from August 2006 to June 2010 (Group A; n = 34) and a three-course steroid pulse during a period from July 2010 to March 2013 (Group B; n = 32). Primary end points were excretory amounts of proteinuria, disappearance of proteinuria and hematuria, and exacerbation of renal function.ResultsIn both the groups, proteinuria decreased significantly 12 months after treatment, and no significant difference in alleviation effects on proteinuria was found between groups. eGFR increased significantly 12 months after treatment in Group A, whereas it tended to decrease in Group B. As for the preservation effect on eGFR, Group A showed significantly higher preservation of eGFR. Similar results were shown in the patients whose eGFR at the start of the treatment was less than 60 mL/min/1.73 m2.ConclusionsSingle-course steroid pulse therapy combined with mizoribine was considered to have a protective effect on the renal function in IgA nephropathy, especially accompanying renal dysfunction.

show abstract

“…MZR is widely used in Japan for the treatment of rheumatoid arthritis [ 18 – 20 ], systemic lupus erythematosus [ 21 , 22 ], nephrotic syndrome (NS) [ 23 , 24 ] and IgA nephropathy [ 25 ] as well as after renal transplantation [ 26 ], and is noted for its low incidence of side effects. In addition, several recent studies have shown that a combination of steroids and MZR is effective in patients with membranous nephropathy (MN) [ 27 – 29 ]. In this report, we describe the case of an elderly patient diagnosed with FS during MZR monotherapy prior to the addition of prednisolone for the treatment of MN.…”

Section: Introductionmentioning

confidence: 99%

Fanconi syndrome in an elderly patient with membranous nephropathy during treatment with the immunosuppressant mizoribine

et al. 2022

View full text Add to dashboard Cite

We report on an 80-year-old man diagnosed with Fanconi syndrome induced by mizoribine after 4 weeks of administration to treat membranous nephropathy. Mizoribine is an oral immunosuppressant that inhibits inosine monophosphate dehydrogenase and is widely used in Japan for the treatment of autoimmune diseases and nephrotic syndrome, as well as after renal transplantation. Acquired Fanconi syndrome is often caused by drugs (antibacterial, antiviral, anticancer, and anticonvulsant drugs) and is sometimes caused by autoimmune diseases, monoclonal light chain-associated diseases, or heavy metal poisoning. In our patient, hypokalemia, hypophosphatemia, glucosuria, hypouricemia, and severe proteinuria resolved gradually after discontinuation of mizoribine administration, despite oral administration of prednisolone followed by a single intravenous injection of rituximab. The patient was ultimately diagnosed with Fanconi syndrome induced by mizoribine based on his clinical course and his typical laboratory data with the absence of proximal tubular acidosis. To our knowledge, this is the first report of Fanconi syndrome possibly induced by mizoribine. Although the precise mechanism by which mizoribine induces proximal tubular dysfunction is unknown, we suggest that nephrologists should be aware of the onset of Fanconi syndrome, a rare complication during mizoribine treatment. Supplementary Information The online version contains supplementary material available at 10.1007/s13730-022-00715-0.

show abstract

Study of mizoribine therapy in elderly patients with membranous nephropathy: comparison with patients not receiving mizoribine

Abstract: Elderly patients with MN who respond poorly to PSL treatment may be treated successfully with MZR.

Cited by 4 publications

References 11 publications

Mizoribine therapy combined with steroids and mizoribine blood concentration monitoring for idiopathic membranous nephropathy with steroid-resistant nephrotic syndrome

Mizoribine therapy combined with steroids and mizoribine blood concentration monitoring for idiopathic membranous nephropathy with steroid-resistant nephrotic syndrome

Comparison of immunosuppressive therapies for IgA nephropathy after tonsillectomy: three-course versus one-course steroid pulse combined with mizoribine

Fanconi syndrome in an elderly patient with membranous nephropathy during treatment with the immunosuppressant mizoribine

Contact Info

Product

Resources

About