A case of acute renal failure due to mizoribine-associated uric acid nephropathy
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患者は50歳代女性で, ループス腎炎 (LN ; type Vb) にてステロイド療法中 (プレドニゾロン10mg/日) であった. LNの活動性は落ち着きクレアチニン (Cr) 1.2mg/dL, 尿酸 (UA) 8.0mg/dL台を推移していたが, 平成17年10月中旬にCrが1.8mg/dLに上昇し, 検尿異常 (尿蛋白+, 沈〓赤血球>100/HPF) を認め, LNの活動性再燃を疑いミゾリビン (MZ) 50mg/日が追加された. 服用開始数日後より気分不快, 倦怠感出現し内服を自己中止した. しかし症状は持続し, 乏尿が出現したため, 服薬自己中止2週間後に受診したところ, Cr14.2mg/dL, UA25.1mg/dLと急激な腎機能の悪化を認めた. MZ血中濃度は内服中止後2週間を経ていたが, 0.43μg/mLと検出された. 血液検査および尿所見上 (尿中Cr/尿酸比=1.47), MZの副作用が一因となった急性尿酸性腎症による急性腎不全 (ARF) と診断した. 乏尿性のARFであり, MZおよび尿酸除去を促すため血液透析を計8回施行したところ, 尿量は増加し, 腎機能は回復した. 本症例は進行する腎機能障害とMZ代謝の遷延, 高尿酸血症との間で悪循環が形成された結果, 尿酸性腎症, 乏尿性ARFを発症したと推察された.Keywords:
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Mizoribine
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Heterotopic renal allografts following bilateral nephrectomies were placed in 21 healthy mongrel dogs. One group of 11 dogs received cyclosporine (5 mg/kg/ 24 hr, orally), and 1 group of 10 dogs received cyclosporine and mizoribine (5 mg/kg and 3 mg/kg/24 hr, orally). Body weights, blood cell counts, serum chemistry profiles, serum electrolyte levels, urinalysis with cytology and culture, lymphocyte stimulation assays, immunoglobulin levels, whole blood levels of cyclosporine, and serum levels of mizoribine were followed. At the end of each survival period, necropsy and histopathologic examinations were performed. The mean survival time for the cyclosporine group was 12.8 ± 7 days. The mean survival time for the cyclo-sporine/mizoribine group was 33.6 ± 16.4 days, significantly longer (P=.0006) than the cyclosporine group. Death in the cyclosporine/mizoribine group was attributed to the combined effects of renal allograft rejection and development of a mizoribine-dependent enteritis. Serum levels of mizoribine were greater in the last half of the survival period due to compromised renal excretion of the drug. There were no complications due to infection, myelosuppression, or hepatotoxicity. Combination cyclosporine/mizoribine immunosuppression enhanced canine renal allograft survival in this study. Monitoring serum concentrations of mizoribine is imperative to determine toxic (enteritis) levels. Availability of an intravenous form of mizoribine would facilitate immunoregulation during periods of variable intestinal absorption or renal excretion.
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Immunosuppressive drug
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Mizoribine
Nephrology
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Mizoribine
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Mizoribine
Rapidly progressive glomerulonephritis
Nephrology
Immunoglobulin A
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Abstract Background : The treatment of nephrotic syndrome (NS) has recently made dramatic progress. The ultimate purpose of treatment is that patients can lead a normal, disease‐free life with no adverse effects from treatment. However, clear treatment guidelines remain to be established in the children with frequent relapsing NS (FRNS) and steroid‐resistant NS (SRNS). The frequent use or large dose of steroids may lead to a serious adverse effect. Immunosuppressive drugs including cyclophasphamide and cyclosporin have been used to induce lasting remission, thereby sparing patients from further exposure to steroids. However, these drugs have both acute and chronic side‐effects. Mizoribine is a relatively safe and effective immunosuppressant. The report discusses the role of mizoribine in FRNS and SRNS in children. Methods : The papers in experimental and clinical studies about mizoribine in NS were reviewed. Our experiences of mizoribine were also added. Results : Mizoribine has been reported as an effective and safe drug for patients with FRNS. However, the efficacy of mizoribine has differed among various reports, depending on the dose given. There have yet to be any conclusive reports on the effects of mizoribine in SRNS in children. Conclusions : Better results might be obtained if the doses of mizoribine increased in children with FRNS. When 5 mg/kg was used, no serious adverse effects were seen, therefore this dose may be safe and effective. An investigation of appropriate, effective and safe doses of mizoribine should be examined in the future. In patients with SRNS, large doses of mizoribine of more than 5 mg/kg might be effective, while the combined use of mizoribine and cyclosporin or methylpredonisolone pulse therapy might also be even more effective. Further studies are called for to examine the use of large doses of mizoribine.
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Clinical efficacy
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목적: Methotrexate (MTX)로는 충분한 질병활성억제를 보지 못했거나, 부작용으로 인해 MTX를 사용할 수 없었던 류마티스 관절염 환자에서 mizoribine의 치료효과를 알아보고자 하였다. 방법: Mizoribine (100 mg/day)을 투여 받은 류마티스 관절염 환자 50명을 대상으로 MTX와 mizoribine의 병합 치료군과 mizoribine 단독 치료군으로 나누어 분석하였으며, mizoribine 투여 전과 16주간의 투여 이후 평가된 질병 활성도와 부작용 등을 비교하였다. 결과: 임상지표를 보면 MTX와 mizoribine 병합 치료 군에서 VAS, 압통관절의 수, 종창관절의 수, DAS28이 치료 전에 비해 유의하게 감소하였으나 mizoribine 단독 치료 군에서는 VAS만이 유의한 차이를 보였다. 또한, 검사실 소견에서는 병합 치료 군에서 치료 후 ESR과 CRP가 유의하게 감소하였다. 치료 약제와 관련된 부작용은 위장장애가 가장 많았고, 기타 다른 부작용도 관찰되었지만 대부분 경미하였으며 부작용으로 인해 투약을 중단한 사례는 없었다. 결론: MTX에 충분한 반응을 보이지 않는 류마티스 관절염 환자에서 mizoribine은 비교적 안전한 치료 약제이며, MTX에 효과가 불충분했을 경우 mizoribine를 추가하면 질병활성도 억제에 좀 더 효과적임을 알 수 있었다.
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Journal Article Efficacy of weekly mizoribine pulse therapy in refractory lupus nephritis Get access Eiko Nishi, Eiko Nishi Department of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama 350-8550, Japan Search for other works by this author on: Oxford Academic Google Scholar Hideto Kameda, Hideto Kameda Division of Rheumatology, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan Search for other works by this author on: Oxford Academic Google Scholar Hiroe Ogawa, Hiroe Ogawa Department of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama 350-8550, Japan Search for other works by this author on: Oxford Academic Google Scholar Hayato Nagasawa, Hayato Nagasawa Department of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama 350-8550, Japan Search for other works by this author on: Oxford Academic Google Scholar Hirofumi Takei, Hirofumi Takei Department of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama 350-8550, Japan Search for other works by this author on: Oxford Academic Google Scholar Ayumi Okuyama, Ayumi Okuyama Department of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama 350-8550, Japan Search for other works by this author on: Oxford Academic Google Scholar Takahiko Kurasawa, Takahiko Kurasawa Division of Rheumatology, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan Search for other works by this author on: Oxford Academic Google Scholar Tsuneo Kondo, Tsuneo Kondo Department of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama 350-8550, Japan Search for other works by this author on: Oxford Academic Google Scholar Koji Nishimura, Koji Nishimura Department of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama 350-8550, Japan Search for other works by this author on: Oxford Academic Google Scholar Yuichiro Shirai, Yuichiro Shirai Division of Rheumatology, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan Search for other works by this author on: Oxford Academic Google Scholar ... Show more Ryota Sakai, Ryota Sakai Department of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama 350-8550, Japan Search for other works by this author on: Oxford Academic Google Scholar Tatsuya Ito, Tatsuya Ito Department of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama 350-8550, JapanDepartment of Internal Medicine, Saitama Yorii Hospital, 395 Yodo, Yorii, Ohsato County, Saitama 369-1211, Japan Search for other works by this author on: Oxford Academic Google Scholar Tsutomu Takeuchi, Tsutomu Takeuchi Division of Rheumatology, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan Search for other works by this author on: Oxford Academic Google Scholar Koichi Amano Koichi Amano Division of Rheumatology, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan Correspondence to: Koichi Amano, Department of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama 350-8550, Japan e-mail: amanokoi@saitama-med.ac.jp Search for other works by this author on: Oxford Academic Google Scholar Modern Rheumatology, Volume 23, Issue 1, 1 January 2013, Pages 97–103, https://doi.org/10.3109/s10165-012-0645-6 Published: 01 January 2013 Article history Received: 02 December 2011 Accepted: 22 March 2012 Published: 01 January 2013
Mizoribine
Refractory (planetary science)
Combination therapy
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We treated twelve patients who had previously received DMARDs to no effect with Mizoribine (100mg-150mg) for one year. We then evaluated their clinical findings (Lansbury index) and laboratory data (CRP, RAHA). Mizoribine was effective in 5 patients (41%) and ineffective in 7 patients (59%). The effective group showed an improvement in their Lansbury index four months after starting the treatment (P<0.01).One patient began to feel anacatesthesia after five months and stopped the medication. One week after stopping their symptoms improved.There were no statistical differrences regarding age, morbidity year, class, stage, combination rate of PSL and Mizoribine dose between the effective and ineffective group, although the effective group had a tendency to use Mizoribine more early than the ineffective group.Drug indications note that Mizoribine should be used if DMARDs are ineffective, but it can be administered earlies than this effective, but it can be used more early.
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Mizoribine, a novel immunosuppressive agent developed in Japan, was administered as a monotherapy to a systemic lupus erythematosus (SLE) patient with the clinical symptoms and immunological abnormalities accompanying SLE showing marked improvement. The result of prolonged administration over 22 months in this case showed neither relapse nor side-effects. Reports have been made about mizoribine used concomitantly with steroids in the treatment of SLE; however, there have not been any reports of mizoribine as a monotherapy for SLE being effective. In this case, mizoribine (150 mg/day) was administered without steroids as a monotherapy on a outpatient basis since the patient's condition overall was relatively good and the serious complications of the heart, kidneys, and lungs that accompany SLE were not observed. The results of this treatment showed improvements in alopecia, arthritis, and systemic malaise from about the 4th week after the start of administration, and the clinical symptoms that accompany SLE had completely disappeared in the 8th week. Also, the immunological tests markedly improved. Four months after the start of administration the immunological abnormalities in the anti-DNA antibody, rheumatoid factor, and immune complex were completely corrected. This case showed dramatic improvement in the SLE clinical symptoms and immunological abnormalities with the mizoribine monotherapy as well as the potential for mizoribine monotherapy to maintain a state of remission over the long term.
Mizoribine
Outpatient clinic
Clinical efficacy
Hydroxychloroquine
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