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| 1.
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Yamanouchi, Masayuki ; Hoshino, Junichi ; Ubara, Yoshifumi ; Takaichi, Kenmei ; Kinowaki, Keiichi ; Fujii, Takeshi ; Ohashi, Kenichi ; Mise, Koki ; Toyama, Tadashi ; Hara, Akinori ; Kitagawa, Kiyoki ; Shimizu, Miho ; Furuichi, Kengo ; Wada, Takashi ; 原, 章規 ; 古市, 賢吾 ; 清水, 美保 ; 和田, 隆志
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金沢大学医薬保健研究域医学系<br />Background There have been a limited number of biopsy-based studies on diabetic nephropathy, and the
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refore the clinical importance of renal biopsy in patients with diabetes in late-stage chronic kidney disease (CKD) is still debated. We aimed to clarify the renal prognostic value of pathological information to clinical information in patients with diabetes and advanced CKD. Methods We retrospectively assessed 493 type 2 diabetics with biopsy-proven diabetic nephropathy in four centers in Japan. 296 patients with stage 3–5 CKD at the time of biopsy were identified and assigned two risk prediction scores for end-stage renal disease (ESRD): the Kidney Failure Risk Equation (KFRE, a score composed of clinical parameters) and the Diabetic Nephropathy Score (D-score, a score integrated pathological parameters of the Diabetic Nephropathy Classification by the Renal Pathology Society (RPS DN Classification)). They were randomized 2:1 to development and validation cohort. Hazard Ratios (HR) of incident ESRD were reported with 95% confidence interval (CI) of the KFRE, D-score and KFRE+D-score in Cox regression model. Improvement of risk prediction with the addition of D-score to the KFRE was assessed using c-statistics, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results During median follow-up of 1.9 years, 194 patients developed ESRD. The cox regression analysis showed that the KFRE,D-score and KFRE+D-score were significant predictors of ESRD both in the development cohort and in the validation cohort. The c-statistics of the D-score was 0.67. The c-statistics of the KFRE was good, but its predictive value was weaker than that in the miscellaneous CKD cohort originally reported (c-statistics, 0.78 vs. 0.90) and was not significantly improved by adding the D-score (0.78 vs. 0.79, p = 0.83). Only continuous NRI was positive after adding the D-score to the KFRE (0.4%; CI: 0.0–0.8%). Conclusions We found that the predict values of the KFRE and the D-score were not as good as reported, and combining the D-score with the KFRE did not significantly improve prediction of the risk of ESRD in advanced diabetic nephropathy. To improve prediction of renal prognosis for advanced diabetic nephropathy may require different approaches with combining clinical and pathological parameters that were not measured in the KFRE and the RPS DN Classification. © 2018 Yamanouchi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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| 2.
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Kitagawa, Kiyoki ; 北川, 清樹
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取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1654号, 学位授与年月日 : 平成16年12月31日, 学位授与大学 : 金沢大学
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Iwata, Yasunori ; Wada, Takashi ; Yokoyama, Hitoshi ; Toyama, Tadashi ; Kitajima, Shinji ; Okumura, Toshiya ; Hara, Akinori ; Yamahana, Junya ; Nakaya, Izaya ; Kobayashi, Motoo ; Kitagawa, Kiyoki ; Kokubo, Satoshi ; Yoshimoto, Keiichi ; Shimizu, Kazuaki ; Sakai, Norihiko ; Furuichi, Kengo ; Koshino, Yoshitaka ; Takaeda, Chikako ; Takeda, Shinichi ; Takasawa, Kazuya ; Ohta, Satoshi ; Takaeda, Masayoshi ; Kaneko, Shuichi
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金沢大学保健管理センター<br />金沢大学大学院医学系研究科<br />金沢大学附属病院<br />Background: In hemodialysis patients, adynamic bone disease has been
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reported to be closely associated with low levels of parathyroid hormone (PTH) due to exposure to high levels of serum calcium following the administration of calcium carbonate (CaCO3) or vitamin D agents. This study was conducted to clarify the therapeutic effect of a non-calcemic phosphate binder, sevelamer hydrochloride (sevelamer), for hypoparathyroidism in hemodialysis patients with or without diabetes mellitus. Methods: Based on entry criteria, 40 Japanese chronic hemodialysis patients (22 males and 18 females with a mean age of 60.6, 14 diabetic patients and 26 non-diabetic patients) were switched from CaCO3 to sevelamer for 48 weeks. Serum calcium, phosphate, intact (i) PTH and PTH-(1-84) were analyzed. Bone remodeling activity was evaluated by determining intact osteocalcine (iOC), bone-specific alkaline phosphatase (BAP). Results: The switch from CaCO3 to sevelamer significantly decreased the serum levels of calcium, resulting in the elevation of iPTH levels from 31±18 pg/mL to 95±96 pg/mL by 48 weeks. In contrast, serum phosphate levels remained similar to those in patients with CaCO3 treatment. Concomitantly, the levels of BAP and iOC were elevated. Further, these beneficial effects on bone turnover were observed in both diabetic and non-diabetic patients. Conclusion: Sevelamer reduced the calcium concentration and thereby increased PTH levels, resulting in the improvement of markers of bone turnover. The administration of sevelamer is of therapeutic benefit for the improvement of bone remodeling activity even in hemodialysis patients with diabetes. © 2007 The Japanese Society of Internal Medicine.
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| 4.
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Iwata, Yasunori ; Wada, Takashi ; Furuichi, Kengo ; Kitagawa, Kiyoki ; Kokubo, Satoshi ; Kobayashi, Motoo ; Sakai, Norihiko ; Yoshimoto, Keiichi ; Shimizu, Miho ; Kobayashi, Kenichi ; Yokoyama, Hitoshi
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金沢大学医薬保健研究域医学系<br />Objective. KL-6 is reported to be excreted from the lung alveolar and bronchial epithelial cells and
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may be a good marker for monitoring disease activity of interstitial pneumonia. This study was designed to ascertain the clinical significance of serum KL-6 levels in interstitial pneumonia associated with anti-neutrophil cytoplasmic antibody (ANCA)-related vasculitis. Methods. Serum KL-6 levels were determined by an enzyme-linked immunosorbent assay. Patients. We examined 20 healthy subjects, 13 patients with perinuclear (myeloperoxidase, MPO) ANCA-related vasculitis and 12 dermatomyositis (DM)/polymyositis (PM) patients as disease controls in this study. Six out of 13 patients with ANCA-related vasculitis had interstitial pneumonia. Results. Serum levels of KL-6 in ANCA-positive patients with interstitial pneumonia were significantly elevated, while they remained as low as those of healthy subjects in ANCA- positive patients without interstitial pneumonia. Similarly, KL-6 levels in sera were higher in 12 dermatomyositis/polymyositis patients with interstitial pneumonia, while they remained low in DM/PM patients without interstitial pneumonia. Moreover, the elevated serum KL-6 level was reduced during the convalescence induced by glucocorticoid therapy and reflected the disease activity of interstitial pneumonia associated with ANCA-related vasculitis. Conclusion. These data suggest that the measurement of serum KL-6 levels may be a good monitoring system for the diagnosis and follow-up of interstitial pneumonia of patients with ANCA-related vasculitis.
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Iwata, Yasunori ; Furuichi, Kengo ; Kitagawa, Kiyoki ; Hara, Akinori ; Okumura, Toshiya ; Kokubo, Satoshi ; Shimizu, Kazuaki ; Sakai, Norihiko ; Sagara, Akihiro ; Kurokawa, Yukie ; Ueha, Satoshi ; Matsushima, Satoshi ; Kaneko, Shuichi ; Wada, Takashi
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金沢大学医薬保健研究域医学系<br />Objective: Myeloid-derived suppressor cells (MDSCs) have been identified as immunosuppressive cells
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in tumor-related inflammation. However, the pathogenesis of MDSCs for autoimmune disease has not been investigated as yet. The aim of this study was to address whether MDSCs contribute to autoimmune organ injury in lupus-prone mice. Methods: MDSCs were analyzed by flow cytometric staining of CD11b+ GR-1+ in MRL-Faslpr mice. CD4+ T-cell proliferation assay was performed by coculture with CD11b+ GR-1+ splenocytes. The percentage of immunosuppressive cells was examined during disease progression. Expression of chemokine receptor on immunosuppressive cells was analyzed, and chemotaxis assay was performed. Results: CD11b+ GR-1low cells had a suppressive effect on CD4+ T-cell proliferation, which was restored by an arginase-1 inhibitor. CD11b+ GR-1low cells increased in percentage during disease progression in kidney and blood. The number of migrated CD11b+ GR-1low cells increased in the presence of monocyte chemoattractant protein-1/CCL2. Conclusion: We assessed the involvement of CD11b+ GR-1low cells in autoimmune disorder in MRL-Faslpr mice. These cells regulate immunological responses via CCL2/CCR2 signaling. The regulation of immunosuppressive monocytes may provide novel therapeutic strategy for organ damage in autoimmune diseases. © 2010 Japanese Society of Nephrology..
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Kitajima, Shinji ; Sakai, Norihiko ; Furuichi, Kengo ; Tomokage, Miki ; Hara, Akinori ; Kitagawa, Kiyoki ; Sawada-Kitamura, Seiko ; Zen, Yoh ; Nakada, Mitsutoshi ; Kaneko, Shuichi ; Wada, Takashi
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金沢大学医薬保健研究域医学系<br />We described a case of neurosarcoidosis with necrotizing sarcoid granulomatosis in a 22-year-old man
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. Contrast-enhanced brain computed tomography scan and magnetic resonance imaging showed intracerebral multiple nodular lesions. Noncaseating and partial necrotizing granulomas were detected in the specimen resected by neurosurgery. In addition, immunohistochemical examination revealed the expression of angiotensin-converting enzyme in necrotizing granuloma. Thus, these findings were consistent with neurosarcoidosis. Clinical and pathological presentation, immunological features, and treatment modalities of neurosarcoidosis are discussed. © 2010 Japan College of Rheumatology.<br />This is the pre-peer reviewed version of the following article: [Full cite], which has been published in final form at [link to final article].
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Oshima, Megumi ; Kitajima, Shinji ; Toyama, Tadashi ; Hara, Akinori ; Kitagawa, Kiyoki ; Iwata, Yasunori ; Shimizu, Miho ; Nishio, Saori ; Imura, Junko ; Yokoyama, Hitoshi ; Furuichi, Kengo ; Kaneko, Shuichi ; Wada, Takashi
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We herein report a case of spontaneous pregnancy and preterm delivery in a 29-year-old patient with myeloperoxidase-anti
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neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis. Her basal serum creatinine level before pregnancy was 1.4 mg/dL and her urinary protein level was approximately 2 g/day. The proteinuria and hematuria increased during pregnancy, and the patient was admitted to our hospital and treated with prednisolone (PSL). At 27 weeks of gestation, she delivered a live infant weighing 848 g via cesarean section. No relapse of ANCA-associated glomerulonephritis occurred. © 2013 The Japanese Society of Internal Medicine.
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Hara, Akinori ; Wada, Takashi ; Kitajima, Shinji ; Toyama, Tadashi ; Okumura, Toshiya ; Kitagawa, Kiyoki ; Iwata, Yasunori ; Sakai, Norihiko ; Furuichi, Kengo ; Higuchi, Masato ; Kaneko, Shuichi
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金沢大学医薬保健研究域医学系<br />A 42-year-old woman with systemic lupus erythematosus was admitted to our hospital because of severe
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anemia. Her bone marrow was almost normocellular and erythroblasts were nearly absent. Laboratory data showed elevated levels of lactate dehydrogenase and positive findings on Coombs' tests. On the basis of these findings, her anemia was diagnosed as the overlap of pure red cell aplasia with autoimmune hemolytic anemia. Radioimmunoprecipitation assay revealed that her serum was positive for anti-erythropoietin antibodies before therapy. Furthermore, the autoantibodies inhibited proliferation of an erythropoietin-dependent cell line in a dose-dependent manner. Immunosuppressive treatment improved the anemia accompanied with disappearance of the autoantibodies. © 2008 Wiley-Liss, Inc.
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