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| 1.
論文 |
論文
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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
概要:
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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論文
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Furuichi, Kengo ; Yuzawa, Yukio ; Shimizu, Miho ; Hara, Akinori ; Toyama, Tadashi ; Kitamura, Hiroshi ; Suzuki, Yoshiki ; Sato, Hiroshi ; Uesugi, Noriko ; Ubara, Yoshifumi ; Hisano, Satoshi ; Ueda, Yoshihiko ; Nishi, Shinichi ; Yokoyama, Hitoshi ; Nishino, Tomoya ; Kohagura, Kentaro ; Ogawa, Daisuke ; Mise, Koki ; Shibagaki, Yugo ; Kimura, Kenjiro ; Haneda, Masakazu ; Makino, Hirofumi ; Matsuo, Seiichi ; Wada, Takashi ; 古市, 賢吾 ; 清水, 美保 ; 原, 章規 ; 遠山, 直志 ; 和田, 隆志
概要:
金沢大学医薬保健研究域医学系<br />Background. The clinical and pathologic manifestations of nephropathy due to type 2 diabetes are div
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erse, but large-scale pathologic studies with long-termobservations are limited. Methods. Kidney biopsies and clinical data of 600 patients with type 2 diabetes were collected retrospectively from 13 centres across Japan. Thirteen pathologic findings (nine glomerular lesions, two interstitial lesions and two vascular lesions) were clearly defined and scored. Results. During the observation period, there were 304 composite kidney events [dialysis, doubling of creatinine or reduction of estimated glomerular filtration rate (eGFR) by half], 31 instances of chronic kidney disease (CKD) G5D, 76 cardiovascular events and 73 deaths. The mean observation period was 72.4 months. The distribution of CKD heat map categories for the 600 patients was 103 green or yellow, 149 orange and 348 red. Even in the cases in the green and yellow category, diffuse lesions (81.6%), polar vasculosis (42.6%) and subendothelial space widening (35.1%) were commonly detected. Cox proportional hazard analysis revealed that the presence of nodular lesions [hazard ratio (HR) 21.1, 95% confidence interval (CI) 5.3-84.6], exudative lesions (HR 5.1, 95% CI 1.3-20.3) and mesangiolysis (HR 7.6, 95% CI 2.0-28.8) in cases in the green and yellow category were associated with significantly great impact on composite kidney events after adjustment for clinical risk factors. Conclusions. This nationwide study on kidney biopsy of 600 cases with type 2 diabetes revealed that pathologic findings (presence of nodular lesions, exudative lesions and mesangiolysis) were strong predictors of kidney events in low-risk patients. © The Author 2017.<br />Embargo Period 12 months
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| 3.
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論文
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Mizushima, Ichiro ; Inoue, Dai ; Yamamoto, Motohisa ; Yamada, Kazunori ; Saeki, Takako ; Ubara, Yoshifumi ; Matsui, Shoko ; Masaki, Yasufumi ; Wada, Takashi ; Kasashima, Satomi ; Harada, Kenichi ; Takahashi, Hiroki ; Notohara, Kenji ; Nakanuma, Yasuni ; Umehara, Hisanori ; Yamagishi, Masakazu ; Kawano, Mitsuhiro ; 水島, 伊知郎 ; 井上, 大 ; 山田, 和徳 ; 和田, 隆志 ; 笠島, 里美 ; 原田, 憲一 ; 中沼, 安二 ; 梅原, 久範 ; 山岸, 正和 ; 川野, 充弘
概要:
金沢大学医薬保健研究域医学系<br />Introduction: Immunoglobulin G4 (IgG4)-related aortitis/periaortitis and periarteritis are vascular
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manifestations of IgG4-related disease. In this disease, the affected aneurysmal lesion has been suspected to be at risk of rupture. In this study, we aimed to clarify the clinical course after corticosteroid therapy in IgG4-related aortitis/periaortitis and periarteritis.Methods: We retrospectively evaluated clinical features, including laboratory data, imaging findings and the course after corticosteroid therapy, in 40 patients diagnosed with IgG4-related aortitis/periaortitis and periarteritis on the basis of periaortic/periarterial radiological findings, satisfaction of the comprehensive diagnostic criteria or each organ-specific diagnostic criteria, and exclusion of other diseases. Results: The patients were mainly elderly, with an average age of 66.4 years and with a marked male predominance and extensive other organ involvement. Subjective symptoms were scanty, and only a small proportion had elevated serum C-reactive protein levels. The affected aorta/artery were the abdominal aortas or the iliac arteries in most cases. Thirty-six patients were treated with prednisolone, and the periaortic/periarterial lesions improved in most of them during the follow-up period. Two (50.0%) of four patients with luminal dilatation of the affected lesions before corticosteroid therapy had exacerbations of luminal dilatation after therapy, whereas none of the twenty-six patients without it had a new appearance of luminal dilatation after therapy. Conclusions: The results of this retrospective multicenter study highlight three important points: (1) the possibility of latent existence and progression of periaortic/periarterial lesions, (2) the efficacy of corticosteroid therapy in preventing new aneurysm formation in patients without luminal dilatation of periaortic/periarterial lesions and (3) the possibility that a small proportion of patients may actually develop luminal dilatation of periaortic/periarterial lesions in IgG4-related aortitis/periaortitis and periarteritis. A larger-scale prospective study is required to confirm the efficacy and safety of corticosteroid therapy in patients with versus those without luminal dilatation and to devise a more useful and safe treatment strategy, including administration of other immunosuppressants. © 2014 Mizushima et al.; licensee BioMed Central Ltd.
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| 4.
論文 |
論文
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Mizushima, Ichiro ; Yamamot, Motohisa ; Inoue, Dai ; Nishi, Shinichi ; Taniguchi, Yoshinori ; Ubara, Yoshifumi ; Matsui, Shoko ; Yasuno, Tetsuhiko ; Nakashima, Hitoshi ; Takahashi, Hiroki ; Yamada, Kazunori ; Nomura, Hideki ; Yamagishi, Masakazu ; Saito, Takao ; Kawano, Mitsuhiro
概要:
Background: In immunoglobulin G4-related kidney disease (IgG4-RKD), focal or diffuse renal cortical atrophy is often obs
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erved in the clinical course after glucocorticoid therapy. This study aimed to clarify the factors related to renal atrophy after glucocorticoid therapy in IgG4-RKD. Methods: We retrospectively evaluated clinical features including laboratory data and computed tomography (CT) findings before and after glucocorticoid therapy in 23 patients diagnosed with IgG4-RKD, all of whom were followed up for more than 24 months. Results: Seventeen patients were men, and six were women (average age 62.0 years). Average follow-up period was 54.9 months. The average estimated glomerular filtration rate (eGFR) at diagnosis was 81.7 mL/min/1.73 m2. All patients had had multiple low-density lesions on contrast-enhanced CT before glucocorticoid therapy, and showed disappearance or reduction of these lesions after it. Pre-treatment eGFR and serum IgE level in 11 patients in whom renal cortical atrophy developed 24 months after the start of glucocorticoid therapy were significantly different from those in 12 patients in whom no obvious atrophy was found at that time (68.9 ± 30.1 vs 93.5 ± 14.1 mL/min/1.73 m2, P = 0.036, and 587 ± 254 vs 284 ± 263 IU/mL, P = 0.008, respectively). Pre-treatment eGFR and serum IgE level were also significant risk factors for renal atrophy development 24 months after the start of therapy with an odds ratio of 0.520 (per 10 mL/min/1.73 m2, 95% confidence interval (CI) 0.273-0.993, P = 0.048) and 1.090 (per 10 IU/mL, 95% CI: 1.013-1.174, P = 0.022), respectively, in age-adjusted, sex-adjusted, serum IgG4 level-adjusted logistic regression analysis. Receiver operating characteristic curve analysis showed that eGFR of less than 71.0 mL/min/1.73 m2 and serum IgE of more than 436.5 IU/mL were the most appropriate cutoffs and yielded sensitivity of 63.6% and specificity of 100%, and sensitivity of 90.9% and specificity of 75.0%, respectively, in predicting renal atrophy development. Conclusions: This study suggests that pre-treatment renal insufficiency and serum IgE elevation predict renal atrophy development after glucocorticoid therapy in IgG4-RKD. © 2016 The Author(s).
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| 5.
図書 |
図書
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Harada, Kenichi ; Ubara, Yoshifumi
概要:
In the literature on IgG4-related urinary tract diseases, reports of cases with involvement of the renal pelvis and uret
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ers are increasing. IgG4-related renal pelvic and ureteral lesions accompany extra-renal organ involvement, including IgG4-related type 1 autoimmune pancreatitis, sialadenitis, and orbital disease, and are characterized by the common pathological features of IgG4-related disease (IgG4-RD), including substantial numbers of IgG4-positive plasma cells, storiform fibrosis, and stenosis in the affected organs. Similar to other mucosal organs affected in IgG4-RD, these inflammatory findings are observed within the fibroadipose tissue in the renal hilum and around the ureters. The urothelial epithelium covering the renal pelvis and ureter is preserved. Nodular lesions such as pseudotumors can also form and it is important to differentiate these from malignant tumors. At present, comprehensive diagnostic criteria that include pathological parameters have been proposed for IgG4-RD; however, obtaining diagnostic findings in small biopsy specimens is often challenging. Therefore, the diagnosis can only be rendered following careful consideration of the patient’s clinical, serologic, radiologic, and pathologic features, including the possibility of involvement in other organs. © Springer Japan 2016.<br />[Book Chapter]
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