担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Clinical and Experimental Nephrology  

Background: Peritoneal dialysis (PD) is essential for patients with end-stage renal disease. Peritoneal fibrosis (PF) is a complex inflammatory, fibrogenic process. No effective treatments are available to prevent these processes. Hepatocyte growth factor (HGF) possesses anti-inflammatory and anti-fibrotic properties. The aim of this study was to analyze whether HGF suppresses MGO-induced peritoneal inflammation and fibrosis in a mouse model. Methods: PF was induced by intraperitoneal (IP) injections of MGO for 14 days. C57/BL/6 mice were divided into three groups: Sham group (only vehicle); Sham + MGO group (PF induced by MGO); and HGF + MGO group (PF mice treated with recombinant human-HGF). PF was assessed from tissue samples by Masson’s trichrome staining. Inflammation and fibrosis-associated factors were assessed by immunohistochemistry and quantitative real-time PCR. Results: MGO-injected mice showed significant thickening of the submesothelial compact zone with PF. Treatment with HGF significantly reduced PM thickness and suppressed the expression of collagen I and III and α-SMA. Expression of profibrotic and proinflammatory cytokines (TGF-β, TNF-α, IL-1β) was reduced by HGF treatment. The number of macrophages, and M1 and M2 macrophage-related markers, such as CD86, CD206, and CD163, was reduced in HGF + MGO mice. Conclusion: HGF attenuates MGO-induced PF in mice. Furthermore, HGF treatment reduces myofibroblast and macrophage infiltration, and attenuates the upregulated expression of proinflammatory and profibrotic genes in peritoneal tissues. HGF might be an effective approach to prevent the development of PF in patients undergoing PD.

DOI： 10.1007/s10157-021-02067-y

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PubMed

記述言語：日本語   出版者・発行元：Scientific Reports  

Chronic kidney disease (CKD) is a risk factor for end-stage renal disease and contributes to increased risk of cardiovascular disease morbidity and mortality. We aimed to develop a risk prediction score and equation for future CKD using health checkup data. This study included 58,423 Japanese participants aged 30–69 years, who were randomly assigned to derivation and validation cohorts at a ratio of 2:1. The predictors were anthropometric indices, life style, and blood sampling data. In derivation cohort, we performed multivariable logistic regression analysis and obtained the standardized beta coefficient of each factor that was significantly associated with new-onset CKD and assigned scores to each factor. We created a score and an equation to predict CKD after 5 years and applied them to validation cohort to assess their reproducibility. The risk score ranged 0–16, consisting of age, sex, hypertension, dyslipidemia, diabetes, hyperuricemia, and estimated glomerular filtration rate (eGFR), with area under the curve (AUC) of 0.78 for the derivation cohort and 0.79 for the validation cohort. The CKD incidence gradually and constantly increased as the score increased from ≤ 6 to ≥ 14. The equation consisted of the seven indices described above, with AUC of 0.88 for the derivation cohort and 0.89 for the validation cohort. We developed a risk score and equation to predict CKD incidence after 5 years in Japanese population under 70 years of age. These models had reasonably high predictivity, and their reproducibility was confirmed through internal validation.

DOI： 10.1038/s41598-023-32279-z

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PubMed

記述言語：日本語   出版者・発行元：CEN case reports  

A 52-year-old woman had been found to have hematuria at her annual checkup 5 years in a row. She hoped to donate her kidney to her husband, so we performed a percutaneous kidney biopsy at our department. It was difficult for us to detect apparent abnormalities under a light microscopic examination, and she was determined to meet the eligibility criteria for living kidney transplantation. However, the sample for electron microscopy was not evaluated before kidney donation. She subsequently underwent living kidney transplantation as a donor. A 1-h biopsy revealed swelling and obvious vacuolation of the glomerular podocytes, which were characteristic of Fabry disease. Her medical history and examinations were reviewed. No findings or episodes were observed. Pre-donation electronmicroscopy revealed numerous zebra bodies in the podocytes. A definite diagnosis of heterozygous Fabry disease was made based on the GLA gene mutation despite the normal range of leukocyte α-Gal A activity. Based on the pathological deposition of GL-3, chaperone therapy was initiated to suppress the progression of organ damage. In this case, we could not confirm a diagnosis of Fabry disease despite performing a renal biopsy prior to kidney donation. Kidney donor candidates may sometimes have factors that cannot be assumed based on medical or family history. Thus, it is important to perform a renal biopsy before kidney donation when necessary, and to always conduct a detailed evaluation including electron microscopy.

DOI： 10.1007/s13730-020-00510-9

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PubMed

記述言語：英語   出版者・発行元：シュプリンガー・ジャパン(株)  

症例は52歳女性で、夫が糖尿病性腎症のため10年前から血液透析を受けており、腎移植ドナーを希望していた。しかし、健診にて血尿が指摘されたことから、腎機能の精査目的に当院を紹介された。臨床検査で蛋白尿やアルブミン尿は認められず、CTでは両腎ともサイズは正常で形状にも異常はみられなかった。血尿の原因精査目的に経皮的腎生検を施行した。光顕所見では7個のみ糸球体が検出され硬化はみられず、潜在性の異常が検出されなかったため、本例をドナーとする生体腎移植を行った。免疫抑制剤にはバシリキシマブ、ステロイド、タクロリムス、ミコフェノール酸モフェチルを用い、移植を受けた夫は良好なグラフト機能を得て退院となった。しかし、生検にて糸球体足細胞の腫脹と明らかな空胞形成が認められ、この時点で初めてFabry病が疑われた。改めて精査したところ、白血球α-Gal A活性は正常範囲内にあったものの、足細胞に多数のゼブラ体がみられFabry病に矛盾しない所見であり、GLA遺伝子解析をもとにヘテロ接合型Fabry病と確定診断を下した。ミガーラスタット投与を開始し、症状は徐々に改善した。

出版者・発行元：Renal Replacement Therapy  

DOI： 10.1186/s41100-020-0257-0

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総ページ数：96   担当ページ：43-47   記述言語：日本語

記述言語：日本語 著書種別：学術書

記述言語：日本語   出版者・発行元：(株)医学出版  

記述言語：日本語