担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：American College of Physicians  

DOI： 10.7326/aimcc.2022.1003

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: While chronic kidney disease (CKD) is one of the most important contributors to mortality from non-communicable diseases, the number of nephrologists is limited worldwide. Medical cooperation is a system of cooperation between primary care physicians and nephrological institutions, consisting of nephrologists and multidisciplinary care teams. Although it has been reported that multidisciplinary care teams contribute to the prevention of worsening renal functions and cardiovascular events, there are few studies on the effect of a medical cooperation system. METHODS: We aimed to evaluate the effect of medical cooperation on all-cause mortality and renal prognosis in patients with CKD. One hundred and sixty-eight patients who visited the one hundred and sixty-three clinics and seven general hospitals of Okayama city were recruited between December 2009 and September 2016, and one hundred twenty-three patients were classified into a medical cooperation group. The outcome was defined as the incidence of all-cause mortality, or renal composite outcome (end-stage renal disease or 50% eGFR decline). We evaluated the effects on renal composite outcome and pre-ESRD mortality while incorporating the competing risk for the alternate outcome into a Fine-Gray subdistribution hazard model. RESULTS: The medical cooperation group had more patients with glomerulonephritis (35.0% vs. 2.2%) and less nephrosclerosis (35.0% vs. 64.5%) than the primary care group. Throughout the follow-up period of 5.59 ± 2.78 years, 23 participants (13.7%) died, 41 participants (24.4%) reached 50% decline in eGFR, and 37 participants (22.0%) developed end-stage renal disease (ESRD). All-cause mortality was significantly reduced by medical cooperation (sHR 0.297, 95% CI 0.105-0.835, p = 0.021). However, there was a significant association between medical cooperation and CKD progression (sHR 3.069, 95% CI 1.225-7.687, p = 0.017). CONCLUSION: We evaluated mortality and ESRD using a CKD cohort with a long-term observation period and concluded that medical cooperation might be expected to influence the quality of medical care in the patients with CKD.

DOI： 10.3390/jpm13040582

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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）  

BACKGROUND: IgA nephropathy (IgAN) is a major cause of chronic glomerulonephritis worldwide. T cell dysregulation has been reported to contribute to the pathogenesis of IgAN. Methods We measured a broad range of Th1, Th2 and Th17 cytokines in the serum of IgAN patients. We searched for significant cytokines, which were associated with clinical parameters and histological scores in IgAN patients. RESULTS: Among 15 cytokines, the levels of soluble CD40L (sCD40L) and IL-31 were higher in IgAN patients and were significantly associated with a higher estimated glomerular filtration rate (eGFR), a lower urinary protein to creatinine ratio (UPCR), and milder tubulointerstitial lesions (i.e., the early phase of IgAN). Multivariate analysis revealed that serum sCD40L was an independent determinant of a lower UPCR after adjustment for age, eGFR, and mean blood pressure (MBP). CD40, a receptor of sCD40L, has been reported to be upregulated on mesangial cells in IgAN. The sCD40L/CD40 interaction may directly induce inflammation in mesangial areas and may therefore be involved in the development of IgAN. CONCLUSIONS: The present study demonstrated the significance of serum sCD40L and IL-31 in the early phase of IgAN. Serum sCD40L may be a marker of the beginning of inflammation in IgAN.

DOI： 10.3390/jcm12052023

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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）  

Podoplanin (PDPN) is intensely expressed on the podocyte membrane in an evolutionally conserved manner. CLEC-2, the endogenous ligand of PDPN, is highly expressed in platelets and also exists in a soluble form in plasma. Normally, podocytes are sequestered from CLEC-2, but when the glomerular barrier is injured, podocytes gain access to CLEC-2. We tested the effects of CLEC-2 in podocytes in vitro and in vivo. Cultured podocytes treated with Fc-CLEC-2 demonstrated that CLEC-2 induced the dephosphorylation of ezrin, radixin, and moesin (ERM) proteins. Podocytes treated with Fc-CLEC-2 also showed the dissociation of F-actin filaments from PDPN, F-actin degradation, detachment, and round morphology. Next, we perfused normal mouse kidney in vivo with FLAG-CLEC-2. CLEC-2 induced dephosphorylation of ERM and widening of the foot processes of podocytes. Platelets were detected by immunostaining for CD41 in the urine of mice with podocyte injury, indicating that podocytes can encounter platelets when glomeruli are injured. Collectively, these observations suggest that when platelets leak through the injured glomeruli, CLEC-2 from the platelets acts on PDPN in podocytes and induces morphological change and detachment, which may further aggravate podocyte injury. Thus, PDPN on podocytes may work as a leaked-platelet sensor.

DOI： 10.1038/s41598-022-26456-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Although apoptosis of podocytes has been widely reported in in vitro studies, it has been less frequently and less definitively documented in in vivo situations. To investigate this discrepancy, we analyzed the dying process of podocytes in vitro and in vivo using LMB2, a human (h)CD25-directed immunotoxin. LMB2 induced cell death within 2 days in 56.8 ± 13.6% of cultured podocytes expressing hCD25 in a caspase-3, Bak1, and Bax-dependent manner. LMB2 induced typical apoptotic features, including TUNEL staining and fragmented nuclei without lactate dehydrogenase leakage. In vivo, LMB2 effectively eliminated hCD25-expressing podocytes in NEP25 mice. Podocytes injured by LMB2 were occasionally stained for cleaved caspase-3 and cleaved lamin A but never for TUNEL. Urinary sediment contained TUNEL-positive podocytes. To examine the effect of glomerular filtration, we performed unilateral ureteral obstruction in NEP25 mice treated with LMB2 1 day before euthanasia. In the obstructed kidney, glomeruli contained significantly more cleaved lamin A-positive podocytes than those in the contralateral kidney (50.1 ± 5.4% vs. 29.3 ± 4.1%, P < 0.001). To further examine the dying process without glomerular filtration, we treated kidney organoids generated from nephron progenitor cells of NEP25 mice with LMB2. Podocytes showed TUNEL staining and nuclear fragmentation. These results indicate that on activation of apoptotic caspases, podocytes are detached and lost in the urine before nuclear fragmentation and that the physical force of glomerular filtration facilitates detachment. This phenomenon may be the reason why definitive apoptosis is not observed in podocytes in vivo.NEW & NOTEWORTHY This report clarifies why morphologically definitive apoptosis is not observed in podocytes in vivo. When caspase-3 is activated in podocytes, these cells are immediately detached from the glomerulus and lost in the urine before DNA fragmentation occurs. Detachment is facilitated by glomerular filtration. This phenomenon explains why podocytes in vivo rarely show TUNEL staining and never apoptotic bodies.

DOI： 10.1152/ajprenal.00080.2022

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Autophagy is a cellular mechanism involved in the bulk degradation of proteins and turnover of organelle. Several studies have shown the significance of autophagy of the renal tubular epithelium in rodent models of tubulointerstitial disorder. However, the role of autophagy in the regulation of human glomerular diseases is largely unknown. The current study aimed to demonstrate morphological evidence of autophagy and its association with the ultrastructural changes of podocytes and clinical data in patients with idiopathic nephrotic syndrome, a disease in which patients exhibit podocyte injury. The study population included 95 patients, including patients with glomerular disease (minimal change nephrotic syndrome [MCNS], n = 41; idiopathic membranous nephropathy [IMN], n = 37) and 17 control subjects who underwent percutaneous renal biopsy. The number of autophagic vacuoles and the grade of foot process effacement (FPE) in podocytes were examined by electron microscopy (EM). The relationships among the expression of autophagic vacuoles, the grade of FPE, and the clinical data were determined. Autophagic vacuoles were mainly detected in podocytes by EM. The microtubule-associated protein 1 light chain 3 (LC3)-positive area was co-localized with the Wilms tumor 1 (WT1)-positive area on immunofluorescence microscopy, which suggested that autophagy occurred in the podocytes of patients with MCNS. The number of autophagic vacuoles in the podocytes was significantly correlated with the podocyte FPE score (r = -0.443, p = 0.004), the amount of proteinuria (r = 0.334, p = 0.033), and the level of serum albumin (r = -0.317, p = 0.043) in patients with MCNS. The FPE score was a significant determinant for autophagy after adjusting for the age in a multiple regression analysis in MCNS patients (p = 0.0456). However, such correlations were not observed in patients with IMN or in control subjects. In conclusion, the results indicated that the autophagy of podocytes is associated with FPE and severe proteinuria in patients with MCNS. The mechanisms underlying the activation of autophagy in association with FPE in podocytes should be further investigated in order to elucidate the pathophysiology of MCNS.

DOI： 10.1371/journal.pone.0228337

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1155/2019/5432453

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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）  

DOI： 10.1111/nep.13444

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Public Library of Science  

Cystatin C is a cysteine protease inhibitor that is produced by nearly all human cells. The serum level of cystatin C is a stronger predictor of the renal outcome and the risk of cardiovascular events than the creatinine level. The resistive index (RI) on renal Doppler ultrasonography is a good indicator of vascular resistance as well as the renal outcomes in patients with chronic kidney disease (CKD). However, it is unclear whether serum cystatin C is associated with signs of vascular dysfunction, such as the renal RI. We measured the serum cystatin C levels in 101 CKD patients and investigated the relationships between cystatin C and markers of vascular dysfunction, including the renal RI, ankle-brachial pulse wave velocity (baPWV), intima-media thickness (IMT), and cardiac function. The renal RI was significantly correlated with the serum cystatin C level (p &lt
0.0001, r = 0.6920). The serum cystatin C level was found to be a significant determinant of the renal RI (p &lt
0.0001), but not the baPWV, in a multivariate regression analysis. The multivariate odds ratio of the serum cystatin C level for a renal RI of more than 0.66 was statistically significant (2.92, p = 0.0106). The area under the receiver-operating characteristic curve comparing the sensitivity and specificity of cystatin C for predicting an RI of more than 0.66 was 0.882 (cutoff value: 2.04 mg/L). In conclusion, the serum cystatin C level is an independent biomarker associated with the renal RI in patients with CKD.

DOI： 10.1371/journal.pone.0193695

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Hindawi Limited  

Introduction. Trefoil factor family (TFF) peptides are increased in serum and urine in patients with chronic kidney disease (CKD). However, whether the levels of TFF predict the progression of CKD remains to be elucidated. Methods. We determined the TFF levels using peptide-specific ELISA in spot urine samples and performed a prospective cohort study. The association between the levels of urine TFFs and other urine biomarkers as well as the renal prognosis was analyzed in 216 CKD patients (mean age: 53.7 years, 47.7% female, 56.9% with chronic glomerulonephritis, and mean EGFR: 58.5 ml/min/1.73 m2). Results. The urine TFF1 and TFF3 levels significantly increased with the progression of CKD stages, but not the urine TFF2 levels. The TFF1 and TFF3 peptide levels predicted the progression of CKD ≥ stage 3b by ROC analysis (AUC 0.750 and 0.879, resp.)
however, TFF3 alone predicted CKD progression in a multivariate logistic regression analysis (odds ratio 3.854, 95% confidence interval 1.316-11.55). The Kaplan-Meier survival curves demonstrated that patients with a higher TFF1 and TFF3 alone, or in combination with macroalbuminuria, had a significantly worse renal prognosis. Conclusion. The data suggested that urine TFF peptides are associated with renal progression and the outcomes in patients with CKD.

DOI： 10.1155/2018/3024698

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担当区分：筆頭著者   記述言語：英語   出版者・発行元：WILEY  

DOI： 10.1111/nep.12973

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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：KARGER  

Background/Aims: Bleeding is the most common complication after renal biopsy. Although numerous predictors of bleeding have been reported, it remains unclear whether arterial stiffness affects bleeding complications. Method: We performed an observational study of the renal biopsies performed in our division over an approximately 6-year period (May 2010 to May 2016). The clinical and laboratory factors were analyzed to reveal the risk factors associated with bleeding, with a focus on anemia (defined as a &gt;= 10% decrease in hemoglobin [Hb] after biopsy). The brachial-ankle pulse wave velocity (baPWV) was measured to evaluate arterial stiffness. Results: This study included 462 patients (male, n=244; female, n=218). Anemia (defined above) was observed in 54 patients (11.7%). The risk of anemia was higher in women, older patients, and patients with lower serum albumin, lower eGFR and lower diastolic blood pressure after biopsy. We then performed a further analysis of 187 patients whose baPWV data were available. Multivariate analysis revealed that a higher baPWV was an independent risk factor for anemia. ROC analysis for predicting anemia found that a baPWV value of 1839 cm/s had the best performance (AUC 0.689). Conclusion: An increased baPWV may be a more valuable predictor of bleeding than any of the other reported risk factors. (C) 2017 The Author(s) Published by S. Karger AG, Basel

DOI： 10.1159/000477453

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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：JAPAN SOC INTERNAL MEDICINE  

Leptospirosis is frequently associated with acute kidney injury. Some survivors are known to progress to chronic kidney disease due to sustained tubulointerstitial inflammation. We present a case of severe leptospirosis with acute renal failure. Although antibiotic therapy resolved the infection, moderate renal dysfunction remained. A renal biopsy demonstrated marked inflammatory infiltration in the tubules and interstitium. Many of the inflammatory cells were CD68-positive monocytes/macrophages, predominantly M1 phenotype. An intermediate dose of oral corticosteroids normalized the patient's serum creatinine levels. We suggest that corticosteroid therapy may be a therapeutic option for some patients with sustained tubulointerstitial nephritis who survive severe leptospirosis.

DOI： 10.2169/internalmedicine.56.8084

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

Background: A link between IgA nephropathy and Crohn's disease has recently been reported. Other researchers hypothesize that intestine-derived IgA complexes deposit in glomerular mesangial cells, eliciting IgA nephropathy. Intestinal mucosal plasma cells mainly secrete IgA(2). Nevertheless, IgA(1) deposition is strongly implicated as being the primary cause of IgA nephropathy.
Case presentation: A 46-year-old Japanese man developed IgA nephropathy 29 years ago, following tonsillectomy. As a result, a normal urinalysis was obtained. The patient previously suffered Crohn's disease followed by urinary occult blood and proteinuria six years ago. Exacerbation of IgA nephropathy was highly suspected. Therefore a renal biopsy was performed. A diagnosis of exacerbation of IgA nephropathy with mesangial cell proliferation and fibrotic cellular crescent was based upon the pathological findings. The patient exhibited a positive clinical course and eventually achieved a remission with immunosuppressive therapy including prednisolone treatment. Immunostaining for the detection of IgA subtypes was performed on both of his kidney and excised ileum. The results revealed IgA(1) and IgA(2) deposition by submucosal cells in intestine. Furthermore, IgA(1) deposition of mesangial areas in the patient's kidney, indicated an association of IgA(1) with the exacerbation of IgA nephropathy.
Conclusion: This case represents the possibility that the intestine-derived IgA(1) can be the origin of galactose-deficient IgA which is known to cause IgA nephropathy exacerbation.

DOI： 10.1186/s12882-016-0344-1

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担当区分：筆頭著者   記述言語：日本語   出版者・発行元：(一社)日本脈管学会  

腎血管性高血圧はさまざまな疾患を原因とする。今回我々は、潰瘍性大腸炎に腎血管性高血圧を合併した症例を経験した。症例は40歳男性。造影CTと血管造影で右腎動脈の閉塞と側副血行路の発達を認めた。さらに左腎区域動脈と肝動脈の狭小化、両側内腸骨動脈の閉塞と腹部大動脈の一部壁不整がみられた。FDG-PETで大動脈炎症候群は否定的であった。皮疹や結腸粘膜の生検で血管炎の所見は得られず、診断に苦慮した症例であった。(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2014&ichushi_jid=J01422&link_issn=&doc_id=20141212320002&doc_link_id=10.7133%2Fjca.14-00031&url=https%3A%2F%2Fdoi.org%2F10.7133%2Fjca.14-00031&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER INST ULTRASOUND MEDICINE  

Objectives-The aim of this study was to identify the main influencing factor of the shear wave velocity (SWV) of the kidneys measured by acoustic radiation force impulse elastography.
Methods-The SWV was measured in the kidneys of 14 healthy volunteers and 319 patients with chronic kidney disease. The estimated glomerular filtration rate was calculated by the serum creatinine concentration and age. As an indicator of arteriosclerosis of large vessels, the brachial-ankle pulse wave velocity was measured in 183 patients.
Results-Compared to the degree of interobserver and intraobserver deviation, a large variance of SWV values was observed in the kidneys of the patients with chronic kidney disease. Shear wave velocity values in the right and left kidneys of each patient correlated well, with high correlation coefficients (r = 0.580-0.732). The SWV decreased concurrently with a decline in the estimated glomerular filtration rate. A low SWV was obtained in patients with a high brachial-ankle pulse wave velocity. Despite progression of renal fibrosis in the advanced stages of chronic kidney disease, these results were in contrast to findings for chronic liver disease, in which progression of hepatic fibrosis results in an increase in the SWV. Considering that a high brachial-ankle pulse wave velocity represents the progression of arteriosclerosis in the large vessels, the reduction of elasticity succeeding diminution of blood flow was suspected to be the main influencing factor of the SWV in the kidneys.
Conclusions-This study indicates that diminution of blood flow may affect SWV values in the kidneys more than the progression of tissue fibrosis. Future studies for reducing data variance are needed for effective use of acoustic radiation force impulse elastography in patients with chronic kidney disease.

DOI： 10.7863/ultra.33.5.793

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担当区分：筆頭著者   記述言語：日本語   出版者・発行元：(一社)中国腎不全研究会  

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担当区分：筆頭著者   記述言語：日本語   出版者・発行元：(公財)大原記念倉敷中央医療機構倉敷中央病院  

症例は77歳の女性で,10年来の糖尿病歴があった.2008年11月に初めて尿蛋白を指摘され,その後およそ2ヵ月で急速に腎機能が低下した.同時にネフローゼ症候群を合併しており,extracorporeal ultrafiltration method(ECUM)でうっ血が改善した後も,胸水や全身浮腫は残存した.炎症反応の上昇を認めていたが,抗菌薬で改善せず,全身状態から腎生検での診断確定は困難であった.第12病日に下腿の紫斑を認めた.紫斑病性腎炎の合併を強く疑い,ステロイド療法を開始したところ,腎機能,尿蛋白や胸水は速やかに改善した.全身状態が落ち着いた第43病日に腎生検を施行し,糖尿病性腎症に紫斑病性腎炎を合併していることを確認した.糖尿病性腎症に他の腎疾患の合併が疑われる場合には,正確に病態把握し全身状態から総合的に判断して治療をすすめてゆく必要がある.(著者抄録)

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J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

透析液重炭酸濃度の低減によりCO2ナルコーシスを防ぎ血液透析(HD)を継続できた高齢透析患者の2例を報告する。症例1は77歳女性。糖尿病性腎症による慢性腎不全でHD歴5年。HD施行中にCO2ナルコーシスをきたし、HDを中断し非侵襲陽圧換気療法(NPPV)を開始した。次のHDでは透析液重炭酸濃度を30mmol/Lから25mmol/Lに変更したが、HD中にCO2ナルコーシスがみられHDを中断した。重炭酸濃度を22mmol/Lまで低減したところCO2ナルコーシスをきたすことなくHDを継続できた。症例2は76歳女性。ANCA関連腎炎による慢性腎不全でHD歴1年半。HD中にCO2ナルコーシスを認め、HDを中断しNPPVを開始した。その後、透析液重炭酸濃度を22mmol/Lに調節したところHD中にシャント血CO2濃度の増悪をきたすことなくHDを継続できた。2例とも生活活動度の低い、るい痩のある高齢透析患者で慢性の高CO2血症がみられており、呼吸筋力低下による換気障害が考えられた。HD中にCO2ナルコーシスをきたしたが、機序としては、重炭酸負荷により血中CO2は上昇する(HCO3-+H+⇒H2CO3⇒CO2+H2O)がCO2排出障害のため高CO2血症を是正できないことや、急激な重炭酸負荷による呼吸抑制が考えられている。慢性の高CO2血症の症例ではHDによる急速なアルカリ化により呼吸状態が悪化することが懸念される。本症例では透析液重炭酸濃度の低減によりHD中の高CO2血症の増悪は認めず、代謝性アシドーシスの悪化をきたすことなくHDを継続することができた。呼吸性アシドーシスと代謝性アシドーシスの併存例でHD中にCO2ナルコーシスをきたす場合には透析液重炭酸濃度の低減は有用な手段と考える。(著者抄録)

DOI： 10.4009/jsdt.47.209

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その他リンク： https://jlc.jst.go.jp/DN/JALC/10031453553?from=CiNii

記述言語：日本語   出版者・発行元：中国腎不全研究会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本透析医学会  

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記述言語：日本語   出版者・発行元：(一社)日本腎臓学会  

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記述言語：日本語   出版者・発行元：中国腎不全研究会  

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