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 Transplantation  

Introduction: Histopathological findings of chronic active T-cell-mediated rejection (CA-TCMR) have been reported to potentially improve with treatment. However, whether this improvement is associated with a better renal prognosis remains unclear. This study was performed to analyze the impact of the histological response to therapy on kidney allograft survival in patients with CA-TCMR. Methods: The data of patients diagnosed with CA-TCMR between January 2018 and May 2023 were retrospectively reviewed. A composite graft endpoint was defined as a two-fold increase in the serum creatinine level or the development of end-stage kidney disease. Results: Thirty-seven patients with CA-TCMR underwent 46 follow-up biopsies. Eleven patients who were diagnosed with CA-TCMR at the last biopsy were classified as the persistent group, while the remaining 26 patients were classified as the transient group. Both before and after treatment, there were no significant changes in serum creatinine, estimated glomerular filtration rate, or proteinuria in either group. However, the transient group showed a significant reduction in interstitial fibrosis and tubular atrophy without a specific etiology (IFTA). This improvement was attributed to better histopathological Banff scores after treatment. Patients with persistent CA-TCMR had significantly worse graft survival than those with transient CA-TCMR (p = 0.002), even after adjusting for significant clinical factors (hazard ratio: 11.4; 95% CI: 1.1–120.0; p = 0.043). Conclusion: Our findings suggest that the persistence of histopathologic evidence of CA-TCMR after treatment is a significant risk factor for allograft loss compared with transient CA-TCMR.

DOI： 10.1111/ctr.70011

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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：一般社団法人 日本動脈硬化学会  

Aims: Diabetic kidney disease is a major vascular complication in patients with diabetes mellitus (DM). However, the association between the hemoglobin (Hb)A1c levels, notably the prediabetic levels, and renal pathological changes remains unclear. We investigated the association between the HbA1c levels and renal arteriolar lesions in subjects without any apparent kidney dysfunction using a living kidney donor cohort. Methods: Between January 2006 and May 2016, 393 living kidney donors underwent a "zero-time" biopsy at Kyushu University Hospital. The patients were divided into four groups (HbA1c levels ＜5.6%, 5.6%–5.7%, 5.8%–6.4%, and ≥ 6.5%, or diagnosed with DM [DM group]). Renal arteriolar hyalinization and wall thickening were assessed using semi-quantitative grading. We then investigated the association between the HbA1c levels and renal pathological changes. Results: 158 (40.2%) patients had arteriolar hyalinization and 148 (37.6%) showed wall thickening. A significant correlation was observed between the HbA1c levels and wall thickening (p for trend ＜0.001). An elevated HbA1c level was significantly associated with wall thickening according to a multivariable logistic analysis in subjects with HbA1c levels of 5.6%–5.7% and 5.8%–6.4%, and the DM group, compared with those with HbA1c levels of ＜5.6% (odds ratio [OR], 1.91; 95% confidence interval [CI]: [1.03–3.54] for 5.6%–5.7%, OR, 1.96; 95% CI: [1.09–3.53] for 5.8%–6.4%, and OR, 2.86; 95% CI: [0.91–9.01] for the DM group), whereas arteriolar hyalinization did not increase within the nondiabetic HbA1c levels. Conclusions: Elevated high-normal HbA1c levels are considered to be independent risk factors for arteriolar wall thickening. Subclinical renal arteriolar sclerosis may develop in patients with prediabetic HbA1c levels.

DOI： 10.5551/jat.64236

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記述言語：英語   出版者・発行元：(一社)日本動脈硬化学会  

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 Kidney Journal  

Background. Phospholipase A2 receptor (PLA2R) is a major target antigen in idiopathic membranous nephropathy (MN). Anti-PLA2R antibodies are mainly of the immunoglobulin G (IgG) subclass IgG4, although other IgG subclass depositions in glomeruli may also be detected. However, the importance of the subclass of the IgG deposit has not been proven. Thus we investigated clinical findings from patients with idiopathic MN in relation to glomerular PLA2R deposition and IgG subclass. Methods. We enrolled 132 Japanese patients with biopsy-proven idiopathic MN in a multicentre retrospective observational study. We investigated the complete remission rate as the primary outcome and the development of end-stage kidney disease (ESKD) as the secondary outcome in relation to glomerular PLA2R deposition. Moreover, we evaluated prognostic factors, including glomerular IgG subclass, in the PLA2R-positive group. Results. The percentage of cases with glomerular PLA2R deposition was 76.5% (n = 101). The first complete remission rate of the PLA2R-positive group was worse than that of the PLA2R-negative group (logrank test P < .001). ESKD incidence did not significantly differ between the glomerular PLA2R-negative and PLA2R-positive MN groups (logrank test P = .608). In the PLA2R-positive group, higher PLA2R intensities and IgG2 staining were associated with a poorer first complete remission rate (logrank test P < .001 and P = .032, respectively). Cox proportional hazards analysis also showed that strong PLA2R deposition and positive IgG2 staining were significantly associated with a failure to reach complete remission [hazard ratio 2.09 (P = .004) and 1.78 (P = .030), respectively]. Conclusions. Our results suggest that intense glomerular PLA2R and IgG2 positivity predict a poor proteinuria remission rate in idiopathic MN.

DOI： 10.1093/ckj/sfae104

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記述言語：英語   出版者・発行元：CEN Case Reports  

DOI： 10.1007/s13730-024-00887-x

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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：Transplantation Proceedings  

Background: Perivascular aggregates (PVAs) often occur in kidney allografts; however, their significance needs to be re-evaluated in light of changes in the concept and criteria of allograft rejection. Methods: We reviewed 1-year protocol biopsies in 258 patients with kidney transplants to identify PVAs and concurrent pathology based on the Banff 2017 classification, including revised criteria for chronic active T-cell mediated rejection (CA-TCMR). We investigated the incidence of PVA, concurrent allograft lesions, diagnosis, and graft survival. No prisoners were used in this study, and no participants were coerced or paid. Results: We identified PVA in 81 biopsies (31.4%). The incidence of previous rejection (32.1% vs 12.4%, P= .0003) and total inflammation (1.3 ± 0.8 vs 0.6 ± 0.8, P < .0001), inflammation (0.7 ± 0.8 vs 0.2 ± 0.5, P < .0001), inflammation in the area of interstitial fibrosis and tubular atrophy (1.3 ± 1.2 vs 0.7 ± 0.9, P < .0001), tubulitis (1.4 ± 1.1 vs 0.6 ± 0.9, P < .0001), and interstitial fibrosis scores (1.2 ± 0.9 vs 0.9 ± 0.9, P= .01) were higher in PVA-positive compared with patients with PVA-negative. Diagnoses in the PVA-positive group revealed no rejection in 49.4%, CA-TCMR in 21.0%, borderline changes in 18.5%, and acute TCMR in 6.2%. CA-TCMR was more frequent in patients with PVA-positive (21.0% vs 4.0%, P < .0001). Graft survival was similar in both groups among all patients, no-rejection, any type of rejection, and CA-TCMR subgroups. Conclusions: PVAs occur heterogeneously and are associated with previous rejection or concurrent CA-TCMR. The prognostic significance of PVAs in kidney transplantation is inconclusive, and further investigations are needed.

DOI： 10.1016/j.transproceed.2024.01.012

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記述言語：英語   出版者・発行元：Journal of Allergy and Clinical Immunology  

Background: IgG4-related disease (IgG4-RD), an example of a type I immune disease, is an immune-mediated fibrotic disorder characterized by dysregulated resolution of severe inflammation and wound healing. However, truly dominant or pathognomonic autoantibodies related to IgG4-RD are not identified. Objective: We sought to perform single-cell RNA sequencing and T-cell receptor and B-cell receptor sequencing to obtain a comprehensive, unbiased view of tissue-infiltrating T and B cells. Methods: We performed unbiased single-cell RNA-sequencing analysis for the transcriptome and T-cell receptor sequencing and B-cell receptor sequencing on sorted CD3+ T or CD19+ B cells from affected tissues of patients with IgG4-RD. We also conducted quantitative analyses of CD3+ T-cell and CD19+ B-cell subsets in 68 patients with IgG4-RD and 30 patients with Sjögren syndrome. Results: Almost all clonally expanded T cells in these lesions were either Granzyme K (GZMK)-expressing CD4+ cytotoxic T cells or GZMK+CD8+ T cells. These GZMK-expressing cytotoxic T cells also expressed amphiregulin and TGF-β but did not express immune checkpoints, and the tissue-infiltrating CD8+ T cells were phenotypically heterogeneous. MKI67+ B cells and IgD−CD27−CD11c−CXCR5− double-negative 3 B cells were clonally expanded and infiltrated affected tissue lesions. GZMK+CD4+ cytotoxic T cells colocalized with MKI67+ B cells in the extrafollicular area from affected tissue sites. Conclusions: The above-mentioned cells likely participate in T-B collaborative events, suggesting possible avenues for targeted therapies. Our findings were validated using orthogonal approaches, including multicolor immunofluorescence and the use of comparator disease groups, to support the central role of cytotoxic CD4+ and CD8+ T cells expressing GZMK, amphiregulin, and TGF-β in the pathogenesis of inflammatory fibrotic disorders.

DOI： 10.1016/j.jaci.2023.11.916

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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：Transplantation Proceedings  

Background: This study aimed to examine the outcomes of kidney retransplantation in patients with allograft failure at Kyushu University. Methods: We reviewed data from 1043 consecutive patients (including 1001 in a first kidney transplantation [KT] group and 42 in a second KT group) who had undergone KT alone at our institution between January 2008 and September 2022. We also studied immunologic risks and outcomes of patients who had undergone preoperative testing for KT at Kyushu University during the same period. Results: No patient received more than 2 transplants. Donor-specific anti-HLA antibody (DSA) had been detected in a greater percentage of patients in the second KT group than in the first (31% vs 11%, respectively; P < .001). There were no significant differences in 5-year death-censored/overall graft survival rates, rates of surgical complications, or incidence of delayed graft function between the groups. During the study period, significantly more candidates for second than first KT were rejected for this procedure because of their high immunologic risk (20% vs 2%, P < 001). Seven of the 42 patients in the second KT group required the removal of the primary graft during the second transplantation. Conclusion: There is a higher percentage of patients whose DSA has been detected among patients undergoing retransplantation after allograft failure than among those receiving first KTs, which often leads to remaining on the waiting list in the former group. However, if the immunologic risk is within acceptable limits, the graft survival for retransplantation is not inferior to that of a first KT.

DOI： 10.1016/j.transproceed.2024.01.053

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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：Nephrology Dialysis Transplantation  

Background: Epidemiological studies have identified smoking as an independent risk factor for development of chronic kidney disease. However, the early renal pathological lesions have not been clearly elucidated. Methods: We investigated time-zero biopsy specimens from 547 living kidney donors and evaluated the relationships between smoking and renal histological changes, including arteriolar hyalinization, intimal thickening of small-medium arteries, global glomerulosclerosis, and interstitial fibrosis and tubular atrophy (IF/TA). Results: A total of 199 subjects (36.4%) had smoking history; 92 (16.8%) and 107 (19.6%) subjects had <20 pack-years and ≥20 pack-years of smoking, respectively. Cumulative smoking dose was significantly associated with prevalence of arteriolar hyalinization: the multivariable-adjusted odds ratio (OR) per 20 pack-year increase was 1.50 (95% confidence interval 1.15-1.97). The ORs for smokers with <20 pack-years and ≥20 pack-years versus never-smokers were 1.76 (1.01-3.09) and 2.56 (1.48-4.44), respectively. Smoking was also associated with prevalence of >10% global glomerulosclerosis: the OR per 20 pack-year increase was 1.24 (0.96-1.59). The ORs for smokers with <20 pack-years and ≥20 pack-years versus never-smokers were 1.50 (0.98-2.78) and 2.11 (1.18-3.79), respectively. The ORs for these pathological changes increased significantly depending on cumulative smoking dose. Intimal thickening of small-medium arteries and IF/TA were not associated with smoking status. The prevalence of arteriolar hyalinization remained higher in patients with ≥10 years since smoking cessation than in never-smokers [OR 2.23 (1.03-4.83)]. Conclusions: Subclinical pathological injury caused by smoking is potentially associated with renal arteriolar hyalinization and glomerular ischaemia.

DOI： 10.1093/ndt/gfad124

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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：Clinical and Experimental Nephrology  

BACKGROUND: Hypertriglyceridemia is increasingly considered a residual risk of cardiovascular disease in patients with chronic kidney disease (CKD). Pemafibrate-a novel selective peroxisome proliferator-activated receptor alpha modulator and a new treatment for hypertriglyceridemia in CKD patients-is reported to have fewer side effects in CKD patients than other fibrates. Appropriate control of hypertriglyceridemia can be expected to improve renal prognosis. However, data on the renal protective effect of pemafibrate are limited. This study aims to evaluate the effectiveness of pemafibrate on urinary protein excretion in CKD patients. METHODS: The Pemafibrate, open-label, Randomized cOntrolled study to evaluate the renal protective eFfect In hyperTriglyceridemia patients with Chronic Kidney Disease (PROFIT-CKD) study is an investigator-initiated, multi-center, open-label, parallel-group, randomized controlled trial. Participants are outpatients with hypertriglyceridemia aged 20 years and over, who have received the care of a nephrologist or a diabetologist for more than 3 months. Inclusion criteria include the following: proteinuria (urine protein/creatinine ratio of ≥ 0.15 g/gCr) within three months before allocation, and hypertriglyceridemia (triglycerides ≥ 150 mg/dL and < 1,000 mg/dL) at allocation. In the treatment group, pemafibrate is added to conventional treatment, while conventional treatment is continued with no additional treatment in the control group. Target patient enrollment is 140 patients. The primary endpoint is the change from baseline in the logarithmic urine protein/creatinine ratio at 12 months after study start. CONCLUSION: This study will provide new findings on the renal protective effect of pemafibrate in CKD patients. CLINICAL TRIAL REGISTRATION: This clinical trial was registered at the University Hospital Medical Information Network (UMIN) Center (UMIN-CTR: UMIN000042284).

DOI： 10.1007/s10157-023-02322-4

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記述言語：英語   出版者・発行元：(一社)日本腎臓学会  

記述言語：日本語   出版者・発行元：一般社団法人 日本移植学会  

<p>【背景】腎移植後の慢性活動性T細胞性拒絶反応（CA-TCMR）は腎予後が不良だと考えられている。一方で治療によりその病理所見が改善する可能性についてはすでに報告した。しかし、病理所見の改善が腎予後の改善につながるかは不明であった。【対象・方法】2018年から2022年2月までに生検でCA-TCMRと診断され、治療後確認生検をおこなった32例を検討した。【結果】32例のうち病理所見上、B/CまたはNormalまで改善したものをResponder群（n=20）、そうでないものをNon-responder群（n=12）とした。Responder群ではti, i-IFTA, t-IFTAのスコアは治療前と比べ有意に改善していたのに対しNon-responder群では改善は見られなかった。血清クレアチニンの倍加、末期腎不全を複合アウトカムとした場合、Non-responder群に観察期間中に3例認めたのに対して、Responder群では認めず二群間の累積発症率に有意差を認めた（P＝0.019）。またeGFRの低下率もNon-responder群では-6.5％/年に対して、Responder群では-0.2％/年と有意差を認めた(Ｐ＜0.001)。一方で治療の前後では二群間で腎機能（eGFR）に変化を認めなかった。【結語】腎移植後CA-TCMRを発症しても治療を行い病理学的にB/CまたはNormalまで改善したものは、腎予後も良好であることが示唆された。一方で病理学的所見上の改善と治療前後の臨床所見は相関せず、確認生検が必要であると思われた。</p>

DOI： 10.11386/jst.58.supplement_s331_1

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出版者・発行元：Scientific Reports  

Previous studies reported conflicting results regarding an association between serum albumin concentration and the cumulative incidence of remission of proteinuria in adult patients with minimal change disease (MCD). The present study aimed to clarify the clinical impact of serum albumin concentration and the cumulative incidence of remission and relapse of proteinuria in 108 adult patients with MCD at 40 hospitals in Japan, who were enrolled in a 5-year prospective cohort study of primary nephrotic syndrome, the Japan Nephrotic Syndrome Cohort Study (JNSCS). The association between serum albumin concentration before initiation of immunosuppressive treatment (IST) and the cumulative incidence of remission and relapse were assessed using multivariable-adjusted Cox proportional hazards models. Remission defined as urinary protein < 0.3 g/day (or g/gCr) was observed in 104 (96.3%) patients. Of 97 patients with remission within 6 month of IST, 42 (43.3%) developed relapse defined as ≥ 1.0 g/day (or g/gCr) or dipstick urinary protein of ≥ 2+. Serum albumin concentration was significantly associated with remission (multivariable-adjusted hazard ratio [95% confidence interval] per 1.0 g/dL, 0.57 [0.37, 0.87]), along with eGFR (per 30 mL/min/1.73 m2: 1.43 [1.08, 1.90]), whereas they were not associated with relapse. A multivariable-adjusted model showed that patients with high eGFR level (≥ 60 mL/min/1.73 m2) and low albumin concentration (≤ 1.5 g/dL) achieved significantly early remission, whereas those with low eGFR (< 60 mL/min/1.73 m2) and high albumin concentration (> 1.5 g/dL) showed significantly slow remission. In conclusion, lower serum albumin concentration and higher eGFR were associated with earlier remission in MCD, but not with relapse.

DOI： 10.1038/s41598-022-13067-7

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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：Nephrology  

Aim: Data on the treatment of chronic active T cell-mediated rejection (CA-TCMR) are scarce, and therapeutical strategies for CA-TCMR have not been established. We retrospectively evaluated the outcomes and effects of treatment on pathological and clinical findings in patients with CA-TCMR. Methods: This study comprised 37 patients who underwent kidney transplantation at our institute who were diagnosed with CA-TCMR between January 2018 and December 2020. Patients were followed until October 2021. Results: A total of 32 of the 37 patients were treated. During the observation period, two patients died (5%), and five patients developed allograft loss (13%). A univariate Cox proportional hazards model showed that indication biopsy, higher spot urine protein/creatinine ratio (UPCR) and Banff ci/ct scores were risk factors for allograft loss. Of the treated patients, 23 underwent follow-up biopsies. The Wilcoxon signed-rank test showed significant improvement in the Baff scores for “ti”, “i-IFTA”, “t” and “t-IFTA” after treatment. On pathology, 13 (57%) of the patients who underwent follow-up biopsy improved to “no evidence of rejection” or “borderline change.” Assuming that improvement in pathology to “borderline change” or “no evidence of rejection” on follow-up biopsy indicates response to treatment, multivariate logistic analysis showed that lower UPCR was a predictive factor for response to treatment. No specific effect of treatment type was observed. Conclusions: Our results indicate that treatment could improve the pathological findings in CA-TCMR.

DOI： 10.1111/nep.14048

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DOI： 10.1016/j.ceja.2022.100266

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出版者・発行元：Journal of Nephrology  

Background: Minimal change disease (MCD) is characterized by a nephrotic syndrome usually steroid-sensitive and a high incidence of relapse of proteinuria. Previous cohort studies have reported conflicting results regarding the association between the time to remission and incidence of relapse. Methods: This multicenter prospective cohort study included 102 adult patients with steroid-sensitive MCD or focal segmental glomerulosclerosis from a 5-year cohort study of primary nephrotic syndrome, the Japan Nephrotic Syndrome Cohort Study, who achieved remission of proteinuria within 2 months of immunosuppressive therapy (IST). The association between the time to remission of proteinuria after immunosuppressive therapy and incidence of relapse was assessed using Cox proportional hazards models adjusted for clinically relevant factors. Results: Remission was observed at 3–7, 8–14, 15–21, 22–28, and 30–56 days after initiation of immunosuppressive therapy in 17 (16.7%), 37 (36.3%), 21 (20.6%), 13 (12.7%), and 14 (13.7%) patients, respectively. During a median observation period of 2.3 years after the end of the 2nd month after initiation of immunosuppressive therapy, 46 (45.1%) patients relapsed. The time to remission was associated with the incidence of relapse in an inverse U-shaped pattern (multivariable-adjusted hazard ratios [95% confidence intervals] of the time to remission of 3–7, 8–14, 15–21, 22–28, 30–56 days: 1.00 [reference], 1.76 [0.56, 5.51], 6.06 [1.85, 19.80], 5.46 [1.44, 20.64], and 2.19 [0.52, 9.30], respectively). Conclusion: The time to remission was identified as a significant predictor of relapse in steroid-sensitive patients.

DOI： 10.1007/s40620-022-01279-z

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記述言語：日本語   出版者・発行元：一般社団法人 日本移植学会  

<p>＜背景＞腎移植後早期の血圧管理には主にカルシウム拮抗薬が用いられ、早期からアンジオテンシンⅡ受容体拮抗薬(ARB)を使用することに関しての安全性や有効性は定かではない。＜方法＞2020年5月〜2022年3月に当科で行われた生体腎移植で、タクロリムス、ミコフェノール酸モフェチル、ステロイドの３剤で免疫抑制導入され、免疫学的低リスクの成人症例で、移植後3ヶ月に腎生検を実施した計78例について検討した。術後早期よりARBを開始した症例をARB群（27例）、それ以外をControl群（51例)とし、さらに逆確率重み付け（IPW）を用いて患者背景を２群間で調整し、3ヶ月後の腎機能および生検結果について比較した。＜結果＞術後3ヶ月時点での血清クレアチニン、推算糸球体濾過量、高K血症や血圧低下などの有害事象の出現頻度については二群間に有意差は認めなかった。尿蛋白/尿クレアチニン比(Up/Uc)はARB群でContorolに比べ低い傾向にあった（0.12 vs. 0.16 , <i>p</i>=0.176)。また術後3ヶ月目に行った腎生検結果では、ARB群ではIF/TAの出現率は低い傾向にあった（9.3% vs 17.6%, p=0.313）。＜結論＞低用量からARBを術後早期に始めることは安全であった。</p>

DOI： 10.11386/jst.57.supplement_s378_1

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

A higher urinary sodium-to-potassium (UNa/K) ratio has been reported to be associated with high blood pressure and subsequent cardiovascular events. However, the association between the UNa/K ratio and renal outcomes remains uncertain. We prospectively investigated the association between the UNa/K ratio and renal outcomes in patients with chronic kidney disease (CKD). We enrolled 716 patients with CKD, and 24-h urinary sodium and potassium excretion were measured. Patients were divided into UNa/K ratio tertiles (T1-T3). Endpoints were defined as a composite of doubling of serum creatinine (SCr), end-stage kidney disease (ESKD), or death and a composite of doubling of SCr or ESKD (added as an alternative outcome). We investigated the association between the UNa/K ratio and renal outcomes using a Cox proportional hazards model. During a median follow-up of 2.3 years, doubling of SCr, ESKD, or death and doubling of SCr or ESKD occurred in 332 and 293 patients, respectively. After adjustment for covariates including potentially confounding variables such as plasma renin activity, plasma aldosterone concentration, and B-type natriuretic peptide, the hazard ratios (HRs) (95% confidence intervals [CIs]) for the composite of doubling of SCr, ESKD, or death for T2 and T3 were 1.44 (1.06-1.96) and 1.59 (1.14-2.21), respectively, compared with T1. Additionally, compared with T1, the highest tertile (T3) of the UNa/K ratio was associated with a composite of doubling of SCr or ESKD (HR 1.55, 95% CI 1.09-2.20). A higher UNa/K ratio was independently associated with poor renal outcomes in patients with CKD.

DOI： 10.1038/s41440-021-00741-y

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: A growing body of evidence has shown that non-alcoholic fatty liver disease (NAFLD) is associated with chronic kidney disease (CKD). Non-invasive fibrosis assessments of NAFLD such as Fibrosis-4 (FIB-4) index and NAFLD fibrosis score (NFS) have been developed to substitute liver biopsy. Little is known about the association between FIB-4 index or NFS and the components of CKD. METHODS: In the present cross-sectional study, we assessed of 3640 Japanese CKD patients. We examined the association between FIB-4index or NFS and the odds of having low estimated glomerular filtration rate (eGFR) defined as eGFR < 60 mL/min/1.73 m2 or albuminuria defined as urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g. Patients were divided into quartiles according to their baseline FIB-4 index and NFS levels. Linear and logistic regression analysis were conducted, with adjustment for potential confounding factors. RESULTS: FIB-4 index and NFS were negatively associated with eGFR, but not UACR, after adjustment for potential confounding factors. Both FIB-4 index and NFS were significantly associated with low eGFR after adjustment for potential confounding factors. Meanwhile, in the multivariable-adjusted model, no associations were found between FIB-4 index or NFS and albuminuria. The addition of FIB-4 index or NFS to the established clinical CKD risk factors improved diagnostic accuracy of prevalence of low eGFR. We also found that there was a significant trend of higher FIB-4 index and NFS with more advanced renal fibrosis using the kidney biopsy data. CONCLUSIONS: Higher non-invasive fibrosis assessments of NAFLD were associated with higher odds of decreased eGFR.

DOI： 10.1007/s10157-020-02018-z

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: It remains unclear whether subclinical hypothyroidism (SCH) is associated with renal prognosis in patients with chronic kidney disease (CKD). Therefore, we prospectively investigated the association of SCH with renal outcomes in CKD. METHODS: We conducted a prospective observational study of 480 euthyroid patients and 89 patients with SCH. The endpoints were defined as a composite of doubling of serum creatinine (SCr), end-stage renal disease (ESRD), or death, and a composite of doubling of SCr or ESRD was added as an alternative outcome. Logistic regression analyses were used to identify the factors associated with SCH. In addition, a Cox proportional hazards model was performed to determine whether SCH was associated with poor renal outcomes. RESULTS: During a median follow-up period of 26.1 months, doubling of SCr, ESRD, or death and doubling of SCr or ESRD occurred in 244 and 213 patients, respectively. In univariable logistic regression analyses, SCH was significantly associated with older age, lower hemoglobin, higher proteinuria, lower estimated glomerular filtration rate (eGFR), and higher log B-type natriuretic peptide (BNP). Multivariable Cox analyses showed that SCH was associated with poorer renal outcomes after adjustment for covariates, including eGFR and log BNP [doubling of SCr, ESRD, or death: hazard ratio (HR) 1.61, 95% confidence interval (CI), 1.16-2.23; doubling of SCr or ESRD: HR 1.53, 95% CI 1.07-2.20], compared with euthyroidism. CONCLUSIONS: In CKD, SCH is independently associated with poor renal outcomes, suggesting that screening for SCH might be needed to accurately predict renal prognosis.

DOI： 10.1007/s12020-021-02611-6

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

HD patients have been reported to have a higher risk of restenosis after percutaneous coronary intervention (PCI). The aim of this study was to investigate the risk factors of coronary restenosis in HD patients. We enrolled 54 HD patients (mean age: 66.5 ± 10.1 years; 72.2% men; mean HD duration: 3.7 years), who received PCI and follow-up coronary angiography. Of the patients, 22 (40.7%) had restenosis within 3 to 12 months of PCI. Univariate logistic analysis showed low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio, LDL-C, non-HDL-C, and history of major adverse cardiovascular events were significantly associated with coronary restenosis (OR]: 1.89, 1.27, 1.22, and 5.79, respectively). Multivariate analysis showed that LDL-C was significantly associated with coronary restenosis (OR: 1.43). These data suggest that LDL-C is an independent risk factor for coronary restenosis in HD patients undergoing PCI, and strict lipid management may be required.

DOI： 10.1111/1744-9987.13558

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUNDS AND AIMS: The geriatric nutritional risk index (GNRI), which is calculated using the serum albumin level and body mass index, is a nutritional marker associated with an increased risk of cardiovascular events in patients who are receiving hemodialysis. However, no studies have examined the association between the GNRI level and the incidence of stroke in this population. METHODS: Three thousand forty-five patients were registered in the Q-Cohort Study, which is a multicenter, observational cohort of hemodialysis patients. The main outcomes were brain infarction and brain hemorrhage. The main exposure was GNRI levels at baseline. Patients were divided into quartiles on the basis of baseline GNRI levels: Q1, <90.7; Q2, 90.7-95.5; Q3, 95.6-99.8; Q4, >99.8. The risk of brain infarction or hemorrhage was estimated using the multivariable-adjusted Cox proportional hazard risk models and restricted cubic spline analyses. RESULTS: During the 10-year follow-up period, 326 patients developed brain infarction and 149 patients developed brain hemorrhage. Cox proportional hazard risk models showed that the risk of brain infarction and hemorrhage in Q1 was significantly higher than that in Q4 group. The hazard ratios [95% confidence intervals] were 1.49 [1.05-2.12] and 1.89 [1.11-3.20], respectively. Restricted cubic spline curves showed that a lower GNRI was incrementally associated with an increased risk for both brain infarction and brain hemorrhage. CONCLUSIONS: Our results suggest that a lower GNRI is an independent risk factor for both brain infarction and hemorrhage in patients who are receiving maintenance hemodialysis.

DOI： 10.1016/j.atherosclerosis.2021.03.006

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Diagnostic criteria for chronic active T cell-mediated rejection (CA-TCMR) were revised in the Banff 2017 consensus, but it is unknown whether the new criteria predict graft prognosis of kidney transplantation. We enrolled 406 kidney allograft recipients who underwent a 1-year protocol biopsy (PB) and investigated the diagnostic significance of Banff 2017. Interobserver reproducibility of the 3 diagnosticians showed a substantial agreement rate of 0.68 in Fleiss's kappa coefficient. Thirty-three patients (8%) were classified as CA-TCMR according to Banff 2017, and 6 were previously diagnosed as normal, 12 as acute TCMR, 10 with borderline changes, and 5 as CA-TCMR according to Banff 2015 criteria. Determinant factors of CA-TCMR were cyclosporine use (vs tacrolimus), previous acute rejection, and BK polyomavirus-associated nephropathy. In survival analysis, the new diagnosis of CA-TCMR predicted a composite graft endpoint defined as doubling serum creatinine or death-censored graft loss (log-rank test, P < .001). In multivariate analysis, CA-TCMR was associated with the second highest risk of the composite endpoint (hazard ratio: 5.42; 95% confidence interval, 2.02-14.61; P < .001 vs normal) behind antibody-mediated rejection. In conclusion, diagnosis of CA-TCMR in Banff 2017 may facilitate detecting an unfavorable prognosis of kidney allograft recipients who undergo a 1-year PB.

DOI： 10.1111/ajt.16093

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Cardiovascular disease (CVD) is a major cause of death in kidney transplant (KT) recipients. To improve their long-term survival, it is clinically important to estimate the risk of CVD after living donor KT via adequate pre-transplant CVD screening. METHODS: A derivation cohort containing 331 KT recipients underwent living donor KT at Kyushu University Hospital from January 2006 to December 2012. A prediction model was retrospectively developed and risk scores were investigated via a Cox proportional hazards regression model. The discrimination and calibration capacities of the prediction model were estimated via the c-statistic and the Hosmer-Lemeshow goodness of fit test. External validation was estimated via the same statistical methods by applying the model to a validation cohort of 300 KT recipients who underwent living donor KT at Tokyo Women's Medical University Hospital. RESULTS: In the derivation cohort, 28 patients (8.5%) had CVD events during the observation period. Recipient age, CVD history, diabetic nephropathy, dialysis vintage, serum albumin and proteinuria at 12 months after KT were significant predictors of CVD. A prediction model consisting of integer risk scores demonstrated good discrimination (c-statistic 0.88) and goodness of fit (Hosmer-Lemeshow test P = 0.18). In a validation cohort, the model demonstrated moderate discrimination (c-statistic 0.77) and goodness of fit (Hosmer-Lemeshow test P = 0.15), suggesting external validity. CONCLUSIONS: The above-described simple model for predicting CVD after living donor KT was accurate and useful in clinical situations.

DOI： 10.1093/ndt/gfaa275

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Several large population-based studies have demonstrated that urinary salt excretion (USALT) is associated with albuminuria. However, this relationship has not been assessed in a large cohort study of patients with chronic kidney disease (CKD). Thus, the present study aimed to elucidate whether USALT was independently associated with albuminuria in a large cohort of patients with CKD. METHODS: This cross-sectional study was conducted in 4075 patients with CKD not on dialysis. USALT (g/day) was estimated from spot urine. Patients were divided into quartiles (Q1-Q4) according to estimated USALT. Multivariable regression models were used to determine whether USALT was independently related to urinary albumin-to-creatinine ratio (UACR) or the presence of macroalbuminuria. RESULTS: In multivariable linear regression analyses, 1-g/day increment in USALT was significantly associated with log UACR [coefficient 0.098, 95% confidence interval (CI) 0.075-0.121]. In addition, compared with the first USALT quartile, the third and fourth quartiles exhibited significant associations with log UACR (Q3: coefficient 0.305, 95% CI 0.154-0.456; Q4: coefficient 0.601, 95% CI 0.447-0.756). Furthermore, multivariable logistic regression analyses showed that USALT (1-g/day increment) was significantly associated with the presence of macroalbuminuria [odds ratio (OR) 1.11, 95% CI 1.07-1.14]; the third and fourth USALT quartiles exhibited significantly greater risks of macroalbuminuria, compared with the first quartile (Q3: OR 1.33, 95% CI 1.09-1.62; Q4: OR 1.89, 95% CI 1.54-2.32). CONCLUSIONS: This significant association of USALT with UACR and macroalbuminuria suggests that higher USALT may cause increased albuminuria, thereby contributing to kidney disease progression.

DOI： 10.1007/s10157-020-01950-4

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The utility of the Columbia classification (Col-class) for focal segmental glomerulosclerosis (FSGS) has not yet been fully proven. METHODS: We extracted 201 FSGS patients from 10 nephrology centers in Japan and investigated the difference of a composite renal endpoint, defined as doubling of serum creatinine and/or development of end-stage renal disease, in pathological variants. Sensitivity analysis was used to prove the utility of the Col-class to predict renal outcomes. Additionally, the renal protective effects of steroids and/or immunosuppression (steroid/IS) were investigated in patients stratified according to the Col-class. RESULTS: The patients were classified into the following variants: not otherwise specified [NOS; n = 121 (60.1%)], perihilar [n = 31 (15.4%)], cellular [n = 19 (9.5%)], tip [n = 17 (8.5%)] and collapsing [n = 13 (6.5%)]. No tip variant patients reached the renal endpoint. The renal outcome in the collapsing variant was significantly poorer than that in the NOS [hazard ratio (HR) 3.71; P = 0.005]. In the sensitivity analysis, the area under the receiver operating characteristic curve for the renal endpoint was increased by adding Col-class to a model including common risk factors (P = 0.021). In a subgroup treated without steroid/IS, the outcome in the cellular variant was worse than that in the NOS (HR 5.10; P = 0.040) but the difference was not observed in the subgroup with steroid/IS (HR 0.54; P = 0.539). CONCLUSIONS: The Col-class is useful to predict renal prognosis in Japanese patients with FSGS. In addition to good prognosis in the tip variant and poor in the collapsing variant, good clinical course in the cellular variant treated with steroid/IS was suggested.

DOI： 10.1093/ndt/gfy374

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語  

DOI： 10.1016/j.jns.2020.116791

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Patients with chronic kidney disease (CKD) reportedly have a high prevalence of aortic valve calcification (AVC). In population-based studies, AVC is considered a manifestation of systemic atherosclerosis. The association of AVC with atherosclerotic lesions has not been fully investigated in predialysis patients. The present study was performed to determine whether carotid artery lesions and peripheral artery disease (PAD) are associated with AVC in patients with CKD not on dialysis. METHODS: In total, 749 patients were included in this cross-sectional study. AVC was evaluated using echocardiography. Carotid artery lesions including carotid artery plaque (CAP) and PAD were simultaneously examined in each patient. A logistic regression analysis was applied to determine the factors associated with AVC. RESULTS: AVC, CAP, and PAD were found in 201, 583, and 123 patients, respectively. In the multivariable analyses adjusted for covariates including the estimated glomerular filtration rate and makers of mineral metabolism (serum calcium, serum phosphorus, parathyroid hormone, 1,25-dihydroxyvitamin D, and fibroblast growth factor 23), AVC was significantly associated with the presence of CAP [odds ratio (OR), 3.37; 95% confidence interval (CI), 1.43-7.95], the presence of PAD (OR, 1.76; 95% CI, 1.10-2.81), the CAP score (per 1.0-point increase) (OR, 1.06; 95% CI, 1.02-1.11), and the ankle-brachial blood pressure index (per 0.1-point increase) (OR, 0.83; 95% CI, 0.72-0.95). CONCLUSIONS: AVC was associated with atherosclerotic lesions independent of kidney function and mineral metabolism. We consider that this association between AVC and atherosclerosis might reflect the burden of shared atherosclerotic risk factors.

DOI： 10.1186/s12882-020-01864-z

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Renin-angiotensin system blockers (RASBs) reduce end-stage kidney disease and cardiovascular event (CVE) development in chronic kidney disease. However, whether RASBs improve long-term prognosis in kidney transplant (KT) recipients remain unknown. METHOD: We investigated 900 kidney transplant patients in a multicenter retrospective cohort study in Japan and compared death-censored graft survival and CVE (total, cardiac events, stroke) based on RASB use within 12 months after KT. The associations were examined using a Cox hazard model and propensity score-matching analysis. RESULTS: The cohort comprised 375 patients treated with RASBs (RASB group) and 525 patients without RASBs (control group). The median observational period was 82 months, with 68 patients reaching graft loss: 79 total CVE, 36 cardiac events, 26 stroke. In a matching cohort comprising 582 patients, death-censored graft survival, total CVE, and cardiac events were not different between the two groups. Only stroke incidence rate was significantly lower in the RASB group compared with the control group (1.4 vs. 6.4 per 1000 patients/year, log-ranked P = 0.005). In a multivariable analysis, stroke events were also significantly lower in the RASB group compared with the control group (Hazard ratio and 95% confidence interval, 0.20 [0.04-0.62]). CONCLUSION: Thus, RASBs potentially reduce stroke events in KT recipients.

DOI： 10.1007/s10157-019-01827-1

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Bilirubin is recognized as an endogenous antioxidant, and low serum bilirubin is reported to be associated with the progression of kidney disease. However, it is unclear whether serum bilirubin levels are associated with the loss of residual kidney function (RKF) in peritoneal dialysis (PD) patients. This study investigated the relationship between serum total bilirubin and loss of RKF. We prospectively followed 94 PD patients who started PD in our hospital between June 2006 and May 2016. Ten patients who had chronic liver disease or cirrhosis were excluded. Patients were divided into three groups based on serum total bilirubin concentration tertiles: tertile 1 (T1) < 0.3, T2 = 0.3, and T3 ≥ 0.4 mg/dL. We estimated the relationship between serum bilirubin and loss of RKF, defined as daily urine volume (<100 mL) within 3 years after starting PD, using a Cox proportional hazards model. During the 3-year observation period, 22 patients lost RKF. The incidence rate of loss of RKF increased linearly with the decrease in serum total bilirubin levels (P for trend < 0.05). After adjusting for confounding factors, low serum total bilirubin level was shown to be an independent predictor of loss of RKF (hazard ratio [HR] for every 0.1 mg/dL decrease, 1.50; 95% confidence interval [CI], 1.01-2.51; HR [95%CI] for T2 and T1 [vs. T3] 2.03 [0.65-7.88] and 3.70 [1.00-15.9]). This study suggests that low serum total bilirubin levels are associated with the loss of RKF in PD patients.

DOI： 10.1111/1744-9987.12865

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Hypocomplementemic urticarial vasculitis syndrome (HUVS) is a small vessel vasculitis characterized by hypocomplementemia and urticaria-like exanthema. Some cases also display abdominal pain and membranoproliferative glomerulonephritis (MPGN) with immune complex deposits. We treated a case of HUVS with biopsy-proven gastrointestinal vasculitis and atypical histological findings in a kidney biopsy. The 36-year-old Japanese man, who was previously diagnosed with diffuse panbronchiolitis, visited our hospital due to transient urticaria-like exanthema and rapid deterioration of kidney function. On admission, the skin lesion was found to be only pigmentation, showing no vasculitis by skin biopsy. In laboratory findings, renal dysfunction with hematuria and proteinuria and hypocomplementemia were observed. Gastrointestinal vasculitis was proven by endoscopy and biopsy of the mucosa. Kidney biopsy revealed MPGN with crescents. No immune complex deposits were observed by immunofluorescence or electron microscopy. Additional examination revealed high titers of anti-C1q antibody. The patient was diagnosed with HUVS and treated with corticosteroids and plasma exchange. Although renal function and gastrointestinal vasculitis partially improved, infectious pneumonia frequently recurred. His renal dysfunction began to progress again and reached end-stage kidney disease. This is the first case of HUVS with biopsy-proven gastrointestinal vasculitis and MPGN without immune complex deposits. Notably, in some case of HUVS, anti-C1q antibody may activate the alternative complement pathway without immune complex deposits, resulting in renal injury.

DOI： 10.1007/s13730-019-00421-4

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Recently, living-donor kidney transplantation from marginal donors has been increasing. However, a simple prediction model for graft function including preoperative marginal factors is limited. Here, we developed and validated a new prediction model for graft function using preoperative marginal factors in living-donor kidney transplantation. METHODS: We retrospectively investigated 343 patients who underwent living-donor kidney transplantation at Kyushu University Hospital (derivation cohort). Low graft function was defined as an estimated glomerular filtration rate of < 45 mL/min/1.73 m2 at 1 year. A prediction model was developed using a multivariable logistic regression model, and verified using data from 232 patients who underwent living-donor kidney transplantation at Tokyo Women's Medical University Hospital (validation cohort). RESULTS: In the derivation cohort, 89 patients (25.9%) had low graft function at 1 year. Donor age, donor-estimated glomerular filtration rate, donor hypertension, and donor/recipient body weight ratio were selected as predictive factors. This model demonstrated modest discrimination (c-statistic = 0.77) and calibration (Hosmer-Lemeshow test, P = 0.83). Furthermore, this model demonstrated good discrimination (c-statistic = 0.76) and calibration (Hosmer-Lemeshow test, P = 0.54) in the validation cohort. Furthermore, donor age, donor-estimated glomerular filtration rate, and donor hypertension were strongly associated with glomerulosclerosis and atherosclerotic vascular changes in the "zero-time" biopsy. CONCLUSIONS: This model using four pre-operative variables will be a simple, but useful guide to estimate graft function at 1 year after kidney transplantation, especially in marginal donors, in the clinical setting.

DOI： 10.1007/s10157-019-01774-x

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Graft biopsy is the gold standard for diagnosis of BK polyomavirus-associated nephropathy (BKPyVAN), and polymerase chain reaction is the most specific screening technique. Development of a noninvasive, cost-effective marker for BKPyVAN is important. METHODS: We reviewed 492 adult kidney transplant patients. We investigated peripheral blood lymphocyte (PBL) count and urinary cytology at graft biopsy in patients with BKVPyAN (n = 21), acute T-cell-mediated rejection (n = 79), and no evidence of acute rejection (n = 149). We performed univariate and multivariate logistic regression and receiver operating characteristics analyses to compare the test performance of PBL count, urinary cytology, and their combination for diagnosis of BKPyVAN. RESULTS: The PBL count at biopsy was significantly lower in the BKPyVAN group than the acute T-cell-mediated rejection and no acute rejection groups (959 ± 290/μL, 1433 ± 673/μL, and 1531 ± 549/μL, respectively; P < .01). The PBL count was 959 ± 290/μL at diagnosis of BKPyVAN and increased to 1123 ± 377/μL, 1238 ± 419/μL, and 1292 ± 491/μL at 1, 2, and 3 months after treatment, respectively (P < .05). On univariate analysis, the area under the curve was significantly higher for the combined model than for PBL and cytology alone (0.930, 0.797, and 0.875, respectively; P < .01). The improved test performance in the combined model remained significant after multivariate adjustment (0.972, 0.844, and 0.928, respectively; P < .01). CONCLUSIONS: Decreased PBL count was found in BKPyVAN, and the predictive performance of the combination of PBL count and urinary cytology was significantly enhanced for diagnosis of BKPyVAN.

DOI： 10.1016/j.transproceed.2019.01.129

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Thrombotic microangiopathy (TMA) develops from various etiologies, and it is often difficult to distinguish the etiology of TMA in kidney transplantation. Antiphospholipid syndrome (APS) is one of the differential diagnoses for TMA that may cause acute loss of graft function or fatal thrombotic complications. This report details a 66-year-old male patient with polycythemia after ABO-incompatible kidney transplantation. Antibody screening tests were negative before transplant. Despite administration of an adequate desensitization therapy including plasmapheresis and rituximab, he developed acute graft dysfunction on postoperative day 112 and graft biopsy revealed prominent microvascular inflammation in the glomerular capillaries without immunoglobulin deposits. Flow cytometric panel-reactive antibody screening failed to detect donor-specific antibodies at both pre-transplant and episode biopsies. Anticardiolipin antibody was repeatedly positive, but neither thrombosis nor previous thrombotic episodes were detected. After excluding several differential diagnoses, the graft dysfunction with unexplained TMA was treated with steroid pulse, plasmapheresis and rituximab re-induction. Anticardiolipin antibody disappeared after this intensive treatment and graft function recovered gradually and stabilized for 52 months. This report suggests that asymptomatic anticardiolipin antibody may be associated with acute graft dysfunction. Even if thrombotic episodes are not observed, an exist of anticardiolipin antibody may be one of the risk factors of renal TMA after kidney transplantation.

DOI： 10.1007/s13730-018-0354-x

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND & AIMS: The geriatric nutritional risk index (GNRI) is a simple but useful nutritional marker for all-cause mortality and cardiovascular mortality in patients undergoing hemodialysis (HD). However, whether the GNRI can predict infection-related mortality in patients undergoing HD remains unclear, and there is insufficient evidence regarding whether the GNRI improves the predictive value for risk assessment beyond the existing conventional nutritional markers. Here, we investigated the association between the GNRI and infection-related mortality in patients undergoing HD and evaluated the predictive value of GNRI. METHODS: A prospective cohort study was performed on a total of 3436 Japanese HD patients aged ≥18 years. Patients were divided into four groups by quartiles of GNRI: (Quartile 1 [Q1], >100.2; Q2, 95.9-100.2; Q3, 90.8-95.8; Q4, <90.8). We estimated the relationship between GNRI and all-cause mortality and infection-related mortality using a Cox proportional hazards model. To assess the additional predictive value of the GNRI in risk assessment, we compared the c-statistic, net reclassification improvement, and integrated discrimination improvement among serum albumin, serum creatinine, and the GNRI. RESULTS: During follow-up period (median, 4.0 years), a total of 564 patients died; 120 of these patients died of infectious disease. All-cause mortality and infection-related mortality increased linearly with lower GNRI levels. After adjusting for confounding risk factors, the GNRI was an independent predictor of infection-related mortality as well as all-cause mortality (hazard ratio [HR], 5.89; 95% confidence interval [CI], 2.85-13.8; P < 0.001 for Q4 vs. Q1, HR, 2.62; 95% CI, 1.23-6.24; P = 0.01 for Q3 vs. Q1). Additionally, when the GNRI was incorporated into a model with potential risk factors instead of serum albumin, the c-statistic increased significantly (0.811 vs. 0.821, P = 0.03), and the net reclassification improvement and integrated discrimination improvement was 0.26 (P = 0.005) and 0.005 (P = 0.01). This association was more apparent in the older patients (0.739 vs. 0.760, P = 0.02) than in the younger patients (0.916 vs. 0.912, P = 0.35). Similar results were observed between serum creatinine and the GNRI, but the difference did not reach statistical significance. CONCLUSIONS: Lower GNRI levels are an independent risk factor for infection-related mortality in patients undergoing HD. Moreover, addition of the GNRI to models with standard risk factors significantly improves the predictive ability of infection-related mortality, especially in older patients.

DOI： 10.1016/j.clnu.2018.01.019

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: Recent studies have suggested that patients with post-transplant immunoglobulin A nephropathy have poor graft survival. There is limited research on the therapeutic effectiveness for post-transplant immunoglobulin A nephropathy, especially steroid pulse therapy. The present study evaluated the efficacy of steroid pulse therapy on post-transplant immunoglobulin A nephropathy. METHODS: We retrospectively analyzed patients diagnosed with de novo or recurrent immunoglobulin A nephropathy at Kyushu University Hospital between January 2013 and August 2015. Patients with moderate proteinuria (≥0.5 g/g creatinine) and/or cellular or fibrocellular crescents on a graft biopsy were treated with steroid pulse therapy. Steroid pulse therapy was 500 mg/day for 3 days in weeks 1 and 2, followed by 20 mg of oral prednisolone that was tapered after 6 months. Patients were followed for 2 years, and the estimated glomerular filtration rate, urinary findings, and adverse events were recorded. RESULTS: Seven patients received steroid pulse therapy. The mean duration after kidney transplantation was 6.6 ± 4.7 years. After 2 years of treatment, 85.7% of patients reached complete remission of proteinuria, urinary protein excretion declined (0.82 ± 0.51 to 0.26 ± 0.22 g/g creatinine, P = 0.007), and the estimated glomerular filtration rate was maintained (48.7 ± 12.8 to 47.4 ± 14.0 mL/min per 1.73 m2 , P = 0.98). Adverse events were observed in one patient who developed herpes zoster infection. CONCLUSION: Steroid pulse therapy for post-transplant immunoglobulin A nephropathy effectively reduces proteinuria over 2 years. However, comparison of steroid pulse therapy and other regimens with a high-quality design is required.

DOI： 10.1111/nep.13272

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIMS: Recent studies have reported an association between serum uric acid (SUA) and renal arteriolar changes in patients with chronic kidney disease (CKD). However, the association in individuals without CKD remains unclear. In this study, we investigated the relationship between SUA and renal arteriolar lesions in individuals without CKD from our living kidney donor cohort. METHODS: Between January 2006 and May 2016, 393 living kidney donors underwent "time-zero" biopsy at Kyushu University Hospital. Patients were divided into sex-specific quartiles of SUA before donation: Q1, Q2, Q3, and Q4 (male: <5.2,5.2-5.8,5.9-6.4, and ≥6.5 mg/dL, female: <3.8,3.8-4.3,4.4-5.0, and ≥5.1 mg/dL). Renal arteriolar hyalinization and wall thickening were assessed using a semiquantitative grading system. Predictive performance was compared between models with and without SUA by calculating the net reclassification improvement (NRI). RESULTS: In total, 158 (40.2%) patients had arteriolar hyalinization, and 148 (37.6%) had wall thickening. High SUA was significantly associated with arteriolar hyalinization in multivariable logistic analysis (odds ratio [OR] per 1-mg/dL increase in SUA, 1.24; 95% confidence interval [CI], 1.00-1.53; p = 0.048. OR for Q4 vs. Q2, 2.22; 95% CI, 1.17-4.21; p = 0.01). We found no association between SUA and wall thickening. When SUA was incorporated into a predictive model with conventional atherosclerotic factors, the NRI was 0.21 (p = 0.04). CONCLUSIONS: High SUA was an independent risk factor for arteriolar hyalinization in individuals without CKD. SUA provided additional predictive value beyond conventional atherosclerotic factors in predicting arteriolar hyalinization.

DOI： 10.1016/j.atherosclerosis.2017.09.017

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Lymphangiogenesis occurs in diseased native kidneys and kidney allografts, and correlates with histological injury; however, the clinical significance of lymphatic vessels in kidney allografts is unclear. METHODS: This study retrospectively reviewed 63 kidney transplant patients who underwent protocol biopsies. Lymphatic vessels were identified by immunohistochemical staining for podoplanin, and were classified according to their location as perivascular or interstitial lymphatic vessels. The associations between perivascular lymphatic density and kidney allograft function and pathological findings were analyzed. RESULTS: There were no significant differences in perivascular lymphatic densities in kidney allograft biopsy specimens obtained at 0 h, 3 months and 12 months. The groups with higher perivascular lymphatic density showed a lower proportion of progression of interstitial fibrosis/tubular atrophy grade from 3 to 12 months (P for trend = 0.039). Perivascular lymphatic density was significantly associated with annual decline of estimated glomerular filtration rate after 12 months (r = -0.31, P = 0.017), even after adjusting for multiple confounders (standardized β = -0.30, P = 0.019). CONCLUSIONS: High perivascular lymphatic density is associated with favourable kidney allograft function. The perivascular lymphatic network may be involved in inhibition of allograft fibrosis and stabilization of graft function.

DOI： 10.1007/s10157-016-1338-9

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Recently, low serum uric acid (SUA) levels and high SUA levels, have emerged as risk factors for cardiovascular disease, as well as for the incidence of acute kidney injury and chronic kidney disease (CKD). However, the effect of low SUA on the progression of CKD remains unclear. To evaluate the association between SUA and renal prognosis in patients with immunoglobulin A nephropathy (IgAN), one of the most common causes of CKD, we retrospectively followed 1218 patients who were diagnosed with primary IgAN by kidney biopsy between October 1979 and December 2010. Patients were divided into three groups on the basis of SUA level tertiles: low (L group), middle (M group) and high (H group) tertiles (<6.1, 6.1-7.0, and >7.0 mg dl-1, respectively, for men and <4.4, 4.4-5.3, and >5.3 mg dl-1, respectively, for women). The risk factors for developing end-stage renal disease (ESRD) were estimated using a Cox proportional hazards model. After a median follow-up of 5.1 years, 142 patients (11.7%) developed ESRD. The hazard ratio (95% confidence interval) showed a J-shaped trend with the tertiles in both men (1.18 (0.55-2.54), 1.00 (reference), and 1.80 (1.01-3.10) in L, M and H groups, respectively) and women (2.73 (1.10-6.76), 1.00 (reference) and 2.49 (1.16-5.34) in L, M and H groups, respectively). Notably, low SUA was significantly associated with incident ESRD in women. This finding suggests that SUA has a J-shaped association with ESRD in patients with IgAN, especially women.

DOI： 10.1038/hr.2016.134

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: IgG4-related disease is a novel disease entity characterized by elevated serum IgG4 and tissue infiltration by IgG4-positive plasma cells. Typical renal pathology is tubulointerstitial nephritis with storiform fibrosis, although the co-existence of various glomerular lesions has been described. Here, we present the first report of a case of IgG4-related kidney disease and membranoproliferative glomerulonephritis showing the discrepancy in IgG subclasses between the kidney interstitium and glomeruli. CASE PRESENTATION: A 70-year-old Japanese woman was diagnosed with membranoproliferative glomerulonephritis and focal tubulointerstitial nephritis with IgG4-positive plasma cells. Immunofluorescence studies revealed predominant deposition of IgG3 and IgG2, but not IgG4 in the glomeruli. We administered oral prednisolone at 30 mg/day, and the abnormalities in urine and blood tests gradually resolved. CONCLUSION: In this case, different patterns of IgG subclasses detected in the glomeruli and interstitial plasma cells suggest overlapping immunologic abnormalities. The favorable clinical course in our patient suggests that steroid therapy is promising in cases of IgG4-related kidney disease accompanied by glomerulonephritis.

DOI： 10.1186/s12882-015-0164-8

記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: Polyomavirus BK nephropathy (BKVN) is an important complication in kidney transplantation. After immunosuppressive agents are reduced, some patients experience a temporal increase in serum creatinine (sCr) before viral clearance. The histological characteristics of re-biopsies were therefore investigated to evaluate the time course of remission. METHODS: sCr was measured and urinary cytology evaluated periodically in 14 patients with biopsy-proven BKVN. Remission of BKVN was defined as re-biopsies negative for SV40 large T antigen (SV40-TAg) or for decoy cells on at least three consecutive cytology tests. Early changes in sCr were correlated with re-biopsy findings. RESULTS: Mean sCr was 1.6 ± 0.6 mg/dL at diagnosis, increasing during the first 2 months to 2.6 ± 2.0 mg/dL, and decreasing thereafter, to 2.3 ± 1.2 mg/dL at 3-4 months. Two patients who experienced further increases in sCr at 3 months showed early graft loss, while the others showed clinical or histological remission. Nineteen re-biopsies were obtained from eight patients over 4 months. Banff i-scores were higher in re-biopsies obtained during the first 2 months than the index biopsies and re-biopsies at 2-4 months (P = 0.02). SV40-TAg positivity was common in re-biopsies during the first 2 months (10/11 biopsies), but rarer at 2-4 months (2/8 biopsies, P = 0.001). CONCLUSIONS: Temporal graft dysfunction and increased inflammation, called immune reconstitution, were observed at 2 months. Later sCr reversal is associated with remission.

DOI： 10.1111/nep.12462

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Bacterial peritonitis remains a life-threatening complication of peritoneal dialysis (PD). Roseomonas is a bacterial genus of pink-pigmented, oxidized, gram-negative coccobacilli that was first named in 1993. Importantly, Roseomonas mucosa exhibits antibiotic resistance, with significant resistance to cephalosporin, which is often selected as an empirical antibiotic regimen for peritonitis in PD patients. We herein report the case of a PD patient with bacterial peritonitis caused by Roseomonas mucosa that was fortunately identified using 16S rRNA gene sequencing and successfully treated with ciprofloxacin. Given that Roseomonas demonstrates resistance to a variety of antibiotics. The administration of empiric antibiotic therapy based on the recommendation of the International Society of Peritoneal Dialysis guidelines occasionally fails, leading to the aggravation of bacterial peritonitis. Hence, nephrologists should consider Roseomonas as one of the potential causative organisms of peritonitis, especially when gram-negative bacilli are resistant to cephalosporin and cannot be identified using standard laboratory methods.

DOI： 10.1007/s13730-013-0101-2

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語  

記述言語：日本語  

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記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語