Kidney International Reports最新文献_第9页

Implementing Patient Navigation for Children With CKD 实施儿童CKD患者导航

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports

Pub Date : 2026-02-01 Epub Date: 2025-12-04 DOI: 10.1016/j.ekir.2025.11.032

Germaine Wong , Luca Torrisi , Angela Rejuso , Chandana Guha , Anita van Zwieten , Winne Chen , Martin Howell , Kirsten Howard , Siah Kim , Kylie-Ann Mallitt , Anh Kieu , David J. Tunnicliffe , Anastasia Hughes , Jiayue Wang , Anna Francis , Nicholas Larkins , Madeleine Reicher , Hugh McCarthy , Stephen Alexander , David W. Johnson , Winnie Chen

Introduction

Children with chronic kidney disease (CKD), particularly those who experienced socioeconomic disadvantage, have poorer health and lower quality of life (QoL), partly because of limited access to high-quality care. Patient navigation may improve access to care, self-advocacy, self-management, and emotional well-being.

Methods

We conducted a national stakeholder workshop involving 38 participants (4 patients, 1 policy-maker/funder, 22 researchers, and 11 health care professionals) from 7 states or territories in Australia and discussed potential strategies to implement navigation programs in diverse CKD clinical settings.

Results

We identified 7 key themes or strategies for implementation. “Securing sustainable funding” was considered necessary for program longevity. Prioritizing the “well-being of navigators” involved protecting their mental health. “Embedding patient navigation within the existing health care system” involved integrating navigators into the multidisciplinary care team. “Encourage robust communication through collaboration” empowered patients and families to make informed, shared decisions. “Targeting the appropriate population and situations” was emphasized to support patients and families during the most difficult phases of their CKD journey. Participants recognized the program’s benefits, including improving care delivery fragmentation and “Adapting the model of care” to ensure appropriateness for diverse populations and settings.

Conclusion

The navigation program can be adopted, adapted, and scaled-up for implementation to improve care coordination and access to quality care for children with CKD. Key strategies include securing long-term funding, supporting navigator well-being through training and peer support, integrating navigation into health care systems, and maintaining flexibility while preserving core elements.

患有慢性肾脏疾病（CKD）的儿童，特别是那些经历过社会经济劣势的儿童，健康状况较差，生活质量（QoL）较低，部分原因是获得高质量护理的机会有限。患者导航可以改善获得护理，自我倡导，自我管理和情绪健康。方法：我们组织了一个全国性的利益相关者研讨会，来自澳大利亚7个州或地区的38名参与者（4名患者、1名政策制定者/资助人、22名研究人员和11名卫生保健专业人员）参与，讨论了在不同的CKD临床环境中实施导航计划的潜在策略。结果我们确定了7个关键主题或实施策略。“确保可持续的资金”被认为是项目寿命的必要条件。优先考虑“航海家的福祉”涉及到保护他们的心理健康。“在现有的医疗保健系统中嵌入病人导航”涉及到将导航员整合到多学科护理团队中。“鼓励通过合作进行强有力的沟通”，使患者和家属能够做出知情的共同决定。“针对适当的人群和情况”被强调，以支持患者和家属在他们的慢性肾病之旅的最困难的阶段。与会者认识到该项目的好处，包括改善护理服务的分散性和“调整护理模式”，以确保适合不同的人群和环境。结论该导航方案可被采用、调整和推广实施，以改善CKD患儿的护理协调和获得优质护理的机会。关键战略包括确保长期资金，通过培训和同伴支持支持导航员的福祉，将导航纳入卫生保健系统，以及在保留核心要素的同时保持灵活性。

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引用次数: 0

Acute Kidney Injury in Immune-Mediated Thrombotic Thrombocytopenic Purpura – Solving the Puzzle? 免疫介导的血栓性血小板减少性紫癜急性肾损伤-解决这个难题？

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports

Pub Date : 2026-02-01 Epub Date: 2025-11-17 DOI: 10.1016/j.ekir.2025.11.018

Juliane Schneider , Camille Schlesser , Michael Fischereder , Anke von Bergwelt-Baildon , Ulf Schönermarck

引用次数: 0

Circulating Testican-2 and MGT5A are Markers of Membranous Nephropathy 循环睾丸素-2和MGT5A是膜性肾病的标志

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports

Pub Date : 2026-02-01 Epub Date: 2025-11-20 DOI: 10.1016/j.ekir.2025.11.020

Taesoo Kim , Wenjun Ju , Aditya Surapaneni , Yang Li , Donghai Wen , Claire Trivin-Avillach , Ivy A. Rosales , Laurence H. Beck Jr. , Viji Nair , Damian Fermin , Jarcy Zee , Insa M. Schmidt , Anand Srivastava , Ragnar Palsson , Isaac E. Stillman , Matthias Kretzler

Introduction

Membranous nephropathy (MN) is a common cause of nephrotic syndrome usually diagnosed using kidney biopsy.

Methods

We examined the association of 6592 plasma proteins with a diagnosis of MN in the Boston Kidney Biopsy Cohort (BKBC, n = 434), with replication of the top hits in the Nephrotic Syndrome Study Network (NEPTUNE, n = 132).

Results

In BKBC, 2 proteins, testican-2 and alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase (MGT5A), were associated with MN when compared with the reference diagnosis (normal or thin basement membrane [TBM] disease) as well as when compared with all other diagnoses among individuals who had undergone kidney biopsy for the indication of proteinuria or nephrotic syndrome. In NEPTUNE, plasma levels of both proteins, as well as glomerular expression of their cognate genes, were increased in MN compared with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). In receiver operating characteristic curve analyses, the addition of plasma testican-2 and MGT5A levels significantly improved discrimination of MN from other diagnoses in BKBC and NEPTUNE compared with models incorporating age, sex, race, estimated glomerular filtration rate (eGFR), and proteinuria.

Conclusion

Together, these findings motivate interest in testican-2 and MGT5A as markers and potential functional participants in MN. More work is required to understand the biological role of these proteins in the glomerular basement membrane in relation to immune complex deposition as well as to assess their performance as biomarkers alongside circulating autoantibodies in patients with MN.

膜性肾病（MN）是肾病综合征的常见病因，通常通过肾活检诊断。方法我们在波士顿肾活检队列（BKBC, n = 434）中检测了6592种血浆蛋白与MN诊断的关系，并在肾病综合征研究网络（NEPTUNE, n = 132）中复制了最热门的结果。结果在BKBC中，睾丸素-2和α -1,6-甘露糖糖蛋白6- β - n-乙酰氨基葡萄糖转移酶（MGT5A）两种蛋白与MN的相关性与参考诊断（正常或薄基底膜[TBM]病）以及其他诊断（以蛋白尿或肾病综合征为指征进行肾活检的个体）均有相关性。在NEPTUNE中，与微小变化病（MCD）和局灶节段性肾小球硬化（FSGS）相比，MN中这两种蛋白的血浆水平以及它们同源基因的肾小球表达均升高。在受试者工作特征曲线分析中，与纳入年龄、性别、种族、估计肾小球滤过率（eGFR）和蛋白尿的模型相比，血浆睾丸素-2和MGT5A水平的增加显著提高了BKBC和NEPTUNE中MN与其他诊断的区别。总之，这些发现激发了人们对睾丸素-2和MGT5A作为MN标记物和潜在功能参与者的兴趣。需要更多的工作来了解这些蛋白质在肾小球基底膜中与免疫复合物沉积有关的生物学作用，以及评估它们与MN患者循环自身抗体一起作为生物标志物的性能。

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引用次数: 0

Virtual Care Utilization and Peritonitis Risk in Rural and Indigenous Peritoneal Dialysis Patients 农村和本地腹膜透析患者的虚拟护理利用和腹膜炎风险

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports

Pub Date : 2026-02-01 Epub Date: 2025-11-20 DOI: 10.1016/j.ekir.2025.11.013

Anurag Singh , Anam Liaqat , Talal Khalid , Karen Walkey , Vanessa Wheeler , Khalid Bashir , Mark Elliott , Adeera Levin

Introduction

Peritoneal dialysis (PD) provides an essential home-based kidney replacement therapy, particularly for rural and Indigenous populations with limited access to in-center hemodialysis. Trust, continuity, and technical proficiency are critical for safe PD care. The COVID-19 pandemic accelerated virtual care delivery, coinciding with increased PD-associated peritonitis.

Methods

We conducted a retrospective cohort study (2021–2023) with an embedded qualitative component at a regional hospital in Northern British Columbia, Canada. Demographic, clinical, and virtual care data were extracted from the provincial databases and patient charts. Peritonitis episodes were classified using structured Root Cause Analysis (RCA). We used multivariable logistic regression to assess associations between patient factors and peritonitis risk. We used semi-structured interviews with 12 patients on PD to explore perceptions of trust, training adequacy, and care continuity.

Results

Among 45 adult patients on PD (mean age 63.5 ± 12.1 years), 78 peritonitis episodes occurred. Patients from rural Indigenous communities represented 33.3% of the cohort but accounted for 70.5% of episodes. RCA attributed 63.8% of episodes to technique failure, 19.1% to acute events, and 17.0% to psychosocial stressors. Peritonitis was associated with residence in an Indigenous community (odds ratio [OR]: 2.45, 95% confidence interval [CI]: 1.01–5.94, P = 0.049), high virtual care exposure (≥ 85% of visits; OR: 2.85, 95% CI: 1.19–6.84, P = 0.019), and technique failure (OR: 3.12, 95% CI: 1.42–6.84, P = 0.005). Qualitative themes included diminished trust, inadequate hands-on training, and perceived clinical detachment.

Conclusion

High virtual care exposure was associated with increased risk of peritonitis, particularly among patients in rural Indigenous communities. Adapting PD models to strengthen trust, hands-on training, and cultural safety may improve outcomes.

腹膜透析（PD）提供了一种基本的家庭肾脏替代疗法，特别是对于农村和土著人口，他们无法获得中心血液透析。信任、连续性和技术熟练是PD安全护理的关键。COVID-19大流行加速了虚拟医疗服务，同时pd相关性腹膜炎增加。方法我们在加拿大不列颠哥伦比亚省北部的一家地区医院进行了一项回顾性队列研究（2021-2023）。人口统计、临床和虚拟护理数据是从省级数据库和患者图表中提取的。使用结构化根本原因分析（RCA）对腹膜炎发作进行分类。我们使用多变量逻辑回归来评估患者因素与腹膜炎风险之间的关系。我们对12名PD患者进行了半结构化访谈，以探讨对信任、培训充分性和护理连续性的看法。结果45例成年PD患者（平均年龄63.5±12.1岁）发生腹膜炎78例。来自农村土著社区的患者占队列的33.3%，但占发作的70.5%。RCA将63.8%的发作归因于技术失败，19.1%归因于急性事件，17.0%归因于心理社会压力。腹膜炎与居住在土著社区（优势比[OR]: 2.45, 95%可信区间[CI]: 1.01-5.94, P = 0.049）、高虚拟护理暴露（≥85%的就诊；OR: 2.85, 95% CI: 1.19-6.84, P = 0.019）和技术失败（OR: 3.12, 95% CI: 1.42-6.84, P = 0.005）相关。定性主题包括信任减少、实践培训不足和感知到的临床脱离。结论高虚拟护理暴露与腹膜炎风险增加有关，特别是在农村土著社区的患者中。调整PD模式以加强信任、实践培训和文化安全可能会改善结果。

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引用次数: 0

Recurrence of C3 Glomerulopathy and Immune Complex–Mediated Membranoproliferative Glomerulonephritis After Kidney Transplantation: Challenges and Opportunities 肾移植后C3肾小球病变和免疫复合物介导的膜增生性肾小球肾炎的复发：挑战和机遇

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports

Pub Date : 2026-02-01 Epub Date: 2025-11-12 DOI: 10.1016/j.ekir.2025.11.008

José Enrique Ruiz-Cabello , Hernando Trujillo , Teresa Cavero , Amado Andrés , Manuel Praga , Fernando Caravaca-Fontán

Recurrent C3 glomerulopathy (C3G) and primary immune complex–mediated membranoproliferative glomerulonephritis (IC-MPGN) remain major causes of kidney allograft dysfunction and loss. Their pathogenesis involves genetic susceptibility, acquired complement dysregulation, and transplant-related triggers, yet no clear validated predictors of recurrence exist. Recurrence rates after kidney transplantation frequently exceed 60% and are associated with progression to graft failure. Early detection, often achievable through protocol biopsies, offers an opportunity for timely intervention, although histologic recognition of early recurrence can be challenging. Comprehensive pretransplant evaluation, including genetic and molecular complement testing and screening for monoclonal gammopathies, may refine risk stratification. Conventional treatments, including intensified immunosuppression, rituximab, and plasma exchange, have shown limited and inconsistent efficacy. Conversely, complement-targeted therapies have yielded promising outcomes. Although eculizumab remains the most extensively studied agent, emerging proximal complement inhibitors such as iptacopan and pegcetacoplan have shown encouraging efficacy in both native and recurrent disease. However, optimal timing, prophylactic use, and long-term safety in transplant recipients remain uncertain. In this review, we outline the clinical spectrum, key diagnostic and therapeutic challenges, and emerging treatment strategies for recurrent C3G and IC-MPGN, highlighting advances that may ultimately improve graft survival and patient outcomes.

复发性C3肾小球病变（C3G）和原发性免疫复合物介导的膜增生性肾小球肾炎（IC-MPGN）仍然是导致同种异体肾功能障碍和丧失的主要原因。其发病机制涉及遗传易感性、获得性补体失调和移植相关的触发因素，但目前尚无明确的复发预测因素。肾移植后的复发率经常超过60%，并伴有移植物衰竭的进展。尽管早期复发的组织学识别可能具有挑战性，但通常通过方案活检可以实现早期检测，为及时干预提供了机会。全面的移植前评估，包括遗传和分子补体检测以及单克隆伽玛病筛查，可能会完善风险分层。常规治疗，包括强化免疫抑制、利妥昔单抗和血浆置换，显示出有限和不一致的疗效。相反，补体靶向治疗已经产生了有希望的结果。尽管eculizumab仍然是研究最广泛的药物，新兴的近端补体抑制剂，如伊普他科泮和pegcetacoplan，在原生和复发性疾病中都显示出令人鼓舞的疗效。然而，移植受者的最佳时机、预防使用和长期安全性仍不确定。在这篇综述中，我们概述了复发性C3G和IC-MPGN的临床谱、关键诊断和治疗挑战，以及新兴的治疗策略，强调了可能最终改善移植物存活和患者预后的进展。

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引用次数: 0

Heterogeneity of Estimated GFR Slopes According to Etiology, Estimated GFR and Urinary Albumin-to-Creatinine Ratio in a Large Cohort of Patients With CKD 在大型CKD患者队列中，根据病因、估计GFR和尿白蛋白/肌酐比值估计GFR斜率的异质性

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports

Pub Date : 2026-02-01 Epub Date: 2025-11-20 DOI: 10.1016/j.ekir.2025.11.021

Charlotte Behning , Ulla T. Schultheiss , Jennifer Nadal , Heike Meiselbach , Sebastian Schönherr , Lukas Forer , Elke Schaeffner , Vera Krane , Markus P. Schneider , Matthias Schmid , Florian Kronenberg , Anna Köttgen , Kai-Uwe Eckardt , Fruzsina Kotsis

Introduction

The rate of decline in estimated glomerular filtration rate (GFR, eGFR) is increasingly recognized as a quantitative marker of chronic kidney disease (CKD) progression. However, data on eGFR slopes have mainly been reported in cohorts enriched for fast progression and the heterogeneity of eGFR slopes across the spectrum of CKD remains poorly defined.

Methods

In 5214 participants of the German CKD (GCKD) study, we modeled eGFR slopes using per-protocol and clinical measurements. We used linear-mixed effects models, with eGFR slope as the outcome and baseline demographics as independent variables to (i) describe eGFR slope heterogeneity; (ii) assess differences by CKD etiology, eGFR and urinary albumin-to-creatinine ratio (UACR) categories, sex, and age; and (iii) determine associations of slopes with estimated eGFR decline (30%, 40%, and 57%) and observed end points (kidney failure with replacement therapy, mortality).

Results

On average, 9 eGFR values per participant (interquartile range: 7–12) over 6.5 years were used for slope calculation. The adjusted mean annual eGFR slope was −1.43 ml/min per 1.73 m². Slopes were similar across eGFR categories, but steeper with higher UACR. Faster eGFR decline was observed in participants of younger age and in those with polycystic kidney disease or diabetic kidney disease (DKD). Although eGFR slopes did not consistently differ by sex, women with diabetes as the leading cause of CKD had lower slopes than their male counterparts. A rapid annual decline (> 5 ml/min per 1.73 m²) occurred in 4.3%, with variation in frequency by CKD cause and UACR.

Conclusion

In conclusion, though the average eGFR slope was low, it varied considerably, depending on CKD etiology and UACR. This data may help to put slope estimates in individual patients and defined subpopulations into perspective.

肾小球滤过率（GFR, eGFR）的下降率越来越被认为是慢性肾脏疾病（CKD）进展的定量标志物。然而，关于eGFR斜率的数据主要是在快速进展的队列中报道的，并且eGFR斜率在整个CKD谱系中的异质性仍然不明确。方法在5214名德国CKD （GCKD）研究参与者中，我们使用每个方案和临床测量来模拟eGFR斜率。我们使用线性混合效应模型，将eGFR斜率作为结果，基线人口统计数据作为自变量来(i)描述eGFR斜率的异质性；（ii）评估CKD病因、eGFR和尿白蛋白与肌酐比（UACR）类别、性别和年龄的差异；（iii）确定坡度与估计eGFR下降（30%，40%和57%）和观察终点（替代治疗肾衰竭，死亡率）的关系。结果平均每个参与者在6.5年期间使用9个eGFR值（四分位数间距为7-12）进行斜率计算。调整后的年平均eGFR斜率为- 1.43 ml/min / 1.73 m2。不同eGFR类别的斜率相似，但UACR越高，斜率越陡。在年龄较小的参与者和患有多囊肾病或糖尿病肾病（DKD）的参与者中观察到eGFR下降更快。虽然eGFR斜率在性别上没有一致的差异，但糖尿病作为CKD主要原因的女性的斜率比男性低。4.3%的患者出现快速的年下降（每1.73 m2下降5 ml/min），随CKD原因和UACR的变化而变化。结论eGFR平均斜率较低，但因CKD病因和UACR的不同而有较大差异。这些数据可能有助于对个体患者和确定的亚群进行斜率估计。

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引用次数: 0

Renal Response Status and Long-Term Kidney Outcomes in Childhood-Onset Lupus Nephritis 儿童期狼疮性肾炎的肾脏反应状态和长期肾脏预后

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports

Pub Date : 2026-02-01 Epub Date: 2025-11-26 DOI: 10.1016/j.ekir.2025.11.024

Eugene Yu-hin Chan , Kevin Chun-hei Wu , Dongyang Zhou , Kyle Ying-kit Lin , Justin Ming-yin Ma , Sze-wa Wong , Fiona Fung-yee Lai , Tsz-wai Ho , Pak-chiu Tong , Wai-ming Lai , Desmond Yat-hin Yap , Tak Mao Chan , Alison Lap-tak Ma

Introduction

The aim of this study was to evaluate the relationship between modified primary efficacy renal response (PERR, mPERR) and modified complete renal response (CRR, mCRR) at 24 months postbiopsy and long-term kidney outcomes in childhood-onset lupus nephritis (LN, cLN).

Methods

We conducted a cohort study of biopsy-proven cLN diagnosed at the age of <18 years between 2001 and 2023, with prospective data collected from 2021 to 2025. We examined the relationship between modified versions of PERR (mPERR) and CRR (mCRR) at 24 months postbiopsy and survival free from advanced chronic kidney disease (CKD), including kidney failure (CKD 4–5D/T).

Results

One hundred seven Chinese children (93 female; median age at diagnosis: 13.7, interquartile range [IQR]: 11.0–16.6 years) were analyzed. Ninety-seven (91%) had proliferative LN. The median observation period was 12.0 (IQR: 6.4–17.8) years. At 24 months postbiopsy, 93 (87%) and 81 (76%) subjects were mPERR and mCRR responders, respectively. Kaplan-Meier analysis showed mPERR responders at 24 months had superior CKD 4–5D/T–free survival (responders: 100%, 98.8%, and 97.2%; nonresponders 92.9%, 78.6%, and 78.6% at 1, 5, and 10 years following 24 months postbiopsy; log-rank P = 0.013). Achieving mCRR trended toward better kidney survival. Multivariable analysis identified 24-months mPERR nonresponse (adjusted hazard: 4.39, 95% confidence interval CI: 1.04–18.4, P = 0.04) and baseline estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m² (adjusted hazard: 6.07, 95% confidence interval: 1.21–30.39, P = 0.03) as predictors of CKD 4–5D/T. Forty-four subjects (41%) experienced 89 kidney relapse episodes. Kaplan-Meier analysis showed that nonresponse by mPERR (log-rank P < 0.001) and mCRR (log-rank P = 0.03) at 24 months were associated with inferior relapse-free survival.

Conclusion

mPERR at 24 months predicts long-term kidney survival in cLN. Achieving mPERR and mCRR shows significant benefits on lower risk of renal relapse.

本研究的目的是评估儿童发作性狼疮性肾炎（LN, cLN）活检后24个月改良原发性疗效肾反应（PERR, mPERR）和改良完全肾反应（CRR, mCRR）与长期肾脏预后之间的关系。方法：我们在2001年至2023年期间对18岁活检证实的cLN进行了队列研究，前瞻性数据收集于2021年至2025年。我们研究了活检后24个月PERR改良版本（mPERR）和CRR （mCRR）与无晚期慢性肾脏疾病（CKD）（包括肾衰竭（CKD 4-5D /T））生存率之间的关系。结果共分析中国儿童107例，其中女性93例，诊断时中位年龄13.7岁，四分位间距[IQR]: 11.0 ~ 16.6岁。97例（91%）为增生性LN。中位观察期为12.0 （IQR: 6.4 ~ 17.8）年。活检后24个月，分别有93名（87%）和81名（76%）受试者对mPERR和mCRR有反应。Kaplan-Meier分析显示，mPERR应答者在24个月时CKD 4-5D / T-free生存率更高（应答者：100%、98.8%和97.2%；无应答者在活检后24个月后的1年、5年和10年分别为92.9%、78.6%和78.6%;log-rank P = 0.013）。实现mCRR趋向于更好的肾脏生存。多变量分析确定24个月mPERR无反应（校正风险：4.39,95%可信区间CI: 1.04-18.4, P = 0.04）和基线估计肾小球滤过率（eGFR）和lt； 60 ml/min / 1.73 m2（校正风险：6.07,95%可信区间：1.21-30.39,P = 0.03）是CKD 4-5D /T的预测因子。44名受试者（41%）经历了89次肾脏复发。Kaplan-Meier分析显示，24个月时mPERR （log-rank P < 0.001）和mCRR （log-rank P = 0.03）无反应与较低的无复发生存期相关。结论24个月时的mperr可预测cLN患者的长期肾脏生存。实现mPERR和mCRR对降低肾脏复发风险有显著益处。

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引用次数: 0

Delphi Consensus on Surrogate End Points in C3 Glomerulopathy and Primary Immune Complex–Mediated Membranoproliferative Glomerulonephritis 关于C3肾小球病变和原发性免疫复合物介导的膜增生性肾小球肾炎替代终点的德尔菲共识

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports

Pub Date : 2026-02-01 Epub Date: 2025-11-05 DOI: 10.1016/j.ekir.2025.10.028

Fernando Caravaca-Fontán , Fadi Fakhouri , Christoph Licht , Matthew C. Pickering , Franz Schaefer , Edwin Wong

Introduction

C3 glomerulopathy (C3G) and primary immune complex–mediated membranoproliferative glomerulonephritis (IC-MPGN) are rare kidney diseases driven by complement dysregulation. Proteinuria is a commonly used clinical end point in trials involving these conditions. However, its recognition as a validated end point by regulatory bodies remains limited, despite growing evidence supporting its prognostic value as a surrogate biomarker for the development of kidney failure. The aim of this study was to establish consensus on the clinical relevance of proteinuria as a prognostic and treatment end point in C3G and primary IC-MPGN.

Methods

A 2-round modified Delphi process was conducted, informed by literature review and expert input. A steering committee composed of 4 European nephrologists, 1 Canadian nephrologist, and 1 European rheumatologist developed 31 statements covering the following 3 domains: (i) treatment efficacy end points, (ii) current assessment end points, and (iii) the role of proteinuria. Statements formed part of an online survey using a 4-point Likert scale, distributed to a broader panel of nephrologists and kidney pathologists across Europe.

Results

Fifty-one and 50 responses were received in rounds 1 and 2. Of the 31 statements, 29 reached consensus (≥ 75% agreement). Key consensus points included the following: (i) reduction in proteinuria preserves long-term kidney function and is a treatment goal; (ii) longitudinal monitoring of proteinuria, alongside other markers is valuable for guiding treatment; (iii) a ≥ 50% proteinuria reduction over 6 months indicates meaningful therapeutic benefit; and (iv) proteinuria < 1 g/d is associated with improved outcomes.

Conclusion

This study demonstrates consensus supporting proteinuria as a meaningful treatment end point for C3G and primary IC-MPGN.

c3型肾小球病（C3G）和原发性免疫复合物介导的膜增生性肾小球肾炎（IC-MPGN）是由补体失调引起的罕见肾脏疾病。蛋白尿是涉及这些疾病的试验中常用的临床终点。然而，尽管越来越多的证据支持其作为肾衰竭发展的替代生物标志物的预后价值，但监管机构对其作为有效终点的认可仍然有限。本研究的目的是就蛋白尿作为C3G和原发性IC-MPGN的预后和治疗终点的临床相关性达成共识。方法采用2轮修正德尔菲法，结合文献查阅和专家意见。由4名欧洲肾病学家、1名加拿大肾病学家和1名欧洲风湿病学家组成的指导委员会制定了31项声明，涵盖以下3个领域：(i)治疗疗效终点，（ii）当前评估终点，（iii）蛋白尿的作用。这些陈述构成了一项使用4分李克特量表的在线调查的一部分，该调查被分发给欧洲更广泛的肾病学家和肾脏病理学家小组。结果第1轮和第2轮分别收到51份和50份回复。31项声明中，29项达成共识（≥75%同意）。关键的共识点包括以下几点：(i)蛋白尿的减少可以保护长期肾功能，是一个治疗目标；（ii）纵向监测蛋白尿，与其他标志物一起对指导治疗有价值；（iii） 6个月内蛋白尿减少≥50%表明有意义的治疗获益；（iv）蛋白尿1 g/d与改善预后相关。结论：本研究一致支持蛋白尿作为C3G和原发性IC-MPGN有意义的治疗终点。

{"title":"Delphi Consensus on Surrogate End Points in C3 Glomerulopathy and Primary Immune Complex–Mediated Membranoproliferative Glomerulonephritis","authors":"Fernando Caravaca-Fontán , Fadi Fakhouri , Christoph Licht , Matthew C. Pickering , Franz Schaefer , Edwin Wong","doi":"10.1016/j.ekir.2025.10.028","DOIUrl":"10.1016/j.ekir.2025.10.028","url":null,"abstract":"<div><h3>Introduction</h3><div>C3 glomerulopathy (C3G) and primary immune complex–mediated membranoproliferative glomerulonephritis (IC-MPGN) are rare kidney diseases driven by complement dysregulation. Proteinuria is a commonly used clinical end point in trials involving these conditions. However, its recognition as a validated end point by regulatory bodies remains limited, despite growing evidence supporting its prognostic value as a surrogate biomarker for the development of kidney failure. The aim of this study was to establish consensus on the clinical relevance of proteinuria as a prognostic and treatment end point in C3G and primary IC-MPGN.</div></div><div><h3>Methods</h3><div>A 2-round modified Delphi process was conducted, informed by literature review and expert input. A steering committee composed of 4 European nephrologists, 1 Canadian nephrologist, and 1 European rheumatologist developed 31 statements covering the following 3 domains: (i) treatment efficacy end points, (ii) current assessment end points, and (iii) the role of proteinuria. Statements formed part of an online survey using a 4-point Likert scale, distributed to a broader panel of nephrologists and kidney pathologists across Europe.</div></div><div><h3>Results</h3><div>Fifty-one and 50 responses were received in rounds 1 and 2. Of the 31 statements, 29 reached consensus (≥ 75% agreement). Key consensus points included the following: (i) reduction in proteinuria preserves long-term kidney function and is a treatment goal; (ii) longitudinal monitoring of proteinuria, alongside other markers is valuable for guiding treatment; (iii) a ≥ 50% proteinuria reduction over 6 months indicates meaningful therapeutic benefit; and (iv) proteinuria < 1 g/d is associated with improved outcomes.</div></div><div><h3>Conclusion</h3><div>This study demonstrates consensus supporting proteinuria as a meaningful treatment end point for C3G and primary IC-MPGN.</div></div>","PeriodicalId":17761,"journal":{"name":"Kidney International Reports","volume":"11 2","pages":"Article 103671"},"PeriodicalIF":5.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145789118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Safety and Effectiveness of Long-Term Isoniazid Treatment for the Prevention of Tuberculosis in High-Risk Dialysis Patients 长期异烟肼治疗预防高危透析患者结核的安全性和有效性

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports

Pub Date : 2026-02-01 Epub Date: 2025-12-04 DOI: 10.1016/j.ekir.2025.11.038

Robert Freercks , Kathryn Manning , Jason Ensor , Noel Walton , Siviwe Ndamase , Elmi Muller , Savania Nagiah , Andrew D. Redd , Elizabeth van der Merwe

Introduction

Patients with chronic kidney disease (CKD) receiving dialysis (CKD-5D) are at increased risk for tuberculosis (TB), which significantly heightens the risk of mortality. Long-term isoniazid prevention therapy (IPT) to prevent TB is a promising strategy, although the safety and effectiveness of the approach in this high-risk population is unknown.

Methods

Between 2019 and 2025, universal long-term IPT was administered to patients with CKD-5D (N = 182) receiving dialysis in Gqeberha, South Africa (post-IPT cohort), an area with high TB rates. The incidence of TB post-IPT was compared with a historical CKD-5D cohort (pre-IPT) from the same unit (n = 111). Primary outcomes included incident TB and adverse events attributable to IPT.

Results

The incidence of TB (per 100,000 person-years [pys]) in the post-IPT cohort was 367, versus 4505 pre-IPT (92% relative risk reduction, P < 0.001). During IPT, 32 patients (17.6%) developed symptoms of peripheral neuropathy (PNP), of whom 20 (62.5%) resolved fully with increased pyridoxine dosing. PNP was associated with older age and hemodialysis (HD). Liver injury was noted in 6 patients (3.3%), of whom 2 continued IPT successfully. Overall, 17 patients (9.3%) required discontinuation of IPT because of side effects attributed to IPT (PNP = 12, liver injury = 4, and pancreatitis = 1). No deaths were attributed to IPT.

Conclusion

Long-term IPT significantly reduced the incidence of TB in a high-risk cohort with CKD-5D. IPT was safe and well-tolerated, with < 10% of patients discontinuing therapy because of adverse events, which were generally mild and reversible. These findings provide strong real-world evidence supporting IPT use in TB-endemic dialysis populations.

慢性肾脏疾病（CKD）接受透析（CKD- 5d）的患者患结核病（TB）的风险增加，这显著增加了死亡风险。长期异烟肼预防治疗（IPT）预防结核病是一种很有前景的策略，尽管该方法在这一高危人群中的安全性和有效性尚不清楚。方法在2019年至2025年期间，对南非Gqeberha （IPT后队列）接受透析的CKD-5D患者（N = 182）进行了普遍的长期IPT治疗，这是一个结核病高发地区。将ipt后的结核病发病率与同一单位的CKD-5D历史队列（ipt前）进行比较（n = 111）。主要结局包括结核事件和IPT引起的不良事件。结果ipt后队列中结核病发病率（每10万人年[pys]）为367例，而ipt前为4505例（相对风险降低92%，P < 0.001）。在IPT期间，32例患者（17.6%）出现周围神经病变（PNP）症状，其中20例（62.5%）随着吡哆醇剂量的增加而完全缓解。PNP与老年和血液透析（HD）相关。6例（3.3%）出现肝损伤，其中2例成功继续IPT治疗。总体而言，17例患者（9.3%）由于IPT引起的副作用（PNP = 12，肝损伤= 4，胰腺炎= 1）需要停止IPT。没有人死于IPT。结论长期IPT可显著降低CKD-5D高危队列患者的TB发病率。IPT是安全且耐受性良好的，10%的患者因不良事件而停止治疗，这些不良事件通常是轻微且可逆的。这些发现提供了强有力的现实证据，支持在结核病流行的透析人群中使用IPT。

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引用次数: 0

Alport Syndrome is a Partial Tubulointerstitial Disease of the Kidney Alport综合征是一种部分肾小管间质性疾病

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports

Pub Date : 2026-02-01 Epub Date: 2025-11-17 DOI: 10.1016/j.ekir.2025.11.019

Lisa Loderbauer , Karl X. Knaup , Daniel Reisenbüchler , Nicolas Kaiser , Stephanie Naas , Karen Schneider , Florian J. Wopperer , Antje Wiesener , Francesca Pasutto , Mario Schiffer , Christoph Daniel , Katharina A.E. Broeker , Dorit Merhof , Maike Buettner-Herold , Michael S. Wiesener

Introduction

Recent genetic studies have shown that Alport syndrome (AS) is much more prevalent than clinically recognized, suggesting that atypical cases may phenocopy other kidney diseases. To date, pathomechanistic studies of AS have focused exclusively on the glomerular membrane, yet equally strong expression of collagen α(IV) chains is found along the distal renal tubule. We hypothesized that genetically determined abnormality of the tubular collagen IV (α345) molecule contributes to kidney failure and may drive atypical phenotypes.

Methods

Histology and primary tubular cells (PTCs) of 8 patients with AS were investigated alongside controls.

Results

Collagen α5 (IV) was detected within the tubular basement membrane (BM) (TBM) of the distal segments of renal tubules by immunohistochemistry. In situ hybridization on human tissues and protein detection of collagen α5 (IV) in PTC cultures clearly showed that the distal tubular apparatus predominantly produces collagen IV for the TBM. Electron microscopy of biopsies from patients with AS demonstrated irregularities of the TBM, somewhat similar as described for the glomerular BM (GBM). Finally, computer-assisted analyses showed that in biopsies of patients with AS, interstitial fibrosis preferentially occurs in spatial vicinity of the affected distal tubules.

Conclusion

Our study demonstrates that the collagen IV (α345) molecule within the TBM is largely produced by the distal tubule itself. In AS, the TBM shows ultrastructural changes, which may induce fibrotic molecular signatures, as tubulointerstitial fibrosis appears to start in the vicinity of the distal tubule. Therefore, we postulate that the progression of kidney disease in AS may in part stem from the (distal) tubular apparatus.

最近的遗传学研究表明，阿尔波特综合征（AS）比临床认识到的更为普遍，这表明非典型病例可能是其他肾脏疾病的表型。迄今为止，AS的病理机制研究仅集中在肾小球膜上，然而沿远端肾小管也发现了同样强烈的胶原α(IV)链表达。我们假设，遗传决定的管状胶原IV （α345）分子异常有助于肾衰竭，并可能导致非典型表型。方法对8例AS患者的组织学和原代小管细胞（ptc）进行观察。结果免疫组化法在肾小管远段基底膜（TBM）内检测到α5 （IV）胶原蛋白。人体组织的原位杂交和PTC培养中α5 （IV）胶原蛋白的检测清楚地表明，远端管状器主要为TBM产生IV胶原。来自AS患者的活检电镜显示TBM不规则，与肾小球BM （GBM）的描述有些相似。最后，计算机辅助分析显示，在AS患者的活检中，间质纤维化优先发生在受影响的远端小管附近。结论TBM内的胶原IV （α345）分子主要由远端小管自身产生。在AS中，TBM显示超微结构变化，这可能诱发纤维化分子特征，因为小管间质纤维化似乎开始于远端小管附近。因此，我们假设AS肾脏疾病的进展可能部分源于（远端）肾小管。

{"title":"Alport Syndrome is a Partial Tubulointerstitial Disease of the Kidney","authors":"Lisa Loderbauer , Karl X. Knaup , Daniel Reisenbüchler , Nicolas Kaiser , Stephanie Naas , Karen Schneider , Florian J. Wopperer , Antje Wiesener , Francesca Pasutto , Mario Schiffer , Christoph Daniel , Katharina A.E. Broeker , Dorit Merhof , Maike Buettner-Herold , Michael S. Wiesener","doi":"10.1016/j.ekir.2025.11.019","DOIUrl":"10.1016/j.ekir.2025.11.019","url":null,"abstract":"<div><h3>Introduction</h3><div>Recent genetic studies have shown that Alport syndrome (AS) is much more prevalent than clinically recognized, suggesting that atypical cases may phenocopy other kidney diseases. To date, pathomechanistic studies of AS have focused exclusively on the glomerular membrane, yet equally strong expression of collagen α(IV) chains is found along the distal renal tubule. We hypothesized that genetically determined abnormality of the tubular collagen IV (α345) molecule contributes to kidney failure and may drive atypical phenotypes.</div></div><div><h3>Methods</h3><div>Histology and primary tubular cells (PTCs) of 8 patients with AS were investigated alongside controls.</div></div><div><h3>Results</h3><div>Collagen α5 (IV) was detected within the tubular basement membrane (BM) (TBM) of the distal segments of renal tubules by immunohistochemistry. <em>In situ</em> hybridization on human tissues and protein detection of collagen α5 (IV) in PTC cultures clearly showed that the distal tubular apparatus predominantly produces collagen IV for the TBM. Electron microscopy of biopsies from patients with AS demonstrated irregularities of the TBM, somewhat similar as described for the glomerular BM (GBM). Finally, computer-assisted analyses showed that in biopsies of patients with AS, interstitial fibrosis preferentially occurs in spatial vicinity of the affected distal tubules.</div></div><div><h3>Conclusion</h3><div>Our study demonstrates that the collagen IV (α345) molecule within the TBM is largely produced by the distal tubule itself. In AS, the TBM shows ultrastructural changes, which may induce fibrotic molecular signatures, as tubulointerstitial fibrosis appears to start in the vicinity of the distal tubule. Therefore, we postulate that the progression of kidney disease in AS may in part stem from the (distal) tubular apparatus.</div></div>","PeriodicalId":17761,"journal":{"name":"Kidney International Reports","volume":"11 2","pages":"Article 103694"},"PeriodicalIF":5.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145789063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0