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Complement Alternative Pathway Dominance in Atypical Hemolytic Uremic Syndrome Revealed by Endothelial Bioassays 内皮生物检测揭示非典型溶血性尿毒症综合征补体替代途径优势
IF 5.7 2区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2025-12-12 DOI: 10.1016/j.ekir.2025.103717
Donata Santarsiero , Sara Gastoldi , Valeria Guaschino , Elena Bresin , Ilaria Pagani , Andrea Pasini , Elena Romano , Ariela Benigni , Giuseppe Remuzzi , Marina Noris , Sistiana Aiello
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引用次数: 0
Corrigendum to “Early and Sensitive Detection of Cisplatin-Induced Kidney Injury Using Novel Biomarkers” [Kidney International Reports Volume 10, Issue 4, April 2025, Pages 1175-1187] “使用新型生物标志物早期和敏感检测顺铂诱导的肾损伤”的更正[肾脏国际报告第10卷,第4期,2025年4月,1175-1187页]
IF 5.7 2区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2025-12-09 DOI: 10.1016/j.ekir.2025.103723
Michael Strader , Gary Friedman , Xavier Benain , Nunzio Camerlingo , Stefan Sultana , Shiran Shapira , Nadir Aber , Patrick T. Murray
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引用次数: 0
Reconstruction of Single-Cell Spatial Transcriptomes in Archival Kidney Biopsies 档案肾活检单细胞空间转录组的重建
IF 5.7 2区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2025-12-05 DOI: 10.1016/j.ekir.2025.11.036
Simen F. Pettersen , Eleni Skandalou , Jessica Furriol , Tarig Osman , Hans Peter Marti , Øystein Eikrem
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引用次数: 0
CKD in Sri Lanka - A Prevalence Study 斯里兰卡CKD患病率研究
IF 5.7 2区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2025-12-05 DOI: 10.1016/j.ekir.2025.11.034
Rajitha A. Abeysekera , Helen G. Healy , S. Samita , Sampath Tennakoon , Sakunthala Jayasinghe , Nuwan D. Wickramasinghe , Indika Gawarammana , Navin Gamage , Vishwa Hemakeerthi , Farook Rafsanjani , T.M.W.V. Tennakoon , Sachini N. Palliyaguru , Wendy E. Hoy
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引用次数: 0
Complement-Mediated Kidney Diseases: Role of Alternative Pathway in Glomerular Inflammation 补体介导的肾脏疾病:替代途径在肾小球炎症中的作用
IF 5.7 2区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2025-12-04 DOI: 10.1016/j.ekir.2025.11.029
Jonathan Barratt , Peter Garred , Richard A. Lafayette , Hong Zhang , Jürgen Floege
Complement-mediated kidney diseases (CMKDs) comprise a diverse group of rare disorders characterized by the activation of the complement system, leading to glomerular inflammation, kidney injury, and in some cases, kidney failure. Although the contribution of complement activation to disease pathogenesis varies across CMKDs, the alternative complement pathway appears to play a pivotal role in driving inflammation and tissue damage in the kidney by amplifying complement activation, regardless of the initiating complement pathway. A growing body of evidence links the alternative pathway with glomerular inflammation in CMKDs, including key mechanistic insights from preclinical in vivo models, the association of alternative pathway components with histologic kidney injury and disease severity, and the efficacy of alternative pathway inhibition in patients with these disorders. With an improved understanding of the mechanisms of alternative pathway overactivation in CMKDs, many novel complement inhibitors targeting the alternative pathway are in clinical development for the management of CMKDs, potentially offering a more precise, better-tolerated, and effective approach than conventional immunosuppressive agents or therapeutics that provide broader inhibition of the common terminal complement pathway. This review summarizes the role of the alternative pathway in the pathogenesis of CMKDs and provides evidence supporting its involvement in glomerular inflammation. In addition, we provide a future perspective on the principles guiding the treatment of glomerular inflammation with therapies that target the alternative pathway.
补体介导的肾脏疾病(CMKDs)包括多种罕见疾病,其特征是补体系统激活,导致肾小球炎症、肾损伤,在某些情况下导致肾衰竭。尽管补体激活对疾病发病机制的贡献因cmkd而异,但替代补体途径似乎通过放大补体激活在驱动肾脏炎症和组织损伤中发挥关键作用,而不管启动补体途径如何。越来越多的证据表明,替代途径与CMKDs的肾小球炎症有关,包括临床前体内模型的关键机制见解,替代途径成分与组织学肾损伤和疾病严重程度的关联,以及替代途径抑制对这些疾病患者的疗效。随着对CMKDs中替代通路过度激活机制的进一步了解,许多针对替代通路的新型补体抑制剂正在临床开发中,用于CMKDs的治疗,可能提供比传统免疫抑制剂或治疗更精确、更耐受性更好、更有效的方法,这些药物或治疗方法可以更广泛地抑制常见的终末补体通路。本文综述了替代途径在CMKDs发病机制中的作用,并提供了支持其参与肾小球炎症的证据。此外,我们提供了一个未来的观点,指导肾小球炎症的治疗原则与靶向替代途径的治疗。
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引用次数: 0
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 Pub 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
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 Pub 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
Clonal Hematopoiesis and Kidney Function in the ASPREE Cohort ASPREE队列的克隆造血和肾功能
IF 5.7 2区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2025-12-04 DOI: 10.1016/j.ekir.2025.11.037
Jasmine Singh , Kevan R. Polkinghorne , Rory Wolfe , Nicholas C. Wong , Sean Byars , Anna Leichter , Paul Lacaze , John J. McNeil , Suzanne G. Orchard , James Phung , Hayley S. Ramshaw , Le T.P. Thao , James B. Wetmore , Erica M. Wood , Robyn L. Woods , David J. Curtis , Zoe K. McQuilten

Introduction

Clonal hematopoiesis of indeterminate potential (CHIP) is emerging as a novel risk factor for many nonhematological diseases. Although some studies suggest that CHIP is associated with adverse kidney outcomes, the results are conflicting across cohorts.

Methods

In this secondary analysis of the ASPirin in Reducing Events in the Elderly (ASPREE) trial, we assessed the association between CHIP and kidney function in 9434 community-dwelling adults aged > 70 years. At baseline, participants were free of cardiovascular disease (CVD) and major life-limiting illness. In addition, we performed meta-analysis of published cohorts investigating the association between CHIP and incident kidney function decline.

Results

Of the participants, 2124 of 9434 (22.5%) had CHIP, of whom 532 had variant allele fraction (VAF) ≥ 10% and 887 had a single non-DNMT3A mutation. After adjusting for age and other confounders, there was no association between CHIP, including large CHIP or non-DNMT3A CHIP, and baseline estimated glomerular filtration rate (eGFR), baseline log-transformed urinary albumin-to-creatinine ratio (UACR), or rate of change of eGFR or log(UACR) over a median of 8.4 years of follow-up. Incident kidney function decline was not increased in this cohort, including in those with non-DNMT3A CHIP. Meta-analysis with other published cohorts supports an increased risk of incident kidney function decline in those with non-DNMT3A CHIP, with considerable heterogeneity.

Conclusion

We propose that the effect of CHIP is modified by participant factors, including comorbidities, partly accounting for heterogeneity across cohorts. This work contributes to a growing understanding of the interplay between CHIP and disease, and considerations in translating findings from large observational studies to individuals with CHIP.
不确定潜力克隆造血(CHIP)正成为许多非血液学疾病的一个新的危险因素。尽管一些研究表明CHIP与不良肾脏结局相关,但不同队列的研究结果相互矛盾。方法在这项阿司匹林降低老年事件(ASPREE)试验的二次分析中,我们评估了9434名70岁社区居民CHIP与肾功能之间的关系。在基线时,参与者无心血管疾病(CVD)和主要限制生命的疾病。此外,我们对已发表的队列进行了荟萃分析,调查CHIP与事件肾功能下降之间的关系。结果9434名参与者中有2124人(22.5%)患有CHIP,其中532人变异等位基因分数(VAF)≥10%,887人有单一非dnmt3a突变。在调整了年龄和其他混杂因素后,CHIP(包括大CHIP或非dnmt3a CHIP)与基线估计肾小球滤过率(eGFR)、基线对数转化尿白蛋白与肌酐比(UACR)或eGFR或对数变化率(UACR)之间没有关联,中位随访时间为8.4年。在该队列中,包括非dnmt3a CHIP患者,肾功能下降发生率没有增加。与其他已发表队列的荟萃分析支持非dnmt3a CHIP患者发生肾功能下降的风险增加,且具有相当大的异质性。我们认为CHIP的效果受到参与者因素的影响,包括合并症,部分解释了队列间的异质性。这项工作有助于加深对CHIP与疾病之间相互作用的理解,并考虑将大型观察性研究的结果转化为CHIP患者。
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引用次数: 0
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引用次数: 0
期刊
Kidney International Reports
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