Kidney International Reports最新文献

英文中文

Sodium-Glucose Cotransporter-2 Inhibitors in ADPKD: Time to Integrate Cardiovascular Outcomes 钠-葡萄糖共转运蛋白-2抑制剂在ADPKD：时间整合心血管结果。

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports

Pub Date : 2025-12-31 DOI: 10.1016/j.ekir.2025.103762

Martina Catania , Rodolfo Fernando Rivera , Kristiana Kola , Liliana Italia De Rosa , Michele Paolisi , Pierpaolo Bianca , Giuseppe Vezzoli , Maria Teresa Sciarrone Alibrandi

引用次数: 0

Phase 1 Study of Oral N-Acetylmannosamine in Primary Podocytopathies 口服n -乙酰氨基甘露糖胺治疗原发性足细胞病变的一期研究

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports

Pub Date : 2025-12-31 DOI: 10.1016/j.ekir.2025.103758

Marjan Huizing , Anirban Ganguli , Jonathan Bolaños , Petcharat Leoyklang , Kenneth J. Wilkins , Yi Zeng , William D. Figg , Francis Rossignol , May Christine V. Malicdan , Jeffrey B. Kopp , William A. Gahl

Introduction

Terminal sialic acid (SA) residues on glycoconjugates are essential for maintaining the glomerular filtration barrier’s charge selectivity and podocyte ultrastructure. SA depletion affects key podocyte glycoproteins, contributing to podocytopathy and proteinuria. Glomerular hyposialylation is commonly seen in experimental podocytopathies and human renal biopsies. In nephrotic mouse models, oral administration of the metabolic SA precursor, N-acetylmannosamine (ManNAc) restored sialylation and reduced proteinuria, suggesting therapeutic potential.

Methods

In this single-center, single-arm, ascending dose phase 1 trial, we evaluated safety and pharmacokinetics (PKs) of oral ManNAc in primary podocytopathies (ClinicalTrials.gov: NCT02639260). Eligible participants had urine protein-to-creatinine ratio (UPCR) > 1 g/g and estimated glomerular filtration rates (eGFR) > 15 ml/min per 1.73 m². Six subjects received a single 3g ManNAc dose followed by 5 days of 1.5 g twice-daily (BID) dosing. One subject received a single 6 g dose.

Results

All enrolled participants had primary podocytopathy, with eGFR of 25 to 89 ml/min per 1.73 m² and UPCR of 1.1 to 9.21 g/g. ManNAc was well-tolerated without serious adverse events (AEs). Maximum plasma ManNAc concentration was reached within 2 to 4 hours postdose, with dose-dependent increases in plasma SA. Subjects with eGFR < 45 ml/min per 1.73 m² showed elevated maximum plasma ManNAc concentration and area under curve for both ManNAc and SA, reflecting reduced renal clearance. Proteinuria reduction of 12% to 52% (regression-adjusted mean 9.69%, P < 0.0001) was observed in subjects receiving ManNAc BID, correlating with glomerular hyposialylation in pre-study renal biopsies.

Conclusion

Oral ManNAc demonstrated short-term safety and increased plasma SA levels in podocytopathy subjects. Early efficacy signals suggest that proteinuria reduction may correlate with glomerular hyposialylation, identifying a potential treatment biomarker. A phase 2 trial (NCT06664814) is underway to assess long-term outcomes.

糖缀合物上的末端唾液酸（SA）残基对于维持肾小球滤过屏障的电荷选择性和足细胞超微结构至关重要。SA耗竭影响关键足细胞糖蛋白，导致足细胞病变和蛋白尿。肾小球低磷酸化常见于实验性足细胞病和人肾活检。在肾病小鼠模型中，口服代谢SA前体n -乙酰氨基甘露糖胺（ManNAc）可恢复唾液化并减少蛋白尿，显示出治疗潜力。方法在这项单中心、单组、递增剂量的1期临床试验中，我们评估了口服ManNAc治疗原发性足细胞病变的安全性和药代动力学（PKs）（临床试验.gov: NCT02639260）。符合条件的参与者尿蛋白与肌酐比值（UPCR）为1 g/g，肾小球滤过率（eGFR）为15 ml/min / 1.73 m2。6名受试者接受单次3g甘露聚糖剂量，随后5天1.5 g每日两次（BID）给药。一名受试者接受单次6克剂量。结果所有入组的参与者都有原发性足细胞病，eGFR为25至89 ml/min / 1.73 m2， UPCR为1.1至9.21 g/g。ManNAc耐受性良好，无严重不良事件（ae）。血浆ManNAc浓度在给药后2至4小时内达到最大值，血浆SA呈剂量依赖性增加。eGFR为45 ml/min / 1.73 m2的受试者显示最大血浆ManNAc浓度和ManNAc和SA曲线下面积升高，反映肾脏清除率降低。在接受ManNAc BID的受试者中，蛋白尿减少了12%至52%（经回归校正的平均值为9.69%,P < 0.0001），这与研究前肾活检中的肾小球低磷酸化有关。结论口服甘露钠对足细胞病患者具有短期安全性，可提高血浆SA水平。早期疗效信号表明，蛋白尿减少可能与肾小球低磷酸化有关，这是一种潜在的治疗生物标志物。2期临床试验（NCT06664814）正在评估长期疗效。

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引用次数: 0

Response to the Letter to the Editor Entitled “SGLT2 Inhibitors in ADPKD: Time to Integrate Cardiovascular Outcomes” 对题为“SGLT2抑制剂治疗ADPKD：是时候整合心血管结局了”的致编辑的回复

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports

Pub Date : 2025-12-31 DOI: 10.1016/j.ekir.2025.103761

Kiyotaka Uchiyama

引用次数: 0

ARPKD With Shrinking Kidneys and Progressive Loss of Kidney Function ARPKD伴肾脏萎缩和肾功能进行性丧失

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports

Pub Date : 2025-12-30 DOI: 10.1016/j.ekir.2025.103755

José Arriola-Montenegro , Arjunmohan Mohan , Adriana V. Gregory , Timothy L. Kline , Peter C. Harris , Neera K. Dahl

引用次数: 0

Sodium-Glucose Cotransporter-2 Inhibitors and Cardiorenal Events in Nonalbuminuric Kidney Disease 钠-葡萄糖共转运蛋白-2抑制剂与非蛋白尿肾病的心肾事件

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports

Pub Date : 2025-12-30 DOI: 10.1016/j.ekir.2025.103756

Fu-Shun Yen , Keong Chong , Chien-Wei Huang , James Cheng-Chung Wei , Jia-Sin Liu , Yi-Ling Wu , Chih-Ming Chen , Chii-Min Hwu , Chih-Cheng Hsu

Introduction

Most patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) do not exhibit albuminuria. However, data are limited regarding the potential benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2is) in this subgroup.

Methods

We conducted a population-based cohort study between May 1, 2016, and December 31, 2021 using Taiwan’s National Health Insurance (NHI) Research Database to examine the association between SGLT2is use and outcome in patients with T2D and nonalbuminuric CKD. Cox proportional hazard models were used to determine the risk of outcomes between the study and control groups.

Results

The study follow-up time was 3 years. In the prematched intention-to-treat (ITT) model, SGLT2is use was associated with lower risks of dialysis (adjusted hazard ratio [aHR]: 0.21; 95% confidence interval [CI]: 0.10–0.44; P < 0.001), progression to macroalbuminuria (aHR: 0.86; 95% CI: 0.79–0.94; P = 0.001), major adverse cardiovascular events (MACE) (aHR: 0.85; 95% CI: 0.76–0.95; P = 0.005), acute kidney injury (AKI) (aHR: 0.68; 95% CI: 0.56–0.82; P < 0.001), and all-cause mortality (aHR: 0.63; 95% CI: 0.52–0.76; P < 0.001) compared with no SGLT2is use. After propensity score matching, multivariable analyses showed that SGLT2is use was associated with a lower risk of progression to macroalbuminuria (aHR: 0.84; 95% CI: 0.73–0.97; P = 0.015), and all-cause mortality (aHR: 0.40; 95% CI: 0.28–0.59; P < 0.001) compared with not using SGLT2is.

Conclusion

This nationwide cohort study showed that SGLT2is use was associated with a significantly lower risk of progression to macroalbuminuria, and all-cause mortality compared with nonuse in patients with T2D and nonalbuminuric CKD.

大多数2型糖尿病（T2D）和慢性肾脏疾病（CKD）患者不表现出蛋白尿。然而，关于钠-葡萄糖共转运蛋白-2抑制剂（SGLT2is）在该亚组中的潜在益处的数据有限。Cox比例风险模型用于确定研究组和对照组之间结果的风险。结果研究随访时间为3年。在预匹配意向治疗（ITT）模型中，SGLT2is的使用与较低的透析风险相关（校正风险比[aHR]: 0.21； 95%可信区间[CI]: 0.10-0.44; P < 0.001）、进展为大量蛋白尿（aHR: 0.86; 95% CI: 0.79-0.94; P = 0.001）、主要不良心血管事件（MACE）（aHR: 0.85; 95% CI: 0.76-0.95; P = 0.005）、急性肾损伤（AKI）（aHR: 0.68; 95% CI: 0.56-0.82; P < 0.001）和全因死亡率(aHR: 0.63; 95% CI: 0.52-0.76；P < 0.001)与未使用SGLT2is的患者相比。在倾向评分匹配后，多变量分析显示，与不使用SGLT2is相比，使用SGLT2is与较低的发展为大量蛋白尿的风险（aHR: 0.84; 95% CI: 0.73-0.97; P = 0.015）和全因死亡率（aHR: 0.40; 95% CI: 0.28-0.59; P < 0.001）相关。结论：这项全国性队列研究表明，与未使用SGLT2is的T2D和非白蛋白尿CKD患者相比，SGLT2is的使用与进展为巨量白蛋白尿的风险和全因死亡率显著降低相关。

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引用次数: 0

Clinical and Genetic Insights Into Isolated Proteinuria With CUBN Variants 与CUBN变异分离蛋白尿的临床和遗传学见解

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports

Pub Date : 2025-12-29 DOI: 10.1016/j.ekir.2025.103754

Nana Sakakibara , Shinya Ishiko , Yu Tanaka , Yuta Inoki , Yuta Ichikawa , Hideaki Kitakado , Chika Ueda , Atsushi Kondo , Yuya Aoto , Tomoko Horinouchi , Tomohiko Yamamura , Shingo Ishimori , Chinatsu Onodera , Aya Inaba , Riku Hamada , Yutaka Harita , China Nagano , Kandai Nozu

Introduction

Cubilin is a multiligand receptor essential for vitamin B12 uptake in the small intestine and for low–molecular-weight protein reabsorption in the proximal tubule. Biallelic CUBN variants cause Imerslund–Gräsbeck syndrome (IGS), often accompanied by proteinuria, whereas C-terminal variants have been associated with autosomal recessive chronic benign proteinuria. This study aimed to clarify the genetic and clinical characteristics of chronic benign proteinuria and the molecular basis distinguishing it from IGS.

Methods

We evaluated patients with proteinuria carrying biallelic CUBN variants identified through targeted panel sequencing and investigated molecular mechanisms underlying the phenotypic differences between IGS and chronic benign proteinuria.

Results

Fifty-two patients from 42 families were analyzed, and 40 CUBN variants, including 30 novel variants, were identified. All patients presented with incidentally detected subclinical proteinuria—most commonly during the 3-year-old mass urinary screening—and none showed hypoalbuminemia, impaired kidney function, or response to renin-angiotensin system (RAS) inhibitors. Light microscopy revealed minor glomerular abnormalities, whereas electron microscopy frequently demonstrated thin basement membranes or mild foot process effacement. We identified a novel CUBN transcript containing an open reading frame that produces a truncated protein with a unique C-terminus. Full-length cubilin was expressed only in the kidney, whereas a smaller isoform was present in both kidney and small intestine.

Conclusion

Patients with biallelic CUBN variants exhibit preserved kidney function despite subtle glomerular changes. Because only the truncated cubilin isoform is expressed in the intestine, C-terminal variants do not affect vitamin B12 absorption, thereby explaining the absence of malabsorption in chronic benign proteinuria associated with CUBN C-terminal variants.

cubilin是一种多配体受体，对小肠中维生素B12的摄取和近端小管中低分子量蛋白质的重吸收至关重要。双等位基因CUBN变异引起Imerslund-Gräsbeck综合征（IGS），通常伴有蛋白尿，而c端变异与常染色体隐性慢性良性蛋白尿有关。本研究旨在阐明慢性良性蛋白尿的遗传学、临床特点及与IGS区分的分子基础。方法对携带CUBN双等位基因变异的蛋白尿患者进行评估，并研究IGS与慢性良性蛋白尿表型差异的分子机制。结果分析42个家庭的52例患者，发现40个CUBN变异，其中30个为新变异。所有患者均表现为偶然发现的亚临床蛋白尿（最常见的是在3岁的大规模尿筛查期间），没有人表现为低白蛋白血症、肾功能受损或对肾素-血管紧张素系统（RAS）抑制剂有反应。光镜显示轻微的肾小球异常，而电子显微镜经常显示基底膜薄或轻度足突消失。我们发现了一个新的CUBN转录本，它包含一个开放阅读框，产生一个具有独特c端的截断蛋白。全长cubilin仅在肾脏中表达，而肾脏和小肠中均存在较小的同种异构体。结论双等位CUBN变异体患者尽管肾小球有细微改变，但肾功能保持不变。由于只有截断的cubilin亚型在肠道中表达，c端变异不影响维生素B12的吸收，从而解释了与CUBN c端变异相关的慢性良性蛋白尿中没有吸收不良的原因。

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引用次数: 0

Through Awareness to Action: Overcoming Gender Inequities in Academic Medicine and Nephrology 从意识到行动：克服学术医学和肾脏病学中的性别不平等。

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports

Pub Date : 2025-12-29 DOI: 10.1016/j.ekir.2025.103759

Swarnalatha Guditi , Saraladevi Naicker , Valerie Luyckx , Deborah Jean Verran , Rhea Liang , Barbara Ballermann , Urmila Anandh

引用次数: 0

Ten Years of Kidney International Reports 十年肾脏国际报告

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports

Pub Date : 2025-12-29 DOI: 10.1016/j.ekir.2025.103751

Jai Radhakrishan , Radha McLean , Sumit Mohan

引用次数: 0

Cultural Diversity and Kidney Replacement Therapy Outcomes in Australia 澳大利亚的文化多样性和肾脏替代治疗的结果

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports

Pub Date : 2025-12-26 DOI: 10.1016/j.ekir.2025.103743

Pedro Franca Gois , Ginger Chu , Namrata Khanal , Kamal Sud , Bobby Chacko , Kate Brotherton , Scott Jones , Tim Spicer , Chandana Guha , Shyam Muthuramalingam , Jasmin Mazis , Stephen McDonald

Introduction

Australia’s population is culturally and linguistically diverse (CALD), with 31% of Australians born overseas and 22% speaking a language other than English at home. However, there is limited evidence on how CALD backgrounds influence access to kidney replacement therapy (KRT) and outcomes. We examined patient characteristics, treatment modality, waitlisting, and outcomes across CALD groups.

Methods

We analyzed the Australia and New Zealand Dialysis and Transplant (ANZDATA) registry data for non-Indigenous adults who initiated KRT in Australia (2002–2023). Patients were grouped by place of birth: Australia or New Zealand (Aus/NZ), other English-speaking countries (CALD-English), and non-English-speaking countries (CALD-non-English). Competing risk and multinomial logistic regression was used to assess associations between CALD status and KRT modality, waitlisting, mortality, and dialysis withdrawal.

Results

Among 72,621 KRT initiations, 52,045 non-Indigenous adults who commenced KRT in Australia met the inclusion criteria. Of these, 285 (0.5%) had missing country-of-birth data, leaving 51,760 patients for grouping (63.8% Aus/NZ-born, 6.5% CALD-English, and 29.7% CALD-non-English). CALD-non-English were less likely to commence home hemodialysis (HD) (relative risk ratio [RRR]: 0.71, 95% confidence interval [CI]: 0.58–0.88) or receive preemptive transplantation (RRR: 0.38, 0.33–0.44) but more likely to start peritoneal dialysis (PD) (RRR: 1.35, 1.29–1.42) than Aus/NZ. After adjustment, CALD-non-English had higher waitlisting (subdistribution hazard ratio [SHR]: 1.34, 1.28–1.40), lower mortality (SHR: 0.76, 0.74–0.78), and lower dialysis withdrawal (RRR: 0.54, 0.51–0.57) than Aus/NZ.

Conclusion

CALD status was independently associated with KRT modality, transplant waitlisting, survival, and dialysis withdrawal. Understanding how cultural values, health literacy, and family involvement shape KRT decisions and outcomes is essential for designing equitable, culturally sensitive kidney care.

澳大利亚的人口在文化和语言上是多样化的（CALD）， 31%的澳大利亚人出生在海外，22%的澳大利亚人在家说英语以外的语言。然而，关于CALD背景如何影响肾脏替代治疗（KRT）和结果的证据有限。我们检查了CALD组的患者特征、治疗方式、等待名单和结果。方法：我们分析了澳大利亚和新西兰透析和移植（ANZDATA）登记数据，这些数据来自2002-2023年在澳大利亚开始KRT的非土著成年人。患者按出生地分组：澳大利亚或新西兰（Aus/NZ）、其他英语国家（CALD-English）和非英语国家（CALD-non-English）。竞争风险和多项逻辑回归用于评估CALD状态与KRT方式、等待名单、死亡率和透析退出之间的关系。结果在72,621例KRT起始治疗中，52,045例在澳大利亚开始KRT治疗的非土著成年人符合纳入标准。其中285例（0.5%）缺少出生国数据，留下51,760例患者进行分组（63.8%的澳大利亚/新西兰出生，6.5%的CALD-English， 29.7%的CALD-non-English）。cald -非英语组开始家庭血液透析（HD）的可能性较低（相对风险比[RRR]: 0.71, 95%可信区间[CI]: 0.58-0.88）或接受先发制人移植（RRR: 0.38, 0.33-0.44），但开始腹膜透析（PD）的可能性较高（RRR: 1.35, 1.29-1.42）。调整后，与澳大利亚/新西兰相比，cald -非英语有更高的等待名单（亚分布风险比[SHR]: 1.34, 1.28-1.40），更低的死亡率（SHR: 0.76, 0.74-0.78），更低的透析停药（RRR: 0.54, 0.51-0.57）。结论cald状态与KRT方式、移植等待名单、生存和透析退出独立相关。了解文化价值观、健康素养和家庭参与如何影响KRT决策和结果，对于设计公平、文化敏感的肾脏护理至关重要。

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引用次数: 0

Predictors of Long-term Response in Patients With Lupus Nephritis 狼疮性肾炎患者长期反应的预测因素

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports

Pub Date : 2025-12-26 DOI: 10.1016/j.ekir.2025.103747

Gabriella Moroni , Marta Calatroni , Martina Uzzo , Matteo Stella , Emanuele Conte , Laura Locatelli , Francesco Reggiani , Claudio Ponticelli

引用次数: 0

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