Kidney International Reports最新文献

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Associations of Urine Epidermal Growth Factor With Kidney and Cardiovascular Outcomes in Individuals With CKD in SPRINT 尿液表皮生长因子与 SPRINT 中慢性肾脏病患者的肾脏和心血管预后的关系

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports

Pub Date : 2024-11-01 DOI: 10.1016/j.ekir.2024.08.004

Merve Postalcioglu , Ronit Katz , Simon B. Ascher , Trenton Hall , Pranav S. Garimella , Stein I. Hallan , Joachim H. Ix , Michael G. Shlipak

Introduction

Urine epidermal growth factor (uEGF) has been found to be inversely associated with kidney function loss, whereas its associations with cardiovascular disease (CVD) and mortality have not been studied.

Methods

We measured baseline uEGF levels among 2346 Systolic Blood Pressure Intervention Trial (SPRINT) participants with an estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m². A linear mixed-effects model was used to investigate the associations of uEGF with the annual eGFR change; Cox proportional hazards regression models were used to analyze its associations with the ≥30% eGFR decline, CVD, and all-cause mortality outcomes. To account for the competing risk of death, the Fine and Gray method was utilized for acute kidney injury (AKI) and end-stage kidney disease (ESKD) outcomes.

Results

At baseline, the study participants had mean age of 73 ± 9 years, mean eGFR of 46 ± 11 ml/min per 1.73 m², and median urine albumin-to-creatinine ratio (UACR) of 15 mg/g (interquartile range: 7–49). In the multivariable-adjusted analysis including baseline urine albumin and eGFR, each 50% lower uEGF concentration was associated with 0.74% (95% confidence interval [CI]: 0.29–1.19) per year faster decline in eGFR and 1.17 times higher risk of ≥30% eGFR decline (95% CI: 1.00–1.36). Lower uEGF concentrations were found to be associated with increased risks of ESKD, AKI, CVD, and all-cause mortality; however, these associations did not reach statistical significance when the models were controlled for baseline urine albumin and eGFR.

Conclusion

Among hypertensive adults with chronic kidney disease (CKD), lower baseline uEGF concentration was associated with faster eGFR decline independent of baseline albuminuria and eGFR; but not with ESKD, AKI, CVD, and all-cause mortality.

研究发现，尿液表皮生长因子（uEGF）与肾功能丧失呈反比关系，但其与心血管疾病（CVD）和死亡率的关系尚未得到研究。我们测量了2346名收缩压干预试验（SPRINT）参与者的基线uEGF水平，这些参与者的估计肾小球滤过率（eGFR）<60 ml/min per 1.73 m。我们采用线性混合效应模型研究了uEGF与eGFR年变化的关系；采用Cox比例危险回归模型分析了uEGF与eGFR下降≥30%、心血管疾病和全因死亡率的关系。为考虑死亡竞争风险，对急性肾损伤（AKI）和终末期肾病（ESKD）结果采用了Fine和Gray方法。基线时，研究参与者的平均年龄为 73±9 岁，平均 eGFR 为 46±11 毫升/分钟/1.73 米，尿白蛋白与肌酐比值（UACR）中位数为 15 毫克/克（四分位间范围：7-49）。在包括基线尿白蛋白和 eGFR 的多变量调整分析中，uEGF 浓度每降低 50%，eGFR 每年下降的速度就会加快 0.74%（95% 置信区间 [CI]：0.29-1.19），eGFR 下降≥30% 的风险就会增加 1.17 倍（95% 置信区间：1.00-1.36）。研究发现，较低的uEGF浓度与ESKD、AKI、心血管疾病和全因死亡率风险的增加有关；但是，当模型与基线尿白蛋白和eGFR进行对照时，这些关联并没有达到统计学意义。在患有慢性肾脏病（CKD）的成人高血压患者中，基线uEGF浓度较低与eGFR下降速度加快有关，而与基线白蛋白尿和eGFR无关；但与ESKD、AKI、心血管疾病和全因死亡率无关。

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引用次数: 0

Adverse Events Associated With SARS-CoV-2 Vaccination in Patients With Glomerular Diseases and the Potential Risk of Disease Reactivation 肾小球疾病患者接种 SARS-CoV-2 疫苗的不良反应及疾病再激活的潜在风险

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports

Pub Date : 2024-11-01 DOI: 10.1016/j.ekir.2024.08.003

Sophia Lionaki , Pelagia Kriki , Smaragdi Marinaki , Dimitra Gkalitsiou , Evangelia Dounousi , Vassilios Liakopoulos , Ioannis Bellos , Vasileios Vaios , Petros Kalogeropoulos , Zoe Kleinaki , Sofia Flouda , Louisa Gkika-Zervou , Marios Papasotiriou , Dimitrios Goumenos , Aliki Venetsanopoulou , Paraskevi Voulgari , Georgios Moustakas , Eirini Grapsa , Kostas Stylianou , Stylianos Panagoutsos , Ioannis Boletis

引用次数: 0

Systematic Review of Individual Patient Data COVID-19 Infection and Vaccination–Associated Thrombotic Microangiopathy 个体患者数据的系统性回顾 COVID-19 感染和疫苗接种相关性血栓性微血管病

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports

Pub Date : 2024-11-01 DOI: 10.1016/j.ekir.2024.07.034

Pujan Moradiya , Priyanka Khandelwal , Rupesh Raina , Ruchi Gupta Mahajan

Introduction

Sporadic cases of atypical hemolytic uremic syndrome (aHUS) have been described in the literature in association with COVID-19 infection and vaccination in adults and pediatric patients. The exact mechanisms underlying COVID-19–associated thrombotic microangiopathies (TMAs) remain incompletely understood. Herein, we present a detailed meta-analysis of the clinical characteristics, outcomes, and management strategies of COVID-19–associated aHUS and thrombotic thrombocytopenic purpura (TTP).

Methods

This study was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses updated guidelines. PubMed was utilized for searching for case reports and series. Adverse outcome at last follow-up was defined as estimated glomerular filtration rate < 30 ml/min per 1.73 m² (patients with aHUS), no remission with therapy, or patient death. Data were analyzed using Wilcoxon rank and Chi-square tests.

Results

Our analysis cohort included 118 studies reporting on 170 patients. These included 84 cases of aHUS and 86 cases of TTP resulting from COVID-19 infection (n = 92) or vaccination (n = 78). Significantly more cases of aHUS were reported after infection (n = 65) than immunization (n = 19), compared to TTP, where the reverse was true (n = 27 and n = 59, respectively; P < 0.001). In patients with aHUS with stage 3 acute kidney injury (AKI), requirement of kidney replacement therapy (KRT) was seen in three-fourths of the cohort for a median of 15. In patients with TTP, severe COVID-19 infection (P = 0.04) predicted nonremission or death at last follow-up. Administration of i.v., rituximab and caplacizumab were protective (P = 0.03 and P = 0.06, respectively). Immune TTP (iTTP) was reported more often than HUS following mRNA vaccines (81% vs. 58%; P = 0.06).

Conclusion

COVID-19 infection and vaccination are a potential trigger for onset or relapse of aHUS and TTP, especially in patients who are not on maintenance complement inhibitors or immunosuppression.

文献中描述了成人和儿童患者感染 COVID-19 和接种 COVID-19 疫苗后出现非典型溶血性尿毒症（aHUS）的零星病例。COVID-19相关的血栓性微血管病（TMAs）的确切机制仍不完全清楚。在此，我们对 COVID-19 相关性 aHUS 和血栓性血小板减少性紫癜（TTP）的临床特征、预后和管理策略进行了详细的荟萃分析。本研究遵循《系统综述和荟萃分析首选报告项目》（Preferred Reporting Items for Systematic Reviews and Meta-analyses）最新指南进行。利用 PubMed 搜索病例报告和系列研究。最后一次随访时的不良结局定义为估计肾小球滤过率< 30 ml/min per 1.73 m（aHUS 患者）、治疗无缓解或患者死亡。数据采用 Wilcoxon 秩检验和卡方检验进行分析。我们的分析队列包括 118 项研究，报告了 170 例患者。其中包括 84 例 aHUS 和 86 例由 COVID-19 感染（= 92 例）或疫苗接种（= 78 例）引起的 TTP。感染后的 aHUS 病例（= 65 例）明显多于免疫接种后的病例（= 19 例），而 TTP 病例则相反（分别为 = 27 例和 = 59 例；< 0.001）。在急性肾损伤（AKI）3期的aHUS患者中，四分之三的患者需要接受肾脏替代治疗（KRT），中位数为15天。在TTP患者中，严重的COVID-19感染（=0.04）预示着最后一次随访时将出现不缓解或死亡。静脉注射利妥昔单抗和卡普拉珠单抗具有保护作用（分别为0.03和0.06）。接种 mRNA 疫苗后，免疫性 TTP (iTTP) 的报告率高于 HUS（81% 对 58%; = 0.06）。COVID-19 感染和疫苗接种是 aHUS 和 TTP 发病或复发的潜在诱因，尤其是在未使用补体抑制剂或免疫抑制剂的患者中。

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引用次数: 0

Open-Label Phase 1/2 Study of Daratumumab-Based Desensitization Before Kidney Transplantation 肾移植前基于达拉单抗的脱敏治疗的开放标签 1/2期研究

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports

Pub Date : 2024-11-01 DOI: 10.1016/j.ekir.2024.08.020

Caroline Pilon , Nizar Joher , Cédric Usureau , Emmanuelle Boutin , Anna Boueilh , Jean-Luc Taupin , Allan Thiolat , José L. Cohen , Vissal David Kheav , Florence Canoui-Poitrine , Maryvonnick Carmagnat , Philippe Grimbert , Marie Matignon

Introduction

The safety and benefit of the anti-CD38 monoclonal antibody daratumumab, which induces lysis of antibody-producing plasma cells in sensitized patients prior to kidney transplantation, remain to be determined.

Methods

A 2-phase (1 and 2), monocentric open-label study was conducted to evaluate the month 6 (M6) safety and efficacy of daratumumab in kidney transplant candidates with calculated panel reactive antibody (cPRA) > 95%. In the first (safety) phase, we used 4-weekly escalating doses of daratumumab. Phase 2 tested desensitization with 8 weekly infusions of 16 mg/kg daratumumab. cPRA 10,000 was calculated considering only human leukocyte antigen (HLA) antibodies with mean fluorescence intensity (MFI) of > 10,000.

Results

Nine patients were enrolled in phase 1 and 14 in phase 2. Safety analysis showed 4 serious non-treatment-emergent adverse events (non-TEAEs), 36 mild TEAEs, mostly infusion-related reactions, grade 1 and 2 (causing 2 temporary drug discontinuations), but no serious TEAEs. Significant reductions in anti-HLA antibodies were observed at month 3 (M3), with cPRA 10,000 (P = 0.003), number of anti-HLA (P < 0.001), maximum MFI (MFI max) (P = 0.053), and the sum of MFI (MFI sum) (P < 0.001), with complete return to baseline levels at month 12 (M12). At M6, 46.15% (19.22%–74.87%) and 76.92% (46.19%–94.96%) of patients showed sustained response (1% decrease in cPRA) for cPRA 2000 and 10,000, respectively. At month 1 (M1), immune cells (T-reg, CD8 + TEMRA, CD19 + CD138 + B cells, and NK cells) significantly decreased. At M3, other antibodies decreased significantly, but returned to baseline levels at M12, except for gamma globulins, without any infectious complications.

Conclusion

The first use of daratumumab in desensitization demonstrated infusion-related adverse (AEs) events and rapid, albeit transient, reductions in anti-HLA antibodies, with less than 40% of durable responders, limiting its potential clinical use.

抗CD38单克隆抗体daratumumab能在肾移植前诱导致敏患者溶解产生抗体的浆细胞，其安全性和益处仍有待确定。我们开展了一项分两个阶段（1和2）的单中心开放标签研究，以评估达拉土穆单抗对肾移植候选者第6个月（M6）的安全性和疗效，这些候选者的计算小组反应性抗体（cPRA）> 95%。在第一阶段（安全性），我们使用了4周递增剂量的daratumumab。cPRA 10,000的计算只考虑平均荧光强度（MFI）大于10,000的抗人类白细胞抗原（HLA）抗体。第一阶段共招募了 9 名患者，第二阶段招募了 14 名患者。安全性分析显示，有4例严重的非治疗突发不良事件（non-TEAEs），36例轻微的TEAEs，主要是输液相关的1级和2级反应（导致2例暂时停药），但没有严重的TEAEs。第3个月（M3）观察到抗-HLA抗体显著降低，cPRA 10,000（=0.003）、抗-HLA数量（<0.001）、最大MFI（MFI max）（=0.053）和MFI总和（MFI sum）（<0.001），第12个月（M12）完全恢复到基线水平。在第 6 个月，分别有 46.15% （19.22%-74.87%）和 76.92% （46.19%-94.96%）的患者对 cPRA 2000 和 10,000 出现持续应答（cPRA 下降 1%）。在第 1 个月（M1），免疫细胞（T-reg、CD8 + TEMRA、CD19 + CD138 + B 细胞和 NK 细胞）显著减少。在M3时，其他抗体明显下降，但在M12时，除γ球蛋白外，其他抗体恢复到基线水平，且未出现任何感染性并发症。达拉土单抗首次用于脱敏治疗时出现了输注相关不良（AEs）事件，抗HLA抗体迅速下降，但只是短暂的，持久应答者不足40%，这限制了其潜在的临床应用。

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引用次数: 0

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports

Pub Date : 2024-11-01 DOI: 10.1016/j.ekir.2024.08.025

Maral Baghai Arassi , Manuel Feißt , Kai Krupka , Atif Awan , Elisa Benetti , Ali Düzova , Isabella Guzzo , Jon Jin Kim , Birgitta Kranz , Mieczysław Litwin , Jun Oh , Anja Büscher , Lars Pape , Licia Peruzzi , Mohan Shenoy , Sara Testa , Lutz T. Weber , Jakub Zieg , Britta Höcker , Alexander Fichtner , Burkhard Tönshoff

Introduction

Data on age-related differences in rejection rates, infectious episodes, and tacrolimus exposure in pediatric kidney transplant recipients (pKTRs) on a tacrolimus-based immunosuppressive regimen are scarce.

Methods

We performed a large-scale analysis of 802 pKTRs from the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry from 40 centers in 14 countries. The inclusion criteria were a tacrolimus-based immunosuppressive regimen and at least 2 years of follow-up. The patient population was divided into 3 age groups (infants and young children aged <6 years, school-aged children 6–12 years, and adolescents aged >12 years) to assess age-related differences in outcome.

Results

Median follow-up was 48 months (interquartile range [IQR], 36–72). Within the first 2 years posttransplant, infants, and young children had a significantly higher incidence of infections (80.6% vs. 55.0% in adolescents, P < 0.001) and a significantly higher number of cumulative hospital days (median 13 days vs. 7 days in adolescents, P < 0.001). Adolescents had a significantly higher rate of biopsy-proven acute rejection episodes in the first-year posttransplant (21.7%) than infants and young children (12.6%, P = 0.007). Infants and young children had significantly lower tacrolimus trough levels, lower tacrolimus concentration-to-dose (C/D) ratios as an approximation for higher tacrolimus clearance, and higher tacrolimus interpatient variability (TacIPV) (all P < 0.01) than adolescents.

Conclusion

This is the largest study to date in European pKTRs on a tacrolimus-based immunosuppressive regimen, and it shows important age-related differences in rejection rates, infection episodes, as well as tacrolimus exposure and clearance. This data suggests that immunosuppressive therapy in pKTRs should be tailored and personalized according to the age-specific risk profiles of this heterogeneous patient population. The data may serve as a benchmark for future studies with novel immunosuppressive drugs.

关于接受他克莫司免疫抑制疗法的小儿肾移植受者（pKTR）在排斥率、感染发作和他克莫司暴露方面与年龄相关的差异的数据很少。我们对来自 14 个国家 40 个中心的欧洲儿科肾移植合作计划（CERTAIN）登记处的 802 名小儿肾移植受者进行了大规模分析。纳入标准是采用他克莫司为基础的免疫抑制方案和至少两年的随访。患者分为 3 个年龄组（婴儿和 12 岁的幼儿），以评估与年龄相关的预后差异。中位随访时间为48个月（四分位数间距[IQR]，36-72）。在移植后的头两年中，婴幼儿的感染率明显更高（80.6%，青少年为 55.0%，<0.001），累计住院天数也明显更高（中位数为 13 天，青少年为 7 天，<0.001）。与婴幼儿（12.6%，=0.007）相比，青少年在移植后第一年经活检证实的急性排斥反应发生率（21.7%）明显更高。与青少年相比，婴幼儿的他克莫司谷值、他克莫司浓度剂量比（C/D）（近似于较高的他克莫司清除率）和他克莫司患者间变异性（TacIPV）（均<0.01）均明显较低。这是迄今为止对使用他克莫司免疫抑制方案的欧洲 pKTR 进行的最大规模研究，研究结果表明，在排斥率、感染发生率以及他克莫司暴露和清除率方面，存在与年龄相关的重要差异。这些数据表明，pKTR 患者的免疫抑制治疗应根据这一异质性患者群体的年龄特异性风险特征进行定制和个性化治疗。这些数据可作为今后使用新型免疫抑制剂进行研究的基准。

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引用次数: 0

Response to: “Implications of the Choice of Different Calculation Concepts for eGFRcys-to-eGFRcre Ratio Among Community-Dwelling Older Adults” 回应对 "社区居住的老年人 eGFRcys 与 eGFRcre 比值选择不同计算概念的影响 "的回应

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports

Pub Date : 2024-11-01 DOI: 10.1016/j.ekir.2024.09.003

Esben Iversen , Louise Westberg Strejby Christensen , Aino Leegaard Andersen , Rikke Lundsgaard Nielsen , Morten Damgaard , Trine Meldgaard Lund , Mads Hornum , Ove Andersen , Morten Baltzer Houlind

引用次数: 0

Response to “Fine-Tuning Dry Weight: a Key Component in Managing Blood Pressure for Dialysis Patients” 对 "微调干重：透析患者血压管理的关键要素 "的回应

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports

Pub Date : 2024-11-01 DOI: 10.1016/j.ekir.2024.09.008

Armida Lefranc Torres , Simon Correa Gaviria , Finnian R. McCausland

引用次数: 0

The Role of Urate in Calcium Stone Formation 尿酸盐在钙结石形成中的作用

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports

Pub Date : 2024-11-01 DOI: 10.1016/j.ekir.2024.08.013

Erika Critell , Amy A. Yau

引用次数: 0

Nephrologists’ Views on a Workflow for Returning Genetic Results to Research Participants 肾脏病学家对向研究参与者返还基因结果的工作流程的看法

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports

Pub Date : 2024-11-01 DOI: 10.1016/j.ekir.2024.08.026

Robyn Weiss , Hila Milo Rasouly , Maddalena Marasa , Hilda Fernandez , Fangming Lin , Maya Sabatello

Introduction

Returning research-based genetic results (gRoR) to participants in nephrology research can improve care; however, the practice raises implementational questions and no established guidelines for this process currently exist. Nephrologists' views on this issue can inform the process but are understudied.

Methods

We developed a conceptual workflow for gRoR from literature and experience, covering aspects such as which results to return, how, and by whom. We surveyed US nephrologists to gauge their views on the workflow and anticipated barriers and collected participants' demographics, including professional backgrounds.

Results

A total of 201 adult and pediatric nephrologists completed the survey. Most of them agreed that all diagnostic kidney-related results (93%), secondary findings (80%), and kidney-related risk variants (83%) should be returned. No significant differences were found between adult and pediatric nephrologists’ responses, except that 48% of adult nephrologists versus 26% of pediatric nephrologists supported returning polygenic risk scores (PRS) (P < 0.01). Seventy-nine percent wanted to know about research results before clinical confirmation. Most of them (63%) believed a genetic counselor should return clinically confirmed results. Key barriers included the cost of clinical validation (77%) and the unavailability of genetic counseling services (63%). Facilitators included educational resources on genetic kidney diseases (91%), a referral list of experts (89%), and clear clinical care guidelines (89%). We discuss findings’ implications and provide “points to consider.”

Conclusion

There is significant interest in gRoR among nephrologists; however, logistical and economic concerns need addressing. Identified facilitators can help large nephrology studies planning to return genetic results to participants.

将基于研究的基因结果（gRoR）返还给肾脏病学研究的参与者可以改善护理工作；但是，这种做法在实施过程中会产生一些问题，而且目前还没有关于这一过程的既定指南。肾脏病学家对这一问题的看法可以为这一流程提供参考，但对这一流程的研究还不够。我们根据文献和经验制定了 gRoR 概念性工作流程，包括哪些结果需要返回、如何返回以及由谁返回等方面。我们调查了美国的肾科医生，以了解他们对工作流程和预期障碍的看法，并收集了参与者的人口统计数据，包括专业背景。共有 201 名成人和儿科肾病专家完成了调查。他们中的大多数人都认为，所有与肾脏相关的诊断结果（93%）、辅助检查结果（80%）和与肾脏相关的风险变异（83%）都应该返回。除了 48% 的成人肾脏病学家和 26% 的儿科肾脏病学家支持返还多基因风险评分 (PRS) 外，成人肾脏病学家和儿科肾脏病学家的回答无明显差异（< 0.01）。79%的人希望在临床确认之前了解研究结果。他们中的大多数（63%）认为遗传咨询师应返回临床确认的结果。主要障碍包括临床确认的费用（77%）和遗传咨询服务的不可获得性（63%）。促进因素包括遗传性肾脏疾病的教育资源（91%）、专家转介名单（89%）和明确的临床护理指南（89%）。我们讨论了研究结果的意义，并提供了 "考虑要点"。肾脏病学家对遗传性肾脏病有浓厚的兴趣，但需要解决后勤和经济方面的问题。确定的促进因素可以帮助计划将基因结果返还给参与者的大型肾脏病研究。

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引用次数: 0

Efficacy and Safety of Subcutaneous Rituximab in Idiopathic Nephrotic Syndrome 皮下注射利妥昔单抗治疗特发性肾病综合征的有效性和安全性

IF 5.7 2区医学 Q1 UROLOGY & NEPHROLOGY

Kidney International Reports

Pub Date : 2024-11-01 DOI: 10.1016/j.ekir.2024.08.021

Paolo Cravedi , Carolina Bigatti , Xhuliana Kajana , Enrico E. Verrina , Gianluca Caridi , Maurizio Bruschi , Gian Marco Ghiggeri , Andrea Angeletti

引用次数: 0

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