Glomerular diseases最新文献_第7页

The significance of anti-PLA2R in diabetic kidney disease: Truly a false positive? 抗 PLA2R 在糖尿病肾病中的意义：真的是假阳性吗？

Glomerular diseases

Pub Date : 2024-04-20 DOI: 10.1159/000538902

Avanti Damle, H. H. Wu, D. Kanigicherla, R. Chinnadurai

引用次数: 0

Glomerulonephritis after Alemtuzumab Treatment for Multiple Sclerosis: A Report of Two Cases 阿仑妥珠单抗治疗多发性硬化症后的肾小球肾炎：两个病例的报告

Glomerular diseases

Pub Date : 2024-04-02 DOI: 10.1159/000538492

Abdullah Al-Muhaiteeb, Kamal Alkeay, Ahmad Altaleb

Abstract Introduction Alemtuzumab, a humanized monoclonal antibody indicated for the treatment of adult patients with active relapsing-remitting multiple sclerosis (MS), has been associated with increased risk of autoimmune adverse events, including thyroid disorders, immune thrombocytopenia, and renal diseases. Renal immune-mediated adverse events, which have been reported in 0.3% of patients treated with alemtuzumab in MS clinical trials, typically occur within 39 months after the last drug administration. However, no consensus has been reached regarding the management of patients who develop glomerulonephritis after treatment with alemtuzumab. Case Presentation We report the cases of two young adults with MS who developed biopsy-proven severe glomerulonephritis after alemtuzumab treatment. Both patients, including a 32-year-old female patient who developed membranous nephropathy and a 31-year-old male who developed drug-induced podocytopathy, were treated successfully with the calcineurin inhibitor tacrolimus followed by the anti-CD20 antibody rituximab. Conclusion Regular renal function monitoring is required in patients who may rarely develop glomerulonephritis following treatment with alemtuzumab. There is no clear consensus on case management. In both cases, immunosuppressive therapy, which was necessary due to disease severity, resulted in successful remission, highlighting the potential utility of this approach.

摘要引言阿来珠单抗是一种人源化单克隆抗体，用于治疗活动性复发性多发性硬化症（MS）成年患者，它与自身免疫不良事件风险增加有关，包括甲状腺疾病、免疫性血小板减少症和肾脏疾病。在多发性硬化症的临床试验中，有 0.3% 接受阿仑妥珠单抗治疗的患者出现了肾脏免疫介导的不良事件，这些不良事件通常发生在最后一次用药后的 39 个月内。然而，对于使用阿仑珠单抗治疗后出现肾小球肾炎的患者的处理方法，目前尚未达成共识。病例介绍我们报告了两名多发性硬化症年轻成人患者的病例，他们在接受阿仑妥珠单抗治疗后出现了活检证实的严重肾小球肾炎。这两名患者中，一名 32 岁的女性患者出现了膜性肾病，另一名 31 岁的男性患者出现了药物诱发的荚膜细胞病，他们在接受钙神经蛋白抑制剂他克莫司治疗后，又接受了抗 CD20 抗体利妥昔单抗治疗，均获得成功。结论使用阿仑妥珠单抗治疗后很少会出现肾小球肾炎，因此需要定期监测患者的肾功能。对于病例的处理还没有明确的共识。在这两个病例中，由于病情严重，必须进行免疫抑制治疗，但结果都成功缓解了病情，这凸显了这种方法的潜在作用。

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引用次数: 0

Kidney Histopathology of Patients with Hepatitis C Infection and Diabetes Mellitus Before and After Availability of Direct Acting Antiviral Therapy 丙型肝炎感染合并糖尿病患者在使用直接作用抗病毒疗法前后的肾组织病理学研究

Glomerular diseases

Pub Date : 2024-03-15 DOI: 10.1159/000537977

Vanderlene L. Kung, Gabriel Giannini, Cynthia C. Nast

Introduction: Type 2 diabetes mellitus (DM) and diabetic kidney disease are increasing. Hepatitis C infection (HCV) occurs in 1% of the world population and can induce several kidney diseases. DM prevalence is increased in individuals with HCV; however, kidney diseases in those with both DM and HCV have not been assessed. Direct acting antiviral agents (DAAs) became available for HCV treatment in 2014; it is unknown if DAAs altered the spectrum of kidney disease in patients with DM and HCV. Methods: Case review identifying patients with kidney biopsy and clinical history of DM and HCV between 2009-2013 (pre-DAA) and 2016-2020 (post-DAA), excluding kidney transplant, hepatitis B, HIV and inadequate biopsy, identified 245 biopsies. Biopsies were evaluated for diabetic glomerulosclerosis (DGS) class, global and focal segmental glomerulosclerosis (FSGS), other glomerular diseases, interstitial fibrosis/tubular atrophy (IFTA), interstitial nephritis, acute tubular injury and degree of arterial and arteriolar sclerosis. Kidney disease differences in pre-DAA versus post-DAA eras and in mild versus severe DGS were assessed by Chi-square and Fisher's exact tests.Results: The most common non-DGS lesions were non-collapsing FSGS (41%), HCV-related IgM dominant immune complex glomerulonephritis (IgM-ICGN, 18%), IgA nephropathy (9%), and membranoproliferative glomerulonephritis (MPGN, 7%). Collapsing FSGS was more common pre-DAA vs post-DAA (8% v 1%, p=0.03). Biopsies from patients with HCV and DM were reduced in post-DAA (0.7%) vs pre-DAA (1.3%) (p< 0.0001). Post-DAA there were less MPGN (2% vs 10%, p=0.02) and more advanced DGS (85% v 61%, p=0.0002), non-collapsing FSGS (57% v 31%, p<0.0001), IFTA (2.0 v 1.6, p=0.0002), and vascular sclerosis (2.1 v 1.6, p<0.0001).Conclusion: Post-DAA there were reduced biopsies and MPGN, with more severe DGS class, non-collapsing FSGS, IFTA and chronic vascular changes. This suggests a modulating effect of DAAs on HCV-related kidney pathology with DM and chronic changes driving indications for kidney biopsy.

导言：2 型糖尿病（DM）和糖尿病肾病的发病率不断上升。丙型肝炎（HCV）感染率占全球人口的 1%，可诱发多种肾脏疾病。丙型肝炎病毒感染者的糖尿病发病率增加，但尚未对同时患有糖尿病和丙型肝炎病毒感染者的肾脏疾病进行评估。2014年，直接作用抗病毒药物（DAAs）开始用于HCV治疗；目前尚不清楚DAAs是否会改变DM和HCV患者的肾脏疾病谱。方法：病例回顾病例回顾：确定了2009-2013年（DAA前）和2016-2020年（DAA后）期间进行肾活检并有DM和HCV临床病史的患者，排除了肾移植、乙型肝炎、HIV和活检不充分的患者，共确定了245例活检病例。对活检样本进行了糖尿病肾小球硬化（DGS）分级、全局性和局灶节段性肾小球硬化（FSGS）、其他肾小球疾病、间质纤维化/肾小管萎缩（IFTA）、间质性肾炎、急性肾小管损伤以及动脉和动脉硬化程度的评估。通过卡方检验（Chi-square）和费雪精确检验（Fisher's exact）评估了DAA前与DAA后以及轻度与重度DGS的肾病差异：最常见的非 DGS 病变是非塌陷性 FSGS（41%）、HCV 相关 IgM 显性免疫复合物肾小球肾炎（IgM-ICGN，18%）、IgA 肾病（9%）和膜增生性肾小球肾炎（MPGN，7%）。DAA前与DAA后相比，塌陷性FSGS更为常见（8%对1%，P=0.03）。DAAA后（0.7%）与DAAA前（1.3%）相比，HCV和DM患者的活检结果减少（p< 0.0001）。DAAA后，MPGN减少（2% vs 10%，p=0.02），晚期DGS（85% vs 61%，p=0.0002）、非塌陷性FSGS（57% vs 31%，p<0.0001）、IFTA（2.0 vs 1.6，p=0.0002）和血管硬化（2.1 vs 1.6，p<0.0001）增加：结论：DAA 后活检和 MPGN 减少，DGS 分级、非塌陷性 FSGS、IFTA 和慢性血管病变更为严重。这表明，DAAs 对 HCV 相关肾脏病理具有调节作用，DM 和慢性病变是肾活检的适应症。

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引用次数: 0

Safety and Tolerability of the APOL1 Inhibitor, Inaxaplin, Following Single- and Multiple-ascending Doses in Healthy Adults 健康成年人服用 APOL1 抑制剂伊奈沙普林单次和多次升剂量后的安全性和耐受性

Glomerular diseases

Pub Date : 2024-03-14 DOI: 10.1159/000538255

O. Egbuna, Vincent Audard, George Manos, Simon Tian, Fanuel Hagos, Glenn M. Chertow

IntroductionToxic gain-of-function Apolipoprotein L1 (APOL1) variants contribute to the development of proteinuric nephropathies collectively referred to as APOL1-mediated kidney disease (AMKD). Despite standard-of-care treatments, patients with AMKD experience accelerated progression to end stage kidney disease. The identification of two APOL1 variants as the genetic cause of AMKD inspired development of inaxaplin, an inhibitor of APOL1 channel activity that reduces proteinuria in patients with AMKD.MethodsWe conducted two phase 1 studies evaluating the safety, tolerability, and pharmacokinetics of single-ascending doses (SAD) and multiple-ascending doses (MAD) of inaxaplin in healthy participants. In the SAD cohorts, participants were randomized to receive inaxaplin as a single dose (range, 7.5 mg to 165 mg) or placebo. In the MAD cohorts, participants were randomized to receive multiple doses of inaxaplin (range, 15 to 120 mg daily) or placebo for 14 days. We assessed safety and tolerability based on adverse events (AEs), clinical laboratory values, electrocardiograms (ECGs), and vital signs.ResultsA total of 178 participants were randomized in the SAD/MAD cohorts of both studies (mean age: 36.7 years; 94.9% male). The proportion of participants with any AEs was similar in the inaxaplin (24.6%) and placebo (22.7%) groups. All AEs were mild or moderate in severity; there were no serious AEs. Headache was the most common AE: 10.4% and 2.3% in the inaxaplin and placebo groups, respectively. There were no drug-related treatment discontinuations and no clinically relevant trends in laboratory values, ECGs, or vital signs.Discussion/ConclusionInaxaplin is safe and well tolerated at single doses up to 165 mg and multiple doses up to 120 mg daily for 14 days. These results are consistent with the favorable safety profile of inaxaplin in a completed phase 2a proof-of-concept study. Together, these findings support continued evaluation of inaxaplin in an ongoing phase 2/3 pivotal trial as a potential precision medicine for patients with AMKD.

导言有毒的功能增益载脂蛋白 L1（APOL1）变异导致蛋白尿性肾病的发生，统称为 APOL1 介导的肾病（AMKD）。尽管接受了标准治疗，AMKD 患者仍会加速发展为终末期肾病。我们进行了两项 1 期研究，评估了健康参与者服用单升剂量 (SAD) 和多升剂量 (MAD) 依那西普林的安全性、耐受性和药代动力学。在单升剂量组中，参与者被随机分配接受伊沙普林单次剂量（7.5毫克至165毫克）或安慰剂。在MAD队列中，参试者随机接受多剂量伊沙普林（剂量范围为每天15至120毫克）或安慰剂治疗14天。我们根据不良事件（AEs）、临床实验室值、心电图（ECGs）和生命体征评估了安全性和耐受性。结果两项研究的SAD/MAD队列中共有178名参与者接受了随机治疗（平均年龄：36.7岁；94.9%为男性）。依那西普林组（24.6%）和安慰剂组（22.7%）出现任何AEs的比例相似。所有不良反应的严重程度均为轻度或中度，没有严重不良反应。头痛是最常见的AE：依那西普林组和安慰剂组分别为10.4%和2.3%。讨论/结论伊那沙普林的安全性和耐受性良好，单次剂量最高可达165毫克，多次剂量最高可达120毫克，每天服用14天。这些结果与已完成的 2a 期概念验证研究中依那西普林良好的安全性特征相一致。这些研究结果支持在正在进行的2/3期关键试验中继续评估inaxaplin，将其作为治疗AMKD患者的潜在精准药物。

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引用次数: 0

Developmental Causes of Focal Segmental Glomerulosclerosis. 局灶节段性肾小球硬化症的发育原因。

Glomerular diseases

Pub Date : 2024-03-14 eCollection Date: 2024-01-01 DOI: 10.1159/000538345

Luna Shane Klomp, Elena Levtchenko, Rik Westland

Background: Focal segmental glomerulosclerosis (FSGS) is a histological pattern of glomerular damage that includes idiopathic conditions as well as genetic and non-genetic forms. Among these various etiologies, different phenotypes within the spectrum of congenital anomalies of the kidney and urinary tract (CAKUT) have been associated with FSGS.

Summary: Until recently, the main pathomechanism of how congenital kidney and urinary tract defects lead to FSGS was attributed to a reduced number of nephrons, resulting in biomechanical stress on the remaining glomeruli, detachment of podocytes, and subsequent inability to maintain normal glomerular architecture. The discovery of deleterious single-nucleotide variants in PAX2, a transcription factor crucial in normal kidney development and a known cause of papillorenal syndrome, in individuals with adult-onset FSGS without congenital kidney defects has shed new light on developmental defects that become evident during podocyte injury.

Key message: In this mini-review, we challenge the assumption that FSGS in CAKUT is caused by glomerular hyperfiltration alone and hypothesize a multifactorial pathogenesis that includes overlapping cellular mechanisms that are activated in both damaged podocytes as well as nephron progenitor cells.

背景：局灶节段性肾小球硬化症（FSGS）是一种肾小球损伤的组织学模式，包括特发性病症、遗传性和非遗传性病症。摘要：直到最近，关于先天性肾脏和泌尿道缺陷如何导致 FSGS 的主要病理机制仍被归结为肾小球数量减少，导致剩余肾小球承受生物力学压力、荚膜细胞脱落以及随后无法维持正常的肾小球结构。PAX2 是一种对肾脏正常发育至关重要的转录因子，也是乳头肾病综合征的已知病因：在这篇微型综述中，我们对 CAKUT 中的 FSGS 仅由肾小球高滤过引起的假设提出质疑，并假设其发病机制是多因素的，包括在受损荚膜细胞和肾小球祖细胞中激活的重叠细胞机制。

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引用次数: 0

Challenges and Opportunities for the Clinical Translation of Spatial Transcriptomics Technologies. 空间转录组学技术临床转化的挑战与机遇。

Glomerular diseases

Pub Date : 2024-03-13 eCollection Date: 2024-01-01 DOI: 10.1159/000538344

Kelly D Smith, David K Prince, James W MacDonald, Theo K Bammler, Shreeram Akilesh

Background: The first spatially resolved transcriptomics platforms, GeoMx (Nanostring) and Visium (10x Genomics) were launched in 2019 and were recognized as the method of the year by Nature Methods in 2020. The subsequent refinement and expansion of these and other technologies to increase -plex, work with formalin-fixed paraffin-embedded tissue, and analyze protein in addition to gene expression have only added to their significance and impact on the biomedical sciences. In this perspective, we focus on two platforms for spatial transcriptomics, GeoMx and Visium, and how these platforms have been used to provide novel insight into kidney disease. The choice of platform will depend largely on experimental questions and design. The application of these technologies to clinically sourced biopsies presents the opportunity to identify specific tissue biomarkers that help define disease etiology and more precisely target therapeutic interventions in the future.

Summary: In this review, we provide a description of the existing and emerging technologies that can be used to capture spatially resolved gene and protein expression data from tissue. These technologies have provided new insight into the spatial heterogeneity of diseases, how reactions to disease are distributed within a tissue, which cells are affected, and molecular pathways that predict disease and response to therapy.

Key message: The upcoming years will see intense use of spatial transcriptomics technologies to better define the pathophysiology of kidney diseases and develop novel diagnostic tests to guide personalized treatments for patients.

背景：首个空间分辨转录组学平台 GeoMx（Nanostring）和 Visium（10x Genomics）于 2019 年推出，并于 2020 年被 Nature Methods 评为年度最佳方法。随后，这些技术和其他技术不断完善和扩展，增加了复合物，可处理福尔马林固定石蜡包埋组织，除分析基因表达外，还可分析蛋白质，这只会增加它们对生物医学科学的意义和影响。在本文中，我们将重点介绍两个空间转录组学平台--GeoMx 和 Visium，以及如何利用这些平台对肾脏疾病提供新的见解。平台的选择在很大程度上取决于实验问题和设计。这些技术在临床活检中的应用为确定特定的组织生物标志物提供了机会，有助于确定疾病的病因，并在未来更精确地确定治疗干预的目标。摘要：在这篇综述中，我们介绍了现有的和新兴的技术，这些技术可用于从组织中捕获空间分辨基因和蛋白质表达数据。这些技术让我们对疾病的空间异质性、疾病反应如何在组织内分布、哪些细胞受到影响以及预测疾病和治疗反应的分子途径有了新的认识：未来几年，空间转录组学技术将得到广泛应用，以更好地确定肾脏疾病的病理生理学，并开发新型诊断测试，为患者的个性化治疗提供指导。

{"title":"Challenges and Opportunities for the Clinical Translation of Spatial Transcriptomics Technologies.","authors":"Kelly D Smith, David K Prince, James W MacDonald, Theo K Bammler, Shreeram Akilesh","doi":"10.1159/000538344","DOIUrl":"https://doi.org/10.1159/000538344","url":null,"abstract":"Background: The first spatially resolved transcriptomics platforms, GeoMx (Nanostring) and Visium (10x Genomics) were launched in 2019 and were recognized as the method of the year by Nature Methods in 2020. The subsequent refinement and expansion of these and other technologies to increase -plex, work with formalin-fixed paraffin-embedded tissue, and analyze protein in addition to gene expression have only added to their significance and impact on the biomedical sciences. In this perspective, we focus on two platforms for spatial transcriptomics, GeoMx and Visium, and how these platforms have been used to provide novel insight into kidney disease. The choice of platform will depend largely on experimental questions and design. The application of these technologies to clinically sourced biopsies presents the opportunity to identify specific tissue biomarkers that help define disease etiology and more precisely target therapeutic interventions in the future.Summary: In this review, we provide a description of the existing and emerging technologies that can be used to capture spatially resolved gene and protein expression data from tissue. These technologies have provided new insight into the spatial heterogeneity of diseases, how reactions to disease are distributed within a tissue, which cells are affected, and molecular pathways that predict disease and response to therapy.Key message: The upcoming years will see intense use of spatial transcriptomics technologies to better define the pathophysiology of kidney diseases and develop novel diagnostic tests to guide personalized treatments for patients.","PeriodicalId":73177,"journal":{"name":"Glomerular diseases","volume":"4 1","pages":"49-63"},"PeriodicalIF":0.0,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11006413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140860923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

APOL1 Genotyping Is Incomplete without Testing for the Protective M1 Modifier p.N264K Variant. 如果不检测保护性 M1 修饰符 p.N264K 变体，APOL1 基因分型是不完整的。

Glomerular diseases

Pub Date : 2024-02-20 eCollection Date: 2024-01-01 DOI: 10.1159/000537948

Rasheed Gbadegesin, Elena Martinelli, Yask Gupta, David J Friedman, Matthew G Sampson, Martin R Pollak, Simone Sanna-Cherchi

引用次数: 0

ANCA-associated vasculitis with active kidney involvement in the United States: 2016–2020 美国活动性肾脏受累的 ANCA 相关性血管炎：2016-2020

Glomerular diseases

Pub Date : 2024-01-10 DOI: 10.1159/000536168

Jianling Tao, Sai Liu, M. Montez-Rath, Vivek Charu, Glenn M. Chertow

Introduction. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and its subtypes, granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic GPA (EGPA), frequently present with acute kidney injury and can often lead to kidney failure, even with successful induction therapy. Few contemporary, nationally representative studies have described hospital complications of AAV. Methods. Using data from the 2016–2020 National Inpatient Sample, a nationally representative database, we identified hospitalizations from adults with a new diagnosis of AAV (subtype or unspecified) and an inpatient kidney biopsy during the index hospitalization. We described baseline characteristics, associated inpatient procedures and complications, and compared lengths of stay and costs by geographic region, hospital characteristics, and AAV subtype. Results. We identified an average of 1329 cases of hospitalized AAV with a concurrent kidney biopsy per year over the 5-year period. More than 50% were not designated as having a specific subtype, likely owing to delays in documentation of histopathology. Kidney involvement was severe as the majority of patients developed acute kidney injury and the proportion of patients who required inpatient dialysis was approximately 24%. Approximately 20% of patients developed hypoxia. Inpatient plasmapheresis was delivered to 20.4% and 20.6% of patients with GPA and MPA, respectively. There were no clinically meaningful or statistically significant differences in adjusted length of stay or inpatient costs among AAV subtypes. Admission in the Midwest region was associated with shorter hospital stays and lower costs than that in the Northeast, South, or West regions of the US (adjusted p=0.007 and <0.001, respectively). Conclusion. AAV with acute kidney involvement remains a challenging, high-risk condition. Maintaining a high index of suspicion and a low threshold for kidney biopsy should help to ameliorate short- and longer-term complications (281 words)

导言。抗中性粒细胞胞浆抗体（ANCA）相关性血管炎（AAV）及其亚型，即肉芽肿伴多血管炎（GPA）、显微镜下多血管炎（MPA）和嗜酸性粒细胞GPA（EGPA），经常出现急性肾损伤，即使诱导治疗成功，也往往会导致肾衰竭。很少有具有全国代表性的当代研究对 AAV 的医院并发症进行描述。研究方法利用具有全国代表性的数据库--2016-2020 年全国住院病人抽样调查的数据，我们确定了新诊断为 AAV（亚型或未指定型）并在住院期间进行了住院肾活检的成人住院病例。我们描述了基线特征、相关住院流程和并发症，并按地理区域、医院特征和 AAV 亚型对住院时间和费用进行了比较。结果。5 年间，我们平均每年发现 1329 例同时进行肾活检的 AAV 住院病例。50%以上的病例未被确定为特定亚型，这可能是由于组织病理学记录的延迟。肾脏受累严重，大多数患者出现急性肾损伤，需要住院透析的患者比例约为 24%。约 20% 的患者出现缺氧。分别有 20.4% 和 20.6% 的 GPA 和 MPA 患者接受了住院血浆置换术。在调整后的住院时间或住院费用方面，AAV亚型之间没有临床意义或统计学意义上的显著差异。与美国东北部、南部或西部地区相比，中西部地区入院患者的住院时间更短，费用更低（调整后 p=0.007 和 <0.001）。结论。急性肾脏受累的 AAV 仍是一种具有挑战性的高风险疾病。保持较高的怀疑指数和较低的肾活检阈值应有助于改善短期和长期并发症 (281 words)

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引用次数: 0

Evaluating sex differences in the characteristics and outcomes of lupus nephritis: a systematic review and meta-analysis 评估狼疮性肾炎特征和结果的性别差异：系统回顾和荟萃分析

Glomerular diseases

Pub Date : 2024-01-04 DOI: 10.1159/000535981

Salman B. Mahmood, Muhammad Aziz, Deepthi C. Malepati, Wade Lee-Smith, Justin Clark, Ann Brearley, Patrick H. Nachman

Introduction: More frequent and severe lupus nephritis (LN) has been reported in men compared to women but data are limited and inconsistent. We conducted a meta-analysis of the literature to compare the histopathologic findings and outcomes between men and women with biopsy-proven LN.Methods: A systematic search of MEDLINE, Embase, Cochrane, and Web of Science databases was conducted through February 2021. Clinical information was extracted and synthesized from 25 studies that met inclusion criteria (1210 men and 6635 women). Pooled odds ratios (OR) with corresponding 95% confidence intervals (CI) were generated via meta-analysis, and meta-regression was performed to assess the impact of several covariates, both using random-effects models.Results: Twenty studies reported kidney histopathology, eleven reported kidney outcomes and eight reported mortality rates. Men had greater odds of class IV ± V LN (OR 1.26, 95% CI 1.01-1.56), and the composite of end-stage kidney disease, persistent eGFR <15 mL/min or doubling of serum creatinine (OR 2.20, 95% CI 1.59-3.06), and lower odds of complete remission (OR 0.52, 95% CI 0.39-0.68). Mortality was not statistically significantly different between sexes (OR 1.50, 95% CI 0.92-2.46). Meta-regression did not reveal statistically significant study-level relationships between sex differences in any of the covariates that could account for the greater odds of worse kidney outcome in males.Conclusion: Our analysis confirms the association between male sex and increased severity of LN as well as worse kidney outcomes. Larger prospective studies are needed to validate this association and inform treatment strategies adapted to this population.

导言：与女性相比，男性狼疮肾炎（LN）的发病率更高，病情更严重，但相关数据有限且不一致。我们对文献进行了荟萃分析，比较了经活检证实的狼疮肾炎患者中男性和女性的组织病理学结果和预后：截至 2021 年 2 月，我们对 MEDLINE、Embase、Cochrane 和 Web of Science 数据库进行了系统检索。从符合纳入标准的 25 项研究（男性 1210 例，女性 6635 例）中提取并综合了临床信息。通过荟萃分析得出汇总的几率比（OR）及相应的95%置信区间（CI），并使用随机效应模型进行荟萃回归以评估几个协变量的影响：20项研究报告了肾脏组织病理学，11项报告了肾脏结果，8项报告了死亡率。男性出现 IV ± V 级 LN 的几率更高（OR 1.26，95% CI 1.01-1.56），出现终末期肾病、eGFR 持续<15 mL/min 或血清肌酐翻倍的复合几率更高（OR 2.20，95% CI 1.59-3.06），完全缓解的几率更低（OR 0.52，95% CI 0.39-0.68）。性别间的死亡率无明显统计学差异（OR 1.50，95% CI 0.92-2.46）。元回归没有发现任何协变量的性别差异与研究水平之间存在统计学意义上的显著关系，而这些协变量可能是导致男性肾脏预后更差几率更大的原因：我们的分析证实了男性性别与 LN 严重程度增加以及肾脏预后恶化之间的关系。需要进行更大规模的前瞻性研究来验证这种关联，并为适合这一人群的治疗策略提供依据。

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引用次数: 0

Advancing Treatments for Rare Renal Diseases: New Hopes and Opportunities to Address a High Unmet Need. 推进罕见肾病的治疗：解决大量未满足需求的新希望和新机遇。

Glomerular diseases

Pub Date : 2023-12-24 DOI: 10.1159/000535955

Davide Garrisi, Andrew Bevan, Carmichael Angeles

Background The etiology of chronic kidney disease (CKD) is varied and complex, with diabetes mellitus and hypertension responsible for the 2/3 of cases and rare conditions, including inherited genetic diseases such as autosomal dominant polycystic kidney disease (ADPKD) and glomerulonephritis (GN), comprising 1/3. We previously reported a 54% increase in clinical studies in CKD in the last 10 years. Summary CT.gov was searched for 39 conditions determined to be rare renal diseases posted between 01-Jan-2003 and 31-Dec-2022. Of 876 records returned, 50 were excluded. 826 in the analysis were divided into 2 time periods: P1(2003-2012) and P2 (2013-2022) and analyzed by study type, phase, primary indication, primary endpoint, population and funding. Studies increased 123% in P2 with the greatest rise in observational studies (283%). Interventional studies increased 93%, with the greatest rise in early phases (205%). The most frequent indications were lupus nephritis (22%), ADPKD (16%) and IgA nephropathy (IGAN) (15%); all increased 77-166% in P2. Proteinuria, measured by 24-hour urine protein (24hUP) excretion or urine protein-creatinine ratio (UPCR), was the most frequent primary endpoint in both periods. Most studies were in adult-only populations (P1 60%; P2 68%); however, there was a 78% increase in studies with pediatric populations in P2. Most studies were non-industry funded (P1 64%; P2 57%); however, the number of industry funded studies increased by 225% in P2. Key Messages Our data provides evidence of a marked rise in clinical research in rare renal diseases in the last 10 years, particularly in GN and ADPKD. Proteinuria correlates with outcomes in GN, which explains the high percentage of studies with this as a primary endpoint. Rare renal diseases disproportionately affect children and the rise in the number of studies with pediatric populations is encouraging. The rise in observational studies signals an increased focus on understanding the natural course and pathophysiology of disease, which may lead to new potential therapeutic targets and future interventional studies.

背景慢性肾脏病（CKD）的病因复杂多样，其中 2/3 的病例与糖尿病和高血压有关，1/3 的病例与罕见疾病有关，包括常染色体显性多囊肾（ADPKD）和肾小球肾炎（GN）等遗传性疾病。我们以前曾报道过，在过去 10 年中，CKD 的临床研究增加了 54%。摘要在 CT.gov 上搜索了 2003 年 1 月 1 日至 2022 年 12 月 31 日期间发布的 39 种被确定为罕见肾病的病症。在返回的 876 条记录中，有 50 条被排除。分析中的 826 条记录分为两个时间段：P1（2003-2012 年）和 P2（2013-2022 年），并按研究类型、阶段、主要适应症、主要终点、人群和资金进行分析。P2 阶段的研究增加了 123%，其中观察性研究的增幅最大（283%）。介入性研究增加了 93%，早期阶段的增幅最大（205%）。最常见的适应症是狼疮性肾炎（22%）、ADPKD（16%）和 IgA 肾病 (IGAN)（15%）；所有适应症在第二阶段都增加了 77-166%。以 24 小时尿蛋白（24hUP）排泄量或尿蛋白-肌酐比值（UPCR）衡量的蛋白尿是这两个时期最常见的主要终点。大多数研究仅针对成人群体（P1 60%；P2 68%）；但在 P2 阶段，针对儿童群体的研究增加了 78%。大多数研究都是非行业资助的（P1 64%；P2 57%）；但在 P2 阶段，行业资助的研究数量增加了 225%。重要信息我们的数据提供了过去 10 年罕见肾病临床研究显著增加的证据，尤其是 GN 和 ADPKD。蛋白尿与 GN 的预后相关，这也是将蛋白尿作为主要终点的研究比例较高的原因。罕见肾病对儿童的影响尤为严重，因此针对儿童群体的研究数量增加令人鼓舞。观察性研究的增加表明，人们越来越重视了解疾病的自然病程和病理生理学，这可能会带来新的潜在治疗目标和未来的干预性研究。

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引用次数: 0