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Correlations of the Complement Proteins MASP-2 and MASP-3 With Clinical Severity and Short-Term Outcomes in Primary Membranous Nephropathy Patients. 补体蛋白MASP-2和MASP-3与原发性膜性肾病患者临床严重程度和短期预后的相关性
IF 2.4 4区 医学 Q2 UROLOGY & NEPHROLOGY Pub Date : 2025-05-01 DOI: 10.1111/nep.70041
Tong Liu, Miao Hu, Yujie Bai, Jiayan Zhang, Yi Deng, Lei Shen, Ling Zhou

Aim: This study aimed to explore the serum levels of mannose binding lectin-associated serine protease 2(MASP-2) and 3(MASP-3) in primary membranous nephropathy (PMN) patients and its correlation with clinical activity and short-term prognosis.

Methods: Serum levels of MASP-2, MASP-3 and C5a were measured in 72 PMN patients, 71 IgAN patients and 30 healthy controls via enzyme-linked immunosorbent assay (ELISA). Correlations between complement activation biomarkers and clinical parameters were analysed using Spearman correlation. Logistic regression analysis was used to identify risk factors for short-term clinical non-remission in PMN patients, and the predictive performance of the factors was evaluated using ROC curves and the area under the ROC curve (AUC).

Results: Serum MASP-2 levels in the PMN group were lower than in both the healthy control and IgAN groups, while levels in the IgAN group were higher than in the healthy control group. Serum levels of MASP-3 and C5a in the PMN group were not significantly different from those in the IgAN group. Both patient groups had significantly elevated serum levels of MASP-3 and C5a compared to the healthy control group. In PMN patients, serum MASP-3 and C5a levels correlated with clinical indicators such as eGFR, serum creatinine and 24-h urinary protein. Multivariate logistic regression analysis revealed that serum anti-phospholipase A2 receptor antibody (anti-PLA2R-ab) and MASP-3 were independent risk factors for the non-remission of PMN at 12 months. The combined detection of serum MASP-3 and anti-PLA2R-ab had a greater AUC for predicting early non-remission than either factor alone.

Conclusion: Serum MASP-3 and C5a can serve as biomarkers reflecting the clinical severity of PMN. The combined detection of serum MASP-3 and anti-PLA2R-ab will improve the prediction efficiency of PMN prognosis.

目的:探讨原发性膜性肾病(PMN)患者血清甘露糖结合凝集素相关丝氨酸蛋白酶2(MASP-2)和3(MASP-3)水平及其与临床活动和短期预后的关系。方法:采用酶联免疫吸附试验(ELISA)检测72例PMN患者、71例IgAN患者和30例健康对照者血清中MASP-2、MASP-3和C5a水平。采用Spearman相关分析补体活化生物标志物与临床参数的相关性。采用Logistic回归分析确定PMN患者短期临床不缓解的危险因素,并采用ROC曲线及ROC曲线下面积(AUC)评价各因素的预测效果。结果:PMN组血清MASP-2水平低于健康对照组和IgAN组,IgAN组高于健康对照组。PMN组与IgAN组血清MASP-3、C5a水平差异无统计学意义。与健康对照组相比,两组患者血清中MASP-3和C5a水平均显著升高。PMN患者血清MASP-3、C5a水平与eGFR、血清肌酐、24小时尿蛋白等临床指标相关。多因素logistic回归分析显示,血清抗磷脂酶A2受体抗体(anti-PLA2R-ab)和MASP-3是PMN 12个月未缓解的独立危险因素。联合检测血清MASP-3和抗pla2r -ab在预测早期非缓解方面的AUC高于单独检测这两种因素。结论:血清MASP-3、C5a可作为反映PMN临床严重程度的生物标志物。联合检测血清MASP-3和anti-PLA2R-ab可提高PMN预后的预测效率。
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引用次数: 0
Diagnostic Value and Mechanism of Action of Serum miR-1281 Involved in T2DM and Complications of DKD. 血清miR-1281参与T2DM及DKD并发症的诊断价值及作用机制
IF 2.4 4区 医学 Q2 UROLOGY & NEPHROLOGY Pub Date : 2025-05-01 DOI: 10.1111/nep.70052
Cuicui Hao, Cui Li, Junhong Wang, Shan Yu

Objective: To research the diagnostic value and mechanism of miR-1281 involved in type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD).

Methods: One hundred and eighteen patients with T2DM (68 DKD patients) and 35 healthy individuals were included. Fasting venous blood and one-time morning urine were collected for biochemical testing. RT-qPCR detected miR-1281 expression, ROC curve assessed the diagnostic value of miR-1281 for T2DM and DKD, and logistic regression predicted risk factors affecting the progression of DKD. ELISA analysed inflammatory cytokine expression, and Pearson correlation assessed its relevance to miR-1281. CCK8 detected cell proliferation and flow cytometry recorded apoptosis.

Results: miR-1281 was upregulated in T2DM patients and increased more significantly in DKD patients. The ROC curves indicated that miR-1281 had diagnostic value in predicting T2DM and DKD, and miR-1281 was closely related to the pathological characteristics of DKD patients. The logistic results showed that increased miR-1281 expression was a risk factor for DKD progression. ELISA showed that inflammatory cytokines (IL-6, IL-18, TNF-α) were significantly increased in patients with T2DM, and Pearson correlation analysis indicated a positive correlation between miR-1281 and inflammatory cytokine expression. The high-glucose environment promoted cell proliferation, decreased apoptosis, and increased inflammatory factor levels, but transfection of the miR-1281 inhibitor resisted the adverse effects of the high-glucose environment on cells.

Conclusion: miR-1281 promotes glomerular cell proliferation, inhibits apoptosis, and increases the level of intracellular inflammation, leading to impaired renal function in T2DM patients.

目的:探讨miR-1281在2型糖尿病(T2DM)及糖尿病肾病(DKD)中的诊断价值及机制。方法:118例T2DM患者(其中DKD患者68例)和35例健康人。采集空腹静脉血和一次性晨尿进行生化检测。RT-qPCR检测miR-1281表达,ROC曲线评估miR-1281对T2DM和DKD的诊断价值,logistic回归预测影响DKD进展的危险因素。ELISA分析炎症细胞因子表达,Pearson相关性评估其与miR-1281的相关性。CCK8检测细胞增殖,流式细胞术记录细胞凋亡。结果:miR-1281在T2DM患者中上调,在DKD患者中升高更为显著。ROC曲线显示miR-1281在预测T2DM和DKD方面具有诊断价值,且miR-1281与DKD患者的病理特征密切相关。逻辑分析结果显示,miR-1281表达增加是DKD进展的危险因素。ELISA结果显示,炎症因子(IL-6、IL-18、TNF-α)在T2DM患者中显著升高,Pearson相关分析显示miR-1281与炎症因子表达呈正相关。高糖环境促进细胞增殖,减少细胞凋亡,增加炎症因子水平,但转染miR-1281抑制剂可抵抗高糖环境对细胞的不良影响。结论:miR-1281促进肾小球细胞增殖,抑制细胞凋亡,增加细胞内炎症水平,导致T2DM患者肾功能受损。
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引用次数: 0
Executive Summary of the Asian Pacific Society of Nephrology Clinical Practice Guideline on Diabetic Kidney Disease-2025 Update. 亚太肾脏病学会糖尿病肾病临床实践指南2025更新执行摘要
IF 2.4 4区 医学 Q2 UROLOGY & NEPHROLOGY Pub Date : 2025-05-01 DOI: 10.1111/nep.70031
Adrian Liew, Sunita Bavanandan, Chuan-Ming Hao, Soo Kun Lim, Narayan Prasad, Manisha Sahay, Paweena Susantitaphong, Veena Roberts, Eranga Wijewickrama, Muh Geot Wong, Sydney C W Tang
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引用次数: 0
Podocyte Infolding Glomerulopathy: Case Series From a Tertiary Hospital in India. 足细胞折叠性肾小球病:来自印度一家三级医院的病例系列。
IF 2.4 4区 医学 Q2 UROLOGY & NEPHROLOGY Pub Date : 2025-05-01 DOI: 10.1111/nep.70045
Devika Chauhan, Swarnim Swarnim, Bhavana Asit Mehta, Aakash Batra, Anurag Rohatgi, Vineeta Vijay Batra

Podocyte infolding glomerulopathy is a rare pathological entity characterised by invagination of the podocyte cell membrane into the glomerular basement membrane with presence of microspheres and/or microtubules on electron microscopy. Without an ultrastructure study, it is often confused with and misdiagnosed as membranous nephropathy. The pathogenesis of this disease remains unclear and the majority of cases show association with connective tissue disorders. There is an ongoing debate on whether it represents a distinct disease entity or merely an unusual renal pathological finding of coexisting disease. Till date, only a single case report has been reported from India. We present a series of 4 cases from India along with a review of literature. This case series aims to provide some insights highlighting the clinical, light microscopic, and diagnostic electron microscopic aspects of this uncommon entity.

足细胞内折叠肾小球病是一种罕见的病理实体,其特征是足细胞细胞膜内陷到肾小球基底膜中,电镜下可见微球和/或微管。未经超微结构检查,常与膜性肾病相混淆,误诊为膜性肾病。这种疾病的发病机制尚不清楚,大多数病例显示与结缔组织疾病有关。关于它是否代表一种独特的疾病实体或仅仅是一种不寻常的肾脏病理发现共存疾病的争论正在进行中。迄今为止,印度只报告了一例病例。我们提出了来自印度的4例病例,并对文献进行了回顾。本病例系列旨在提供一些见解,突出临床,光镜和诊断电子显微镜方面的这种不常见的实体。
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引用次数: 0
Evolving Gender Dynamics in India's Nephrology Workforce: A Decadal Analysis (2013-2023). 印度肾脏病工作人员的性别动态变化:十年分析(2013-2023)。
IF 2.4 4区 医学 Q2 UROLOGY & NEPHROLOGY Pub Date : 2025-05-01 DOI: 10.1111/nep.70047
Priti Meena, Garima Aggarwal, Urmila Anandh, Manjusha Yadla, Manisha Sahay, Arpita Ray Chaudhury, Vinant Bhargava, P S Priyamvada, Natarajan Gopalakrishnan, Swarnalatha Guditi, Manjuri Sharma, Vivek Kute, M Edwin Fernando, Vinoi G David

The field of medicine has long been marked by gender disparities, with men predominantly occupying higher academic ranks while women were underrepresented. In recent years, there have been marked changes in the gender ratio among medical professionals in Nephrology. This study analysed gender dynamics within the Indian Nephrology fraternity. The primary objectives were to evaluate the gender distribution among nephrology residents/fellows in subspecialty courses over the past decade (2013-2023), faculty members, and heads of departments (HODs). Data was collected from 27 academic centres. Data from 27 institutions showed a consistent increase in nephrology residents, from 76 in 2013 to 112 in 2023. The proportion of female residents increased significantly from 22.4% in 2013 to 38.4% in 2023. A statistically significant increase in female residents (p < 0.05), alongside a corresponding decrease in male residents, was noted. Among faculty members, 22.4% were females, and 20.4% of HODs were female. Female representation on the governing council of the Indian Society of nephrology (ISN) was limited. Since its inception, the role of ISN secretary has been held by eight individuals, all of whom have been male. Since 1971, the ISN has had a total of 42 presidents, with only 4 being female. The editorialship of IJN has never been stewarded by a female member to date. The findings demonstrate a positive trend towards gender parity in India's nephrology workforce over the past decade, reflecting broader societal acceptance and enhanced support for women in nephrology.

长期以来,医学领域一直存在性别差异,男性主要占据较高的学术职位,而女性的代表性不足。近年来,肾内科医疗专业人员的性别比例发生了显著变化。这项研究分析了印度肾病学界的性别动态。主要目的是评估过去十年(2013-2023年)肾脏病专科住院医师/研究员、教师和系主任(HODs)的性别分布。数据收集自27个学术中心。来自27家机构的数据显示,肾脏病住院医师人数持续增加,从2013年的76人增加到2023年的112人。女性居民的比例从2013年的22.4%大幅上升到2023年的38.4%。统计上,女性居民显著增加(p
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引用次数: 0
Diagnostic Potential of Dp-ucMGP as a Biomarker for Early Detection of Diabetic Kidney Disease in Patients With Type 2 Diabetes Mellitus: A Cross-Sectional Study. Dp-ucMGP作为2型糖尿病患者糖尿病肾病早期检测的生物标志物的诊断潜力:一项横断面研究
IF 2.4 4区 医学 Q2 UROLOGY & NEPHROLOGY Pub Date : 2025-05-01 DOI: 10.1111/nep.70050
Farazul Hoda, Mawrah Arshad, Mohammad Ahmad Khan, Mohammad Anwar Habib, Abul Kalam Najmi

Aim: The limited evidence reports the relationship between plasma dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP) and Diabetic kidney disease (DKD) in patients with Type 2 Diabetes Mellitus (T2DM). Therefore, the present study aimed to evaluate the diagnostic potential of dp-ucMGP in DKD among T2DM patients.

Method: This cross-sectional study was conducted from December 2023 to January 2025, including 75 T2DM patients. Participants were classified into three groups based on urinary albumin-to-creatinine ratio (UACR): Normoalbuminuria, microalbuminuria, and macroalbuminuria with n = 25 in each group. Pearson correlation analysis was performed to assess the relationship between dp-ucMGP and other biochemical parameters. Receiver Operating Characteristic (ROC) curve analysis was used to evaluate the diagnostic potential of dp-ucMGP for early detection of DKD. A p value < 0.05 was considered statistically significant.

Results: The plasma dp-ucMGP levels were significantly higher in T2DM patients in the macroalbuminuria group, with a mean of 1069.86 ± 417.56 pmol/L, followed by the microalbuminuria (842.72 ± 342.02 pmol/L) and normoalbuminuria (586.38 ± 336.15 pmol/L) groups. Similarly, higher dp-ucMGP levels were observed in patients with DKD severity stage IV (1401.53 ± 401.49 pmol/L). A negative correlation with eGFR (r = -0.807, p < 0.0001) and a positive correlation with age, serum creatinine, UACR, blood urea, uric acid and triglycerides were observed. The area under the curve (AUC) was 0.913 (95% CI: 0.820-0.960; p < 0.0001) for dp-ucMGP.

Conclusion: In conclusion, our findings revealed that plasma dp-ucMGP could be a potential biomarker to predict the early detection of DKD in patients with T2DM.

目的:有限的证据报道了2型糖尿病(T2DM)患者血浆去磷酸化非羧化基质Gla蛋白(dp-ucMGP)与糖尿病肾病(DKD)之间的关系。因此,本研究旨在评估dp-ucMGP对T2DM患者DKD的诊断潜力。方法:本横断面研究于2023年12月至2025年1月进行,包括75例T2DM患者。参与者根据尿白蛋白与肌酐比值(UACR)分为三组:正常白蛋白尿、微量白蛋白尿和大量白蛋白尿,每组n = 25。采用Pearson相关分析评价dp-ucMGP与其他生化指标的关系。采用受试者工作特征(ROC)曲线分析评价dp-ucMGP对DKD早期检测的诊断潜力。结果:大蛋白尿组T2DM患者血浆dp-ucMGP水平显著升高,平均为1069.86±417.56 pmol/L,其次为微量蛋白尿组(842.72±342.02 pmol/L)和正常蛋白尿组(586.38±336.15 pmol/L)。同样,DKD严重程度IV期患者的dp-ucMGP水平较高(1401.53±401.49 pmol/L)。结论:血浆dp-ucMGP可能是预测T2DM患者早期发现DKD的潜在生物标志物。
{"title":"Diagnostic Potential of Dp-ucMGP as a Biomarker for Early Detection of Diabetic Kidney Disease in Patients With Type 2 Diabetes Mellitus: A Cross-Sectional Study.","authors":"Farazul Hoda, Mawrah Arshad, Mohammad Ahmad Khan, Mohammad Anwar Habib, Abul Kalam Najmi","doi":"10.1111/nep.70050","DOIUrl":"https://doi.org/10.1111/nep.70050","url":null,"abstract":"<p><strong>Aim: </strong>The limited evidence reports the relationship between plasma dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP) and Diabetic kidney disease (DKD) in patients with Type 2 Diabetes Mellitus (T2DM). Therefore, the present study aimed to evaluate the diagnostic potential of dp-ucMGP in DKD among T2DM patients.</p><p><strong>Method: </strong>This cross-sectional study was conducted from December 2023 to January 2025, including 75 T2DM patients. Participants were classified into three groups based on urinary albumin-to-creatinine ratio (UACR): Normoalbuminuria, microalbuminuria, and macroalbuminuria with n = 25 in each group. Pearson correlation analysis was performed to assess the relationship between dp-ucMGP and other biochemical parameters. Receiver Operating Characteristic (ROC) curve analysis was used to evaluate the diagnostic potential of dp-ucMGP for early detection of DKD. A p value < 0.05 was considered statistically significant.</p><p><strong>Results: </strong>The plasma dp-ucMGP levels were significantly higher in T2DM patients in the macroalbuminuria group, with a mean of 1069.86 ± 417.56 pmol/L, followed by the microalbuminuria (842.72 ± 342.02 pmol/L) and normoalbuminuria (586.38 ± 336.15 pmol/L) groups. Similarly, higher dp-ucMGP levels were observed in patients with DKD severity stage IV (1401.53 ± 401.49 pmol/L). A negative correlation with eGFR (r = -0.807, p < 0.0001) and a positive correlation with age, serum creatinine, UACR, blood urea, uric acid and triglycerides were observed. The area under the curve (AUC) was 0.913 (95% CI: 0.820-0.960; p < 0.0001) for dp-ucMGP.</p><p><strong>Conclusion: </strong>In conclusion, our findings revealed that plasma dp-ucMGP could be a potential biomarker to predict the early detection of DKD in patients with T2DM.</p>","PeriodicalId":19264,"journal":{"name":"Nephrology","volume":"30 5","pages":"e70050"},"PeriodicalIF":2.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
New Diagnosis of Lupus Nephritis in the Third Trimester-A Case Report. 晚期狼疮性肾炎新诊断1例报告。
IF 2.4 4区 医学 Q2 UROLOGY & NEPHROLOGY Pub Date : 2025-05-01 DOI: 10.1111/nep.70037
Umesha Pathmanathan, Sivasaaini Sivakumaran, Jade Eccles-Smith, Ann-Maree Craven, Jill Parkes Smith, Prianka Puri, Kirsten Hepburn

New-onset lupus nephritis (LN) poses a diagnostic and management challenge during pregnancy. This is more pertinent in the indigenous population, where the prevalence is higher, and the clinical phenotype tends to be more severe. We report the case of a 30-year-old G3P2 indigenous female, living in remote Queensland, with a late presentation of nephrotic syndrome at 30 weeks gestation. A clinical diagnosis of Class V LN was made without a kidney biopsy due to maternal and foetal risk, and she was empirically treated with steroids and disease-modifying agents to good effect. She remained normotensive with appropriate foetal growth and delivered a healthy male infant at 37 weeks. A renal biopsy taken 9 weeks after commencement of therapy demonstrated Class II LN, likely representing a resolving flare in the presence of improved clinical symptoms.

新发狼疮肾炎(LN)提出了诊断和管理的挑战,在怀孕期间。这在土著人群中更为相关,那里的患病率更高,临床表型往往更严重。我们报告一例30岁的G3P2土著女性,生活在偏远的昆士兰州,在妊娠30周出现肾病综合征。临床诊断为V级LN,由于母婴风险,未行肾活检,并经验性使用类固醇和疾病改进剂治疗,效果良好。她保持血压正常,胎儿生长正常,并在37周时生下了一个健康的男婴。治疗开始9周后进行的肾活检显示为II级LN,可能代表在临床症状改善的情况下耀斑消退。
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引用次数: 0
The Significance of Menopausal Hormone Therapy on Cognitive Function in Women With CKD. 绝经期激素治疗对慢性肾病妇女认知功能的影响。
IF 2.4 4区 医学 Q2 UROLOGY & NEPHROLOGY Pub Date : 2025-05-01 DOI: 10.1111/nep.70053
Lin Wang, Hong Xia
{"title":"The Significance of Menopausal Hormone Therapy on Cognitive Function in Women With CKD.","authors":"Lin Wang, Hong Xia","doi":"10.1111/nep.70053","DOIUrl":"https://doi.org/10.1111/nep.70053","url":null,"abstract":"","PeriodicalId":19264,"journal":{"name":"Nephrology","volume":"30 5","pages":"e70053"},"PeriodicalIF":2.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Case Report: Something Is Brewing. 病例报告:有些事情正在酝酿。
IF 2.4 4区 医学 Q2 UROLOGY & NEPHROLOGY Pub Date : 2025-05-01 DOI: 10.1111/nep.70051
Kate Brotherton, Bobby Chacko

Kava plant root (piper methysticum) is an ingredient used in ceremonial drinks throughout Pacific and South Sea Island communities. Kava is made up of kavalactones; psychoactive compounds that act as central nervous system depressants. The rare occurrence of kavalactone toxicity manifests most commonly with hepatotoxicity, and cases of myoglobinuria have been reported. Our case describes an association of significant kava tea ingestion with acute tubulo-interstitial nephritis. An 18-year-old male, without any medical comorbidities, presented with oliguric acute kidney injury after ingesting 15 cups of kava tea. His creatinine at admission was 223umolL and peaked at 96 h post ingestion at 970umol/L despite intravenous fluid administration. His urine ACR was 196 mg/mmol, with microscopic haematuria; a creatinine kinase was 780 U/L, C3 was mildly reduced (0.77 g/L) with normal C4, and the remainder of a glomerulonephritis screen was negative. He did not have any evidence of hepatotoxicity but was bradycardic with a prolonged QT interval. A urine drug screen was negative for other substances. A kidney biopsy demonstrated severe acute tubulointerstitial nephritis without acute tubular necrosis or evidence of myoglobulin-related injury. He was commenced on oral corticosteroids and had complete recovery of his kidney function after 2 weeks, without requiring kidney replacement therapy. Toxicology analysis of the kava powder identified four different kavalactones without additional substances.

卡瓦植物根是太平洋和南海岛屿社区礼仪饮料中使用的一种成分。卡瓦是由卡瓦内酯组成的;作为中枢神经系统抑制剂的精神活性化合物。罕见的卡瓦内酯毒性表现为肝毒性,肌红蛋白尿的病例也有报道。我们的病例描述了卡瓦茶摄入与急性肾小管间质性肾炎的关系。一名18岁男性,无任何医学合并症,在摄入15杯卡瓦茶后出现少尿急性肾损伤。入院时肌酐为223umol /L,尽管静脉输液,但服药后96 h肌酐峰值为970umol/L。尿ACR 196 mg/mmol,镜下血尿;肌酐激酶780 U/L, C3轻度降低(0.77 g/L), C4正常,其余肾小球肾炎筛检为阴性。他没有任何肝毒性的证据,但心动过缓,QT间期延长。尿药筛查其他物质呈阴性。肾活检显示严重的急性小管间质性肾炎,无急性小管坏死或肌红蛋白相关损伤的证据。患者开始口服皮质类固醇,2周后肾功能完全恢复,无需肾脏替代治疗。卡瓦粉的毒理学分析鉴定出四种不同的卡瓦内酯,无其他物质。
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引用次数: 0
A Mendelian Randomization Study on the Association Between Sex Hormone-Binding Globulin and Membranous Nephropathy Risk. 性激素结合球蛋白与膜性肾病风险相关性的孟德尔随机研究。
IF 2.4 4区 医学 Q2 UROLOGY & NEPHROLOGY Pub Date : 2025-05-01 DOI: 10.1111/nep.70049
Yingxin Fang, Qiuhua Gu, Junya Jia, Tiekun Yan

Aim: Membranous nephropathy (MN) is the leading cause of nephrotic syndrome in adults, with 80% of cases being primary MN of unknown origin. While the influence of sex hormones on chronic kidney disease (CKD) is thoroughly established, the role of sex hormone-binding globulin (SHBG) in MN is still uncertain.

Methods: We performed a Mendelian randomization (MR) analysis to assess the causal impact of SHBG on MN, utilising data from genome-wide association studies (GWAS). The main analysis utilised the inverse variance weighted (IVW) method, while various additional and sensitivity analyses were conducted to evaluate the causal estimates.

Results: We obtained 51 valid instrumental variables (IVs) of SHBG from large-scale open-access GWASs. Genetic forecasting of SHBG notably raised the likelihood of MN in males (IVW odds ratios [OR] = 2.992, 95% confidence interval [CI] = [1.643, 5.446], p = 3.370 × 10-4). Three additional MR analyses consistently demonstrated a positive causal relationship between SHBG and MN, with all p values being less than 0.05. MR-Egger intercept analysis showed no evidence of horizontal pleiotropy (p > 0.05).

Conclusion: Elevated serum SHBG concentrations were directly associated with an increased risk of primary MN in males. Further research is needed to explore the effectiveness of SHBG in assessing and predicting MN risk.

目的:膜性肾病(MN)是成人肾病综合征的主要原因,80%的病例为原发性不明原因的MN。虽然性激素对慢性肾脏疾病(CKD)的影响已经完全确定,但性激素结合球蛋白(SHBG)在MN中的作用仍不确定。方法:利用全基因组关联研究(GWAS)的数据,我们进行了孟德尔随机化(MR)分析,以评估SHBG对MN的因果影响。主要分析采用反方差加权(IVW)方法,同时进行各种附加分析和敏感性分析来评估因果估计。结果:从大规模开放获取的GWASs中获得51个有效的SHBG工具变量(IVs)。SHBG的遗传预测显著提高了男性罹患MN的可能性(IVW比值比[OR] = 2.992, 95%可信区间[CI] = [1.643, 5.446], p = 3.370 × 10-4)。另外三项MR分析一致表明SHBG和MN之间存在正因果关系,p值均小于0.05。MR-Egger截距分析未显示水平多效性(p < 0.05)。结论:血清SHBG浓度升高与男性原发性MN风险增加直接相关。SHBG在评估和预测MN风险方面的有效性有待进一步研究。
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引用次数: 0
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Nephrology
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