Pub Date : 2023-12-13DOI: 10.1101/2023.12.11.23299722
Zhihang Su, Qingqing Rao, Di Wu, Zheng Yin, Wen Liu, Qijun Wan
Background Idiopathic membranous nephropathy (IMN) is a predominant cause of nephrotic syndrome among adults. Existing drugs are ineffective in about one-third of IMN patients, and the high recurrence rate makes them far from satisfactory. Therefore, it is imperative to find new therapeutic targets for membranous nephropathy. Circulating inflammatory proteins in plasma have been found to be related to the disease and prognosis of IMN patients, yet the causal relationship between them still remains unclear. A better understanding of the inflammatory response of IMN can help us better understand the occurrence of IMN, as well as a good way to find new therapeutic targets. In this study, we aim to use proteome-wide Mendelian Randomization and colocalization analysis to identify plasma inflammatory proteins as potential therapeutic targets for IMN.
{"title":"Circulating inflammatory proteins may be potential drug targets for Idiopathic Membranous Nephropathy: proteome-wide Mendelian Randomization and colocalization analysis","authors":"Zhihang Su, Qingqing Rao, Di Wu, Zheng Yin, Wen Liu, Qijun Wan","doi":"10.1101/2023.12.11.23299722","DOIUrl":"https://doi.org/10.1101/2023.12.11.23299722","url":null,"abstract":"<strong>Background</strong> Idiopathic membranous nephropathy (IMN) is a predominant cause of nephrotic syndrome among adults. Existing drugs are ineffective in about one-third of IMN patients, and the high recurrence rate makes them far from satisfactory. Therefore, it is imperative to find new therapeutic targets for membranous nephropathy. Circulating inflammatory proteins in plasma have been found to be related to the disease and prognosis of IMN patients, yet the causal relationship between them still remains unclear. A better understanding of the inflammatory response of IMN can help us better understand the occurrence of IMN, as well as a good way to find new therapeutic targets. In this study, we aim to use proteome-wide Mendelian Randomization and colocalization analysis to identify plasma inflammatory proteins as potential therapeutic targets for IMN.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138715633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-08DOI: 10.1101/2023.12.07.23299612
Christopher D. Manko, Benjamin J. Apple, Alexander R. Chang, Bobbie L. Johannes
Rationale & Objective: While the use of telemedicine has increased dramatically across disciplines, patient perspectives on telemedicine related to chronic kidney disease are not well understood. We systematically reviewed qualitative studies on patients with chronic kidney disease to better understand these patients' perspectives related to telemedicine. Study Design: Qualitative Meta–Analysis Setting & Study Populations: Pre–dialysis chronic kidney disease and kidney transplant patients that used telemedicine. Selection Criteria for Studies: English language studies published in the year 2000 and beyond that investigated patient perspectives in a qualitative manner. Works that were not qualitative or did not focus on provider-patient interactive modes of telemedicine were excluded. Data Extraction: 375 papers were pulled from PubMed, Embase, and Academic Science Premier. After filtering, 8 final papers were selected. These papers were critically appraised for quality and were used in the final analysis. Analytical Approach: We developed a codebook to systematically review each of the selected papers through qualitative meta-analysis. Results: Four primary themes were identified (autonomy, logistics, privacy/confidentiality, and trust) with additional subthemes and further subdivisions to signify positive versus negative experiences. The majority of subthemes and subdivisions (n=9) identified were positively attributed by patients compared to negative attributes (n=6). The subtheme most commonly found was avoiding travel to the hospital, which was identified in all 8 papers. There was substantial variability in the number of papers demonstrating the other subthemes and subdivisions. Limitations: Lack of provider perspectives, non-English studies, and studies published before the year 2000. Papers published after the start of data extraction were also not included. Conclusions: Telemedicine should continue to be offered to patients with kidney disease and kidney transplant patients to facilitate access. Additional research should focus on ways to decrease negative factors experienced by some patients such as difficulty with using the technology.
理由与目标：虽然远程医疗的使用在各学科中急剧增加，但患者对与慢性肾病有关的远程医疗的看法却不甚了解。我们系统回顾了有关慢性肾病患者的定性研究，以更好地了解这些患者对远程医疗的看法。研究设计：定性 Meta 分析；研究人群：使用远程医疗的透析前慢性肾病和肾移植患者。研究的选择标准：2000 年及以后发表的以定性方式调查患者观点的英文研究。不包括非定性研究或不关注远程医疗中医患互动模式的研究。数据提取：从 PubMed、Embase 和 Academic Science Premier 中提取了 375 篇论文。经过筛选，最终选出 8 篇论文。对这些论文进行了严格的质量评估，并将其用于最终分析。分析方法：我们制定了一个编码手册，通过定性荟萃分析对每篇入选论文进行系统审查。结果我们确定了四个主要主题（自主性、后勤、隐私/保密性和信任）以及其他次主题和进一步的细分，以表示积极与消极的经历。与负面属性（6 个）相比，大多数副主题和细分主题（9 个）都得到了患者的积极评价。最常见的次主题是避免前往医院，所有 8 篇论文都提到了这一点。展示其他次主题和分主题的论文数量差异很大。局限性：缺乏医疗服务提供者的观点、非英语研究以及 2000 年之前发表的研究。数据提取开始后发表的论文也未包括在内。结论：应继续向肾病患者和肾移植患者提供远程医疗，以方便他们就医。其他研究应关注如何减少一些患者遇到的负面因素，如使用技术的困难。
{"title":"Telemedicine Perspectives of Patients with Non-Dialysis Kidney Disease and Kidney Transplant - A Qualitative Meta-Analysis","authors":"Christopher D. Manko, Benjamin J. Apple, Alexander R. Chang, Bobbie L. Johannes","doi":"10.1101/2023.12.07.23299612","DOIUrl":"https://doi.org/10.1101/2023.12.07.23299612","url":null,"abstract":"Rationale & Objective: While the use of telemedicine has increased dramatically across disciplines, patient perspectives on telemedicine related to chronic kidney disease are not well understood. We systematically reviewed qualitative studies on patients with chronic kidney disease to better understand these patients' perspectives related to telemedicine. Study Design: Qualitative Meta–Analysis Setting & Study Populations: Pre–dialysis chronic kidney disease and kidney transplant patients that used telemedicine. Selection Criteria for Studies: English language studies published in the year 2000 and beyond that investigated patient perspectives in a qualitative manner. Works that were not qualitative or did not focus on provider-patient interactive modes of telemedicine were excluded. Data Extraction: 375 papers were pulled from PubMed, Embase, and Academic Science Premier. After filtering, 8 final papers were selected. These papers were critically appraised for quality and were used in the final analysis. Analytical Approach: We developed a codebook to systematically review each of the selected papers through qualitative meta-analysis. Results: Four primary themes were identified (autonomy, logistics, privacy/confidentiality, and trust) with additional subthemes and further subdivisions to signify positive versus negative experiences. The majority of subthemes and subdivisions (n=9) identified were positively attributed by patients compared to negative attributes (n=6). The subtheme most commonly found was avoiding travel to the hospital, which was identified in all 8 papers. There was substantial variability in the number of papers demonstrating the other subthemes and subdivisions. Limitations: Lack of provider perspectives, non-English studies, and studies published before the year 2000. Papers published after the start of data extraction were also not included. Conclusions: Telemedicine should continue to be offered to patients with kidney disease and kidney transplant patients to facilitate access. Additional research should focus on ways to decrease negative factors experienced by some patients such as difficulty with using the technology.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138559778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-08DOI: 10.1101/2023.12.06.23299590
Viola D'Ambrosio, Giovanna Capolongo, Chiara Caletti, Maria Teresa Vietri, Martina Ambrogio, Gianmarco Lombardi, Alessandra Perna, Giuseppe Orefice, Elisa Gremese, Valentina Varriano, Davide Gatti, Angelo Fassio, Giovambattista Capasso, Giovanni Gambaro, Pietro Manuel Ferraro
Introduction Cystinuria is a rare genetic disease characterized by impaired tubular transport of cystine. Clinical features of cystinuria include mainly nephrolithiasis and its complications, although cystinuric patients may present with other comorbidities. There are currently no data on bone features of patients with cystinuria. Our aim is to characterize bone mineral density (BMD) in cystinuria. Methods Our study included adult cystinuric patients followed at 3 specialized outpatient clinics in Italy (Rome, Naples and Verona). Markers of bone turnover were analyzed in a centralized laboratory. Clinical, biochemical and dual-energy X-ray absorptiometry (DEXA) data were collected from September 2021 to December 2022. One sample t-tests were used to assess whether BMD Z-scores were significantly different from 0. Results 39 patients were included in the study. Mean (SD) age was 38 (15) years, 40% were women. Mean estimated glomerular filtration rate was 92 mL/min/1.73 m2. Serum parameters associated with bone remodeling (parathyroid hormone, FGF23, calcium and phosphate) were all in the normal range, with only 4 patients showing mild hypophosphatemia. Prevalence of low BMD, defined as T-score < ⁻1 at any site, was 65%, higher at the femur and lumbar spine. Average Z-scores were negative across most sites. Conclusions Our data show a high prevalence of low BMD in cystinuric patients, despite having normal (or moderately impaired) kidney function and being relatively young.
导言胱氨酸尿症是一种罕见的遗传性疾病，其特点是胱氨酸的肾小管转运功能受损。胱氨酸尿症的临床特征主要包括肾结石及其并发症，但胱氨酸尿症患者也可能出现其他合并症。目前还没有关于胱氨酸尿症患者骨骼特征的数据。我们的研究包括在意大利（罗马、那不勒斯和维罗纳）3 家专科门诊随访的成年胱氨酸尿患者。骨转换标志物在中央实验室进行分析。从 2021 年 9 月到 2022 年 12 月，收集了临床、生化和双能 X 射线吸收测量（DEXA）数据。采用单样本 t 检验来评估 BMD Z 值是否与 0 有显著差异。平均（标清）年龄为 38（15）岁，40% 为女性。平均肾小球滤过率为 92 mL/min/1.73 m2。与骨重塑相关的血清参数（甲状旁腺激素、FGF23、钙和磷酸盐）均处于正常范围，只有 4 名患者出现轻度低磷血症。任何部位的低 BMD（定义为 T 评分 <-1）发生率为 65%，股骨和腰椎的发生率较高。大多数部位的平均 Z 值均为负值。结论我们的数据显示，尽管胱氨酸尿症患者的肾功能正常（或中度受损）且相对年轻，但他们的低 BMD 患病率很高。
{"title":"Bone mineral density assessment in patients with cystinuria","authors":"Viola D'Ambrosio, Giovanna Capolongo, Chiara Caletti, Maria Teresa Vietri, Martina Ambrogio, Gianmarco Lombardi, Alessandra Perna, Giuseppe Orefice, Elisa Gremese, Valentina Varriano, Davide Gatti, Angelo Fassio, Giovambattista Capasso, Giovanni Gambaro, Pietro Manuel Ferraro","doi":"10.1101/2023.12.06.23299590","DOIUrl":"https://doi.org/10.1101/2023.12.06.23299590","url":null,"abstract":"Introduction\u0000Cystinuria is a rare genetic disease characterized by impaired tubular transport of cystine. Clinical features of cystinuria include mainly nephrolithiasis and its complications, although cystinuric patients may present with other comorbidities. There are currently no data on bone features of patients with cystinuria. Our aim is to characterize bone mineral density (BMD) in cystinuria.\u0000Methods\u0000Our study included adult cystinuric patients followed at 3 specialized outpatient clinics in Italy (Rome, Naples and Verona). Markers of bone turnover were analyzed in a centralized laboratory. Clinical, biochemical and dual-energy X-ray absorptiometry (DEXA) data were collected from September 2021 to December 2022. One sample t-tests were used to assess whether BMD Z-scores were significantly different from 0.\u0000Results\u000039 patients were included in the study. Mean (SD) age was 38 (15) years, 40% were women. Mean estimated glomerular filtration rate was 92 mL/min/1.73 m2. Serum parameters associated with bone remodeling (parathyroid hormone, FGF23, calcium and phosphate) were all in the normal range, with only 4 patients showing mild hypophosphatemia. Prevalence of low BMD, defined as T-score < ⁻1 at any site, was 65%, higher at the femur and lumbar spine. Average Z-scores were negative across most sites. Conclusions\u0000Our data show a high prevalence of low BMD in cystinuric patients, despite having normal (or moderately impaired) kidney function and being relatively young.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138560308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-07DOI: 10.1101/2023.12.05.23299516
Jessy Korina Peña Esparragoza, Alina Chávez Guillén, Paloma Ramos López, Oscar Rueda Elias, Susana López Ongil, Matilde Alique, Rafael Ramírez-Chamond, Julia Carracedo, Diego Rodriguez-Puyol, Patricia Martínez-Miguel
Background: The use of higher doses of iron for the treatment of anemia in hemodialysis patients allows lower doses of erythropoiesis-stimulating agents; however, there are concerns regarding the risk of iron toxicity. This study aimed to evaluate the potential toxicity of iron deposition in prevalent hemodialysis patients on iron therapy and its relationship with parameters used to assess iron status, plasma protein oxidation, and cellular iron toxicity. Methods: Magnetic resonance imaging was performed in 56 patients to assess hepatic iron deposition, which was related to clinical and analytical parameters. In patients included in the first and fourth quartiles according to hepatic iron deposition, plasma protein oxidative stress was quantified, as well as iron and cytokine levels in peripheral blood mononuclear cells (PBMCs). Results: Patients with higher hepatic iron deposition had a longer time on hemodialysis (41.0±44.9 vs 4.9±3.4 months, p<0.001) and higher ferritin levels (1181±532 vs 429±278 ng/ml, p<0.001) than those with lower hepatic iron deposition, without differences in transferrin saturation or hepatic enzyme serum concentration. No differences were found in plasma protein oxidation, iron content, or cytokine mRNA content in PBMCs, except for a decrease in IL-6 levels in patients with higher hepatic iron deposition. Conclusions: Patients with longer hemodialysis times had higher iron stores, suggesting that iron treatment over time increases hepatic iron deposition. No parameters supporting increased toxicity in patients with higher hepatic iron deposition were observed; therefore, more proactive treatment with intravenous iron to improve anemia management may not necessarily induce deleterious effects in hemodialysis patients.
背景：使用大剂量铁治疗血液透析患者的贫血可降低促红细胞生成药物的剂量；然而，铁毒性的风险也令人担忧。本研究旨在评估接受铁剂治疗的流行性血液透析患者铁沉积的潜在毒性及其与评估铁状态、血浆蛋白氧化和细胞铁毒性的参数之间的关系。方法：对 56 名患者进行了磁共振成像，以评估肝脏铁沉积，并将其与临床和分析参数联系起来。结果：肝铁沉积较高的患者接受血液透析的时间较长（41.结果：与肝铁沉积较低的患者相比，肝铁沉积较高的患者血液透析时间更长（41.0±44.9 个月 vs 4.9±3.4 个月，p<0.001），铁蛋白水平更高（1181±532 vs 429±278 ng/ml，p<0.001），但转铁蛋白饱和度或肝酶血清浓度无差异。结论：血液透析时间较长的患者铁储存量较高，这表明长期铁治疗会增加肝脏铁沉积。结论：肝铁沉积较高的患者体内铁的储存量较高，这表明铁治疗随着时间的推移会增加肝铁沉积，但没有观察到任何参数支持肝铁沉积较高的患者毒性增加；因此，为改善贫血管理而更积极地进行静脉铁治疗不一定会对血液透析患者产生有害影响。
{"title":"Analysis of potential iron toxicity in hemodialysis patients under intravenous iron treatment","authors":"Jessy Korina Peña Esparragoza, Alina Chávez Guillén, Paloma Ramos López, Oscar Rueda Elias, Susana López Ongil, Matilde Alique, Rafael Ramírez-Chamond, Julia Carracedo, Diego Rodriguez-Puyol, Patricia Martínez-Miguel","doi":"10.1101/2023.12.05.23299516","DOIUrl":"https://doi.org/10.1101/2023.12.05.23299516","url":null,"abstract":"Background:\u0000The use of higher doses of iron for the treatment of anemia in hemodialysis patients allows lower doses of erythropoiesis-stimulating agents; however, there are concerns regarding the risk of iron toxicity. This study aimed to evaluate the potential toxicity of iron deposition in prevalent hemodialysis patients on iron therapy and its relationship with parameters used to assess iron status, plasma protein oxidation, and cellular iron toxicity.\u0000Methods:\u0000Magnetic resonance imaging was performed in 56 patients to assess hepatic iron deposition, which was related to clinical and analytical parameters. In patients included in the first and fourth quartiles according to hepatic iron deposition, plasma protein oxidative stress was quantified, as well as iron and cytokine levels in peripheral blood mononuclear cells (PBMCs).\u0000Results:\u0000Patients with higher hepatic iron deposition had a longer time on hemodialysis (41.0±44.9 vs 4.9±3.4 months, p<0.001) and higher ferritin levels (1181±532 vs 429±278 ng/ml, p<0.001) than those with lower hepatic iron deposition, without differences in transferrin saturation or hepatic enzyme serum concentration. No differences were found in plasma protein oxidation, iron content, or cytokine mRNA content in PBMCs, except for a decrease in IL-6 levels in patients with higher hepatic iron deposition.\u0000Conclusions:\u0000Patients with longer hemodialysis times had higher iron stores, suggesting that iron treatment over time increases hepatic iron deposition. No parameters supporting increased toxicity in patients with higher hepatic iron deposition were observed; therefore, more proactive treatment with intravenous iron to improve anemia management may not necessarily induce deleterious effects in hemodialysis patients.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138553329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-04DOI: 10.1101/2023.12.04.23299387
Abigail O. Smith, William Tyler Frantz, Kenley M. Preval, Yvonne J.K. Edwards, Craig J. Ceol, Julie A. Jonassen, Gregory J. Pazour
Polycystic kidney disease (PKD) is an important cause of end stage renal disease, but treatment options are limited. While later stages of the disease have been extensively studied, mechanisms driving the initial conversion of renal tubules into cysts are not understood. To identify factors that promote the initiation of cysts we deleted polycystin-2 (Pkd2) in mice and surveyed transcriptional changes before and immediately after cysts developed. We identified 74 genes which we term cyst initiation candidates (CICs). To identify conserved changes with relevance to human disease we compared these murine CICs to single cell transcriptomic data derived from patients with PKD and from healthy controls. Tumor-associated calcium signal transducer 2 (Tacstd2) stood out as an epithelial-expressed gene whose levels were elevated prior to cystic transformation and further increased with disease progression. Human tissue biopsies and organoids show that TACSTD2 protein is low in normal kidney cells but is elevated in cyst lining cells. While TACSTD2 has not been studied in PKD, it has been studied in cancer where it is highly expressed in solid tumors while showing minimal expression in normal tissue. This property is being exploited by antibody drug conjugates that target TACSTD2 for the delivery of cytotoxic drugs. Our finding that Tacstd2 is highly expressed in cysts, but not normal tissue, suggests that it should be explored as a candidate for drug development in PKD. More immediately, our work suggests that PKD patients undergoing TACSTD2 treatment for cancer should be monitored for kidney effects.
{"title":"The Tumor-Associated Calcium Signal Transducer 2 (TACSTD2) oncogene is upregulated in pre-cystic epithelial cells revealing a new target for polycystic kidney disease","authors":"Abigail O. Smith, William Tyler Frantz, Kenley M. Preval, Yvonne J.K. Edwards, Craig J. Ceol, Julie A. Jonassen, Gregory J. Pazour","doi":"10.1101/2023.12.04.23299387","DOIUrl":"https://doi.org/10.1101/2023.12.04.23299387","url":null,"abstract":"Polycystic kidney disease (PKD) is an important cause of end stage renal disease, but treatment options are limited. While later stages of the disease have been extensively studied, mechanisms driving the initial conversion of renal tubules into cysts are not understood. To identify factors that promote the initiation of cysts we deleted polycystin-2 (Pkd2) in mice and surveyed transcriptional changes before and immediately after cysts developed. We identified 74 genes which we term cyst initiation candidates (CICs). To identify conserved changes with relevance to human disease we compared these murine CICs to single cell transcriptomic data derived from patients with PKD and from healthy controls. Tumor-associated calcium signal transducer 2 (Tacstd2) stood out as an epithelial-expressed gene whose levels were elevated prior to cystic transformation and further increased with disease progression. Human tissue biopsies and organoids show that TACSTD2 protein is low in normal kidney cells but is elevated in cyst lining cells. While TACSTD2 has not been studied in PKD, it has been studied in cancer where it is highly expressed in solid tumors while showing minimal expression in normal tissue. This property is being exploited by antibody drug conjugates that target TACSTD2 for the delivery of cytotoxic drugs. Our finding that Tacstd2 is highly expressed in cysts, but not normal tissue, suggests that it should be explored as a candidate for drug development in PKD. More immediately, our work suggests that PKD patients undergoing TACSTD2 treatment for cancer should be monitored for kidney effects.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138534826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-04DOI: 10.1101/2023.12.03.23299357
Amit Sharma, Ekansh Chauhan, Megha S Uppin, Rajasekhar Liza, C.V. Jawahar, P K Vinod
Lupus Nephritis classification has historically relied on labor-intensive and meticulous glomerular-level labeling of renal structures in whole slide images (WSIs). However, this approach presents a formidable challenge due to its tedious and resource-intensive nature, limiting its scalability and practicality in clinical settings. In response to this challenge, our work introduces a novel methodology that utilizes only slide-level labels, eliminating the need for granular glomerular-level labeling. A comprehensive multi-stained lupus nephritis digital histopathology WSI dataset was created from the Indian population, which is the largest of its kind. LupusNet, a deep learning MIL-based model, was developed for the subtype classification of LN. The results underscore its effectiveness, achieving an AUC score of 91.0%, an F1-score of 77.3%, and an accuracy of 81.1% on our dataset in distinguishing membranous and diffused classes of LN.
{"title":"LUPUS NEPHRITIS SUBTYPE CLASSIFICATION WITH ONLY SLIDE LEVEL LABELS","authors":"Amit Sharma, Ekansh Chauhan, Megha S Uppin, Rajasekhar Liza, C.V. Jawahar, P K Vinod","doi":"10.1101/2023.12.03.23299357","DOIUrl":"https://doi.org/10.1101/2023.12.03.23299357","url":null,"abstract":"Lupus Nephritis classification has historically relied on labor-intensive and meticulous glomerular-level labeling of renal structures in whole slide images (WSIs). However, this approach presents a formidable challenge due to its tedious and resource-intensive nature, limiting its scalability and practicality in clinical settings. In response to this challenge, our work introduces a novel methodology that utilizes only slide-level labels, eliminating the need for granular glomerular-level labeling. A comprehensive multi-stained lupus nephritis digital histopathology WSI dataset was created from the Indian population, which is the largest of its kind. LupusNet, a deep learning MIL-based model, was developed for the subtype classification of LN. The results underscore its effectiveness, achieving an AUC score of 91.0%, an F1-score of 77.3%, and an accuracy of 81.1% on our dataset in distinguishing membranous and diffused classes of LN.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138534827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-27DOI: 10.1101/2023.11.27.23299065
Zhihang Su, Liu Wen, Xiangning Feng, Qijun Wan
Background Membranous nephropathy (MN), an autoimmune disease, has not yet been fully elucidated regarding its relationship with immune cells.
膜性肾病(MN)是一种自身免疫性疾病，其与免疫细胞的关系尚未完全阐明。
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Pub Date : 2023-11-22DOI: 10.1101/2023.11.21.23298831
Zhihang Su, Qijun Wan
Background The currently available medications for treating membranous nephropathy (MN) still have unsatisfactory efficacy in inhibiting disease recurrence, slowing down its progression, and even halting the development of end-stage renal disease. There is still a need to develop novel drugs targeting MN.
{"title":"Potential therapeutic targets for Membranous Nephropathy: proteome-wide Mendelian randomization and colocalization analysis","authors":"Zhihang Su, Qijun Wan","doi":"10.1101/2023.11.21.23298831","DOIUrl":"https://doi.org/10.1101/2023.11.21.23298831","url":null,"abstract":"<strong>Background</strong> The currently available medications for treating membranous nephropathy (MN) still have unsatisfactory efficacy in inhibiting disease recurrence, slowing down its progression, and even halting the development of end-stage renal disease. There is still a need to develop novel drugs targeting MN.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138534828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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