medRxiv - Nephrology最新文献

{"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}

{"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 &amp; 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 &amp; 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}

{"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 &lt; ⁻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}

{"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&lt;0.001) and higher ferritin levels (1181±532 vs 429±278 ng/ml, p&lt;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}

{"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}

{"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}

{"title":"Causality between Peripheral Immune Cell Counts and Membranous Nephropathy: A Bidirectional Mendelian Randomization Study","authors":"Zhihang Su, Liu Wen, Xiangning Feng, Qijun Wan","doi":"10.1101/2023.11.27.23299065","DOIUrl":"https://doi.org/10.1101/2023.11.27.23299065","url":null,"abstract":"<strong>Background</strong> Membranous nephropathy (MN), an autoimmune disease, has not yet been fully elucidated regarding its relationship with immune cells.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138534830","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}

{"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}