medRxiv - Nephrology最新文献

{"title":"Selected miRNAs in urinary extracellular vesicles show promise for non-invasive diagnostics of diabetic kidney disease","authors":"Karina Barreiro, Jenni Karttunen, Erkka Valo, Essi Viippola, Ileana Quintero, Annemari Karajamaki, Antti Rannikko, Harry Holthofer, Andrea Ganna, Niina Sandholm, Lena Thorn, Per-Henrik Groop, Tiinamaija Tuomi, Om Prakash Dwivedi, Maija Puhka","doi":"10.1101/2024.09.12.24312889","DOIUrl":"https://doi.org/10.1101/2024.09.12.24312889","url":null,"abstract":"Diabetic kidney disease is a growing health burden that lacks specific early non-invasive diagnostic procedures. To approach a solution for this clinical need, we sequenced microRNAs of urinary extracellular vesicles and performed biomarker discovery by small RNA sequencing in a type 1 diabetes cohort including males with and without albuminuria. The results were replicated by sequencing or qPCR in two independent cohorts and four previously published datasets including type 1 and 2 diabetes as well as both sexes. Non-diabetic and prostate cancer cohorts were used as additional controls and miRNAs changed due to preanalytical urine collection variables were excluded. Using these data, we additionally validated previously identified reference candidate miRNAs. Correlations with clinical parameters, receiver operating characteristic analysis, targeted mRNAs and pathways including integrated single cell data, and targeted circulating proteins from type 1 and 2 diabetes cohorts were analyzed. We pinpointed 6 stable microRNAs, 11 differentially expressed microRNAs, 9 target proteins and 16 DKD-associated pathways in individuals with diabetic kidney disease. Replication showed that the differentially expressed miRNAs in DKD were partly shared between diabetes subtypes and sexes with overall strongest evidence for miR-192-5p, miR-146a-5p, miR-486-5p, and miR-574-5p. Combination of these miRNAs with clinical variables showed potential to classify individuals with the fastest kidney function decline (sensitivity 0.75-1.00 and specificity 0.83-1.00) even in the normoalbuminuria group, thus holding the potential as early diagnostic markers. Altogether, the candidate microRNAs show specificity for diabetic kidney disease, identify declining kidney function, and target key kidney cell types, mRNAs, proteins, and pathogenic mechanisms.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142177760","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":"Lower estimated glomerular filtration rate relates to cognitive impairment and brain alterations","authors":"Shady Rahayel, Remi Goupil, Dominique Suzanne Genest, Florence Lamarche, Mohsen Agharazii, Violette Ayral, Christina Tremblay, Francois Madore","doi":"10.1101/2024.09.10.24313312","DOIUrl":"https://doi.org/10.1101/2024.09.10.24313312","url":null,"abstract":"Introduction: Chronic kidney disease is associated with cognitive decline and changes in brain structure. However, their associations remain unclear, particularly the selective vulnerability characteristics that make some brain regions more vulnerable.\u0000Methods: We investigated the association between eGFR and cognitive function in 15,897 individuals from the CARTaGENE cohort. We performed vertex-based MRI analyses between eGFR and cortical thickness in the 1,397 participants who underwent brain MRI after six years. Imaging transcriptomics was used to characterize the gene expression and neurodegenerative features associated with this association.\u0000Results: Lower eGFR correlated with reduced cognitive performance and brain structure. Brain regions associated with eGFR were enriched for mitochondrial and inflammatory-related genes. These associations occurred independently from age, sex, education, body mass index, Framingham risk score, and white matter lesion volume.\u0000Discussion: This study highlights the link between reduced eGFR, cognitive impairment, and brain structure, revealing some of the kidney-brain axis mechanisms.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142177758","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":"Evaluating the kidney disease progression using a comprehensive patient profiling algorithm: A hybrid clustering approach","authors":"Mohammad A. Al-Mamun, Ki Jin Jeun, Todd Brothers, Ernest Asare, Khaled Shawwa, Imtiaz Ahmed","doi":"10.1101/2024.09.08.24313275","DOIUrl":"https://doi.org/10.1101/2024.09.08.24313275","url":null,"abstract":"Background\u0000Among 35.5 million U.S. adults with chronic kidney disease (CKD), more than 557,000 are on dialysis with incurred cost ranges from $97,373 to $102,206 per patient per year. Acute kidney injury (AKI) can lead to an approximate ninefold increased risk for developing CKD. Significant knowledge gaps exist in understanding AKI to CKD progression. We aimed to develop and test a hybrid clustering algorithm to investigate the clinical phenotypes driving AKI to CKD progression. Methods\u0000This retrospective observational study utilized data from 90,602 patient electronic health records (EHR) from 2010 to 2022. We classified AKI into three groups: Hospital Acquired AKI (HA-AKI), Community Acquired AKI (CA-AKI), and No-AKI. We developed a custom phenotypic disease and procedure network and a complementary variable clustering to examine risk factors among three groups. The algorithm identified top three matched clusters. Results\u0000Among 58,606 CKD patients, AKI group had a higher prevalence of heart failure (21.1%) and Type 2 Diabetes (45.3%). The No-AKI group had a higher comorbidity burden compared to AKI group, with average comorbidities of 2.84 vs. 2.04; p < 0.05; 74.6% vs. 53.6%. Multiple risk factors were identified in both AKI cohorts including long-term opiate analgesic use, atelectasis, history of ischemic heart disease, and lactic acidosis. The comorbidity network in HA-AKI patients was more complex compared to the No-AKI group with higher number of nodes (64 vs. 55) and edges (645 vs. 520). The HA-AKI cohort had several conditions with higher degree and betweenness centrality including high cholesterol (34, 91.10), chronic pain (33, 103.38), tricuspid insufficiency (38, 113.37), osteoarthritis (34, 56.14), and removal of GI tract components (37, 68.66) compared to the CA-AKI cohort. Conclusion\u0000Our proposed custom patient profiling algorithm identifies AKI phenotypes based on comorbidities and medical procedures, offering a promising approach to identify early risk factors for CKD using large EHR data.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142177757","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":"Meta‑analysis study of the therapeutic impact of Mesenchymal stem cells derived exosomes for chronic kidney diseases","authors":"Himanshu K, Gunjan K, Ramendra Pati Pandey, Riya Mukherjee, Chung-Ming Chang","doi":"10.1101/2024.09.04.24313060","DOIUrl":"https://doi.org/10.1101/2024.09.04.24313060","url":null,"abstract":"Mesenchymal stem cell-derived exosomes (EXOs) represent a promising avenue for treating chronic kidney diseases (CKD), though their precise impact remains somewhat elusive. To address this gap, we conducted a systematic analysis, scouring databases and clinical trial repositories for relevant studies from 2019 to 2023. Seventeen papers were meticulously selected for their focus on mesenchymal stem cell-derived exosomes (MSC-EXOs) and their potential in CKD treatment. Our comprehensive meta-analysis, incorporating 15 preclinical and 6 clinical studies, underscores the efficacy of MSC-EXOs in improving renal function while attenuating tubular injury, inflammation, apoptosis, collagen deposition, and renal fibrosis. Notably, post-treatment with MSC-EXOs exhibited significant associations with various CKD markers, with pooled proportions indicating a considerable impact on blood urea nitrogen (BUN) and serum creatinine (SCR) levels. Subgroup analyses based on animal models further elucidated heterogeneity within the studies. In conclusion, MSC-EXOs demonstrate promise in enhancing renal function and reducing CKD risk, as evidenced by both preclinical and clinical data. Their efficacy in lowering SCR and BUN levels while enhancing filtration rate suggests MSC-EXOs as a viable and secure alternative to cell-based therapies, thereby providing valuable insights for personalized CKD treatments despite inherent limitations.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142177759","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 prevalence of chronic kidney disease in people with severe mental illness: A systematic review protocol","authors":"C. Carswell, K. Bramham, J. Chilcot, R. Jacobs, D. Osborn, N. Siddiqi","doi":"10.1101/2024.09.04.24313090","DOIUrl":"https://doi.org/10.1101/2024.09.04.24313090","url":null,"abstract":"<strong>Background</strong> People with severe mental illness (SMI) are more likely to develop long-term physical health conditions, including type 2 diabetes and cardiovascular disease, compared to people without SMI. This contributes to an inequality in life expectancy known as the ‘mortality gap’. Chronic kidney disease (CKD) is a growing global health concern set to be the 5th leading cause of life-years lost by 2040. However, there is limited research exploring the relationship between CKD and SMI. This systematic review will aim to examine the prevalence and incidence of CKD among people with SMI.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142177762","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":"Incidence of postoperative acute kidney injury is higher in men than women after colorectal surgery – PROSACC: a posthoc analysis of a global, multicenter, randomized controlled trial","authors":"Robert Frithiof, Mats Enlund, Stephanie Franzén","doi":"10.1101/2024.09.02.24312832","DOIUrl":"https://doi.org/10.1101/2024.09.02.24312832","url":null,"abstract":"Postoperative acute kidney injury (AKI) is a common postoperative complication. Approximately 7% of the general, elective, non-cardiac surgical population develop AKI after surgery. The female sex was previously believed to be associated with higher incidence of AKI however more recent literature implies that men have higher risk for AKI. Estrogen has been suggested to have renoprotective properties. We therefore aimed to analyze AKI incidence after colorectal cancer resection surgery in men and women on a global, multicenter, level.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142177761","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":"Phenol as a breath marker for hemodialysis of chronic kidney disease patients","authors":"Isabell Eickel, Anne-Christine Zygmunt, Frank Streit, Björn Tampe, Nils Kunze-Szikszay, Thorsten Perl","doi":"10.1101/2024.09.02.24310987","DOIUrl":"https://doi.org/10.1101/2024.09.02.24310987","url":null,"abstract":"<strong>Background</strong> We aimed to identify biomarkers in breath analysis with MCC-IMS to monitor the haemodialysis for CKD patients fast and non-invasive.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142177795","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":"Comparison of the prevalence and associated factors of chronic kidney disease diagnosed by serum creatinine or cystatin C among young people living with HIV in Uganda","authors":"Esther M Nasuuna, Laurie A Tomlinson, Robert Kalyesubula, Chido Dziva Chikwari, Barbara Castelnuovo, Yukari C Manabe, Damalie Nakanjako, Helen A. Weiss","doi":"10.1101/2024.09.02.24312932","DOIUrl":"https://doi.org/10.1101/2024.09.02.24312932","url":null,"abstract":"<strong>Introduction</strong> Young people living with HIV (YPLHIV) are at increased risk of developing chronic kidney disease (CKD) which is associated with high mortality and morbidity. Early diagnosis is important to halt progression. We aimed to estimate the prevalence and factors associated with CKD among YPLHIV in Kampala, Uganda, and to compare serum creatinine and cystatin C for early diagnosis of CKD in this population.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142177763","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":"Serum fibrinogen level and fibrinogen administration in patients with traumatic brain injury: a systematic review and meta-analysis protocol","authors":"Joanne Igoli, Jeremiah Oluwatomi Itodo Daniel, Halleluyah Oludele, Adedoyin Esther Alao, Idemudia Stephen Ogedegbe, Adewale Olaniyan, Michael Adeshola Adebayo, Damilola Matthew, Temidayo Elizabeth Oyepitan, Daniel Brabi, Olatomiwa Olukoya, Temidayo Osunronbi","doi":"10.1101/2024.08.26.24312610","DOIUrl":"https://doi.org/10.1101/2024.08.26.24312610","url":null,"abstract":"<strong>Introduction</strong> Traumatic Brain Injury (TBI) is a leading cause of disability and death globally. It has a significant economic burden. Coagulopathy has been identified as one of the key factors contributing to the poor outcomes observed in TBI patients, and it has been theorised that the management of coagulopathy will improve patient outcomes. Low serum fibrinogen levels denote a coagulopathic state, and the therapeutic administration of fibrinogen has been proposed to correct this state. However, there is no consensus on its efficacy in patients with TBI.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142177794","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":"Repurposing Ivermectin and ATRA as Potential Therapeutics for Glioblastoma Multiforme","authors":"Saed Sayad, Mark Hiatt, Hazem Mustafa","doi":"10.1101/2024.08.26.24312575","DOIUrl":"https://doi.org/10.1101/2024.08.26.24312575","url":null,"abstract":"Background. Glioblastoma multiforme (GBM) is the most aggressive and lethal form of primary brain tumor, characterized by rapid growth and resistance to conventional therapies. Despite advances in treatment, most patients succumb to the disease within 15 months. Drug repurposing, which involves finding new uses for existing drugs, is a promising strategy to develop new GBM treatments faster and more cost-effectively.\u0000Method. We obtained single-cell RNA sequencing (scRNA-seq) data (GSE84465) from the National Institutes of Health (NIH) Gene Expression Omnibus (GEO) repository to compare gene expression in GBM neoplastic cells and non-neoplastic cells. We identified genes that were abnormally expressed in tumor cells and linked these genes to potential drug targets. To identify potential repurposed drugs for GBM, we leveraged the Chemical Entities of Biological Interest (ChEBI) database to assess the interaction of various compounds with the differentially expressed genes identified in the scRNA-seq analysis. We focused on compounds that could reverse the aberrant gene expression observed in GBM neoplastic cells.\u0000Results. Our analysis suggests that ivermectin and all-trans-retinoic acid (ATRA) could be repurposed as effective treatments for GBM. Ivermectin, typically used as an antiparasitic, demonstrated strong anti-tumor activity by downregulating 40 of the top 100 upregulated genes in GBM, indicating its potential to suppress tumor growth. ATRA, known for promoting cell differentiation, upregulated 60 genes typically downregulated in GBM neoplastic cells, showing its potential to correct transcriptional dysregulation and support tumor suppression. These findings underscore the promise of drug repurposing to target key pathways in GBM, offering new therapeutic options for this aggressive cancer.\u0000Conclusions. Our results provide compelling evidence that ivermectin and ATRA may be effective in treating GBM. The observed alterations in gene expression indicate the ability of these two agents to disrupt key genes and pathways crucial for tumor progression. Given the increasing interest in drug repurposing for cancer treatment, comprehensive preclinical and clinical investigations are warranted to assess fully the therapeutic efficacy of these compounds against this disease.","PeriodicalId":501513,"journal":{"name":"medRxiv - Nephrology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142177764","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}