Kidney360最新文献

{"title":"RENAL SINGLE-NUCLEAR TRANSCRIPTOMICS IDENTIFIES NOVEL THERAPEUTIC TARGETS IN A PRECLINICAL MODEL OF CHRONIC KIDNEY DISEASE.","authors":"Alejandro R Chade, Sathesh K Sivasankaran, Rhys Sitz, Elizabeth A McCarthy, Alfonso Eirin","doi":"10.34067/KID.0000000945","DOIUrl":"https://doi.org/10.34067/KID.0000000945","url":null,"abstract":"<p><strong>Background and hypothesis: </strong>The prevalence of chronic kidney disease (CKD) is on the rise, and precision strategies to offset the progression to end-stage kidney disease are needed. We used a well-established pre-clinical translational model of CKD in swine and single nucleus RNA sequencing (snRNA-seq) to identify potential therapeutic targets via characterization of the renal cell-specific transcriptomic landscape.</p><p><strong>Methods: </strong>Normal and CKD pigs were studied in vivo and ex vivo after 14 weeks (n=6/group). In randomly selected pigs (n=3/group), kidneys were harvested, nuclei isolated, libraries prepared, and snRNA-seq performed. Protein expression of candidate differentially expressed genes (DEGs, log2FC>0.25, adjusted p-value<0.05) was determined by immunohistochemistry, and their expression in primary normal and CKD renal vascular endothelial cells (RECs) was modulated (siRNA) in vitro.</p><p><strong>Results: </strong>A total of 52,213 nuclei were analyzed. Thirty clusters were identified and filtered by canonical gene markers, revealing 16 unique renal cell types. Endothelial cells were the top cell type exhibiting the highest number of DEGs; which were subsequently filtered by angiogenesis-, inflammation-, and fibrosis (major injurious pathways altered in CKD kidneys). Venn diagram analysis identified 5 unique overlapping DEGs in endothelial cells: VWF, LAMA3, and KDR upregulated, and PTGIS and ICAM1 downregulated in CKD versus normal kidneys. Venn diagram analysis indicates that VWF, LAMA3, and ICAM1 participate in inflammatory and fibrotic signaling. Renal protein expression of these DEGs matched snRNA-seq findings. Furthermore, in vitro silencing of VWF and LAMA3 ameliorated endothelial cell inflammatory and fibrotic signaling.</p><p><strong>Conclusions: </strong>Our work characterized the single-nuclear renal cell transcriptomic landscape of a translational model of CKD and singled out genes implicated in major renal injury pathways. These genes could serve as potential targets to pave the way for new therapeutic strategies in patients with CKD.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804290","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":"Should Kidney Transplantation be Offered to Patients with BMI>40?: CON.","authors":"Tomoki Tsukahara, Rita L McGill","doi":"10.34067/KID.0000000711","DOIUrl":"10.34067/KID.0000000711","url":null,"abstract":"","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804292","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":"Dotinurad, a novel urate reabsorption inhibitor, prolongs survival in Alport mice.","authors":"Ryosuke Saiki, Kan Katayama, Mutsuki Mori, Lupiya Kimena, Keiko Oda, Yasuo Suzuki, Tomohiro Murata, Ryuji Okamoto, Kaoru Dohi","doi":"10.34067/KID.0000000910","DOIUrl":"https://doi.org/10.34067/KID.0000000910","url":null,"abstract":"<p><strong>Background: </strong>Hyperuricemia contributes to inflammatory conditions such as gout and is associated with liver dysfunction, cardiovascular disease, and immune cell activation. While the benefits of uric acid-lowering therapy in patients with chronic kidney disease (CKD) remain uncertain, dotinurad, a selective urate transporter 1 (URAT1) inhibitor, may provide renal benefits by reducing excessive uric acid reabsorption. This study investigates the effects of dotinurad on kidney function in a mouse model of Alport syndrome, a genetic model of CKD.</p><p><strong>Methods: </strong>A mouse model of Alport syndrome was used to evaluate the effects of dotinurad on kidney function. Mice were treated with dotinurad, and their lifespan, urinary albumin-to-creatinine ratios, serum creatinine levels, urinary uric acid-to-creatinine ratios, and serum uric acid levels were assessed. Histological analysis was performed to evaluate glomerulosclerosis and tubulointerstitial fibrosis. Additionally, RNA sequencing was conducted to identify gene expression changes, with real-time reverse transcription polymerase chain reaction (RT-PCR) used to validate key findings.</p><p><strong>Results: </strong>Dotinurad-treated mice exhibited a significantly longer lifespan than control mice. They also showed lower urinary albumin-to-creatinine ratios and serum creatinine levels, while urinary uric acid-to-creatinine ratios and serum uric acid levels remained unchanged. Histological analysis demonstrated reduced glomerulosclerosis and tubulointerstitial fibrosis in dotinurad-treated mice. RNA sequencing revealed a downregulation of inflammatory cytokines, which was further validated by RT-PCR.</p><p><strong>Conclusions: </strong>These findings suggest that dotinurad may exert renoprotective effects in CKD. Further research is needed to confirm these effects in clinical settings.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804288","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":"Association Between Age of Onset of Hypertension and Risk of CKD: Cohort Study Based on the UK Biobank.","authors":"Xi Lu, Dawei Chen, Long Kang, Linsu Sun, Xinlan Xie, Xinyi Tan, Yuanyuan Meng, Fang Lei, Tao Sun, Junxin Chen","doi":"10.34067/KID.0000000872","DOIUrl":"https://doi.org/10.34067/KID.0000000872","url":null,"abstract":"<p><strong>Background: </strong>The onset age of hypertension has decreased significantly due to lifestyle changes over the years. However, the link between hypertension onset age and subsequent incidence of chronic kidney disease (CKD) remains unclear.</p><p><strong>Methods: </strong>Individual-level data were obtained from the UK Biobank. Information on the diagnosis of hypertension and CKD was collected at baseline and follow-up. The propensity score matching method and Cox proportional hazards models were used to evaluate the relationship between different hypertension morbidity ages and the incidence of CKD.</p><p><strong>Results: </strong>A total of 485,101 participants without CKD at baseline were included in this analysis (women, 265,343 [54.70%]). Among the 186,880 participants with hypertension, the multivariable-adjusted hazard ratio (HR) for developing CKD was 1.117 (95% CI: 1.102-1.132) for each 10-year decrease in age at the onset of hypertension. After applying propensity score matching, the risk of CKD in hypertensive patients was significantly higher compared to those without hypertension across all age groups. Additionally, the hazard ratios tended to increase with a decrease in age at the onset of hypertension. Subgroup analysis showed that participants with cardiovascular disease (CVD) at baseline increased the adverse effect of hypertension on CKD in younger participants.</p><p><strong>Conclusions: </strong>Our research indicated that the younger the age at hypertension diagnosis, the greater the risk of developing CKD. Individuals who experience the onset of hypertension before the age of 45 may constitute a high-risk CKD subpopulation, highlighting the need for vigilant monitoring and early intervention.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804287","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":"Should Kidney Transplantation be Offered to Patients with BMI>40?: Commentary.","authors":"Phillipe Abreu, Jesse D Schold","doi":"10.34067/KID.0000000954","DOIUrl":"https://doi.org/10.34067/KID.0000000954","url":null,"abstract":"","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804291","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":"Kidney Transplantation Should Be Accessible to Patients Living with Morbid Obesity (BMI >40 kg/m 2 ): PRO.","authors":"Amanda J Vinson","doi":"10.34067/KID.0000000624","DOIUrl":"10.34067/KID.0000000624","url":null,"abstract":"","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804285","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":"Association of Post-transplant Circulating 25-Hydroxyvitamin D and Long-term Patient and Graft Outcomes among Kidney Transplant Recipients: The Wisconsin Allograft Recipient Database (WisARD).","authors":"Zhongyu Yuan, Sandesh Parajuli, Didier Mandelbrot, Michal L Melamed, Brad C Astor","doi":"10.34067/KID.0000000942","DOIUrl":"https://doi.org/10.34067/KID.0000000942","url":null,"abstract":"<p><strong>Background: </strong>Vitamin D inadequacy at or shortly after kidney transplantation is associated with poor outcomes. Circulating 25-hydroxyvitamin D [25(OH)D] levels generally increase over time after transplantation, but inadequacy remains common. Few studies have examined associations of later circulating 25(OH)D levels and long-term outcomes.</p><p><strong>Methods: </strong>We analyzed data from the Wisconsin Allograft Recipient Database to assess the association of post-transplant 25(OH)D with overall graft failure, death-censored graft failure (DCGF), death with a functioning graft (DWFG), cause-specific mortality and eGFR trajectory over the next 4 years.</p><p><strong>Results: </strong>A total of 2504 recipients who maintained a functioning graft for at least 13 months were included in our analysis. A total of 867 overall graft failures occurred during a median follow-up of 6.8 years. Vitamin D deficiency (≤20 ng/ml) was associated with a 43% higher hazard of overall graft failure (95% confidence interval [CI]: 1.16, 1.78), a 2.24-fold higher hazard of DCGF (95% CI: 1.60, 3.12) and a 2.10-fold higher hazard (95% CI: 1.37, 3.21) of infection-related mortality compared with sufficiency. It also was associated with a 1.38 ml/min/1.73m2/year faster (95% CI: -1.97, -0.79) annual eGFR decline compared with sufficiency. No association was detected for DWFG or other cause-specific mortality.</p><p><strong>Conclusions: </strong>In conclusion, post-transplant vitamin D deficiency is associated with a higher risk of DCGF, infection-related mortality and a faster decline of graft function in kidney transplant recipients.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799518","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":"Acute Kidney Injury in Patients With Veno-venous Extracorporeal Membrane Oxygenation: An Observational Retrospective Analysis of Risk-factors and Outcome.","authors":"Franziska Fuchs, Clemens Wiest, Alois Philipp, Maik Foltan, Roland Schneckenpointner, Alexander Dietl, Dirk Lunz, Christoph Fisser, Thomas Müller, Matthias Lubnow","doi":"10.34067/KID.0000000920","DOIUrl":"10.34067/KID.0000000920","url":null,"abstract":"<p><strong>Background: </strong>AKI is a frequent concomitant organ failure during veno-venous extracorporeal membrane oxygenation (VV-ECMO). This study investigated the prevalence and the impact of AKI on survival to hospital discharge and up to 365 days after discharge, and risk-factors for developing AKI during VV-ECMO.</p><p><strong>Methods: </strong>This is an observational retrospective study of 500 consecutive patients receiving VV-ECMO between November 2014 and December 2021. Patients were divided into three groups: 1)AKI onset before ECMO 2)AKI onset during ECMO 3)AKI onset before and new onset during ECMO. Kidney Disease: Improving Global Outcomes (KDIGO) definition was used to define AKI. Follow-up was 365 days after hospital discharge. Propensity-score-matching was performed for patients without AKI and patients with AKI onset during ECMO to analyse risk-factors for AKI onset during VV-ECMO.</p><p><strong>Results: </strong>320 patients (64.0%) had AKI, 182 (36.4%) with onset before ECMO and 158 (31.6%) with onset during ECMO. At ECMO-initiation, patients with AKI onset before VV-ECMO presented significantly higher inflammatory markers and higher norepinephrine dosage, while patients developing AKI during VV-ECMO did not differ from those without AKI. Survival to hospital discharge was 67.0% (AKI: 60.9%, No-AKI: 77.8%, p<0.001). Cox-regression-analysis revealed AKI KDIGO-stage 3, independent from onset, as independent risk-factor for reduced survival to hospital discharge (HR 2.15, 95% CI: 1.37-3.37, p=0.001). During follow-up, survival was 92.5%; age was shown as the sole risk-factor for reduced survival in hospital survivors in the multivariate-logistic-regression-model. In the propensity-score-matched cohort (41 patients in each group), the AKI-group had lower MAP and significantly higher CRP levels the days before AKI. Factors associated with VV-ECMO support (blood-flow, cell-free haemoglobin) did not differ.</p><p><strong>Conclusions: </strong>Severe AKI is associated with reduced hospital survival, regardless of whether it occurs before or during ECMO. AKI onset during VV-ECMO is less due to ECMO-related factors than to recurrent septic episodes.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675187","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":"Association of Transthyretin Val122Ile Variant with Kidney Outcomes in Community-Dwelling Black Adults: The REGARDS Cohort.","authors":"Soumya Khanna, Katharine L Cheung, Pankaj Arora, Marguerite R Irvin, Leslie A Lange, Titi Ilori, Mary Cushman, Akhil Pampana, Orlando M Gutierrez","doi":"10.34067/KID.0000000935","DOIUrl":"10.34067/KID.0000000935","url":null,"abstract":"","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144742428","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":"Optimizing Quality of Care for CKD in Sweden.","authors":"Anders Christensson, Karl-Göran Prütz","doi":"10.34067/KID.0000000940","DOIUrl":"https://doi.org/10.34067/KID.0000000940","url":null,"abstract":"","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144742429","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}