Journal of The American Society of Nephrology最新文献

{"title":"Adamts1 and Cyst Expansion in Polycystic Kidney Disease.","authors":"Vijayakumar R Kakade, Zafer Akman, Manga Motrapu, Marcelo F Cassini, Leyuan Xu, Gilbert Moeckel, Stefan Somlo, Lloyd G Cantley","doi":"10.1681/ASN.0000000557","DOIUrl":"https://doi.org/10.1681/ASN.0000000557","url":null,"abstract":"<p><strong>Background: </strong>Autosomal dominant polycystic kidney disease (ADPKD) is characterized by mutations in either the Pkd1 or Pkd2 genes leading to progressive cyst growth and often kidney failure. We have previously demonstrated that tubules can enlarge following loss of Pkd1 without an increase in tubular cell numbers, suggesting that tubular basement membrane remodeling is important for cystic dilation. RNA sequencing of Pkd1 null kidneys revealed increased expression of 17 metalloproteinases, of which A Disintegrin and Metalloproteinase with Thrombospondin Motif 1 (Adamts1) is the most highly expressed and upregulated.</p><p><strong>Methods: </strong>Mice were generated with inducible tubule-specific knockout of Adamts1 alone (AtsTKO), Pkd1 alone (PkdTKO), or both (P/ATKO) following doxycycline induction from 4-6 weeks age. Uninduced mice were used as controls. AtsTKO mice had no detectable phenotype through 12 weeks age.</p><p><strong>Results: </strong>Upregulation of Adamts1 in PkdTKO kidneys correlated with a significant increase in the 70 kDa cleavage product of the V1 isoform of versican, which localized to the tubular basement membrane and adjacent interstitial mononuclear cells. Simultaneous deletion of both Adamts1 and Pkd1 (P/ATKO) reduced Adamts1 expression levels by >90%, prevented V1 versican cleavage, and reduced interstitial macrophage accumulation and activation. P/ATKO mice demonstrated reduced cystic enlargement, improved BUN and creatinine and better survival than did PkdTKO mice.</p><p><strong>Conclusions: </strong>Preventing Adamts1 upregulation following loss of tubular Pkd1 effectively reduced cyst growth and preserved kidney function.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baseline Diastolic BP and BP-Lowering Effects on Cardiovascular Outcomes and All-Cause Mortality: A Meta Analysis.","authors":"Amara Sarwal, Robert E Boucher, Sydney E Hartsell, Guo Wei, Jincheng Shen, Glenn M Chertow, Paul K Whelton, Alfred K Cheung, John William McEvoy, Tom Greene, Srinivasan Beddhu","doi":"10.1681/ASN.0000000539","DOIUrl":"https://doi.org/10.1681/ASN.0000000539","url":null,"abstract":"<p><strong>Background: </strong>Lowering blood pressure (BP) in persons with low diastolic BP could be harmful. Hence, we examined whether baseline diastolic BP modifies the effects of BP lowering on clinical outcomes in a meta-analysis of five large BP lowering trials.</p><p><strong>Methods: </strong>In a study-level meta-analysis based on individual participant data of the Systolic Blood Pressure Intervention Trial (N = 9361), the Action to Control Cardiovascular Risk in Diabetes Blood Pressure (N = 2362), the Secondary Prevention of Small Subcortical Strokes (N = 3020), the African American Study of Kidney Disease and Hypertension (N = 1094) and the Modification of Diet in Renal Disease (N = 840) studies, we used DerSimonian-Laird random-effects models to examine the dependence of the effect of the BP lowering intervention on baseline diastolic BP for cardiovascular, all-cause mortality and kidney outcomes.</p><p><strong>Results: </strong>Mean baseline age was 65 ± 10 years old. Mean baseline systolic and diastolic BP were 141 ± 17 and 79 ± 12 mm Hg, respectively. More intensive BP control resulted in lower risk of composite cardiovascular outcome (HR 0.79, 95% CI 0.72, 0.87) and all-cause mortality (HR 0.86, 95% CI 0.75, 0.99) without evidence that the BP intervention effects differed by level of baseline diastolic BP (interaction p = 0.76 for cardiovascular composite and 0.85 for all-cause mortality). The mean baseline diastolic BP in the lowest and the upper three quartiles of baseline diastolic BP were 65 ± 6 mm Hg and 84 ± 9 mm Hg, respectively but the effects of the BP interventions on the outcomes were similar in both groups. Furthermore, there was no evidence of interaction of the BP intervention and baseline diastolic BP for kidney outcomes.</p><p><strong>Conclusions: </strong>Within the included diastolic BP range, there was no evidence that baseline diastolic BP modified the beneficial effects of intensive BP lowering.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is IgA Class Switching Epigenetically Wired?: Untangling the Evidence.","authors":"Ghazal Z Quinn, Katalin Susztak","doi":"10.1681/ASN.0000000550","DOIUrl":"10.1681/ASN.0000000550","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective Cytopheretic Device (QUELimmuneTM): A Leukocyte Processing, Immunomodulatory Device.","authors":"Christopher J Pino, Kimberly A Johnston, Angela J Westover, H David Humes","doi":"10.1681/ASN.0000000569","DOIUrl":"https://doi.org/10.1681/ASN.0000000569","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"External Validation of an Electronic Health Record-Based Diagnostic Model for Histological Acute Tubulointerstitial Nephritis.","authors":"Dennis G Moledina, Kyra Shelton, Steven Menez, Abinet M Aklilu, Yu Yamamoto, Bashar A Kadhim, Melissa Shaw, Candice Kent, Amrita Makhijani, David Hu, Michael Simonov, Kyle O'Connor, Jack Bitzel, Heather Thiessen-Philbrook, F Perry Wilson, Chirag R Parikh","doi":"10.1681/ASN.0000000556","DOIUrl":"10.1681/ASN.0000000556","url":null,"abstract":"<p><strong>Background: </strong>Accurate diagnosis of acute tubulointerstitial nephritis (AIN) often requires a kidney biopsy. We previously developed a diagnostic statistical model for predicting biopsy-confirmed AIN by combining four laboratory tests after evaluating over 150 potential predictors from the electronic health record. Here, we validate this diagnostic model in two biopsy-based cohorts at Johns Hopkins Hospital (JHH) and Yale, which were geographically and temporally distinct from the development cohort, respectively.</p><p><strong>Methods: </strong>We analyzed patients who underwent kidney biopsy at JHH and Yale University (2019-2023). We assessed discrimination (AUC) and calibration using previously derived model coefficients and recalibrated the model using an intercept correction factor that accounted for differences in baseline prevalence of AIN between development and validation cohorts.</p><p><strong>Results: </strong>We included 1982 participants: 1454 at JHH and 528 at Yale. JHH (5%) and Yale (17%) had lower proportions of biopsies with AIN than the development set (23%). The AUC was 0.73 (0.66-0.79) at JHH and 0.73 (0.67-0.78) at Yale, similar to the development set (0.73 (0.64-0.81)). Calibration was imperfect in validation cohorts, particularly at JHH, but improved with application of an intercept correction factor. The model increased AUC of clinicians' prebiopsy suspicion for AIN by 0.10 to 0.77 (0.71-0.82).</p><p><strong>Conclusions: </strong>An AIN diagnostic model retained discrimination in two validation cohorts but needed recalibration to account for local AIN prevalence. The model improved clinicians' ability to predict AIN.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Involving Patients in the Design of Clinical Trials in Nephrology.","authors":"Andrea K Viecelli, Allison Jaure, Katharine Hegerty, Nicole Scholes-Robertson","doi":"10.1681/ASN.0000000566","DOIUrl":"https://doi.org/10.1681/ASN.0000000566","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticoagulation for Patients with Atrial Fibrillation Receiving Dialysis: A Pilot Randomized Controlled Trial.","authors":"Ziv Harel, Brendan Smyth, Sunil V Badve, Daniel Blum, William Beaubien-Souligny, Samuel A Silver, Edward Clark, Rita Suri, Thomas A Mavrakanas, Joanna Sasal, Bhanu Prasad, John Eikelboom, Karthik Tennankore, Claudio Rigatto, Ivana Prce, Francois Madore, Fabrice Mac-Way, Andrew Steele, Yangmin Zeng, Michelle Sholzberg, Paul Dorian, Andrew T Yan, Manish M Sood, David J Gladstone, Eric Tseng, Abhijat Kitchlu, Michael Walsh, Danny Sapir, Matthew J Oliver, Murali Krishnan, Mercedeh Kiaii, Nikki Wong, Sradha Kotwal, Marissa Batisstella, Rey Acedillo, Charmaine Lok, Matthew Weir, Ron Wald","doi":"10.1681/ASN.0000000000000495","DOIUrl":"https://doi.org/10.1681/ASN.0000000000000495","url":null,"abstract":"<p><strong>Background: </strong>Atrial fibrillation is common in individuals receiving dialysis. The role of oral anticoagulation in this population is uncertain given its exclusion from previous seminal clinical trials. Our objective was to determine the feasibility of performing a large definitive trial to establish the optimal anticoagulation strategy in individuals with atrial fibrillation receiving dialysis.</p><p><strong>Methods: </strong>The SAFE-D trial was a parallel-group, open-label, allocation-concealed, pilot randomized control trial that took place at 28 centres in Canada and Australia. The trial included adults (≥18 y) undergoing dialysis with a history of non-valvular atrial fibrillation who met the CHADS-65 criteria. Participants were randomized 1:1:1 to receive dose-adjusted warfarin, apixaban 5 mg twice daily, or no oral anticoagulation and followed for 26 weeks. The primary outcomes evaluated the following measures of feasibility: a) recruitment of the target population within 2 years from the start of the trial; and b) adherence of >80% of randomized patients to the allocated treatment strategy at the conclusion of follow-up. Secondary outcomes included stroke and bleeding.</p><p><strong>Results: </strong>From December 2019 through June 2022, 151 patients were enrolled and randomized to apixaban (n =51), warfarin (n=52) or no oral anticoagulation (n=48). Allowing for pauses related to the COVID pandemic, recruitment was completed in 30 months, and 123 (83%) of participants completed follow-up in their allocated treatment arm. There was one adjudicated stroke event. Eight participants had a major bleeding event (4 warfarin, 2 apixaban, 2 no oral anticoagulation). Death occurred in 15 participants (9 warfarin, 2 apixaban, 4 no oral anticoagulation). Time in the therapeutic range for warfarin recipients was 58% (IQR 47%-70%).</p><p><strong>Conclusions: </strong>We have demonstrated the feasibility of recruitment and adherence in a trial that compared different anticoagulation strategies in patients with atrial fibrillation receiving dialysis.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Let Food Be Thy Medicine: Potential of Dietary Management in Cystinosis.","authors":"Elena Levtchenko, Fanny Oliveira Arcolino","doi":"10.1681/ASN.0000000509","DOIUrl":"10.1681/ASN.0000000509","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"1456-1459"},"PeriodicalIF":10.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ketogenic Diet and Progression of Kidney Disease in Animal Models of Nephropathic Cystinosis.","authors":"Francesco Bellomo, Sara Pugliese, Sara Cairoli, Patrick Krohn, Cristiano De Stefanis, Roberto Raso, Laura Rita Rega, Anna Taranta, Ester De Leo, Andrea Ciolfi, Nicolò Cicolani, Stefania Petrini, Alessandro Luciani, Bianca Maria Goffredo, Ottavia Porzio, Olivier Devuyst, Carlo Dionisi-Vici, Francesco Emma","doi":"10.1681/ASN.0000000000000439","DOIUrl":"10.1681/ASN.0000000000000439","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"1493-1506"},"PeriodicalIF":10.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141600283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: HNF1B Alters an Evolutionarily Conserved Nephrogenic Program of Target Genes.","authors":"","doi":"10.1681/ASN.0000000000000472","DOIUrl":"10.1681/ASN.0000000000000472","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"1620"},"PeriodicalIF":10.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}