American Journal of Nephrology最新文献

{"title":"Additive Obinutuzumab Achieves High Remission Rates in Rituximab-Refractory Membranous Nephropathy.","authors":"Huixian Li, Li Jin, Xinfang Xie, Jiping Sun, Dan Niu, Jie Feng, Guiqing Xu, Xiaotian Zhang, Abdulrahman Majeed S Khalaf, Wanhong Lu","doi":"10.1159/000545995","DOIUrl":"10.1159/000545995","url":null,"abstract":"<p><strong>Introduction: </strong>Rituximab has become the first-line therapy for patients with membranous nephropathy (MN). However, approximately 30-40% of patients with MN do not respond to rituximab. We presented our single-center experience of treating rituximab-refractory MN with obinutuzumab which is a humanized and glycoengineered type II anti-CD20 monoclonal antibody.</p><p><strong>Methods: </strong>Seventeen patients with rituximab-refractory phospholipase A2 receptor (PLA2R)-associated MN who received obinutuzumab at the First Affiliated Hospital of Xi'an Jiaotong University were included in this case series study. Clinical and laboratory parameters were evaluated at presentation, before and after obinutuzumab administration.</p><p><strong>Results: </strong>Of all patients with an average age of 49.7 ± 13.7 years, 11 (64.7%) patients were men. The median disease duration was 12 (12, 42) months. At presentation, the proteinuria and serum albumin levels were 7.51 ± 3.55 g/day and 22.1 ± 3.6 g/L, respectively. The mean estimated glomerular filtration rate level was 103.5 ± 12.9 mL/min/1.73 m2, and the patients had a baseline anti-PLA2R level of 183.2 ± 92.9 RU/mL. At obinutuzumab administration, proteinuria and albumin levels were still consistent with nephrotic syndrome. After a median follow-up of 12.6 ± 5.0 months, complete remission was achieved in 9 (52.9%) and partial remission was achieved in 6 (41.2%) cases. Of the patients who achieved remission, the median remission time was 4.4 (4.0, 6.0) months. At 6 months, 12 (70.6%) patients achieved remission and 11 of 12 patients with available PLA2R measurements reached immunological remission.</p><p><strong>Conclusion: </strong>Obinutuzumab may represent an attractive alternative therapy in rituximab-refractory patients. Larger prospective studies are needed to validate these findings.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-9"},"PeriodicalIF":4.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time in Target Range of Systolic Blood Pressure and Cardiovascular Disease in Patients with Chronic Kidney Disease: A Korean Nationwide Cohort Study.","authors":"Soo-Young Yoon, Su Jin Jeong, Jin Sug Kim, Hyeon Seok Hwang, Kyunghwan Jeong","doi":"10.1159/000546380","DOIUrl":"10.1159/000546380","url":null,"abstract":"<p><strong>Introduction: </strong>Time in target range of systolic blood pressure (SBP-TTR) is the percentage of time that the SBP remains within 110-130 mm Hg. The association between the SBP-TTR and clinical outcomes in patients with chronic kidney disease (CKD) remains unclear. We evaluated the risks of cardiovascular disease (CVD), all-cause mortality, and renal events across the SBP-TTR groups.</p><p><strong>Methods: </strong>Overall, 193,289 patients with CKD who underwent at least two health checkups between 2012 and 2015 were selected from the Korean National Health Insurance Database. The patients were categorized into three categories based on their SBP-TTR levels: 76-100%, 26-75%, and 0-25%. The primary outcome was CVD risk and the secondary outcomes were all-cause mortality and progression to end-stage kidney disease (ESKD) according to SBP-TTR using Cox regression analysis.</p><p><strong>Results: </strong>Compared with patients with SBP-TTR of 76-100%, the adjusted hazard ratios (HRs) for CVD were 1.07 (95% confidence interval [CI], 1.03-1.10) and 1.09 (95% CI: 1.06-1.13) for patients with SBP-TTR of 26-75%, and 0-25%, respectively. The adjusted HR for all-cause mortality was 1.04 (95% CI: 1.003-1.07) and 1.37 (95% CI: 1.28-1.46) for patients with SBP-TTR of 26-75% and 0-25%, respectively. The adjusted HRs for ESKD progression increased gradually: 1.14-fold (95% CI: 1.07-1.21) for the SBP-TTR 26-75% group and 1.37-fold (95% CI: 1.28-1.46) for the SBP-TTR 0-25% group. For patients not taking antihypertensive medications, a lower SBP-TTR was associated with a higher risk of CVD events and ESKD progression than in those taking antihypertensive medications.</p><p><strong>Conclusion: </strong>Among patients with CKD, those with a lower SBP-TTR had a higher risk of cardiovascular events, mortality, and progression to ESKD.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-12"},"PeriodicalIF":4.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utilizing Deep Learning to Identify Electron-Dense Deposits in Renal Biopsy Electron Microscopy Images.","authors":"Shuangshuang Zhu, Bei Luo, Sendong Lai, Shuling Yue, Guang Yang, Zhen Song, Xiaomeng Xu, Yangyang Gui, Anlan Chen, Hongmei Yu, Yanqiu Liu, Hongyu Liu, Chao Yang, Lei Zheng","doi":"10.1159/000546131","DOIUrl":"10.1159/000546131","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Electron microscopy (EM) is a crucial technique for identifying and distinguishing the specific location of deposits within glomeruli. Manual classification of these deposit locations is not only time-consuming but also yields inconsistent results among pathologists. This study aimed to develop a deep learning-based platform to automatically classify the locations of electron-dense deposits in EM images of kidney biopsies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We retrospectively collected 4,303 EM images at magnifications of ×4,000 to ×8,000 from 1,039 kidney biopsies performed on native kidneys at the Renal Pathology of King Medical Diagnostics Center in Guangzhou between June 1, 2022, and July 2, 2022. EM images were independently evaluated by pathologists Zhu and Luo for electron-dense deposits, categorized into mesangial, subepithelial, intramembranous, and subendothelial if present. These evaluations served as ground truth for model training and evaluation. Of these, 3,443 EM images were allocated to the training group and 860 to the test group. The ResNet18 architecture was selected for our task. To evaluate the model's classification capability, we created a binary classification model to identify the presence of deposits in EM images. Furthermore, we implemented a subnet classification network to predict the probability of mesangial, subepithelial, intramembranous, and subendothelial deposits. Four renal pathologists (two EM pathologists and two comprehensive renal pathologists) were invited to compare their agreement with the deep learning model. Comparing deep learning models against pathologists with Cohen's Kappa and accuracy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The deep learning model can accurately identify the presence of electron-dense deposits in EM images, with an area under the receiver operating characteristic curve (AUC) of 0.959 and an accuracy of 0.899. The classification subnet trained to identify mesangial, subepithelial, intramembranous, and subendothelial deposits yielded AUCs of 0.928, 0.987, 0.986, and 0.944, with accuracies of 0.880, 0.962, 0.959, and 0.883, respectively. Subepithelial and intramembranous deposits had near-perfect agreement, while mesangial and subendothelial deposits showed substantial agreement with the ground truth. The accuracy of deep learning models in assessing the presence and locations of deposits was lower than that of EM pathologists but higher than that of comprehensive renal pathologists. A web platform has been developed in which users can upload EM images of renal biopsies to receive probabilities regarding the four locations of deposits based on our algorithm.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;We successfully developed a web platform for the automated assessment of the locations of electron-dense deposits in kidney biopsy EM images. The performance of this model surpasses that of experienced comprehensive renal pathologists, offering an efficient and reliable ","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-11"},"PeriodicalIF":4.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intradialytic Cognitive and Aerobic Exercise Training to Preserve Cognitive Function: IMPCT, a Multi-Dialysis Center 2 × 2 Factorial Block-Randomized Controlled Trial.","authors":"Nidhi Ghildayal, Yi Liu, Jingyao Hong, Yiting Li, Xiaomeng Chen, Marlís González Fernández, Michelle C Carlson, Derek M Fine, Lawrence J Appel, Marie Diener-West, David M Charytan, Aarti Mathur, Dorry L Segev, Mara McAdams-DeMarco","doi":"10.1159/000546296","DOIUrl":"10.1159/000546296","url":null,"abstract":"<p><strong>Introduction: </strong>Patients with end-stage kidney disease develop cognitive impairment due to comorbidities and dialysis dependence. Among community-dwelling older adults, cognitive (CT) and exercise training (ET) are promising interventions to preserve cognition; these interventions may be tailored for adults undergoing in-center hemodialysis.</p><p><strong>Methods: </strong>Adult (≥18 years) English-speaking patients undergoing hemodialysis (within 3 months to 3 years of initiation) were enrolled in a 2 × 2 factorial randomized controlled trial: Interventions Made to Preserve Cognitive Function Trial (IMPCT). Participants (n = 121) were block-randomized (September, 2018-February, 2023) into 4 arms: control (SC) (n = 26), intradialytic web-based CT (n = 31), ET using foot peddler (n = 29), and combined CT+ET (n = 35). Participants underwent assessments at baseline and 3 months for executive function, global cognitive function, clinical outcomes, and patient-centered outcomes. We estimated 3-month executive function change (primary outcome) and secondary outcomes using linear regression.</p><p><strong>Results: </strong>There were no differences in 3-month executive function change by arm. Participants exhibited improvement in 3-month global cognitive function in CT+ET arm (Montreal Cognitive Assessment score difference = 2.1, 95% CI: 0.4-3.9), and self-reported 3-month improvement in perceived health change (score difference = 0.8, 95% CI: 0.2-1.4) in ET arm.</p><p><strong>Conclusion: </strong>Clinicians may encourage CT+ET for hemodialysis patients to improve short-term global cognitive function and perceived health. The long-term benefits of these interventions warrant further study.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-13"},"PeriodicalIF":4.3,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peridialytic Erythropoietin versus Roxadustat in Hemodialysis-Dependent Chronic Kidney Disease Patients.","authors":"Lihua Wang, Yueqi Cao, Weijie Yuan, Chuanming Hao, Li Yao, Cheng Xue, Pei Yu, Changlin Mei","doi":"10.1159/000546158","DOIUrl":"10.1159/000546158","url":null,"abstract":"<p><strong>Introduction: </strong>Erythropoietin and roxadustat are commonly used to manage anemia in hemodialysis-dependent chronic kidney disease (CKD) patients, but the comparative safety and effectiveness are unknown.</p><p><strong>Methods: </strong>This is a retrospective cohort study. Data were extracted from Tianjin Healthcare and Medical Big Data Platform. We screened all patients with CKD stage G5 and anemia (hemoglobin <100 g/L) who were treated with either erythropoietin or roxadustat between January 1, 2015, and December 31, 2021. The primary endpoints included expanded composite of major adverse cardiovascular events (MACE+), cardio-cerebrovascular events, and thromboembolic events in the peridialytic period, defined as the duration from the time of estimated glomerular filtration rate decrease to <15 mL/min × 1.73 m2 to 3 months after dialysis initiation. A propensity score-matched analysis (1:1 ratio; caliper width: 0.02) was conducted to minimize the impact of confounding factors.</p><p><strong>Results: </strong>The initial screen identified a total of 40,324 patients; 1,092 were included in the propensity score-matched analysis (546 in each group). In comparison to the roxadustat group, the erythropoietin group had a lower rate of MACE+ events within 6 months (13.4% vs. 21.2%, p < 0.001) and 12 months of treatment initiation (17.0% vs. 24.0%, p = 0.004), as well as within 3 months of hemodialysis initiation (12.9% vs. 28.7%, p < 0.001). The rate of cardio-cerebrovascular events was also lower in the erythropoietin group within 6 months (38.5% vs. 50.7%, p < 0.001) and 12 months of treatment initiation (49.1% vs. 56.2%, p < 0.001). The rate of thromboembolic events did not differ between the two groups.</p><p><strong>Conclusion: </strong>Peridialytic erythropoietin was associated with a more favorable cardiovascular safety profile versus roxadustat in hemodialysis-dependent CKD patients.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-15"},"PeriodicalIF":4.3,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between Rheumatoid Arthritis and the Incidence of IgA Nephropathy.","authors":"Tatsuhiko Azegami, Hidehiro Kaneko, Akira Okada, Yuta Suzuki, Katsuhito Fujiu, Takashin Nakayama, Norifumi Takeda, Hiroyuki Morita, Norihiko Takeda, Akira Fukui, Takashi Yokoo, Yuko Kaneko, Hideo Yasunaga, Masaomi Nangaku, Kaori Hayashi","doi":"10.1159/000546196","DOIUrl":"10.1159/000546196","url":null,"abstract":"<p><strong>Introduction: </strong>IgA nephropathy and rheumatoid arthritis are both common autoimmune diseases, but epidemiological data are limited on the relationship between these two diseases. We aimed to assess the association between rheumatoid arthritis and the risk of developing IgA nephropathy.</p><p><strong>Methods: </strong>In this study, we analyzed 4,311,393 adults using a nationwide epidemiological database in Japan. The definitions of rheumatoid arthritis and IgA nephropathy were based on ICD-10 codes. After excluding individuals with a prior history of IgA nephropathy, study participants were categorized into two groups according to the presence of rheumatoid arthritis. The primary outcome was the incidence of IgA nephropathy between January 2005 and May 2022.</p><p><strong>Results: </strong>Median (interquartile range) age was 44 (36-53) years, and 2,497,313 (58%) were men. Rheumatoid arthritis was observed in 41,828 individuals (1.0%). During a median follow-up of 1,089 (532-1,797) days, there were 2,610 and 43 incidences of IgA nephropathy in individuals without and with rheumatoid arthritis, yielding incidence rates with 95% confidence intervals (CIs) of 1.74 (1.67-1.81) and 2.99 (2.22-4.04) per 10,000 person-years, respectively, indicating a higher cumulative incidence in individuals with rheumatoid arthritis (log-rank p = 0.0002). Multivariable Cox regression analysis demonstrated that comorbid rheumatoid arthritis had a higher risk for developing IgA nephropathy (hazard ratio (HR) 1.50, 95% CI 1.10-2.02). Results were consistent even when IgA nephropathy was defined as both the ICD-10 code with the confirmation of performance of kidney biopsy (HR 1.70, 95% CI 1.02-2.83).</p><p><strong>Conclusion: </strong>Our analysis utilizing a large-scale population-based cohort concluded that rheumatoid arthritis may increase risk of developing IgA nephropathy.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-10"},"PeriodicalIF":4.3,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12165629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between Parathyroid Hormone Concentration and Incident Atrial Fibrillation in Older Persons with Kidney Failure Initiating Dialysis.","authors":"Pascale Khairallah, Sai Liu, Maria E Montez-Rath, Kevin F Erickson, Tara I Chang, Wolfgang C Winkelmayer","doi":"10.1159/000546266","DOIUrl":"10.1159/000546266","url":null,"abstract":"<p><strong>Introduction: </strong>Atrial fibrillation (AF) is common in persons with kidney failure on hemodialysis. In the general population, higher intact parathyroid hormone (iPTH) levels were found to be associated with presence of AF. Whether iPTH associates with AF in patients on hemodialysis is unknown.</p><p><strong>Methods: </strong>Using merged USRDS-DaVita data (2006-2011), we selected persons aged 67+ years who initiated hemodialysis and survived 120 days. Eligible persons had continuous Medicare A + B coverage from 2 years prior to kidney failure and no diagnosis of AF. Sociodemographic, comorbidity, and clinical information were abstracted from Medicare forms, billing claims, and electronic health records. iPTH was categorized consistent with previous work: <150; 150 to <300; 300 to <600; and ≥600 pg/mL. Patients were followed for incident (i.e., newly diagnosed) AF as reflected in inpatient and outpatient claims. Unadjusted and multivariable Cox regression were used to estimate the associations of time-updated iPTH category (referent: 150 to <300 pg/mL) with incident AF.</p><p><strong>Results: </strong>Of 15,225 patients initiating hemodialysis, surviving 120 days, and without a prior diagnosis of AF, iPTH (in pg/mL) at baseline was <150 in 4,479, 150 to <300 in 5,964, 300 to <600 in 3,479, and ≥600 in 1,064 persons. During 21,845 patient-years, 2,857 patients had incident AF (rate, 13.1/100 person-years). After multivariable adjustment, patients with iPTH <150 pg/mL had 13% (95% confidence interval [CI]: 3-25%) higher relative AF incidence compared with the 150 to <300 pg/mL group, but no association was found for those with iPTH 300 to <600 (hazard ratio [HR]: 1.04; 95% CI: 0.95-1.14) or iPTH ≥600 pg/mL (HR: 0.90; 95% CI: 0.75-1.08).</p><p><strong>Conclusion: </strong>Among persons with incident kidney failure on hemodialysis, compared with those whose iPTH was between 150 and <300 pg/mL, lower iPTH was independently associated with higher AF incidence; however, no association with AF was identified for higher iPTH levels.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-11"},"PeriodicalIF":4.3,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sociodemographic Barriers to Starting the Kidney Transplantation Evaluation Process and Waitlisting in the Ohio River Valley.","authors":"Catherine E Kelty, Jade Buford, Kelsey M Drewry, Oluwafisayo Adebiyi, Asif Sharfuddin, Jonathan A Fridell, Syed Jawad Sher, Anne M Huml, Adam S Wilk, Stephen O Pastan, Sharon M Moe, Rachel E Patzer","doi":"10.1159/000546108","DOIUrl":"10.1159/000546108","url":null,"abstract":"<p><strong>Introduction: </strong>Individuals with end-stage kidney disease face barriers and delays in access to kidney transplantation, but little is known about access before waitlisting due to the lack of national data on pre-waitlisting measures. The Early Steps to Transplant Access Registry (E-STAR) captures referral and evaluation data in four US regions, including the Ohio River Valley, and this study utilizes E-STAR data to describe sociodemographic factors associated with starting the transplant evaluation and waitlisting in this region.</p><p><strong>Methods: </strong>Adults referred to a transplant center for evaluation within the Ohio River Valley during 2015-2021 and captured within E-STAR were included. Linked E-STAR, US Renal Data System, and American Community Survey data were used to assess the association between sociodemographic (age, sex, race or ethnicity, insurance status), clinical, and neighborhood factors and time from referral to evaluation start and time from evaluation start to waitlisting by Cox proportional hazards analyses.</p><p><strong>Results: </strong>Among 15,673 referred adults, the mean age was 55 years, and the majority were male (61.4%) and had public insurance (56.6%), while 21.3% were preemptively referred. Compared to individuals aged 18-29, all other age groups had a lower likelihood of starting the evaluation in the adjusted model. Black adults (vs. White; adjusted hazard ratio: 0.89 [95% CI: 0.81-0.98]), and those with Medicaid or Medicare were less likely to start the evaluation (vs. employer-sponsored, 0.58 [0.50-0.66]; 0.66 [0.66-0.82], respectively). Among individuals who started the evaluation, those with Black (vs. White) race, and Medicaid or Medicare (vs. employer-sponsored) were less likely to be waitlisted in the adjusted analysis.</p><p><strong>Conclusion: </strong>Associations between age, sex, race, and economic characteristics and access to evaluation start and waitlisting were observed. Future research investigating underlying causes and points of intervention in this region is warranted.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-13"},"PeriodicalIF":4.3,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urinary Cytokeratin 20 Predicts Severe Acute Kidney Injury and Major Adverse Kidney Events in Adults Undergoing Cardiac Surgery.","authors":"Rui Ma, Han Ouyang, Chunbo Chen, Xin Xu, Jianwei Tian, Ruhe Zhong, Yan Zha, Siyuan Teng, Guisen Li, Huafeng Liu, Xiaobing Yang, Fan Fan Hou","doi":"10.1159/000546159","DOIUrl":"10.1159/000546159","url":null,"abstract":"<p><strong>Introduction: </strong>It remains a big challenge to identify patients who are at high risk of developing severe acute kidney injury (AKI) after cardiac surgery. This study investigated the clinical utility of urinary cytokeratin 20 (uCK20), a novel biomarker reflecting severity of histological acute tubular injury, for identifying patients at risk of developing severe AKI.</p><p><strong>Methods: </strong>This prospective multicenter cohort study enrolled a test set comprising 413 patients who underwent cardiac surgery at 5 centers and a validation set comprising 131 patients at an external center. uCK20 and six reported renal tubular injury biomarkers were measured within 6 h after cardiopulmonary bypass (CPB). The primary outcome was severe AKI after surgery. The secondary outcome was major adverse kidney events within 30 days (MAKE30).</p><p><strong>Results: </strong>In test set, 54 patients (13.1%) reached the primary endpoint. Levels of uCK20 peaked at 4 h after CPB and remained elevated for 5 days after surgery in patients with severe AKI. After multivariable adjustment, the highest tertile of uCK20 was associated with a 67-fold higher risk of the primary outcome and 29-fold higher risk of the secondary outcome. For predicting the primary and the secondary outcomes, uCK20 at 4 h after CPB had area under the curves (AUCs) of 0.86 (95% confidence interval [CI]: 0.81-0.91) and 0.85 (95% CI: 0.78-0.92), outperforming some reported kidney injury biomarkers. Adding uCK20 to the clinical variables enhanced the predicting ability for severe AKI with an AUC of 0.90 (95% CI: 0.85-0.94) and largely improved the risk reclassification. The ability of uCK20 in predicting the primary and the secondary outcomes was further confirmed in an external validation set.</p><p><strong>Conclusion: </strong>Urinary CK20 predicted early the risk of severe AKI and MAKE30 with excellent performances in patients undergoing cardiac surgery.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-11"},"PeriodicalIF":4.3,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GLPG2737, a CFTR Inhibitor, Prevents Cyst Growth in Preclinical Models of Autosomal Dominant Polycystic Kidney Disease.","authors":"Vincent Dumont, Sandrine Meurisse, Katleen Verdonck, Valérie Salgues, Tiffany Robert, Florence Anquetil, Carole Delachaume, Roland Blanqué, Daisy Liekens, Yan Huang, Jinghua Hu, Peter C Harris, Jessica Nakhlé, Katja Conrath, Nick Vandeghinste, Thierry Christophe, Daniel Comas","doi":"10.1159/000545614","DOIUrl":"10.1159/000545614","url":null,"abstract":"<p><strong>Introduction: </strong>Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder that is characterized by the development of fluid-filled kidney cysts, which often lead to kidney failure. The vasopressin receptor 2 antagonist, tolvaptan, is the only approved treatment that slows the progression of ADPKD. There is an unmet need for treatment options for patients with ADPKD because tolvaptan has limited efficacy and non-negligible side effects. In vitro and in vivo data suggest that inhibition of the cystic fibrosis transmembrane conductance regulator (CFTR) may be a suitable approach to treating ADPKD. Here, we assessed the capacity of GLPG2737, a CFTR inhibitor, to inhibit cyst growth in preclinical models of ADPKD.</p><p><strong>Methods: </strong>We investigated the ability of GLPG2737 to modulate CFTR activity in mouse kidney inner medullary collecting duct (mIMCD-3) epithelial cells by measuring chloride flux and to prevent cyst growth in mIMCD-3 cells, cells from human ADPKD kidney donors, and metanephric organ cultures (MOCs). We assessed cyst volume, kidney weight or volume, and blood urea nitrogen (BUN) in two mouse ADPKD models (Pkd1 kidney-specific knockout mouse model; Pkd1RC/RC mouse model) that received GLPG2737, tolvaptan, or their combination. Statistical tests used for data analysis were based on the normality and variance of the data.</p><p><strong>Results: </strong>GLPG2737 inhibited chloride flux in mIMCD-3 cells with an IC50 of 2.41 µ<sc>m</sc>. In a 3D assay, GLPG2737 inhibited cyst growth in both wild-type (IC50 = 2.36 µ<sc>m</sc>) and Pkd1 knockout (IC50 = 2.5 µ<sc>m</sc>) mIMCD-3 cells. Preincubation of human ADPKD kidney cells with 10 µ<sc>m</sc> of GLPG2737, 10 µ<sc>m</sc> of tolvaptan, or their combination prevented forskolin-induced cyst growth by 40%, 29%, and 70%, respectively. Furthermore, 10 µ<sc>m</sc> of GLPG2737 inhibited cyst growth in MOCs, decreasing the cyst area by 67% and the number of cysts per area by 46% after 6 days of culture. In both in vivo models, GLPG2737, tolvaptan, or their combination improved the projected cyst volume. In the Pkd1RC/RC model, GLPG2737 also improved the total kidney volume normalized to tibia length (LnTKV) and BUN, while tolvaptan improved the LnTKV and fibrosis but did not lower BUN at sacrifice. The combination reduced all parameters measured in the Pkd1RC/RC model, including cyclic adenosine monophosphate content in the kidneys.</p><p><strong>Conclusions: </strong>Our findings in preclinical models provide evidence of the therapeutic potential of CFTR inhibition and its possible combination with tolvaptan. The present work shows that targeting CFTR is a valid strategy to slow ADPKD progression.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-10"},"PeriodicalIF":4.3,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12140590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}