Nephron最新文献

{"title":"Global, Regional, and National Burden of Hypertension-Associated Chronic Kidney Disease Attributable to High and Low Temperatures from 1990 to 2021 and Projections to 2050: A Finding from the Global Burden of Disease Study 2021.","authors":"Deliang Kong, Ruikang Hu, Juan Li, Lu Li, Haiyang Wu, Shuangxi Li, Wen Wu","doi":"10.1159/nef/adtag001","DOIUrl":"10.1159/nef/adtag001","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic kidney disease (CKD), particularly hypertension-associated CKD (HCKD), is a significant global health burden, with hypertension and diabetes as leading causes. Rising global temperatures and climate variability exacerbate HCKD risks by triggering mechanisms like dehydration, renal ischemia, and increased blood pressure. Using Global Burden of Disease (GBD) 2021 data and predictive models, this study examines trends in HCKD attributable to high and low temperatures.</p><p><strong>Method: </strong>Drawing on data from the 2021 GBD Study, this study focuses on HCKD burden from temperature extremes. Age-standardized mortality rates (ASMRs) and age-standardized disability-adjusted life years rates (ASDRs) were analyzed using descriptive statistics and trend evaluations through estimated annual percentage change (EAPC). Exponential smoothing (ES) and autoregressive integrated moving average (ARIMA) approaches were adopted for predictive modeling. p < 0.05 is considered statistically significant, with uncertainty intervals enhancing robustness.</p><p><strong>Result: </strong>In 2021, 5,013 (95% uncertainty interval [UI]: -117 to 12,053) deaths and 117,175 (95% UI: 4,333-270,676) disability-adjusted life years (DALYs) from HCKD attributable to high temperature were recorded worldwide, with increases in ASMR (EAPC: 3.43) and ASDR (EAPC: 3.18) since 1990. Low temperature caused 22,892 deaths and 420,310 DALYs, with slower ASMR and ASDR growth. Men consistently exhibited higher ASMR and ASDR than women. Mortality and burden peaked in the 95+ age group and varied across sociodemographic index (SDI) regions, with the highest burdens in low-SDI areas. ARIMA and ES models project continued growth in HCKD burden due to temperature, though growth rates may decelerate by 2050.</p><p><strong>Conclusion: </strong>Males, the elderly, and people living in low- and middle-income countries need to be particularly concerned about the threat of HCKD attributed to high and low temperatures.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"1"},"PeriodicalIF":2.3,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated Intraocular Pressure Independently Predicts Long-Term Progression to Advanced Chronic Kidney Disease: A 20-Year Longitudinal Cohort Study.","authors":"Riri Oh, Jun Ogino, Yukie Sakuma, Kaoru Ogawa, Yurina Ishihara, Koji Takemura, Daisuke Shimizu, Yukie Ito, Yuko Endo, Haruhisa Shimura, Yasunori Sato, Shouji Yoshida, Naotake Hashimoto","doi":"10.1159/000553647","DOIUrl":"10.1159/000553647","url":null,"abstract":"<p><strong>Background: </strong>Glaucoma is the leading cause of irreversible blindness worldwide, and chronic kidney disease (CKD) is associated with progression to end-stage renal disease, cardiovascular events, and increased mortality. Although both conditions share common vascular and metabolic risk factors, the long-term relationship between intraocular pressure (IOP) and CKD progression remains unclear. We investigated whether elevated IOP is associated with advanced CKD progression in a long-term observational cohort.</p><p><strong>Methods: </strong>A total of 4,170 participants who underwent health screening at a preventive medicine research center were followed for up to 20 years. Progression to an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 was defined as the primary endpoint. Hazard ratios (HRs) were estimated using competing risks regression with cumulative incidence function analyses. Multivariable analysis was performed using the Fine-Gray subdistribution hazard model. Propensity score matching was applied to validate the robustness of the results.</p><p><strong>Results: </strong>Participants with baseline IOP ≥17.5 mm Hg had a significantly higher risk than those with IOP <17.5 mm Hg (HR: 1.49; 95% CI: 1.08-2.05; p = 0.015) in multivariate analysis. The annual decline in eGFR associated with higher baseline IOP levels was -0.939 mL/min/year, based on ROC-derived risk stratification. Multivariable Fine-Gray analysis identified IOP ≥17.5 mm Hg as an independent risk factor for advanced CKD, together with older age, obesity, diabetes, and proteinuria. These findings were consistent in the propensity score-matched cohort (HR: 1.56; 95% CI: 1.01-2.39; p = 0.043).</p><p><strong>Conclusion: </strong>Elevated IOP independently predicted long-term progression to advanced CKD. Incorporating IOP into conventional risk assessment may improve identification of individuals at high risk for CKD progression.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"1-10"},"PeriodicalIF":2.3,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Organoids as Drug Development Tools for Polycystic Kidney Disease.","authors":"Hongxia Fu, Benjamin S Freedman","doi":"10.1159/000553552","DOIUrl":"10.1159/000553552","url":null,"abstract":"<p><strong>Background: </strong>Polycystic kidney disease (PKD) is commonly inherited as a loss-of-function mutation in PC1 (polycystin-1) or PC2. The molecular functions of polycystins remain uncertain, and therapeutics remain limited for millions of patients. One major roadblock has been the scarcity of assays that re-create PKD-specific cystogenesis in vitro, to complement mouse models.</p><p><strong>Summary: </strong>Over the past decade, a human organoid model of PKD has emerged that promises to bridge this gap. Human kidney organoids derived from PKD1-/- or PKD2-/- pluripotent stem cells recapitulate the pathognomonic cystic phenotype in a PKD-specific manner. Here we review important achievements, current limitations, and future strategies, with a focus on translational \"bench to bedside\" potential of PKD organoids as drug development tools.</p><p><strong>Key messages: </strong>Human PKD organoids reveal that PKD cystogenesis is a cell intrinsic process that can be re-created in vitro. These systems have revealed unexpected mechanisms for PKD cystogenesis and have been utilized to blueprint new therapeutic strategies, but their potential is not yet fully realized. The complexity and cost of organoids remain significant barriers to entry, and dedicated technology development is required to improve their physiological relevance.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"1-9"},"PeriodicalIF":2.3,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148550138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sustained Terminal Complement Inhibition on the Endothelium with Ravulizumab in Patients with Atypical Haemolytic Uraemic Syndrome.","authors":"Sara Gastoldi, Elena Bresin, Andrea Pasini, Beatrice Nardini, Osmy Paci Della Costanza, Raffaela Sciri, Caterina Mele, Ariela Benigni, Giuseppe Remuzzi, Marina Noris, Sistiana Aiello","doi":"10.1159/000553556","DOIUrl":"10.1159/000553556","url":null,"abstract":"<p><strong>Introduction: </strong>Atypical haemolytic uraemic syndrome (aHUS) is a rare and severe form of thrombotic microangiopathy caused by dysregulation of the alternative complement pathway, leading to sustained complement activation at the endothelial level and microvascular thrombosis, predominantly affecting the kidney. Anti-C5 therapy with eculizumab has markedly improved patient outcomes, with ex vivo studies showing suppression of endothelial C5b-9 deposition by sera from treated patients, in contrast to the marked C5b-9 formation induced by acute-phase sera. Ravulizumab, a long-acting anti-C5 antibody derived from eculizumab, has recently been approved for aHUS, offering extended dosing intervals and maintaining (in patients switched from eculizumab) or inducing (in de novo treated patients) disease remission. Its ability to inhibit terminal complement activation at the endothelial level has not yet been evaluated.</p><p><strong>Methods: </strong>In this retrospective study, six patients with primary aHUS were assessed, including 4 switched from eculizumab and 2 treated de novo with ravulizumab. Serum-induced C5b-9 formation on human microvascular endothelial cells (HMEC-1) was measured ex vivo at multiple time points during treatment.</p><p><strong>Results: </strong>C5b-9 formation was in normal range on HMEC-1 exposed to sera collected from all aHUS patients treated with ravulizumab, regardless of prior eculizumab exposure, and all patients remained in or achieved clinical remission.</p><p><strong>Conclusion: </strong>These findings provide mechanistic evidence supporting ravulizumab as an effective inhibitor of terminal complement activation and highlight ex vivo C5b-9 assessment as a potential tool for monitoring treatment efficacy in aHUS.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"1-10"},"PeriodicalIF":2.3,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148550152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peri-Transplant Apolipoprotein L1 Pore Inhibition in High-Risk Donor Kidneys: A Testable Hypothesis.","authors":"Lucas Maciel de Almeida Corrêa, Gabriel Rian Mazur, Clara Belo Gamon Santiago, Alexandre de Assis Barbosa, Luiggi Kevin Virgino Brandão, Gabriel Costa de Santana","doi":"10.1159/000553622","DOIUrl":"10.1159/000553622","url":null,"abstract":"","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"1-5"},"PeriodicalIF":2.3,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Any Role for Renal-Derived Extracellular Vesicles Manipulation for Cardioprotection in Chronic Kidney Disease?","authors":"Aneliya Parvanova, Piero Ruggenenti","doi":"10.1159/000552762","DOIUrl":"10.1159/000552762","url":null,"abstract":"","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"1-6"},"PeriodicalIF":2.3,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and Genetic Epidemiology of Autosomal Dominant Polycystic Kidney Disease among Patients Incident on First Kidney Replacement Therapy between 1990 and 2023, in a Major Hospital in the Northwest of Portugal.","authors":"Alexandra Silva, Pedro Lisboa Gonçalves, Liliana Capela, Liliana Rocha, Isabel Tavares, Susana Fernandes, João Paulo Oliveira","doi":"10.1159/000550753","DOIUrl":"10.1159/000550753","url":null,"abstract":"<p><strong>Introduction: </strong>Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic kidney disease, accounting for 5-10% of incident patients requiring kidney replacement therapy (KRT). Although most cases result from pathogenic variants in PKD1 (≈75%) or PKD2 (≈15%), clinical experience at a major academic hospital in Porto (ULSSJ) suggested a higher regional prevalence of ADPKD-PKD2, particularly involving the truncating variant PKD2 p.(Gln61*). This study aimed to characterize the clinical and genetic epidemiology of ADPKD in patients initiating KRT at ULSSJ, compare ADPKD-PKD1 with ADPKD-PKD2, and contrast local and national ADPKD prevalence among incident KRT patients.</p><p><strong>Methods: </strong>Nephrology reports for KRT initiation (NR-KRT) issued at ULSSJ from 1990 to 2023 were reviewed to identify ADPKD cases and extract demographic and clinical data. Genotypes were obtained from the Genetics Laboratory, Faculty of Medicine, University of Porto, or inferred through pedigree analysis. Next-generation sequencing was the first-tier genotyping test, with Sanger sequencing and multiplex ligation-dependent probe amplification for unresolved cases. National prevalence figures for ADPKD among incident KRT were retrieved from the Portuguese Society of Nephrology registry.</p><p><strong>Results: </strong>Among 6791 NR-KRT reviewed, 426 ADPKD patients were identified. Genotyping information was available for 168 individuals (39.4%), including 101 (60.1%) with inferred genotypes. Among genetically resolved cases, 70.2% had ADPKD-PKD1 and 29.8% had ADPKD-PKD2. Mean age at KRT initiation was 54.5 years in ADPKD-PKD1 and 66.9 years in ADPKD-PKD2. The PKD2 p.(Gln61*) variant was present in 39 patients (23.2%). Between 2010 and 2023, ADPKD prevalence among incident KRT patients was 7.48% at ULSSJ versus 5.19% nationwide (p < 0.0001).</p><p><strong>Conclusion: </strong>The prevalence of ADPKD among incident KRT patients at ULSSJ exceeded national rates. ADPKD-PKD1 was associated with earlier kidney failure compared to ADPKD-PKD2. The PKD2 p.(Gln61*) variant was the most frequent pathogenic allele identified. Given historical patterns of Portuguese emigration, these findings likely have broader international clinical relevance.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"1-13"},"PeriodicalIF":2.3,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary Potassium and Blood Pressure.","authors":"Lena K Rosenbaek, Adrienne M Assmus, Robert A Fenton","doi":"10.1159/000553460","DOIUrl":"10.1159/000553460","url":null,"abstract":"<p><strong>Background: </strong>With the rising prevalence of hypertension and the limitations of current treatment and prevention strategies, modifying potassium (K+) intake has emerged as a potential new approach to help control blood pressure (BP). While the renal mechanisms behind the detrimental effects of high salt intake on BP are relatively well described, how and why alterations in dietary K+ can influence BP are less clear. In general, adequate dietary K+ intake appears to be critical for maintaining healthy BP, but specific guidelines for achieving beneficial effects are lacking.</p><p><strong>Summary: </strong>Interventional trials modifying K+ intake show a general beneficial effect of increasing K+ on BP, predominantly in hypertensive individuals or when sodium (Na+) intake is high. The molecular mechanisms in the kidney, a major site of K+ homeostasis, that contribute to dietary K+ effects on BP have in recent years become clearer. The hypertension associated with low K+ intake is predominantly due to increased activity of the sodium-chloride cotransporter in the distal convoluted tubule. In contrast, the effects of greater K+ intake on BP are not linear and the molecular basis of these diverse responses remains unresolved, but they appear to be interlinked with concurrent Na+ intake. This article briefly covers the major effects of altered K+ intake in humans on BP, then expands on the current knowledge of renal responses to low and high K+ that contribute to these effects.</p><p><strong>Key messages: </strong>K+ intake is important for BP control, especially when considering Na+ intake or hypertensive status. The renal mechanisms of K+ homeostasis highlight the importance of the urinary Na+/K+ ratio for optimal effects, but key molecular pathways still require investigation.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"1-14"},"PeriodicalIF":2.3,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of High-Altitude Acclimatization on Frontal Lobe Executive Function: The Mediating Effect of Creatinine.","authors":"Hongyan Li, Yonghao Ou, Shenglong Li","doi":"10.1159/000552915","DOIUrl":"10.1159/000552915","url":null,"abstract":"<p><strong>Objective: </strong>High-altitude hypoxia impairs frontal executive functions. This study examines whether serum creatinine (CR) mediates the relationship between altitude acclimatization (AAI) peripheral oxygen saturation (SpO₂)/hematocrit (HCT) ratio and frontal neural oscillations.</p><p><strong>Methods: </strong>In 190 adults at 3,650 m (Lhasa), we measured SpO₂, hematocrit, CR, and resting-state frontal electroencephalography. Power spectral density was calculated across multiple frequency bands (1-80 Hz) and Z-standardized. Mediation analysis with bootstrap tested the indirect effect of AAI on each band via CR.</p><p><strong>Results: </strong>AAI significantly negatively predicted CR (p < 0.001). CR significantly negatively predicted frontal Z-PSD in theta (4-7 Hz), alpha (8-13 Hz), and beta (14-30 Hz) bands (all p < 0.01), but not in other bands. The indirect effect via CR was significant for theta (p = 0.011, partial mediation), alpha (p = 0.031, full mediation), and beta (p = 0.020, full mediation).</p><p><strong>Conclusion: </strong>The kidney-brain axis mediates hypoxic neurocognitive adaptation with frequency-specific patterns. CR dynamics reflect acclimatization efficacy, suggesting a target for preserving frontal executive function at high altitude.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"1-10"},"PeriodicalIF":2.3,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expert Commentary of the Recent International Pediatric Nephrology Association IgA Vasculitis Nephritis Guidelines.","authors":"Manya Raina, Jieji Hu, Shay Tanna, Nafees Sathik","doi":"10.1159/000553151","DOIUrl":"10.1159/000553151","url":null,"abstract":"","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"1-6"},"PeriodicalIF":2.3,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148331164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}