American Journal of Nephrology最新文献

{"title":"Polycystin dysfunction and cardiac electrical abnormalities in ADPKD.","authors":"Pallavi Devapatla, Chu-Yu Hsu, Hsiu Mei Hsieh-Li, Li-Yen Huang","doi":"10.1159/ajn/ablag030","DOIUrl":"https://doi.org/10.1159/ajn/ablag030","url":null,"abstract":"<p><p>Autosomal Dominant Polycystic Kidney Disease (ADPKD) is one of the most common inherited kidney disorders characterized by the progressive formation of renal cysts. It is a systemic disease with significant extra-renal manifestations. Among these, cardiac electrical abnormalities are increasingly recognized as clinically important yet underappreciated contributors to cardiovascular morbidity and mortality. Beyond cyst formation, pathogenic variants in PKD1 or PKD2, which encode polycystin-1 (PC1) and polycystin-2 (PC2), respectively, interfere with calcium homeostasis, mechanotransduction, and mitochondrial function in both kidney and heart tissues. These molecular changes trigger a cascade of pathological events, including RAAS activation, TGF-driven fibrosis, and oxidative stress, leading to structural and electrical remodeling of the heart. These alterations contribute to cardiac electrical remodeling, manifesting clinically as QT interval and corrected QT (QT/QTc) prolongation, left ventricular hypertrophy, atrial fibrillation, ventricular arrhythmias, and other electrocardiographic abnormalities. Despite growing evidence, cardiac electrical abnormalities in ADPKD remain understudied in clinical practice. Early detection of subclinical cardiovascular abnormalities may be facilitated by electrocardiographic monitoring, cardiac imaging, and complementary biomarker assessment. Additionally, findings from iPSC-derived cardiomyocyte models support the translational potential of personalized drug-screening platforms. This review summarizes current evidence linking polycystin dysfunction to cardiac electrical abnormalities in ADPKD by integrating molecular mechanisms with experimental and clinical findings. It also highlights the need for integrated cardio-renal approaches to improve cardiovascular surveillance, risk stratification, and future therapeutic development in ADPKD.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1"},"PeriodicalIF":3.8,"publicationDate":"2026-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149242494","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":"Osteoporosis Causes Nephrolithiasis: A Bidirectional Two-Sample Mendelian Randomization Study.","authors":"Gwo-Tsann Chuang, Chia-Ni Hsiung, Tony Pan-Hou Che, Yi-Cheng Chang, I-Jung Tsai, Shang-Jen Chang","doi":"10.1159/ajn/ablag019","DOIUrl":"10.1159/ajn/ablag019","url":null,"abstract":"<p><strong>Introduction: </strong>Epidemiological evidence suggests a strong association between osteoporosis (OP) and nephrolithiasis (NL), yet the causal direction of this relationship remains debated. This study aimed to elucidate the bidirectional causal relationship between OP and NL using a two-sample mendelian randomization (MR) approach.</p><p><strong>Methods: </strong>We utilized genome-wide association study summary statistics from Taiwan Biobank (TWB; OP: 14,507 cases/79,846 controls; NL: 6,318 cases/88,035 controls) and BioBank Japan (BBJ; OP: 9,794 cases/159,138 controls; NL: 11,699 cases/155,328 controls). Genetic instruments were selected using a suggestive genome-wide threshold of p value <1.0 × 10-5, followed by LD clumping and weak-instrument filtering. The primary causal estimates were calculated using the inverse variance-weighted (IVW) method. Sensitivity analyses, including weighted median, MR-Egger regression, and MR-PRESSO, were performed to evaluate the robustness of the results and assess pleiotropy.</p><p><strong>Results: </strong>In total, 46 single-nucleotide polymorphisms (SNPs) were used for OP-causing NL in the TWB-to-BBJ analysis, 10 SNPs for OP-causing NL in the BBJ-to-TWB analysis, 14 SNPs for NL-causing OP in the TWB-to-BBJ analysis, and 10 SNPs for NL-causing OP in the BBJ-to-TWB analysis. In the analysis assessing the effect of OP on NL, using genetic instruments from BBJ and outcome data from TWB, we observed a significant causal association (IVW β = 0.211, 95% CI: 0.039-0.384, p = 0.016). This finding was corroborated by the weighted median (p = 0.043) and robust MR-Egger (p = 0.025) analyses, with no evidence of directional pleiotropy (MR-Egger intercept p = 0.858). Conversely, in the reverse analysis, NL did not show a significant causal effect on OP risk in either cohort configuration (IVW p > 0.05).</p><p><strong>Conclusions: </strong>Our findings provide suggestive evidence that OP causally increases the risk of NL, whereas NL does not causally affect OP risk. Clinically, patients with OP may represent a high-risk population warranting screening for urinary tract stones.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1"},"PeriodicalIF":3.8,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149242535","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":"LONGITUDINAL CLINICAL AND INTEGRATIVE MULTI-OMICS DATA REVEAL TRAJECTORY-DEFINED SUBGROUPS WITH DISTINCT KIDNEY FAILURE RISK IN DIABETIC KIDNEY DISEASE.","authors":"Heather R Jackson, Andrew Parton, Karina Gutheridge, Will R Marshall, Rajkumar Chinnadurai, Yaiza Rivero Viera, Ivona Baricevic-Jones, Atanu Bhattacharjee, Valeryia Kuzmuk, Noa Díaz Novo, Antonio Tugores, Abirami Veluchamy, Richard Nkulikiyinka, Colin Palmer, Mauro Boronat Cortés, Michael L Sierra, Philip A Kalra, Ariella Cohain","doi":"10.1159/ajn/ablag032","DOIUrl":"https://doi.org/10.1159/ajn/ablag032","url":null,"abstract":"<p><p>Background Diabetic kidney disease (DKD) is the leading cause of CKD globally. Despite marked heterogeneity in progression, risk stratification remains anchored to single-timepoint measures that fail to capture individual patient trajectories. We aimed to identify clinically meaningful DKD subgroups from real-world longitudinal data and characterise their molecular signatures using integrative multi-omics. Methods In this retrospective cohort study, unsupervised clustering of longitudinal creatinine and haematocrit trajectories was performed in the Salford Kidney Study (SKS; n=335 eligible for clustering, n=303 DKD) and validated in two independent cohorts: Scottish Health Research Register (SHARE; n=824) and CERCA-Diabetes (Spain; n=187). Prognostic performance was assessed by C-statistic, time-dependent area under the curve (AUC), IDI (integrated discrimination improvement), and decision curve analysis relative to the Kidney Failure Risk Equation (KFRE) and Kidney Disease Improving Global Outcomes (KDIGO) risk categorisation. Multi-omic characterisation (proteomics, metabolomics, DNA methylation) was performed in an 87-patient SKS subset using Data Integration Analysis for Biomarker Discovery using Latent Components (DIABLO). Results Two groups with markedly different progression rates were identified: high-risk (SKS-HR; n=173) and low-risk (SKS-LR; n=162). SKS-HR showed eGFR decline nearly four times faster and a higher rate of the composite kidney failure endpoint (HR 4.05 [95% CI 2.77-5.92] adjusted for age, sex, and eGFR; 2.95 [1.90-4.56] after further adjustment for haemoglobin, proteinuria, HbA1c, and cardiovascular burden; both p<0.0001). The signal was specific to renal progression (fully adjusted HR 5.98 [3.32-10.79], p<0.0001) and absent for cardiovascular or renal death (HR 1.00 [0.58-1.71], p=0.984). The subgroup-outcome association was independently replicated in SHARE (p=3.83×10⁻²⁷) and CERCA-Diabetes (p=1.72×10⁻⁴). The subgrouping added prognostic information complementary to the KFRE, raising the C-statistic from 0.689 to 0.721 when added to static KFRE and 0.711 to 0.732 when added to longitudinal KFRE. KDIGO risk categories showed limited discriminatory capacity in this predominantly G3b-G4 cohort. Hypothesis-generating multi-omic profiling showed FDR-significant enrichment for lipid transport pathways and for an independent DKD progression proteomic signature; all multi-omic findings require independent validation. Conclusions Longitudinal creatinine and haematocrit trajectories, available from routine clinical records, identify DKD patients at high risk of kidney failure with prognostic information beyond current risk tools. The high-risk subgroup warrants prospective validation and evaluation of whether subgroup assignment can improve risk stratification beyond existing clinical tools.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1"},"PeriodicalIF":3.8,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149226904","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":"Daily Caloric Restriction in Overweight and Obese Adults with ADPKD: Rationale and Protocol of a Randomized Controlled Trial.","authors":"Kristen L Nowak, Cortney N Steele, Wei Wang, Megan Little, Diana George, Heather Farmer-Bailey, Daniel H Bessesen, Kristen Bing, Danielle M Ostendorf, Zhiying You, Katharina Hopp, Timothy Lee Kline, Berenice Gitomer, Victoria A Catenacci, Michel Chonchol","doi":"10.1159/ajn/ablag025","DOIUrl":"https://doi.org/10.1159/ajn/ablag025","url":null,"abstract":"<p><strong>Introduction: </strong>Mounting evidence suggests dysregulated metabolism as a feature of autosomal dominant polycystic kidney disease (ADPKD) and that mild-to-moderate food restriction significantly slows cyst growth in murine models. Epidemiological data and a pilot and feasibility study in humans further support that targeting weight and adiposity loss via daily caloric restriction (DCR) is a potential strategy to slow kidney growth in adults with ADPKD and overweight or obesity.</p><p><strong>Methods: </strong>This is a single site, randomized, single blind (investigator), parallel-group, controlled trial that randomized 120 participants to a 24-month DCR-based behavioral weight loss intervention or control (standard clinical dietary advice for ADPKD) (NCT04907799). The primary outcome is change in height-adjusted total kidney volume by magnetic resonance imaging over a 24-month duration. 84 women and 36 men were randomized, and the study population was 93% Non-Hispanic White. At baseline, mean ± s.d. age was 45 ± 11 years, the mean CKD-EPI eGFR was 68 ± 26 ml/min/1.73m2, and the median (interquartile range) htTKV was 986 (700, 1398) ml/m. Twenty-nine (24%) participants were using tolvaptan at baseline. The final study cohort will be completed in July 2027.</p><p><strong>Conclusions: </strong>This is the first phase 2, randomized clinical trial targeting caloric restriction in patients with ADPKD, and will provide important insight to the research community, patients, and providers.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1"},"PeriodicalIF":3.8,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149214777","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 biomarkers at hospital admission and community-acquired acute kidney injury: A prospective cohort.","authors":"Farid Samaan, Flávia Barros de Azevedo, Dirce Maria Trevisan Zanetta, Luis Yu, Irineu Tadeu Velasco, Lia Junqueira Marçal, Leila Antonangelo, Emmanuel A Burdmann","doi":"10.1159/ajn/ablag026","DOIUrl":"https://doi.org/10.1159/ajn/ablag026","url":null,"abstract":"<p><strong>Background: </strong>We aimed to determine the sensitivity and specificity of a 13-urinary biomarker (uBM) panel for identifying community-acquired acute kidney injury (CA-AKI) and to assess whether these biomarkers were independently associated with CA-AKI.</p><p><strong>Methods: </strong>This prospective observational study was conducted at a tertiary care hospital. Adults admitted through the emergency department were included. CA-AKI was defined as a ≥0.3 mg/dl decrease in serum creatinine (SCr) within 48 hours or a ≥50% decrease within 7 days. Blood samples were collected daily for SCr measurement, and urine samples were obtained at admission for uBM assessment. All the uBM were classified as abnormal when they exceeded the 75th percentile of the distribution.</p><p><strong>Results: </strong>731 patients were included (55% male, median age of 61 years; 48% had hypertension, 28% had diabetes mellitus, and 23% had heart failure). The main reasons for hospitalization were respiratory (32%), genitourinary (15%), and cardiovascular (11%) diseases. CA-AKI was diagnosed in 26% of the patients. Compared with patients without CA-AKI, those with CA-AKI showed higher rates of elevation in four uBM: KIM-1 (31% vs. 23%; p=0.032), TIMP-2*IGFBP-7 (30% vs. 23%; p=0.045), clusterin (32% vs. 22%; p=0.011), and MCP-1 (33% vs. 22%; p=0.003). The sensitivity and specificity of uBM for detecting CA-AKI ranged from 23% to 33% and from 74% to 78%, respectively, and the area under the receiver operating characteristic curve (AUC) ranged from 0.485 to 0.554. Logistic regression analyses identified conditions independently associated with CA-AKI, including: hypotension [OR (95% CI): 2.07 (1.33-3.23); p=0.001], dehydration [OR (95% CI): 2.01 (1.40-2.91); p<0.001], chronic kidney disease [OR (95% CI): 2.00 (1.19-3.35); p=0.009], genitourinary tract disease [OR (95% CI): 2.00 (1.26-3.10); p=0.003], chronic liver disease [OR (95% CI): 1.69 (1.09-2.61); p=0.018], and elevation of one or more of the following uBM: KIM-1, TIMP-2*IGFBP-7, clusterin, and MCP-1 [OR (95% CI): 1.51 (1.06-2.14); p=0.022].</p><p><strong>Conclusion: </strong>The expression of one or more of four uBM at emergency department admission (KIM-1, TIMP-2*IGFBP-7, clusterin, and MCP-1) may help identify patients with a higher probability of having CA-AKI, even with modest AUC results.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1"},"PeriodicalIF":3.8,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206523","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":"Deciphering the Molecular and Cellular Landscape of Early Diabetic Nephropathy through Single-Cell RNA Sequencing and Protein-Protein Interaction Networks.","authors":"Li Qin, Yan Liang, Liying Xuan, Ruibin He, Shiqing Pang, Tingting Ding, Weizhen Xie, Jiangzi Yuan","doi":"10.1159/ajn/ablag024","DOIUrl":"https://doi.org/10.1159/ajn/ablag024","url":null,"abstract":"<p><p>Diabetic nephropathy (DN) arises through complex pathological mechanisms that remain incompletely understood. This study employs transcriptomic and single-cell RNA sequencing (scRNA-seq) approaches to systematically characterize gene expression patterns, cellular composition changes, and intercellular communication networks in early DN. Analysis of the GSE111154 transcriptome dataset identified 259 differentially expressed genes (DEGs), including 118 protein-coding genes (70 downregulated and 189 upregulated) in DN samples. Functional enrichment analysis revealed significant involvement of these DEGs in immune response pathways and extracellular matrix (ECM) organization. Single-cell analysis of the GSE131882 dataset resolved 12 distinct renal cell populations, demonstrating significant shifts in cellular proportions in DN, with notable expansions of endothelial cells (ENDO), fibroblasts (FIB), principal cells (PC), and parietal epithelial cells (PEC). Protein-protein interaction network analysis identified COL1A2, FLNA, A2M, and PLG as central hub genes in DN pathogenesis. Cell-cell communication analysis revealed enhanced interaction frequency and intensity in DN, particularly involving FIB cells through specific signaling pathways including CDH5, KIT, THBS, EGF, and FN1. In DN originated FIBs, the differential genes enriched transcription factor was NR2F2. Through immunohistochemical staining, NR2F2 was up-expressed in DN samples while CD31 was down-regulated. These findings collectively demonstrate profound dysregulation of immune responses, ECM remodeling, and cellular crosstalk during DN progression, highlighting key molecular and cellular drivers of disease pathogenesis.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1"},"PeriodicalIF":3.8,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206486","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":"Fluid Intake and Kidney Function: A Systematic Review and Dose-Response Meta-analysis.","authors":"Jia-Jin Chen, Tao Han Lee, Cheng-Chia Lee, Ming-Jen Chan, Tsung-Yu Tsai, Pei-Chun Fan, Chieh-Li Yen, Huang-Yu Yang, Yu-Kang Tu, Dmytro Ivanov, Yung-Chang Chen, Chih-Hsiang Chang","doi":"10.1159/ajn/ablag027","DOIUrl":"https://doi.org/10.1159/ajn/ablag027","url":null,"abstract":"<p><strong>Introduction: </strong>Fluid intake is widely recommended in clinical practice, yet evidence linking habitual fluid intake to kidney outcomes remains inconsistent. We evaluated dose-response associations between fluid intake volume and kidney function decline or prevalent advanced chronic kidney disease.</p><p><strong>Methods: </strong>We searched EMBASE, PubMed, and the Cochrane Library through Feb 2025 for adult studies reporting total fluid intake, plain water intake, or urine volume in relation to eGFR decline or prevalent advanced-stage chronic kidney disease. Random-effects meta-regression and two-stage dose-response meta-analysis were used to assess linear and non-linear associations, with prespecified subgroup analyses by baseline kidney function.</p><p><strong>Results: </strong>Sixteen studies including 70,053 participants were included. Higher total fluid intake was linearly associated with slower eGFR decline (p = 0.02; β = 0.97 mL/min/1.73 m²/year; 95% CI 0.15-1.79) and with lower odds of prevalent advanced-stage chronic kidney disease (p < 0.001; log-OR -0.27; 95% CI -0.43 to -0.11). In subgroup analyses, this association was observed in studies with mean baseline eGFR ≥60 mL/min/1.73 m² (p = 0.016), but not in studies with mean baseline eGFR <60 mL/min/1.73 m². Evidence for plain water intake and urine volume was limited.</p><p><strong>Conclusions: </strong>Higher daily total fluid intake, within the ranges studied, was associated with slower eGFR decline and lower odds of prevalent advanced CKD, particularly among studies with mean baseline eGFR ≥60 mL/min/1.73 m². Because the evidence was predominantly observational, these findings cannot establish that increasing fluid intake preserves kidney function. Future studies should distinguish plain water from other beverage categories and incorporate objective biomarkers of hydration and volume status.</p><p><strong>Registration: </strong>CRD42024627796.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1"},"PeriodicalIF":3.8,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206440","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":"Tubuloreticular Inclusions in Kidney Tissues of Patients with Lupus Nephritis: An Ultrastructural Biomarker of Type I Interferon-Driven Disease Activity.","authors":"Tianyuan Wei, Jiahui Zhang, Fan Yang, Changming Zhang, ZhiHong Liu, Xiaodong Zhu","doi":"10.1159/ajn/ablag021","DOIUrl":"https://doi.org/10.1159/ajn/ablag021","url":null,"abstract":"<p><strong>Background: </strong>Tubuloreticular inclusions (TRIs) in kidney tissues associate with type I interferon (IFN-I) pathway activation, but their clinical and pathological significance in lupus nephritis (LN) remains incompletely defined.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study of 327 patients with biopsy-confirmed LN at the National Clinical Research Center for Kidney Diseases from January 2023 to December 2025. TRIs were identified in kidney tissues by transmission electron microscopy in both glomerular endothelial cells (GEC) and peritubular capillary (PTC) endothelial cells. For semi-quantitative assessment, 10 capillary loops per glomerulus and 10 peritubular capillaries per case were examined; in cases with more than one glomerulus, loops were randomly selected from each glomerulus and the maximum score across all glomeruli was recorded as the GEC-TRI grade. The final TRI grade for each case was defined as the higher of the GEC-TRI and PTC-TRI grades, classified as grade 0 (no TRIs), grade 1 (TRIs in 1 of 10 capillary profiles) or grade 2 (TRIs in ≥2 of 10 capillary profiles), with patients subsequently grouped as TRI-negative (grade 0) or TRI-positive (grade 1 or 2). Clinical, pathological, immunofluorescence and extrarenal manifestations were compared between groups. In a subset, peripheral blood RNA sequencing was performed to calculate IFN I scores and assess pathway activation.</p><p><strong>Results: </strong>TRIs were observed in 207 of 327 patients (63.3%). Pathologically, TRI-positive patients exhibited lower chronicity index, higher frequency of segmental loop necrosis, along with reduced rates of vascular lesions, interstitial fibrosis and tubular atrophy (all P < 0.05). On immunofluorescence, increased deposition of IgM and C1q and a higher prevalence of full-house pattern were observed in TRI-positive patients (all P < 0.05); C3 deposition showed a significant stepwise increase across TRI grades (P = 0.03), though the dichotomized comparison was not significant (P = 0.06). Clinically, they had higher SLE Disease Activity Index scores, increased urinary red blood cell counts and elevated proteinuria (all P < 0.05). They also demonstrated lower serum complement levels, increased immunoglobulin levels (e.g., IgA) and higher prevalence of multiple autoantibodies (e.g., anti-dsDNA; all P < 0.05). TRI-positive patients also showed heightened IFN-I signatures and higher prevalence of extrarenal manifestations, including mucocutaneous, musculoskeletal, hematological, pulmonary involvement, serositis and organic brain syndrome (all P < 0.05).</p><p><strong>Conclusion: </strong>TRIs are highly prevalent in kidney tissues of patients with LN. They identify a distinct IFN-I-driven disease subset, offering a practical histopathological marker of heightened activity and potential target for therapeutic stratification.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1"},"PeriodicalIF":3.8,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190615","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":"Risk of kidney failure in biopsy-verified kidney disease type in type 2 diabetes: A registry-based longitudinal cohort study.","authors":"Karina Haar, Martin Baek Blond, Frederik Persson, Iain Bressendorff, Ditte Hansen, Marie Møller, Peter Rossing, Rikke Borg","doi":"10.1159/ajn/ablag016","DOIUrl":"https://doi.org/10.1159/ajn/ablag016","url":null,"abstract":"<p><strong>Introduction: </strong>The risk of kidney failure (KF) varies among people with diabetes and chronic kidney disease. We aimed to investigate whether the risk of progression to KF differs by biopsy-proven type of kidney disease in type 2 diabetes (T2D).</p><p><strong>Methods: </strong>In this registry-based longitudinal cohort study, we identified all Danish adults with T2D who had a clinical kidney biopsy performed between 1994 and 2022. Using Poisson regression, we calculated the cumulative risk of KF with death as a competing risk.</p><p><strong>Results: </strong>We included 1203 individuals in the study, of which 1164 could be included in the final analysis: 483 had Diabetic Nephropathy (DN), 117 had mixed disease (coexistence of DN and non-DN (NDN)), and 564 had NDN. The risk of KF [95% CI] was 35% [29-42%] in DN, 18% [14-23%] in NDN and 33% [24-43%] in mixed disease after 3 years, and 47% [40-54%] in DN and 23% [18-29%] in NDN after 5 years. The 5xyear risk was not estimated for mixed disease due to the low number of cases. In DN, there was a significantly higher risk of KF from 3 to 5 years after the biopsy compared to NDN. In mixed disease, there was a significantly higher risk of KF compared to NDN after 3 years. There was no significant difference in the risk of KF between DN and mixed disease, however, the study may have been underpowered to detect a meaningful difference.</p><p><strong>Conclusion: </strong>Biopsy-proven DN and mixed disease are associated with an increased risk of KF compared to NDN in T2D. The study underscores the severity of kidney disease in T2D when histopathological changes caused by diabetes are present.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1"},"PeriodicalIF":3.8,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190662","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":"Real-World Effectiveness of Targeted-Release Budesonide in IgA Nephropathy with Near-Universal SGLT2 Inhibitor Use.","authors":"Thomas McDonnell, William R Marshall, Sharmilee Rengarajan, Jude Allen, Rajkumar Chinnadurai, Smeeta Sinha, Philip A Kalra","doi":"10.1159/ajn/ablag015","DOIUrl":"10.1159/ajn/ablag015","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and a leading cause of end-stage kidney disease. Targeted-release formulation (TRF) budesonide demonstrated significant reductions in proteinuria and attenuation of estimated glomerular filtration rate (eGFR) decline in the randomised NefIgArd trial. However, real-world effectiveness and tolerability in routine clinical practice remain less well characterised. We report real-world outcomes following initiation of TRF budesonide in a tertiary renal centre.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We conducted a retrospective cohort study of all patients with biopsy-proven IgAN initiated on TRF budesonide between 1st January 2024 and 31st July 2025 at a single renal centre in the UK, with follow-up until 31st January 2026. Outcomes were changes in urine protein-to-creatinine ratio (UPCR) and eGFR from baseline to 3, 6, and 9 months and to the latest follow-up, assessed within patients using the Wilcoxon signed rank test. Intention-to-treat (ITT; all 33 patients commencing therapy) and per-protocol (PP; ≥6 months of therapy and not switched directly from modified-release budesonide) analyses were performed. Pre- and post-treatment eGFR slopes were compared using linear mixed-effects models, and a historical comparator cohort matched on baseline UPCR was drawn from the Salford Kidney Study; both are reported as exploratory.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Thirty-three patients commenced TRF budesonide, of whom 23 met PP criteria. Median age was 44 (IQR 37-60) years, baseline UPCR 212 (133-289) mg/mmol, and eGFR 48 (30-61) mL/min/1.73 m2. Renin-angiotensin system (RAS) inhibitor and sodium-glucose cotransporter-2 (SGLT2) inhibitor use were 94% and 91%, respectively. At the latest follow-up (median 11.2 months after treatment initiation), UPCR decreased by 60% (IQR 31-71%) in the ITT cohort (p &lt; 0.001) and 57% (IQR 26-72%) in the PP cohort (p &lt; 0.001). eGFR was stable across the treatment period, with no significant change from baseline at 9 months or at the latest follow-up in either analysis set. Pre- to post-treatment slope comparison was confounded by initiation of SGLT2 inhibitor therapy within the pre-treatment observation window and is reported as exploratory. An adverse effect was recorded in 9 of 33 patients (27%). Seven patients (21%) discontinued treatment, 6 for non-serious adverse effects and 1 for a serious adverse event (staphylococcal septicaemia requiring hospital admission); treatment was temporarily suspended in 1 further patient.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;In a real-world IgAN cohort with near-universal RAS and SGLT2 inhibitor use, TRF budesonide was associated with substantial proteinuria reduction, additive to optimised background therapy. eGFR was stable over the treatment period. Slope-based analyses could not be interpreted, because background SGLT2 inhibitor therapy was initiated within the pre-treatment observation ","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1"},"PeriodicalIF":3.8,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13686600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190635","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}