Clinical journal of the American Society of Nephrology : CJASN最新文献

{"title":"Glucagon-Like Peptide-1 Receptor Agonist Use and Risks of Hospitalization and Mortality in Patients with ESKD.","authors":"Steph Karpinski, Rizwan Qazi, Terrence Bjordahl, Scott Sibbel, Eric Weinhandl, Francesca Tentori, Steven M Brunelli","doi":"10.2215/CJN.0000001208","DOIUrl":"10.2215/CJN.0000001208","url":null,"abstract":"<p><strong>Key points: </strong>Glucagon-like peptide-1 receptor agonist have shown clinical benefits in patients with chronic kidney disease, but there are no randomized trials to support their efficacy in ESKD. This matched retrospective cohort study used electronic health record from a dialysis provider and was conducted in diabetic, incident in-center hemodialysis patients. Results indicated that continued use of glucagon-like peptide-1 receptor agonist is associated with a 9% lower hospitalization and a 17% lower mortality rate.</p><p><strong>Background: </strong>The recent clinical trial FLOW showed that semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), reduced the risk of clinical outcomes and death from cardiovascular causes in patients with CKD and type 2 diabetes. Given the substantial benefit to patients with CKD, the question remains whether these drugs benefit patients with ESKD. We sought to evaluate the impact of GLP-1 RA use in patients with incident ESKD on clinical outcomes.</p><p><strong>Methods: </strong>Patients included in this matched retrospective cohort study were adult patients with ESKD who initiated thrice-weekly in-center hemodialysis at a kidney care organization between January 2018 and April 2024. Using internal electronic health record data, eligible patients who initiated dialysis on a GLP-1 RA (with evidence of a GLP-1 RA prescription in the first 30 days after dialysis initiation; n =2492) were matched 1:1 to those not on a prescription. Patients were followed from index date until death or the end of the study (July 31, 2024). Incident rate ratios were estimated using a negative binomial distribution with a random intercept to account for the matched nature of the data.</p><p><strong>Results: </strong>Patients with a GLP-1 RA prescription in the first month of dialysis had a mean±SD age of 63±12 years and were predominately male (59%). Compared with other eligible dialysis patients, nearly all patients on a GLP-1 RA had a known diagnosis of diabetes (98% versus 73%), a majority had evidence of predialysis nephrology care (76% versus 67%), were of White race (46% versus 39%), and had a mean±SD body mass index of 33±8 kg/m 2 (versus 30±8). After matching and adjustment, GLP-1 RAs were independently associated with lower hospitalization (incidence rate ratios, 0.91 [0.87 to 0.96]) and mortality (Incidence rate ratios, 0.83 [0.73 to 0.95]) rates.</p><p><strong>Conclusions: </strong>Among incident in-center hemodialysis patients, GLP-1 RA use was independently associated with a 9% lower hospitalization rate and a 17% lower mortality rate.</p>","PeriodicalId":520592,"journal":{"name":"Clinical journal of the American Society of Nephrology : CJASN","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148820679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating Patterns and Outcomes in the Prescription of Incremental Peritoneal Dialysis in Support of Shared Decision Making.","authors":"Jessica Selwood, Rishana Shuaib, Ted J FitzGerald, Sally Punzalan, Gaetano Lucisano, Edwina A Brown, Richard W Corbett","doi":"10.2215/CJN.0000001187","DOIUrl":"10.2215/CJN.0000001187","url":null,"abstract":"<p><strong>Key points: </strong>Most people on incremental peritoneal dialysis did not require changes to their starting prescription within the first 12 months. Age, male sex, and lower serum albumin at dialysis start were associated with the timing of dialysis prescription increments. Low rates of transfer to hemodialysis and death rates confirmed the safety of incremental peritoneal dialysis regimens.</p><p><strong>Introduction: </strong>Incremental peritoneal dialysis (PD), where less than full-dose prescriptions are increased as residual kidney function declines, contributes to increased quality of life and reduced dialysis burden. Evidence supporting the safety of incremental regimens and informing patient expectations is limited. This study examined time to increment in dialysis prescriptions, PD modality transfer, transfer to hemodialysis, and mortality rates within a single center delivering incremental PD.</p><p><strong>Methods: </strong>Patients incident to PD and on incremental regimens were followed for changes in prescription, modality transfer, and death between January 1, 2012, and December 31, 2023. Multivariable Cox regression assessed factors associated with time to increment, and Kaplan-Meier methods with log-rank testing were used for time-to-event analyses.</p><p><strong>Results: </strong>The cohort included 527 patients. At 1 year, 64% (95% confidence interval [CI], 60% to 69%) remained on the same starting regimen, with 36% of people (95% CI, 31% to 41%) having not incremented by 2 years. Time to increment was shorter for younger age at PD start (per decade, hazard ratio [HR], 0.92; 95% CI, 0.85 to 0.99; P = 0.02), male sex (HR, 1.67; 95% CI, 1.29 to 2.16; P < 0.001), and lower serum albumin (HR, 0.96; 95% CI, 0.94 to 0.98; P < 0.001). PD modality transfer was driven by lifestyle, fluid overload, and uremic symptoms. Transfer to hemodialysis was associated with younger age ( P = 0.03) and diabetes mellitus ( P = 0.04), while time to hemodialysis transfer was correlated with lower albumin ( P = 0.01) and starting eGFR ( P = 0.006). Mortality rates were low at 0.11 events per person-year.</p><p><strong>Conclusion: </strong>Younger age, male sex, and lower albumin at dialysis start are associated with a shorter time to increment. Low rates of transfer to hemodialysis and death rates in this cohort support the safety of incremental PD prescribing. A simple clinical score was subsequently constructed and tested as a method of supporting shared decision making and informing patient expectations of treatment, but requires validation in future studies.</p>","PeriodicalId":520592,"journal":{"name":"Clinical journal of the American Society of Nephrology : CJASN","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148820617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Levels of Growth Differentiation Factor-15 and Adverse Kidney Outcomes: Proteomics-Based Mediation Analysis and Mendelian Randomization.","authors":"Hee Byung Koh, Hyo Jeong Kim, Seok-Jae Heo, Cheol Ho Park, Hyung Woo Kim, Young Su Joo, Tae Ik Chang, Jung Tak Park, Tae-Hyun Yoo, Shin-Wook Kang, Seung Hyeok Han","doi":"10.2215/CJN.0000001177","DOIUrl":"10.2215/CJN.0000001177","url":null,"abstract":"<p><strong>Key points: </strong>Elevated growth differentiation factor-15 was associated with higher CKD risk, whereas Mendelian randomization suggested a possible protective association with kidney function. Proteomics identified TNF receptor signaling, extracellular matrix organization, and leukocyte chemotaxis as candidate pathways. Growth differentiation factor-15 may serve as a prognostic biomarker, while its possible protective role and underlying mechanisms require further study.</p><p><strong>Background: </strong>Growth differentiation factor-15 (GDF-15) has been implicated in adverse outcomes in cardiovascular disease and diabetes, highlighting its potential as a prognostic marker. However, its association with CKD development remains unclear. Therefore, we investigated the association between GDF-15 and incident CKD and explored potential causal mechanisms.</p><p><strong>Methods: </strong>We analyzed 31,965 UK Biobank participants without preexisting CKD. The primary outcome was incident CKD, defined by diagnostic codes or an eGFR <60 ml/min per 1.73 m 2 (eGFR-based CKD). Proteomics-based mediation and protein-protein interaction analyses identified potential mediators linking GDF-15 to CKD. A bidirectional 2-sample Mendelian randomization (MR) analysis using genome-wide association study summary statistics evaluated the potential causal relationship between GDF-15 and eGFR.</p><p><strong>Results: </strong>In multivariable cause-specific analyses, higher GDF-15 levels were significantly associated with increased CKD risk (hazard ratios: Q2, 1.05 [0.87 to 1.26]; Q3, 1.21 [1.01 to 1.45]; Q4, 1.87 [1.56 to 2.26] versus Q1; P for trend < 0.001). Similar results were observed for eGFR-based CKD. Mediation analysis identified candidate proteins potentially involved in TNF receptor signaling, extracellular matrix organization, and immune cell chemotaxis. MR analysis demonstrated a significant association between genetically predicted higher GDF-15 levels and higher eGFR (inverse-variance weighted coefficient, 0.003; 95% confidence interval, 0.001 to 0.004; P = 0.004). Conversely, higher genetically predicted eGFR was associated with lower GDF-15 levels (inverse-variance weighted coefficient, -1.238; 95% confidence interval, -1.591 to -0.886; P < 0.001).</p><p><strong>Conclusions: </strong>This study provides evidence supporting the role of GDF-15 as a prognostic biomarker for CKD and MR analyses provide suggestive evidence of a possible protective association of GDF-15 with kidney function. Further studies are needed to explore the mechanistic pathways and therapeutic implications of GDF-15 in kidney diseases.</p>","PeriodicalId":520592,"journal":{"name":"Clinical journal of the American Society of Nephrology : CJASN","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148820656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating Ephrin-Eph Signaling Reflects Interstitial Fibrosis and Tubular Atrophy in Diabetic Kidney Disease.","authors":"Seung Seok Han, Aditya L Surapaneni, Insa M Schmidt, Donghwan Yun, Xufan Ma, Kyung Chul Moon, Anand Srivastava, Ragnar Palsson, Isaac E Stillman, Sushrut S Waikar, Morgan E Grams, Eugene P Rhee","doi":"10.2215/CJN.0000001191","DOIUrl":"10.2215/CJN.0000001191","url":null,"abstract":"<p><strong>Key points: </strong>The ephrin-Eph signaling pathway emerged as the strongest blood proteomic correlate of interstitial fibrosis and tubular atrophy burden in a biopsy-confirmed diabetic kidney disease cohort. This association was independently validated in 2 external multiethnic cohorts and was associated with a higher risk of subsequent kidney failure. Kidney multiome analyses linked ephrin-Eph signaling to intrarenal epithelial-mesenchymal transition-related molecular programs in diabetic kidney.</p><p><strong>Background: </strong>Diabetic kidney disease (DKD) is characterized by heterogeneous renal histological patterns, among which interstitial fibrosis and tubular atrophy (IFTA) is a key determinant of patient outcomes and treatment response. However, blood biomarkers reflecting IFTA burden remain unestablished.</p><p><strong>Methods: </strong>We conducted SomaScan-based blood proteomic profiling in Korean patients with biopsy-confirmed diabetic nephropathy from the Seoul National University Hospital ( n =129). Linear regression analyses were used to identify pathways associated with IFTA area, and those additionally upregulated compared with healthy individuals were prioritized. Findings were validated in 2 external cohorts with available SomaScan data and histologic IFTA assessment: the Kidney Precision Medicine Project (KPMP; n =73) and the Boston Kidney Biopsy Cohort ( n =414). Renal expression and downstream signaling of pathway components were evaluated using human kidney multiome data from KPMP.</p><p><strong>Results: </strong>In the diabetic nephropathy from Seoul National University Hospital cohort, the ephrin receptor signaling pathway emerged as the top pathway both positively associated with IFTA area and upregulated in patients with DKD. This association was replicated in the KPMP and Boston Kidney Biopsy Cohort cohorts. High activity of the ephrin receptor signaling pathway was also associated with a higher risk of kidney failure. Kidney tissue analyses demonstrated a higher expression of ephrin-Eph signaling components, particularly genes encoding EPHA4 and EPHB1, in diabetic kidneys. Renal expression of these genes correlated with epithelial-mesenchymal transition signatures, accompanied by downstream activation of hypoxia, Janus kinase-signal transducer and activator of transcription, and TGF β signaling pathways across multiple kidney cell types.</p><p><strong>Conclusions: </strong>Upregulation of the ephrin receptor signaling pathway represents a robust and reproducible blood proteomic signature reflecting IFTA in DKD.</p>","PeriodicalId":520592,"journal":{"name":"Clinical journal of the American Society of Nephrology : CJASN","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148805103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kidney Tubular Secretion Capacity and Risk of Cardiovascular Mortality in the General Population: The HUNT Study.","authors":"Alexander L Bullen, Ronit Katz, Simon B Ascher, Pranav S Garimella, Yngvar Haaskjold, Marius Altern Øvrehus, Michael G Shlipak, Joachim H Ix, Stein Ivar Hallan","doi":"10.2215/CJN.0000001183","DOIUrl":"10.2215/CJN.0000001183","url":null,"abstract":"<p><strong>Key points: </strong>For the first time, we evaluated the association between kidney secretion and cardiovascular mortality in community-dwelling individuals. Worse tubular secretion was associated with a greater mortality risk, independent of eGFR, albuminuria, and other traditional risk factors. The association between worse tubular secretion and cardiovascular disease mortality was similar across major demographic categories.</p><p><strong>Background: </strong>Kidney tubular secretion is a critical mechanism for the clearance of numerous metabolites, toxins, and drugs. In populations with advanced CKD, low (worse) tubular secretion has been associated with an increased risk of cardiovascular disease (CVD). However, it remains unknown whether this relationship is also present in the general population.</p><p><strong>Methods: </strong>In this case-cohort study, we selected a 10% random subcohort ( n =1246) from the Nord-Trøndelag Health Study-3 (a Norwegian community-dwelling population cohort) and we also sampled 141 CVD death cases that occurred outside of the subcohort. We developed a summary secretion score by averaging urine-to-plasma ratios of 12 endogenous secreted solutes, with lower ratios indicating worse tubular secretion. Weighted Cox proportional hazards models were used to assess the relationship between the summary secretion score and the risk of CVD mortality.</p><p><strong>Results: </strong>The mean (SD) age was 51 (14) years, 54.4% were female, 6% had prevalent CVD, and median (interquartile range) eGFR was 99 (90-110) ml/min per 1.73 m 2 at baseline. In multivariable models adjusted for demographics, CVD risk factors, eGFR, and albuminuria, each SD lower summary secretion score was associated with 27% higher risk of CVD mortality (95% confidence interval, 1.03 to 1.56). The results were similar across major demographic categories and among those with or without eGFR <60 ml/min per 1.73 m 2 or albuminuria >30 mg/g at baseline.</p><p><strong>Conclusions: </strong>Among community-dwelling participants, lower tubular secretion is associated with increased CVD mortality independent of eGFR, albuminuria, and other CKD risk factors.</p>","PeriodicalId":520592,"journal":{"name":"Clinical journal of the American Society of Nephrology : CJASN","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148805184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Global Future of Cardiovascular Kidney Metabolic Syndrome Care.","authors":"Debasish Banerjee, Vivekananda Jha","doi":"10.2215/CJN.0000001222","DOIUrl":"10.2215/CJN.0000001222","url":null,"abstract":"","PeriodicalId":520592,"journal":{"name":"Clinical journal of the American Society of Nephrology : CJASN","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148805159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How I Treat Vascular Access-Associated Heart Failure.","authors":"Lee Kirksey, Enrico Prajiante Bertolino, Abdullah Khan, Ahmed A Sorour, Heba Wassif, Daniel Raskin, Sasan Partovi, Tushar J Vachharajani, J Emanuel Finet","doi":"10.2215/CJN.0000001223","DOIUrl":"10.2215/CJN.0000001223","url":null,"abstract":"","PeriodicalId":520592,"journal":{"name":"Clinical journal of the American Society of Nephrology : CJASN","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148805092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Eye as a Window to Cardio-Kidney-Metabolic Disease.","authors":"Jung Tak Park, Yong Yu Tan, Ye Eun Ko, Sahil Thakur, Tyler Hyungtaek Rim, Young Su Joo","doi":"10.2215/CJN.0000001224","DOIUrl":"10.2215/CJN.0000001224","url":null,"abstract":"<p><p>The cardiovascular-kidney-metabolic (CKM) syndrome reframes cardiovascular (CV), kidney, and metabolic disease as an integrated continuum, yet its management relies on reactive laboratory markers with substantial resource burdens. Retinal oculomics offers a noninvasive window into this continuum, grounded in structural and functional parallels between the retina and kidney. Their shared vulnerability to metabolic and hemodynamic stressors allows the retina to reflect subclinical CKM injury. Evidence is strongest for CV end points, where retinopathy and quantitative vessel metrics are associated with incident stroke, CV mortality, and coronary heart disease. Similar associations are reported for new-onset hypertension, diabetes, and incident CKD, although the CKD association attenuates after adjustment for conventional kidney markers. Artificial intelligence (AI) extends retinal analysis beyond categorical grading and predefined vessel metrics by learning latent features from fundus photographs. Systemic biomarker estimation and CV risk stratification are the most mature, whereas kidney-specific models remain confined to cross-sectional CKD detection and prediction of CKD development. However, retinal AI is supported by evidence that remains largely observational, retrospective, and dependent on cross-sectional surrogates. Albuminuria, sustained decline in eGFR, KRT, and kidney-related mortality have not been targeted. Advanced CKD, dialysis, and kidney transplant populations are underrepresented in development and validation cohorts. No retinal model has reported CV risk prediction in CKD or direct comparison with established kidney risk equations. Discrimination in these models falls in ethnically distinct cohorts, and calibration is infrequently reported. Management-impact trials have not been conducted, and cost-effectiveness remains unevaluated. Algorithmic opacity and imaging standardization remain unresolved. Once these gaps are addressed, retinal AI may support screening, risk stratification, progression monitoring, and treatment prioritization, shifting from screening in early CKM to complementary phenotyping in advanced CKD. Retinal AI would then complement conventional kidney biomarkers as an integrative, low-burden window into CKM injury.</p>","PeriodicalId":520592,"journal":{"name":"Clinical journal of the American Society of Nephrology : CJASN","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148805187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estimating and Interpreting Total eGFR Slope through Shared Parameter Models.","authors":"Vivek Charu, June Li, Manjula Kurella Tamura, Lu Tian, Maria E Montez-Rath","doi":"10.2215/CJN.0000001221","DOIUrl":"10.2215/CJN.0000001221","url":null,"abstract":"","PeriodicalId":520592,"journal":{"name":"Clinical journal of the American Society of Nephrology : CJASN","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148805105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scaling up Genomics: A Mainstream Model of Care in Nephrology.","authors":"Kushani Jayasinghe, Rigan Tytherleigh, Stephanie Best, Simon Bodek, Paula Bussa, Grainne Butler, Ainsley Campbell, Amy Clarke, Brendan Cusack, Elizabeth Donaldson, Yoni Elbaum, Clara Gaff, Russell Gear, Asheeta Gupta, Paul James, Lilian Johnstone, Peter G Kerr, Emma Krzesinski, Anna Leaver, Benjamin Lazarus, Mandy Law, Po Yee Mia Leung, Sebastian Lunke, Melissa Martyn, Briannah Miles, Kathleen Nicholls, Lokman Pang, Matthew Regan, Jessica Ryan, Judy Savige, Bryony Thompson, Alison Trainer, Giulia Valente, Kathryn Visser, Andrea Ward, Jack Wheeler, John Whitlam, Ella J Wilkins, Ingrid Winship, Kenneth Xie, Zornitza Stark, Catherine Quinlan","doi":"10.2215/CJN.0000001184","DOIUrl":"10.2215/CJN.0000001184","url":null,"abstract":"<p><strong>Key points: </strong>We evaluated a hub and spoke mainstreaming model to enable nephrologists to order genomic tests independently in their clinic across the state of Victoria. Over 1000 tests were ordered, with the diagnostic yield remaining similar regardless of ordered by local nephrologists or tertiary genomics services. A mainstreaming model proved feasible, scalable, and clinically effective, offering a practical framework for integrating genomics to routine kidney care.</p><p><strong>Background: </strong>Genomic testing has substantial diagnostic and clinical value in nephrology, yet integrating testing into routine care requires service-level changes to ensure timely and equitable access.</p><p><strong>Methods: </strong>We conducted an observational cohort study at four tertiary centers, with a pragmatic, quasi-experimental design to evaluate evidence-informed, service-level interventions to make genomic testing more accessible and routinely embedded within nephrology practice. We implemented a hub and spoke model which provided nephrologists with training, practical resources, and regular case-based discussions, to support test ordering and interpretation within their own clinics. Laboratory audits (June 2021-July 2024) evaluated how public reimbursement and implementation interventions influenced testing patterns. Three periods were compared: prefunding, postfunding, and postintervention.</p><p><strong>Results: </strong>Across the study period, 1028 genomic tests were ordered (63% adults, 37% children; median age 32 years). Results were available for 1014 tests, with an overall diagnostic yield of 34%, which remained stable across all time points. The diagnostic yield was similar regardless of whether testing occurred at tertiary genomics services (249 of 772, 32%) or via local nephrologists (92 of 242, 38%). The number of unique providers ordering tests was higher (T1: 37, T2: 69, T3: 87). The proportion of testing in mainstream nephrology settings rose from 23% to 74%, while absolute testing numbers in multidisciplinary clinics remained consistent over the study period.</p><p><strong>Conclusion: </strong>Mainstreaming genomic testing in nephrology was feasible, scalable, and clinically effective. This model was associated with better access without compromising diagnostic yield and provides a practical framework for integrating genomic medicine into routine kidney care.</p>","PeriodicalId":520592,"journal":{"name":"Clinical journal of the American Society of Nephrology : CJASN","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148805132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}