Nephrology Dialysis Transplantation最新文献

{"title":"Temporal trends in the treatment of relapsing minimal change podocytopathy-a binational cohort study.","authors":"Tilde Kristensen, Rutger Maas, Henrik Birn, Per Ivarsen","doi":"10.1093/ndt/gfaf072","DOIUrl":"10.1093/ndt/gfaf072","url":null,"abstract":"<p><strong>Background and hypothesis: </strong>While the primary treatment for minimal change disease (MCD) is prednisolone, the immunosuppressive treatment at relapse is less well defined. More treatment options for MCD have become available and concerns about the adverse effects of prednisolone have been raised. It is unclear to what extent this has influenced the treatment of relapsing disease. Thus, the objective of this study is to characterize the changes in the immunosuppressive treatment of relapse in MCD over the past 35 years.</p><p><strong>Methods: </strong>A multicentre, retrospective cohort including adult patients with biopsy-proven MCD from 13 hospitals in Denmark and the Netherlands between 1985 and 2022. Patients were identified from pathology registers. Information on treatment and clinical outcomes was retrieved from health records. Treatment before and after 2010 was compared.</p><p><strong>Results: </strong>The study included 239 patients with a median age of 46 years, 55% female and 64% being diagnosed before 2010. A first relapse was identified in 50% and a second relapse in 28%. The most frequently prescribed treatment at first relapse was prednisolone monotherapy before and after 2010 (67% and 44% of patients, respectively), while the use of calcineurin inhibitors (CNI) increased 3-fold after 2010 compared with before 2010. At second relapse CNI was the most frequently prescribed treatment after 2010, while the use of both cyclophosphamide and prednisolone decreased when compared with before 2010. A similar trend was observed at the 3rd to 14th relapse with CNI (44% of patients) and rituximab (35% of patients) being the most frequently prescribed treatments after 2010 while the use of cyclophosphamide and prednisolone decreased (0% and 21% of patients, respectively). Regardless of treatment, remission rates remained high.</p><p><strong>Conclusion: </strong>The treatment of relapses in MCD has changed since 2010 with reduced use of prednisolone monotherapy and cyclophosphamide, and increased use of CNI and rituximab.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1941-1948"},"PeriodicalIF":5.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Active glomerular inflammation versus chronicity and fibrosis: the role of targeted therapies in IgA nephropathy.","authors":"Jai Radhakrishnan, Richard A Lafayette","doi":"10.1093/ndt/gfaf059","DOIUrl":"10.1093/ndt/gfaf059","url":null,"abstract":"","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1811-1814"},"PeriodicalIF":5.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute kidney injury in very old patients-incidence, severity, risk factors and short-term outcomes.","authors":"Stefan Herget-Rosenthal, Kolja Stille, Klaus Albrecht, Hajo Findeisen, Martin Scharpenberg, Andreas Kribben","doi":"10.1093/ndt/gfaf074","DOIUrl":"10.1093/ndt/gfaf074","url":null,"abstract":"<p><strong>Background and hypothesis: </strong>Although old age is a risk factor for acute kidney injury (AKI), data on AKI in individuals ≥80 years is limited. We aimed to provide data on AKI incidence, severity and outcomes to identify risk factors for AKI and 30-day mortality in those ≥80 years old.</p><p><strong>Methods: </strong>This was a cohort study of 2132 patients admitted to hospital. AKI was defined and classified by extended KDIGO criteria to detect community-acquired AKI, frailty as a clinical frailty score ≥5. Primary endpoints were AKI and its stages, secondary endpoints 30-day mortality and major adverse kidney events (MAKE30), a composite of mortality, new renal replacement therapy or serum creatinine values ≥200% of baseline, all at 30 days.</p><p><strong>Results: </strong>Median age was 86 years. AKI was frequent (35.3%) and predominately community-acquired (80.2%). The incidence rate of AKI rose with increasing age, reaching the maximum in patients 95 years old. Some 48.9% of AKI patients developed stage 1, while 27.0% and 24.1% reached stages 2 and 3, respectively. Frailty was identified as an independent AKI risk factor {adjusted odds ratio (aOR) 2.42 [95% confidence interval (CI) 1.93-3.03]}. The 30-day mortality rate was significantly higher in AKI compared with non-AKI patients (25.4% vs 7.6%), 44.4% of AKI patients developed MAKE30. Among others, AKI and frailty were risk factors for 30-day mortality [aOR 3.02 (95% CI 2.25-4.07) and 1.53 (95% CI 1.16-2.02)], with frailty exceeding AKI in patients ≥90 years.</p><p><strong>Conclusions: </strong>AKI occurs frequently, increases with age, is severe and is predominately community-acquired in individuals ≥80 years admitted to hospital. Frailty is a risk factor for AKI besides established factors. Very old patients with AKI more frequently died or developed a high rate of the composite endpoint MAKE30. AKI and frailty are risk factors for 30-day mortality. The effect of frailty on mortality exceeded that of AKI in nonagenarians.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1949-1960"},"PeriodicalIF":5.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional outcomes in pediatric patients on renal replacement therapy in a worldwide registry.","authors":"Kristin J Dolan, Katja M Gist, Abby Basalely, Gabriella Bottari, Abhishek Chakraborty, Mihaela Damian, Dana Fuhrman, Denise C Hasson, Catherine Joseph, Dave Kwiatkowski, Susan Martin, Jenn Nhan, Nicolas Ollberding, David T Selewski, Danielle Soranno, Michelle C Starr, Amy Strong, Sameer Thadani, Huaiyu Zang, Ayse Akcan Arikan","doi":"10.1093/ndt/gfaf067","DOIUrl":"10.1093/ndt/gfaf067","url":null,"abstract":"<p><strong>Background and hypothesis: </strong>Mortality rates of children supported with continuous renal replacement therapy (CRRT) have improved, yet morbidity remains high. We aimed to evaluate the functional outcomes of children receiving CRRT using Functional Status Scale (FSS). We hypothesized that children receiving CRRT will have worse FSS compared with their baseline and acquire new morbidity at hospital discharge and 6 and 12 months post-discharge, and that lack of renal recovery will contribute to worsening functional status.</p><p><strong>Methods: </strong>This is a retrospective chart review from The Worldwide Exploration of Renal Replacement Outcomes Collaborate in Kidney Disease (WE-ROCK), an international multi-center registry. Twenty-eight centers across five countries participated in this analysis. Children from birth to 25 years, on CRRT for acute kidney injury (AKI) or fluid overload, were included. Patients with underlying kidney disease, on extracorporeal membrane oxygenation and non-survivors were excluded. FSS was collected at discharge (n = 527), 6 months (n = 387) and 12 months post-discharge (n = 344). The primary outcome was FSS at discharge and 6 months. Secondary outcomes included: new morbidity at discharge and 6 months; FSS at 12 months; and the impact of renal recovery on functional outcomes.</p><p><strong>Results: </strong>A total of 527 patients had median FSS of 7 (6, 90) at hospital discharge. Thirty-nine percent (n = 204) had worse FSS. Eighteen percent (95/527) acquired a new morbidity at discharge. Predictors of FSS at discharge were baseline FSS {odds ratio (OR) 1.30 [95% confidence interval (CI) 1.11-1.52]}, weight [OR 0.99 (95% CI 0.98-0.9997)], comorbidities [OR 1.88 (95% CI 1.16-3.04)], mechanical ventilation [OR 1.72 (95% CI 1.04-2.85)] and sepsis on intensive care unit admission [OR 1.46 (95% CI 1.01-2.21)]. A total of 387 patients had median FSS score of 6 (6, 8) at 6 months. Ten percent (n = 39/387) acquired new morbidity at 6 months. The significant predictors of FSS at 6 months were FSS at discharge [OR 2.36 (95% CI 1.95-2.84)] and presence of comorbidities [OR 1.77 (95% CI 1.03-3.06)].</p><p><strong>Conclusion: </strong>This is the first large, multi-center study evaluating functional outcomes of children on CRRT. Persistent morbidity following discharge emphasizes the importance of comprehensive identification and multidisciplinary follow-up to optimize patient outcomes.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1919-1930"},"PeriodicalIF":8.3,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12709130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma trimethylamine N-oxide concentration and all-cause mortality in kidney transplant recipients.","authors":"Manuela Yepes-Calderón, Fernando Martín Del Campo Sanchez, Daan Kremer, Tim J Knobbe, Antonio W Gomes Neto, Margery A Connelley, Robin P F Dullaart, Eva Corpeleijn, Martin H de Borst, Stephan J L Bakker","doi":"10.1093/ndt/gfaf071","DOIUrl":"10.1093/ndt/gfaf071","url":null,"abstract":"<p><strong>Background and hypothesis: </strong>Trimethylamine N-oxide (TMAO) is a pro-atherosclerotic molecule produced by intestinal microbiome. TMAO has been linked to increased mortality risk in chronic kidney disease, but its effect in kidney transplant recipients (KTR) is unclear. We investigated the pre-post-transplantation plasma TMAO change, and the association of post-transplantation plasma TMAO with all-cause mortality in KTR.</p><p><strong>Methods: </strong>This prospective study included two cohorts. Cohort A comprised 623 KTR from the TransplantLines Cohort and Biobank Study (ClinicalTrials.gov: NCT03272841), and assessed pre-transplantation and at 3, 6, 12 and 24 months post-transplantation. Cohort B included 544 KTR with a functioning graft for ≥1 year [median 7.4 (3.9-13.0) years post-transplantation] to study late associations. Potential kidney donors (n = 315) served as healthy controls. Plasma TMAO was measured by proton nuclear magnetic resonance. Time-dependent coefficient Cox regression analyses were performed to assess TMAO association with all-cause mortality.</p><p><strong>Results: </strong>Plasma TMAO concentration significantly declined after transplantation {from 29.0 [interquartile range (IQR) 20.6-48.5] µmol/L to 4.5 (IQR 2.7-8.6) mol/L at 3-months post-transplantation, P < .001}. Afterwards it remained stable [β -0.4 (95% confidence interval -2.2 to 1.34) µmol/L per post-transplantation year, P = .63], remaining consistently higher than that of healthy control [2.6 (IQR 1.8-4.3) µmol/L]. In Cohort A, during a median follow-up of 2.2 years, 41 KTR (7%) died. In Cohort B, over a median follow-up of 4.1 years, 78 KTR (14%) died. A 1-SD higher plasma TMAO concentration was independently associated with an increased risk of all-cause mortality in both cohorts [hazard ratio (95% confidence interval) 1.35 (1.19‒1.53); P < .001, and 1.34 (1.23‒1.47); P < .001; respectively].</p><p><strong>Conclusion: </strong>Plasma TMAO decreases sharply after kidney transplantation, without reaching healthy controls levels. A higher plasma TMAO concentration was independently associated with an increased mortality risk in KTR. Further research is warranted to assess whether accounting for gut dysbiosis and TMAO could improve clinical outcomes in KTR.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1931-1940"},"PeriodicalIF":5.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary vitamin E and tocopherol isoform intake and the progression of chronic kidney disease.","authors":"Yanjun Zhang, Ziliang Ye, Yuanyuan Zhang, Sisi Yang, Xiaoqin Gan, Yu Huang, Hao Xiang, Yiting Wu, Yiwei Zhang, Xianhui Qin","doi":"10.1093/ndt/gfaf052","DOIUrl":"10.1093/ndt/gfaf052","url":null,"abstract":"<p><strong>Background and hypothesis: </strong>It is unclear whether dietary vitamin E and tocopherol isoform intake is associated with health outcomes in patients with chronic kidney disease (CKD). We hypothesize that different dietary tocopherol isoforms have different health effects in people with CKD. Therefore, we aimed to investigate the association between dietary vitamin E and tocopherol isoforms and risks of CKD progression and all-cause mortality in patients with CKD.</p><p><strong>Methods: </strong>In this prospective cohort study, 3791 participants with CKD in the Chronic Renal Insufficiency Cohort (CRIC) were included. The main exposures included dietary vitamin E and tocopherol isoforms, which were estimated by the validated Diet History Questionnaire at baseline, Year 2 and Year 4 before the study outcome was diagnosed. The primary outcome was CKD progression, defined as a 50% decline in the estimated glomerular filtration rate from baseline or initiation of kidney replacement therapy. The secondary outcome was all-cause mortality.</p><p><strong>Results: </strong>During a median follow-up of 5.5 years, 1188 (31.3%) CKD progression events occurred. There was an L-shaped relationship between total vitamin E intake and risks of CKD progression and all-cause mortality. Regarding dietary tocopherol isoforms, there was an L-shaped relationship of dietary beta-tocopherol with risks of CKD progression and all-cause mortality, a reversed J-shaped relationship between dietary gamma-tocopherol and the risk of CKD progression and a U-shaped association between dietary delta-tocopherol and the risk of CKD progression. There was no significant association between dietary alpha-tocopherol and risks of CKD progression and all-cause mortality.</p><p><strong>Conclusions: </strong>There was an L-shaped association between total vitamin E and CKD progression in patients with CKD. Different dietary tocopherol isoforms have different relationships with CKD progression in patients with CKD, which included an L-shaped association for beta-tocopherol, a reversed J-shaped association for gamma-tocopherol, a U-shaped association for delta-tocopherol and a non-significant association for alpha-tocopherol.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1854-1864"},"PeriodicalIF":5.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matrix metalloproteinase (MMP)-10 aggravates podocyte injury in glomerulonephritis.","authors":"Takuya Ishimura, Keisuke Osaki, Sayaka Sugioka, Akira Ishii, Hiroyuki Yamada, Naohiro Toda, Shoko Ohno, Yukiko Kato, Taiji Matsusaka, Takeshi Tokudome, Motoko Yanagita, Hideki Yokoi","doi":"10.1093/ndt/gfaf076","DOIUrl":"10.1093/ndt/gfaf076","url":null,"abstract":"<p><strong>Background: </strong>Podocytes are integral to maintaining glomerular filtration barrier. Our previous research underscored the crucial role of podocyte guanylyl cyclase-A (GC-A) in the pathogenesis of severe albuminuria in both systemic and podocyte-specific GC-A knockout mice subjected to heminephrectomy, high salt, and aldosterone (ALDO) treatment. This study investigates the role of matrix metalloproteinase-10 (MMP-10) on glomerular injury, which was found to be highly expressed in glomeruli of ALDO-treated GC-A knockout mice.</p><p><strong>Methods: </strong>To investigate the role of MMP-10 in glomerulonephritis, we used MMP-10 knockout mice subjected to anti-glomerular basement membrane (GBM) nephritis. Additionally, we created systemic GC-A and MMP-10 double knockout mice, as well as podocyte-specific GC-A and systemic MMP-10 double knockout mice, to analyze glomerular injury. In vitro, changes in inflammatory mRNA are examined in MMP-10-overexpressing or -knockdown mouse podocytes following stimulation of tumor necrosis factor (TNF)-α.</p><p><strong>Results: </strong>We demonstrate that MMP-10 is highly expressed in the kidneys of patients with glomerulonephritis. MMP-10 knockout mice showed less albuminuria and lower expression of pro-inflammatory and pro-fibrotic mRNAs compared to control mice in anti-GBM nephritis. Additionally, systemic or podocyte-specific GC-A and systemic MMP-10 knockout mice exhibited improved albuminuria, preserved nephrin expression, and reduced GBM thickening compared to systemic or podocyte-specific GC-A knockout mice with ALDO treatment. MMP-10 was co-localized with podocytes and endothelial cells. In vitro studies using mouse podocytes revealed that MMP-10 overexpression upregulated inflammatory mRNA changes induced by TNF-α, whereas MMP-10 knockdown mitigated inflammation. Co-culture of mouse podocytes with human endothelial cells showed reduced inflammation following MMP-10 reduction in endothelial cells. Moreover, activated MMP-10 cleaved nephrin in vitro, contributing to podocyte injury.</p><p><strong>Conclusion: </strong>These findings suggest that GC-A ablation leads to upregulation of MMP-10, resulting in nephrin loss, and that systemic deletion of MMP-10 ameliorates GC-A-induced podocyte injury.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1961-1976"},"PeriodicalIF":5.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How to individualize renoprotective therapy in obese patients with chronic kidney disease: a commentary by the Diabesity Working Group of the ERA.","authors":"Enrique Morales, William P Martin, Sebastjan Bevc, Trond G Jenssen, Marius Miglinas, Matias Trillini","doi":"10.1093/ndt/gfaf069","DOIUrl":"10.1093/ndt/gfaf069","url":null,"abstract":"<p><p>The interrelated pandemics of obesity and type 2 diabetes mellitus (T2DM) are fuelling an increase in the prevalence of chronic kidney disease (CKD), which amplifies the risk of cardiovascular events and may progress to end-stage kidney disease (ESKD). Treatment options for such patients have rapidly expanded over the past decade and continue to evolve. Herein, we primarily focus on glucagon-like peptide-1 receptor agonists (GLP-1RAs) and their role in the management of CKD in the setting of overweight/obesity and T2DM. Recommendations from the recent Kidney Disease: Improving Global Outcomes CKD guidelines are summarized and new evidence arising since publication of these guidelines is highlighted. We review clinical studies supporting the role of GLP-1RAs in patients with diabesity and CKD, including the FLOW trial, as well as exploring potential mechanisms of their nephroprotective effects. Their role in the management of patients with ESKD on maintenance dialysis and after kidney transplantation, while less evidence-based, is also discussed. The potential for other gut hormone-based therapies, including GLP-1/glucose-dependent insulinotropic polypeptide dual agonists (tirzepatide), triple agonists (incorporating glucagon agonism) and amylin analogues to improve cardiovascular and kidney outcomes in patients with CKD, is explored. We highlight the role of novel therapies distinct from the gut-kidney axis, including non-steroidal mineralocorticoid receptor antagonists (nsMRAs). We outline the potential for multitarget therapy incorporating renin-angiotensin-aldosterone system inhibitors, sodium-glucose co-transporter-2 inhibitors, incretin-based treatments and nsMRAs to improve cardiovascular and kidney outcomes in patients with overweight/obesity and T2DM. Current unknowns in the timing and sequence of multitarget therapy in patients with CKD are emphasized. Priority research questions for the future are highlighted throughout the review.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1977-1988"},"PeriodicalIF":5.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12548029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific cardiac dysfunction in mice with chronic kidney disease.","authors":"Yitong Zhao, Karen Yang, Christy M Nguyen, Hongmei Wu, Han Liu, Leandro M Velez, Jin Kyung Kim, Marcus Seldin, Wei Ling Lau","doi":"10.1093/ndt/gfaf056","DOIUrl":"10.1093/ndt/gfaf056","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular disease (CVD) is the leading cause of death among patients with chronic kidney disease (CKD). Rodent models are widely used to study uremic CVD pathophysiology. We compared cardiac function parameters in male and female animals from two established mouse CKD models and examined associations between gut-derived uremic toxins and echocardiogram findings.</p><p><strong>Methods: </strong>Male and female adult C57Bl/6J mice were randomly assigned to control, adenine-induced CKD and 5/6 nephrectomy CKD groups. Echocardiography was performed on all mice at age 17 weeks (5 weeks after CKD induction). Serum creatinine, cystatin C and gut-derived uremic toxins were analyzed at study termination, and RNA sequencing of left ventricle tissue was performed and analyzed.</p><p><strong>Results: </strong>Markers of kidney dysfunction were elevated in both CKD models. The gut-derived uremic toxin indoxyl sulfate was increased in both CKD models, while trimethylamine N-oxide was increased in adenine CKD mice and p-cresyl sulfate in nephrectomy animals. Left ventricular volume was increased in nephrectomy animals. Cardiac output was decreased in male CKD animals from both models compared with controls, and ejection fraction was decreased in male 5/6 nephrectomy mice. Female controls had lower stroke volume and cardiac output than male counterparts, and female CKD animals had preserved cardiac output and ejection fraction when compared with female controls. The gut-derived uremic toxins trimethylamine N-oxide and indoxyl sulfate correlated with decreased cardiac output in male animals. Transcriptomics of cardiac tissue revealed sex-based variations in matrix metalloproteinase and mitochondrial pathways associated with cardiac dysfunction.</p><p><strong>Conclusions: </strong>Our work highlights sex differences in cardiac function and serum chemistries in two established preclinical CKD models. Gut-derived uremic toxins may impact cardiorenal pathophysiology and low cardiac output in male CKD animals.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1865-1875"},"PeriodicalIF":5.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12548047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SGLT2 inhibitors in CKD: are they really effective in all patients?","authors":"Paola Romagnani","doi":"10.1093/ndt/gfaf051","DOIUrl":"10.1093/ndt/gfaf051","url":null,"abstract":"<p><p>Sodium-glucose cotransporter 2 (SGLT2) inhibitors effectively slow chronic kidney disease (CKD) progression and reduce cardiovascular events. However, their efficacy across all CKD subgroups remains uncertain. Major clinical trials primarily included overweight or obese patients with advanced CKD, where sodium retention, volume expansion and glomerular hyperfiltration are key disease drivers. In contrast, many underrepresented CKD subgroups, such as Alport syndrome or most immune-mediated glomerular disorders, often affect lean individuals whose CKD progression is not linked to these mechanisms. Emerging evidence suggests that the renal benefits of SGLT2 inhibitors may depend on body mass index (BMI), with greater effects observed in patients with higher BMI, while those with BMI <25 may show minimal/no benefit. This raises concerns about their applicability in lean, non-diabetic CKD patients, whose disease progression may involve alternative pathways, such as inflammation, autoimmunity or genetic abnormalities. Animal studies further suggest that SGLT2 inhibitors provide limited renal protection in certain genetic and immune-mediated kidney diseases. Additionally, molecular data indicate that SGLT2 expression is predominantly restricted to the proximal tubule, implying a limited role in CKD driven by non-hyperfiltration mechanisms. While SGLT2 inhibitors have revolutionized CKD treatment in diabetes, obesity and heart failure, their role in lean, non-diabetic patients remains unclear. Dedicated clinical trials are needed to assess their efficacy in underrepresented CKD subgroups, including pediatric patients, and ensure evidence-based, personalized treatment strategies.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1838-1842"},"PeriodicalIF":5.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}