Nephrology Dialysis Transplantation最新文献

{"title":"Mineralocorticoid receptor antagonism attenuates arteriovenous fistula stenosis by modulating the phenotype of vascular smooth muscle cells.","authors":"Yamin Liu, Bohan Chen, Kai Chen, Yufei Wang, Chunyu Zhou, Xianhui Liang, Kai Wang, Pei Wang","doi":"10.1093/ndt/gfae247","DOIUrl":"10.1093/ndt/gfae247","url":null,"abstract":"<p><strong>Background: </strong>Fistula stenosis is a primary contributor to arteriovenous fistula (AVF) failure in maintenance hemodialysis patients. Emerging data indicated excessive fibrotic remodeling was the primarily contributor to fistula stenosis during AVF remodeling. The mineralocorticoid receptor (MR) has been implicated in vascular remodeling across various cardiovascular pathologies. However, its role in AVF remodeling, particularly concerning fibrotic remodeling, remains elusive.</p><p><strong>Methods: </strong>MR expression and the phenotypes of vascular smooth muscle cells (VSMC) were assessed in dysfunctional AVF. The effects of MR on VSMC phenotypic switching were examined in vitro, and the protective effects of MR antagonists on AVF outcome were evaluated in a rat AVF model.</p><p><strong>Results: </strong>Dysfunctional fistula exhibited significant medial fibrosis and extracellular matrix deposition, alongside markedly increased MR activity. In the dysfunctional fistula vessels, VSMC displayed reduced expression of the contractile marker SMMHC and features characteristic of a synthetic phenotype, including increased osteopontin expression and heightened proliferation. In vitro studies with cultured VSMC revealed that MR overactivity induced by aldosterone led to phenotypic switching from contractile to synthetic state, concomitant with EGFR-ERK1/2 pathway overactivation. These effects were largely abolished by the MR antagonist finerenone. Knockdown of EGFR expression abrogated ERK1/2 phosphorylation and inhibited the VSMC phenotypic switching. Conversely, ectopic overexpression of EGFR in VSMC diminished the protective effect of finerenone. In rat AVF models, pharmacologic targeting of MR with finerenone significantly improved AVF outcomes, characterized by increased luminal diameters and flow volume, reduced medial fibrosis, and inhibited VSMC phenotypic switching. These beneficial outcomes were likely attributable to a restrained activity of the EGFR-ERK1/2 pathway in VSMC.</p><p><strong>Conclusions: </strong>Our study demonstrated that therapeutic targeting of MR may improve AVF outcome by modulating VSMC phenotypic switching. These findings offer promising avenues for further clinical investigations aimed at optimizing AVF outcomes in the hemodialysis population.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1124-1136"},"PeriodicalIF":4.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605446","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":"The soluble guanylate cyclase activator runcaciguat significantly improves albuminuria in patients with chronic kidney disease: a randomized placebo-controlled clinical trial.","authors":"Ron T Gansevoort, David C Wheeler, Francisco Martínez Debén, Marijn Speeckaert, Dirk Thomas, Mario Berger, Stefan Klein, Frauke Friedrichs, Karen Paraschin, Roland E Schmieder","doi":"10.1093/ndt/gfae261","DOIUrl":"10.1093/ndt/gfae261","url":null,"abstract":"<p><strong>Background and hypothesis: </strong>In chronic kidney disease (CKD) the nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway is impaired. Runcaciguat, an sGC activator, activates heme-free sGC, restoring cGMP production. This phase 2a trial studied the efficacy, safety, and tolerability of runcaciguat in CKD patients with or without sodium-glucose co-transporter-2 inhibitor (SGLT2i).</p><p><strong>Methods: </strong>Patients with CKD and established atherosclerotic cardiovascular disease or heart failure, plus type 2 diabetes (T2D) and/or hypertension, were enrolled. All were receiving stable maximum tolerated renin-angiotensin system inhibitors with or without SGLT2i. They were randomized 3:1 to runcaciguat once daily, titrated weekly (30-120 mg if tolerated), or placebo for 8 weeks. The primary efficacy endpoint was urine albumin-to-creatinine ratio (UACR) (average of post-randomization Days 22, 29, and 57 vs baseline). CONCORD was separately powered for CKD and T2D with stable SGLT2i comedication, CKD and T2D without SGLT2i, and non-diabetic CKD.</p><p><strong>Results: </strong>Of 243 patients randomized, 229 were included in the full analysis set (FAS) and 170 in the per-protocol set (PPS). In the PPS, UACR decreased by -45.2% versus placebo with runcaciguat in patients with CKD without SGLT2i (P < 0.001) and by -48.1% versus placebo in patients with CKD taking SGLT2i (P = 0.02) In the FAS, the relative reductions were -46.9% (P < 0.001) and -44.8% (P = 0.01), respectively. No significant difference was observed between patients with or without SGLT2i. In non-diabetic CKD, UACR was reduced versus baseline with runcaciguat, but the change was not statistically significant (P = 0.10). Serious treatment-emergent adverse events were reported in 7% of patients receiving runcaciguat and 8% receiving placebo.</p><p><strong>Conclusion: </strong>Runcaciguat improved albuminuria in patients with CKD, irrespective of concomitant SGLT2i. Runcaciguat was well tolerated. sGC activation may represent a novel kidney-protective treatment in CKD patients (funded by Bayer AG; ClinicalTrials.gov number, NCT04507061).</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1147-1160"},"PeriodicalIF":4.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829523","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":"The potential for improving cardio-renal outcomes in chronic kidney disease with the aldosterone synthase inhibitor vicadrostat (BI 690517): a rationale for the EASi-KIDNEY trial.","authors":"Parminder K Judge, Katherine R Tuttle, Natalie Staplin, Sibylle J Hauske, Doreen Zhu, Rebecca Sardell, Lisa Cronin, Jennifer B Green, Nikita Agrawal, Ryoki Arimoto, Kaitlin J Mayne, Emily Sammons, Martina Brueckmann, Shimoli V Shah, Peter Rossing, Masaomi Nangaku, Martin J Landray, Christoph Wanner, Colin Baigent, Richard Haynes, William G Herrington","doi":"10.1093/ndt/gfae263","DOIUrl":"10.1093/ndt/gfae263","url":null,"abstract":"<p><p>Patients with chronic kidney disease (CKD) are at risk of progressive loss of kidney function, heart failure, and cardiovascular death despite current proven therapies, including renin-angiotensin system inhibitors (RASi), sodium glucose co-transporter-2 inhibitors (SGLT2i), and statin-based regimens. RASi and SGLT2i reduce risk of CKD progression irrespective of primary cause of kidney disease, suggesting they target final common pathways. Targeting aldosterone overactivity with a nonsteroidal mineralocorticoid receptor antagonist (MRA) also reduces cardiorenal risk in patients with albuminuric diabetic kidney disease already treated with RASi. Together, these observations provide the rationale for trials to assess effects of inhibiting the aldosterone pathway in a broader range of patients with CKD, including those with non-diabetic causes of CKD or low albuminuria. Aldosterone synthase inhibitors (ASi) have emerged as an alternative to MRAs for aldosterone pathway inhibition. Phase II data from 586 patients with albuminuric CKD have shown that 10 mg of an ASi, vicadrostat (BI 690517), reduced urine albumin-to-creatinine ratio by ∼40% compared with placebo, with or without concurrent empagliflozin treatment. MRA and ASi increase risk of hyperkalaemia. Combining their use with an SGLT2i may mitigate some of this risk, improving tolerability, and allowing a wider range of patients to be treated (including those with higher levels of blood potassium than in previous trials). The EASi-KIDNEY (NCT06531824) double-blind placebo-controlled trial will test this approach by assessing the safety and cardiorenal efficacy of vicadrostat in combination with empagliflozin in ∼11 000 patients with CKD. It will be sufficiently large to assess effects in patients with and without diabetes separately.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1175-1186"},"PeriodicalIF":4.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624555","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":"Normalization dynamics of donor-derived cell-free DNA predicts future kidney transplant rejection.","authors":"David Cucchiari, Elena Cuadrado-Payán, Eva Gonzalez-Roca, Ignacio Revuelta, Maria José Ramirez-Bajo, Pedro Ventura-Aguiar, Jordi Rovira, Elisenda Bañon-Maneus, Mireia Musquera, Lluís Peri, Silvia Casas, Eduard Palou, Joan Anton Puig-Butille, Fritz Diekmann","doi":"10.1093/ndt/gfae291","DOIUrl":"10.1093/ndt/gfae291","url":null,"abstract":"","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1248-1250"},"PeriodicalIF":4.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736055","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":"Acquired and genetic drivers of C3 and C5 convertase dysregulation in C3 glomerulopathy and immunoglobulin-associated MPGN.","authors":"Julia Roquigny, Marie-Sophie Meuleman, Carine El Sissy, Paula Vieira Martins, Seppo Meri, Anna Duval, Moglie Le Quintrec, Fadi Fakhouri, Sophie Chauvet, Véronique Frémeaux-Bacchi","doi":"10.1093/ndt/gfae243","DOIUrl":"10.1093/ndt/gfae243","url":null,"abstract":"<p><p>Dysregulation of the alternative pathway of complement plays a central role in the pathophysiology of C3 glomerulopathy (C3G). Various autoimmune and genetic factors targeting the alternative pathway have been associated with both C3G and primary immunoglobulin-associated membranoproliferative glomerulonephritis (Ig-MPGN), suggesting shared pathophysiological mechanisms. This review highlights the wide range of disease drivers identified that mainly target components or protein complexes of the alternative pathway, both in C3G and Ig-MPGN. Nephritic factors, which constitute a heterogeneous group of autoantibodies targeting the C3 or the C5 convertase, are the most common abnormalities. Monoclonal gammopathies are frequent in aging adults. They may promote complement activation and have in some cases also been found to target alternative pathway regulatory proteins. Additionally, some patients with C3G and Ig-MPGN carry rare variants in genes encoding complement activating or regulating proteins of the alternative pathway. This review provides an informative overview of pathogenetic mechanisms associated with each abnormality, acting at different steps in the complement cascade. The diversity of targets involved in the C3G pathophysiology suggests the potential benefit of therapeutical approaches tailored to the underlying disease drivers, with a pivotal impact upstream or at the level of the C3 or C5 convertase activity.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1081-1090"},"PeriodicalIF":4.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624546","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":"Diagnosis, management and treatment of the Alport syndrome - 2024 guideline on behalf of ERKNet, ERA and ESPN.","authors":"Roser Torra, Beata Lipska-Zietkiewicz, Frederic Acke, Corinne Antignac, Jan Ulrich Becker, Emilie Cornec-Le Gall, Albertien M van Eerde, Nicolas Feltgen, Rossella Ferrari, Daniel P Gale, Susie Gear, Oliver Gross, Stefanie Haeberle, Laurence Heidet, Rachel Lennon, Laura Massella, Kristina Pfau, Maria Del Prado Venegas Pizarro, Rezan Topaloglu, Tanja Wlodkowski, Heidi Zealey","doi":"10.1093/ndt/gfae265","DOIUrl":"10.1093/ndt/gfae265","url":null,"abstract":"<p><p>Glomerular nephropathy resulting from the genetic defects in COL4A3/4/5 genes including the classical Alport syndrome is the second most common hereditary kidney disease characterized by persistent haematuria progressing to the need for kidney replacement therapy, frequently associated with sensorineural deafness, and occasionally with ocular anomalies. Diagnosis and management of COL4A3/4/5 glomerulopathy is a great challenge due to its phenotypic heterogeneity, multiple modes of inheritance, variable expressivity, and disease penetrance of individual variants as well as imperfect prognostic and progression factors and scarce and limited clinical trials, especially in children. As a joint initiative of the European Rare Kidney disease reference Network (ERKNet), European Renal Association (ERA Genes&Kidney), and European Society for Paediatric Nephrology (ESPN) Inherited renal disorders working group, a team of experts including adult and paediatric nephrologists, kidney geneticists, audiologists, ophthalmologists, and a kidney pathologist were selected to perform a systematic literature review on 21 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions. The experts formulated recommendations and formally graded them at a consensus meeting with input from patient representatives and a voting panel of nephrologists representing all regions of the world. Genetic diagnostics comprising joint analysis of COL4A3/4/5 genes is already the key diagnostic test during the initial evaluation of an individual presenting with persistent haematuria, proteinuria, kidney failure of unknown origin, focal segmental sclerosis of unknown origin, and possibly cystic kidney disease. Early renin-angiotensin system blockade is the standard of care therapy; sodium-glucose cotransporter-2 inhibitors may be added in adults with proteinuria and chronic kidney disease. Relatives with heterozygous COL4A3/4/5 variants should only be considered as the last possible resource for living kidney donation. This guideline provides guidance for the diagnosis and management of individuals with pathogenic variants in COL4A3/4/5 genes.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1091-1106"},"PeriodicalIF":4.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824305","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":"Disease-modifying anti-nephropathic drugs (DMANDs)-a definition proposed by the Immunonephrology Working Group (IWG) of the European Renal Association (ERA).","authors":"Y K Onno Teng, Eleni Frangou, Andreas Kronbichler, Annette Bruchfeld, Fernando Caravaca-Fontan, Jürgen Floege, Sarah M Moran, Safak Mirioglu, Kate I Stevens, Stefanie Steiger, Paola Romagnani, Hans-Joachim Anders","doi":"10.1093/ndt/gfaf033","DOIUrl":"10.1093/ndt/gfaf033","url":null,"abstract":"<p><p>A definition of 'disease modification' for kidney disease is long overdue. Here, we propose three key criteria for disease modification in immune-mediated glomerulonephritis and podocytopathies: minimizing disease activity, preventing loss of kidney structure and function, and reducing treatment-related toxicity. To be considered a disease-modifying anti-nephropathic drug (DMAND), a drug must fulfil all three criteria, hence the DMAND status of a drug may not be clear at the time of regulatory approval. Notably, the aspect of chronic kidney disease (CKD) in immune-mediated kidney diseases must be considered and treated separately, e.g. renin-angiotensin system inhibitor is a DMAND for the CKD aspect but not for the immune disease itself. Defining DMANDs is an ambitious goal but one that may help to set the priorities for future treatment strategies in immune-mediated kidney disease. This may mean much more rapid tapering or even avoidance of unselective, non-targeted immunosuppressive agents, which carry considerable short (teratogenicity) and long term risks (malignancies). The criteria proposed here set a high bar for 'disease modification' in immune-mediated kidney disease. Inevitably, this must dictate altered priorities with the focus for new therapeutic agents and strategies shifting from solely reduction of proteinuria to preservation of GFR and attenuation of decline, whilst also eliminating long-term toxicity.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1243-1247"},"PeriodicalIF":4.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382788","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":"Kidney Stone Biology: insights from Genetics.","authors":"Andrea Spasiano, Emmanuel Letavernier, Pietro Manuel Ferraro, Robert J Unwin, Giovanni Gambaro","doi":"10.1093/ndt/gfaf062","DOIUrl":"https://doi.org/10.1093/ndt/gfaf062","url":null,"abstract":"<p><p>Kidney Stone Disease (KSD) affects more than 10% of the global population and has a high likelihood of recurrence. Its prevalence has risen significantly in recent decades, posing a substantial economic burden. Moreover, KSD is linked to several comorbidities, amplifying its impact on general health and well-being. Environmental factors play a critical role in KSD development, acting upon an underlying genetic substratum. These genetic factors affect the regulation of stone-forming elements and natural inhibitors of crystallization within the kidney. Understanding the interplay between genetic and environmental factors is essential for improving KSD management. Tailored dietary interventions and targeted therapies can address individual risk profiles, reducing the burden of this complex disease. We believe that the common form of KSD, which is the one observed in the general population, is indeed a heterogeneous condition characterized by significant variability in the influence of environmental and genetic factors among patients, as well as distinct biological pathways involved in lithogenesis for each individual. The aim of this review is to describe the relevant biology of nephrolithiasis, leveraging 'experiments of nature,' specifically the known genetic associations of KSD and the resulting biological and physiological derangements. We hypothesize that the carriers, molecular pathways, and physiological processes identified in this manner play a major role in the biology of lithogenesis, not only in rare genetic nephrolithiasis but also in 'common' KSD.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079248","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":"Complement activation in secondary thrombotic microangiopathies.","authors":"Johann Morelle, Fernando Caravaca-Fontan, Fadi Fakhouri, Eleni Frangou, Annette Bruchfeld, Jürgen Floege, Safak Mirioglu, Sarah M Moran, Stefanie Steiger, Kate I Stevens, Onno Y K Teng, Selda Aydin, Anuja Java, Sjoerd A M E G Timmermans, Andreas Kronbichler","doi":"10.1093/ndt/gfaf091","DOIUrl":"https://doi.org/10.1093/ndt/gfaf091","url":null,"abstract":"<p><p>Secondary thrombotic microangiopathies (TMA) represent a heterogeneous group of diseases associated with a high risk of kidney failure and death despite available therapeutic strategies. Strong evidence implicates complement dysregulation in the pathogenesis of secondary TMA, and emerging data increasingly suggest that pharmacological blockade of the complement improves the outcomes in patients with secondary TMA. Certain forms of secondary TMA, including postpartum TMA, TMA with coexisting hypertensive emergency and de novo TMA after kidney transplantation exhibit a high prevalence of pathogenic variants in complement genes, similar to those observed in primary atypical hemolytic uremic syndrome. These conditions should be considered as complement-mediated TMA triggered by pregnancy or transplantation, or in which severe hypertension represents a symptom rather than the etiology of TMA. Their optimal management relies on early initiation of complement inhibition. Other etiologies of secondary TMA (i.e. autoimmune diseases, hematopoietic stem cell transplantation, drugs, infections) are typically not linked with complement gene variants and their management primarily focuses on removal of the culprit trigger or treatment of the underlying condition. While well-designed trials are still awaited, a growing body of evidence suggests that complement activation is also involved in the pathopathophysiology of these diseases. Complement inhibitors, which have been associated with better outcomes, should be considered in patients with severe (life- or organ-threatening TMA) or refractory secondary TMA despite adequate management of the underlying condition. This review summarizes the current understanding and future directions in the management of secondary TMA, emphasizing the potential of complement inhibition as therapeutic strategy.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079238","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 individualise 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":"https://doi.org/10.1093/ndt/gfaf069","url":null,"abstract":"<p><p>The inter-related pandemics of obesity and type 2 diabetes mellitus (T2DM) are fueling a rise in the prevalence of chronic kidney disease (CKD), which amplifies the risk of cardiovascular events and which 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 KDIGO CKD guidelines are summarised, 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/GIP 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 nsMRAs. We outline the potential for multi-target therapy incorporating RAASis, SGLT2is, 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 multi-target therapy in patients with CKD are emphasised. Priority research questions for the future are highlighted throughout the review.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}