Mingfang Sun , Fei Xiao , Xue Chen , Ling Wang , Huanzi Dai
{"title":"Finerenone as a Nonsteroidal Mineralocorticoid Receptor Antagonist for Lupus Nephritis","authors":"Mingfang Sun , Fei Xiao , Xue Chen , Ling Wang , Huanzi Dai","doi":"10.1016/j.ekir.2025.07.039","DOIUrl":"10.1016/j.ekir.2025.07.039","url":null,"abstract":"","PeriodicalId":17761,"journal":{"name":"Kidney International Reports","volume":"10 10","pages":"Pages 3694-3695"},"PeriodicalIF":5.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145242238","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":"Is Monotherapy Enough? Rethinking Strategies for Active Lupus Nephritis Network Meta-Analysis of Active Lupus Nephritis Treatment","authors":"Vittorio Di Maso , Giacomo Emmi","doi":"10.1016/j.ekir.2025.08.028","DOIUrl":"10.1016/j.ekir.2025.08.028","url":null,"abstract":"","PeriodicalId":17761,"journal":{"name":"Kidney International Reports","volume":"10 10","pages":"Pages 3302-3304"},"PeriodicalIF":5.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145242375","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":"Gut to Stone: The Woes of Malabsorption and Kidney Stone Growth","authors":"Paavana Varanasi , Amy A. Yau , Mira Keddis","doi":"10.1016/j.ekir.2025.07.036","DOIUrl":"10.1016/j.ekir.2025.07.036","url":null,"abstract":"","PeriodicalId":17761,"journal":{"name":"Kidney International Reports","volume":"10 10","pages":"Pages 3678-3680"},"PeriodicalIF":5.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145242478","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}
Janaka Karalliedde , Kieran McCafferty , Peter Winocour , Tahseen A. Chowdhury , Naresh Kanumilli , Parijat De , Andrew H. Frankel , Ciara Doherty , Nicola Milne , Rosa M. Montero , Eirini Loudaki , Debasish Banerjee , Ritwika Mallik , Adnan Sharif , Sagen Zac-Varghese , Srikanth Bellary , Gabrielle Goldet , Ketan Dhatariya , Stephen C. Bain , Indranil Dasgupta
{"title":"Association of British Clinical Diabetologists and UK Kidney Association Joint Clinical Practice Guidelines for the Pharmacological Management of Hyperglycemia in Adults With Type 2 Diabetes Mellitus and CKD","authors":"Janaka Karalliedde , Kieran McCafferty , Peter Winocour , Tahseen A. Chowdhury , Naresh Kanumilli , Parijat De , Andrew H. Frankel , Ciara Doherty , Nicola Milne , Rosa M. Montero , Eirini Loudaki , Debasish Banerjee , Ritwika Mallik , Adnan Sharif , Sagen Zac-Varghese , Srikanth Bellary , Gabrielle Goldet , Ketan Dhatariya , Stephen C. Bain , Indranil Dasgupta","doi":"10.1016/j.ekir.2025.07.028","DOIUrl":"10.1016/j.ekir.2025.07.028","url":null,"abstract":"<div><div>A growing and significant number of people with diabetes develop chronic kidney disease (CKD), and diabetes-related CKD is a leading cause of end-stage kidney disease (ESKD). People with diabetes and CKD have high morbidity and mortality, predominantly related to cardiovascular disease (CVD).</div><div>Hyperglycemia and hypertension are modifiable risk factors to prevent the onset and progression of CKD and related CVD. Recent clinical trials of people with type 2 diabetes mellitus (T2DM) and CKD have demonstrated reduction in composite kidney end point events (significant decline in kidney function, need for kidney replacement therapy, and kidney-related death) and cardiovascular risk with sodium-glucose cotransporter 2 (SGLT-2) inhibitors, nonsteroidal mineralocorticoid receptor antagonists (nsMRAs) and glucagon-like peptide 1 (GLP-1) receptor agonists (RAs).</div><div>The Association of British Clinical Diabetologists and UK Kidney Association Diabetic Kidney Disease Clinical Speciality Group have previously undertaken a narrative review and critical appraisal of the available evidence to inform clinical practice guidelines for the pharmacological management of hyperglycemia in adults with T2DM and CKD. This 2025 abbreviated updated guidance by a multidisciplinary group of health care professionals from primary and secondary care settings summarizes the key recommendations, clinical considerations and recent evidence that has implications for clinical practice for health care professionals who treat people with T2DM and CKD.</div></div>","PeriodicalId":17761,"journal":{"name":"Kidney International Reports","volume":"10 10","pages":"Pages 3318-3331"},"PeriodicalIF":5.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145242302","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}
Maria Salman , Mark Canney , Ana Maria Naidas , Vimal K. Derebail , Silke R. Brix , Nataliya Milman , Mats L. Junek , Ayub Akbari , Michael Walsh , David Massicotte-Azarniouch
{"title":"Glucocorticoid Dosing and Outcomes in ANCA-Associated Vasculitis With Kidney Involvement","authors":"Maria Salman , Mark Canney , Ana Maria Naidas , Vimal K. Derebail , Silke R. Brix , Nataliya Milman , Mats L. Junek , Ayub Akbari , Michael Walsh , David Massicotte-Azarniouch","doi":"10.1016/j.ekir.2025.07.022","DOIUrl":"10.1016/j.ekir.2025.07.022","url":null,"abstract":"<div><h3>Introduction</h3><div>There may be reservations about the guideline-recommended use of reduced glucocorticoid (GC) therapy in severe ANCA-associated vasculitis (AAV). We examined differences in outcomes based on oral GC use during induction therapy for AAV with kidney involvement.</div></div><div><h3>Methods</h3><div>We conducted a single-center, retrospective cohort study (2010–2023) of patients with biopsy-proven kidney involvement from AAV. Patients were divided into eras 2020 onward (reduced-GC) versus pre-2020 (standard-GC) according to practice shift after adopting a reduced-GC regimen. The primary outcome was the composite of end-stage kidney disease (ESKD) or death within 12 months postbiopsy. Secondary outcomes included serious infection, clinical remission, and change in estimated glomerular filtration rate (eGFR).</div></div><div><h3>Results</h3><div>There were 138 participants (mean age: 65.2 years, 46.4% female, 68.1% anti-myeloperoxidase), comprising 41 in the reduced-GC era and 97in the standard-GC era. The former group was older (70.3 vs 63.1 years) and had worse baseline kidney function (eGFR: 15.6 vs 22.6 ml/min). The reduction of cumulative GC for reduced-GC compared with the standard-GC era was 39% in the first month, 28% in the first 3 months, and 34% in the first 6 months. For reduced-GC compared with standard-GC era, there was no significant difference in ESKD or death (24.4% vs. 21.6%), serious infection (14.6% vs. 17.5%), or remission (63.4% vs. 63.9%); and both groups showed similar improvement in eGFR over 12 months.</div></div><div><h3>Conclusion</h3><div>Reduced-GC during induction therapy in individuals with organ-threatening kidney involvement was not associated with a change in outcomes or kidney function recovery. This supports data from a large, randomized trial.</div></div>","PeriodicalId":17761,"journal":{"name":"Kidney International Reports","volume":"10 10","pages":"Pages 3456-3464"},"PeriodicalIF":5.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145242335","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}
Anastasia Adella , François Jouret , Leire Madariaga , Pieter A. Leermakers , Pedro Arango , Gema Ariceta , Bodo B. Beck , Anna Bjerre , Detlef Bockenhauer , Paula Coccia , Radhika Dhamija , Fernando de Frutos , Alejandro Garcia-Castano , Sara B. van Katwijk , Jesus Lucas , Thomas Möller , Dominik Müller , Filippo Pinto e Vairo , Melinda Raki , Jonathan Rips , Jeroen de Baaij
{"title":"Novel RRAGD Variants in Autosomal Dominant Kidney Hypomagnesemia and Therapeutic Perspectives","authors":"Anastasia Adella , François Jouret , Leire Madariaga , Pieter A. Leermakers , Pedro Arango , Gema Ariceta , Bodo B. Beck , Anna Bjerre , Detlef Bockenhauer , Paula Coccia , Radhika Dhamija , Fernando de Frutos , Alejandro Garcia-Castano , Sara B. van Katwijk , Jesus Lucas , Thomas Möller , Dominik Müller , Filippo Pinto e Vairo , Melinda Raki , Jonathan Rips , Jeroen de Baaij","doi":"10.1016/j.ekir.2025.07.035","DOIUrl":"10.1016/j.ekir.2025.07.035","url":null,"abstract":"<div><h3>Introduction</h3><div>Variants in the Ras-related GTPase D (<em>RRAGD</em>) gene have been associated with autosomal dominant kidney hypomagnesemia (ADKH) characterized by hypokalemia, nephrocalcinosis, and dilated cardiomyopathy (DCM). <em>RRAGD</em>, which encodes for the RagD protein, is involved in the activation of the mechanistic target of rapamycin complex 1 (mTORC1). Owing to the limited characterization of patients’ phenotypes, the understanding of <em>RRAGD-</em>associated ADKH (ADKH-RRAGD) remains incomplete. Consequently, available treatment strategies are primarily symptomatic and insufficient.</div></div><div><h3>Methods</h3><div>In the present case series, 13 new patients and 3 novel <em>RRAGD</em> variants, that is, p.(Ser77Phe), p.(Thr91Ile), and p.(Ile100Arg), are described. To assess the pathogenicity of the novel variants, an <em>in vitro</em> assay of mTORC1 activity was performed. In addition, the clinical response to diuretics (furosemide and thiazide, <em>n</em> = 4) and Na<sup>+</sup>-glucose cotransporter 2 (SGLT2) inhibitor, dapagliflozin (<em>n</em> = 6) was evaluated in patients carrying the <em>RRAGD</em> p.(Thr97Pro) variant during routine.</div></div><div><h3>Results</h3><div>The patients presented with kidney tubulopathies, including hypomagnesemia, hypercalciuria, and nephrocalcinosis. Five patients also exhibited DCM. <em>In vitro</em> assays demonstrated constitutive activation of noncanonical mTORC1 signaling caused by the p.(Ser77Phe) and p.(Ile100Arg) variants. Clinically, patients remained sensitive to diuretic challenges, whereas dapagliflozin treatment increased serum magnesium (Mg<sup>2+</sup>) levels by 0.04 mM but exacerbated hypokalemia.</div></div><div><h3>Conclusion</h3><div>To date, 37 patients with ADKH-RRAGD have been identified. Kidney tubulopathy is the most prominent feature within the phenotypic spectrum of ADKH-RRAGD. Molecularly, constitutive activation of noncanonical mTORC1 is present in most <em>RRAGD</em> variants. From a therapeutic perspective, dapagliflozin may increase serum Mg<sup>2+</sup> levels in patients with <em>RRAGD</em> variants.</div></div>","PeriodicalId":17761,"journal":{"name":"Kidney International Reports","volume":"10 10","pages":"Pages 3640-3655"},"PeriodicalIF":5.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145242446","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}
Julia Bartels , Mansoureh Tabatabaeifar , Marietta Kirchner , Karolis Azukaitis , Anke Doyon , Aysun Bayazit , Ali Düzova , Nur Canpolat , Ipek Kaplan Bulut , Lukasz Obrycki , Bruno Ranchin , Rukshana Shroff , Francesca Lugani , Cengiz Candan , Jerome Harambat , Harika Alpay , Mieczyslaw Litwin , Augustina Jankauskiene , Günter Klaus , Dorota Drozdz , R. Shroff
{"title":"GDF-15 and uEGF Independently Associate With CKD Progression in Children","authors":"Julia Bartels , Mansoureh Tabatabaeifar , Marietta Kirchner , Karolis Azukaitis , Anke Doyon , Aysun Bayazit , Ali Düzova , Nur Canpolat , Ipek Kaplan Bulut , Lukasz Obrycki , Bruno Ranchin , Rukshana Shroff , Francesca Lugani , Cengiz Candan , Jerome Harambat , Harika Alpay , Mieczyslaw Litwin , Augustina Jankauskiene , Günter Klaus , Dorota Drozdz , R. Shroff","doi":"10.1016/j.ekir.2025.07.004","DOIUrl":"10.1016/j.ekir.2025.07.004","url":null,"abstract":"<div><h3>Introduction</h3><div>Currently, there is limited ability to predict the progression of chronic kidney disease (CKD) in children. Previously we reported that low levels of urinary epidermal growth factor (uEGF) predict CKD progression in children. In the present study, we investigated a novel serum biomarker, growth differentiation factor 15 (GDF-15), in 2 European pediatric CKD cohorts. We additionally explored the combined effect of GDF-15 and/or uEGF on CKD progression in children.</div></div><div><h3>Methods</h3><div>The association between serum GDF-15 levels and CKD progression was analyzed in 671 patients of the Cardiovascular Comorbidity in Children with CKD (4C) study, aged 6 to 17 years with an estimated glomerular filtration rate (eGFR) of 10 to 60 ml/min per 1.73 m<sup>2</sup> at baseline, and median follow-up of 8 years. The composite end point was start of kidney replacement therapy, 50% eGFR loss, or eGFR < 10 ml/min per 1.73 m<sup>2</sup>. Results were validated in 329 participants from the ESCAPE trial.</div></div><div><h3>Results</h3><div>Higher GDF-15 levels were associated with an increased risk of CKD progression (hazard ratio: 1.40; 95% confidence interval [CI]: 1.10–1.77), independent of age, sex, baseline eGFR, proteinuria, and systolic blood pressure. Whereas adding either GDF-15 or uEGF individually to a model containing these variables improved model fit, combining both markers improved the model further. External validation in the ESCAPE cohort confirmed these results.</div></div><div><h3>Conclusion</h3><div>Serum GDF-15 and urine EGF levels may provide complementary information on the risk of CKD progression in children and might be included in future prognostic biomarker panels aimed at personalized, risk-stratified management of pediatric CKD.</div></div>","PeriodicalId":17761,"journal":{"name":"Kidney International Reports","volume":"10 10","pages":"Pages 3369-3378"},"PeriodicalIF":5.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145242233","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":"Klotho’s Impact on Cardiovascular Disease, Fractures, and Mortality in Hemodialysis","authors":"Akio Nakashima , Kazuhiko Kato , Arisa Kobayashi , Rena Kawai , Yuriko Shibata , Saya Tanimoto , Chiharu Aizawa , Ichiro Ohkido , Takashi Yokoo","doi":"10.1016/j.ekir.2025.07.032","DOIUrl":"10.1016/j.ekir.2025.07.032","url":null,"abstract":"<div><h3>Introduction</h3><div>Klotho, an aging-suppressor protein, has been shown to promote cardiovascular and bone health in animal models of chronic kidney disease (CKD). However, limited data exist on its role in clinical outcomes among patients undergoing hemodialysis. This study aimed to investigate the association between soluble Klotho (sKlotho) levels and cardiovascular disease (CVD) events, fractures, and all-cause mortality in this population.</div></div><div><h3>Methods</h3><div>We enrolled 1241 patients on hemodialysis from multiple medical institutions, with a median follow-up of 39 months. The primary outcome was a composite of CVD events, fractures, and all-cause mortality.</div></div><div><h3>Results</h3><div>The median sKlotho concentration was 325.6 pg/ml (interquartile range [IQR]: 248.9–434.4 pg/ml). During the follow-up, 436 CVD and 100 fracture events were recorded, along with 228 deaths. Patients in the lowest quartile of sKlotho had significantly higher risks of CVD events (hazard ratio [HR] = 1.76; 95% confidence interval [CI]: 1.20–2.60), fractures (HR = 1.99; 95% CI: 1.01–3.91) and mortality (HR = 1.74; 95% CI: 1.00–3.03) than those in the highest quartile.</div></div><div><h3>Conclusion</h3><div>These findings suggest that low serum sKlotho levels are strongly associated with poor cardiovascular and skeletal outcomes and increased mortality in patients on hemodialysis. This study highlights the potential utility of sKlotho as a biomarker for risk stratification in this high-risk population.</div></div>","PeriodicalId":17761,"journal":{"name":"Kidney International Reports","volume":"10 10","pages":"Pages 3516-3526"},"PeriodicalIF":5.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145242369","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}
Mary A. Cunningham , Audra A. Hargett , Amanda K. Holloway , Stacy D. Hall , Ellenore P. Craine , Nicolas Maillard , Dana V. Rizk , Bruce A. Julian , Jan Novak , Matthew B. Renfrow
{"title":"Proteomic Analysis of Circulating IgA1-Containing Immune Complexes in Patients with IgA Nephropathy","authors":"Mary A. Cunningham , Audra A. Hargett , Amanda K. Holloway , Stacy D. Hall , Ellenore P. Craine , Nicolas Maillard , Dana V. Rizk , Bruce A. Julian , Jan Novak , Matthew B. Renfrow","doi":"10.1016/j.ekir.2025.07.005","DOIUrl":"10.1016/j.ekir.2025.07.005","url":null,"abstract":"<div><h3>Introduction</h3><div>IgA1-containing immune complexes (IgA1-IC) consisting of galactose-deficient IgA1 (Gal-deficient IgA1) and IgG autoantibodies are central to the pathogenesis of IgA nephropathy (IgAN). These IgA1-IC form in circulation, and additional proteins may be added before the deposition in the glomeruli. However, the composition of these circulating IgA1-IC is not fully understood. To address this gap in knowledge, we developed a novel proteomic workflow.</div></div><div><h3>Methods</h3><div>IgA1-IC from sera of patients with IgAN and healthy controls (HCs) were isolated by lectin-affinity chromatography followed by size-exclusion chromatography (SEC). IgA1 yield and molecular integrity were assessed by enzyme-linked immunosorbent assay and sodium dodecyl sulfate–polyacrylamide gel electrophoresis. After proteolytic digestion, IgA1-IC samples were analyzed by using liquid chromatography-mass spectrometry (LC-MS). LC-MS results were analyzed by label-free quantification (LFQ) to identify proteins in IgA1-IC of patients with IgAN versus HCs versus proteomes of monomeric IgA1 (mIgA1) and polymeric IgA1 (pIgA1).</div></div><div><h3>Results</h3><div>We ascertained that 22 proteins were more abundant in the chromatographic fractions with IgA1-IC from patients with IgAN compared with similar fractions from HCs and other, uncomplexed IgA1 molecular forms. These proteins encompassed immunoglobulins, several complement proteins, including those with regulatory functions, and apolipoproteins. In addition, the identified proteins were validated by use of orthogonal serum preparation and analysis of previously published proteomics data.</div></div><div><h3>Conclusion</h3><div>Our new workflow better characterized the serum IgA1-IC of patients with IgAN by identifying proteins with elevated abundance in IgA1-IC in patients with IgAN, including complement components and apolipoproteins. Complement proteins identified in this study indicate that the alternative and lectin pathways are involved, but not the classical pathway.</div></div>","PeriodicalId":17761,"journal":{"name":"Kidney International Reports","volume":"10 10","pages":"Pages 3611-3623"},"PeriodicalIF":5.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145242378","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}