Pub Date : 2025-12-23DOI: 10.1016/j.kint.2025.12.011
Anastasia Paulmann,Matthew D Cox,Tom Boewer,Hannah M Somers,Heath Fuqua,Ryan P Seaman,Joel H Graber,Anchal Mahajan,Cory P Johnson,Laura L Beverly-Staggs,Sonia Sandhi,Heiko Schenk,Hermann Haller
INTRODUCTIONAging is associated with progressive loss of kidney function and vascular structure, with and without chronic kidney disease. However, the mechanisms driving kidney vascular aging and potential therapeutic interventions remain poorly understood.METHODSAfrican turquoise killifish (Nothobranchius furzeri), a naturally short-lived vertebrate, were used to investigate the natural course of kidney aging. We inhibited the sodium-glucose co-transporter 2 using dapagliflozin (SGLT2i) to test a potential therapeutic intervention. Histological, immunofluorescent, and 3D vascular imaging were used to evaluate glomerular, tubular, vascular and functional changes. Single nuclei transcriptomic profiling was performed on whole kidneys to identify age, sex and treatment-associated molecular signatures.RESULTSAged killifish kidneys exhibited hallmark features of kidney aging, including glomerulosclerosis, tubular atrophy, and vascular rarefaction. Functional changes included increased proteinuria and altered tubular transporter function. Transcriptomic profiling revealed a metabolic shift from oxidative phosphorylation to glycolysis and upregulation of pro-inflammatory pathways. Aged vasculature displayed a marked reduction in tight junctions and cell-cell contacts. SGLT2i attenuated age-related vascular rarefaction, preserved functional capillary networks, reduced albuminuria, preserved a youthful transcriptional profile and enhanced key intercellular signaling pathways.CONCLUSIONSOur study establishes the killifish as a translational model for investigating kidney vascular aging. SGLT2i preserves kidney microvascular structure and function, reduces proteinuria, and maintains a more youthful transcriptome. These results support a vascular-protective role of SGLT2i in mitigating age-related kidney deterioration.
{"title":"Sodium-glucose co-transporter 2 inhibition improves age-dependent kidney microvascular rarefaction.","authors":"Anastasia Paulmann,Matthew D Cox,Tom Boewer,Hannah M Somers,Heath Fuqua,Ryan P Seaman,Joel H Graber,Anchal Mahajan,Cory P Johnson,Laura L Beverly-Staggs,Sonia Sandhi,Heiko Schenk,Hermann Haller","doi":"10.1016/j.kint.2025.12.011","DOIUrl":"https://doi.org/10.1016/j.kint.2025.12.011","url":null,"abstract":"INTRODUCTIONAging is associated with progressive loss of kidney function and vascular structure, with and without chronic kidney disease. However, the mechanisms driving kidney vascular aging and potential therapeutic interventions remain poorly understood.METHODSAfrican turquoise killifish (Nothobranchius furzeri), a naturally short-lived vertebrate, were used to investigate the natural course of kidney aging. We inhibited the sodium-glucose co-transporter 2 using dapagliflozin (SGLT2i) to test a potential therapeutic intervention. Histological, immunofluorescent, and 3D vascular imaging were used to evaluate glomerular, tubular, vascular and functional changes. Single nuclei transcriptomic profiling was performed on whole kidneys to identify age, sex and treatment-associated molecular signatures.RESULTSAged killifish kidneys exhibited hallmark features of kidney aging, including glomerulosclerosis, tubular atrophy, and vascular rarefaction. Functional changes included increased proteinuria and altered tubular transporter function. Transcriptomic profiling revealed a metabolic shift from oxidative phosphorylation to glycolysis and upregulation of pro-inflammatory pathways. Aged vasculature displayed a marked reduction in tight junctions and cell-cell contacts. SGLT2i attenuated age-related vascular rarefaction, preserved functional capillary networks, reduced albuminuria, preserved a youthful transcriptional profile and enhanced key intercellular signaling pathways.CONCLUSIONSOur study establishes the killifish as a translational model for investigating kidney vascular aging. SGLT2i preserves kidney microvascular structure and function, reduces proteinuria, and maintains a more youthful transcriptome. These results support a vascular-protective role of SGLT2i in mitigating age-related kidney deterioration.","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"10 1","pages":""},"PeriodicalIF":19.6,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145830316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-22DOI: 10.1016/j.kint.2025.11.017
Sean J Barbour,Michelle A Hladunewich,Michael L McCaleb,Richard Robson,Terrance D Barrett,Lixuan Yin,Ashley Frazer-Abel,Jay P Garg,Richard Geary,Eugene Schneider,Gary T Brice
INTRODUCTIONActivation of the complement system and subsequent local inflammation in the kidney plays a key role in the pathogenesis of IgA nephropathy (IgAN). Here, we investigated the efficacy and safety of sefaxersen, an antisense oligonucleotide inhibitor of complement factor B (FB), for the treatment of IgAN in a global exploratory, single arm, open-label trial (NCT04014335).METHODSPatients were included with biopsy-confirmed IgAN with kidney C3 deposits, hematuria, 24-hour proteinuria above 1.5 g/day, and eGFR under 40mL/min/1.73m2 despite maximum tolerated renin-angiotensin-aldosterone-system blockade. Patients received sefaxersen 70 mg (RO7434656) subcutaneously monthly for 24 weeks followed by voluntary treatment extension. The primary endpoint was a change in 24-hour urinary protein excretion (UPE) at week 29 compared to baseline.RESULTSThe trial enrolled 23 patients with baseline geometric mean proteinuria of 2.5 g/day. There were selective reductions of plasma complement FB and Bb, urinary factor Ba and serum complement alternative pathway activity, without changes in classical pathway activity. At week 29, UPE was reduced by 43% to a geometric mean of 1.4 g/day, with similar reductions in UPCR and UACR. Estimated GFR at baseline was mean 70.4 ml/min/1.73m2, remained stable through week 29 (mean 73.2 ml/min/1.73m2). Proteinuria reduction was sustained in all seven participants who opted to participate in the treatment extension, including four patients treated for over 12 months. There was one treatment emergent serious adverse event not related to study drug. Transient and reversible alanine amino transferase elevations (3-5X fold upper limit normal) without a change in bilirubin were observed in three individuals, who remained on study and completed treatment.CONCLUSIONSSefaxersen inhibited complement alternative pathway activity in patients with IgAN and reduced proteinuria with stable eGFR. Our findings support further evaluation of sefaxersen as a new therapy for IgAN in the Phase 3 IMAGINATION trial.
{"title":"A single-arm phase 2 trial of an investigational RNA therapeutic to complement factor B sefaxersen for treatment of IgA nephropathy.","authors":"Sean J Barbour,Michelle A Hladunewich,Michael L McCaleb,Richard Robson,Terrance D Barrett,Lixuan Yin,Ashley Frazer-Abel,Jay P Garg,Richard Geary,Eugene Schneider,Gary T Brice","doi":"10.1016/j.kint.2025.11.017","DOIUrl":"https://doi.org/10.1016/j.kint.2025.11.017","url":null,"abstract":"INTRODUCTIONActivation of the complement system and subsequent local inflammation in the kidney plays a key role in the pathogenesis of IgA nephropathy (IgAN). Here, we investigated the efficacy and safety of sefaxersen, an antisense oligonucleotide inhibitor of complement factor B (FB), for the treatment of IgAN in a global exploratory, single arm, open-label trial (NCT04014335).METHODSPatients were included with biopsy-confirmed IgAN with kidney C3 deposits, hematuria, 24-hour proteinuria above 1.5 g/day, and eGFR under 40mL/min/1.73m2 despite maximum tolerated renin-angiotensin-aldosterone-system blockade. Patients received sefaxersen 70 mg (RO7434656) subcutaneously monthly for 24 weeks followed by voluntary treatment extension. The primary endpoint was a change in 24-hour urinary protein excretion (UPE) at week 29 compared to baseline.RESULTSThe trial enrolled 23 patients with baseline geometric mean proteinuria of 2.5 g/day. There were selective reductions of plasma complement FB and Bb, urinary factor Ba and serum complement alternative pathway activity, without changes in classical pathway activity. At week 29, UPE was reduced by 43% to a geometric mean of 1.4 g/day, with similar reductions in UPCR and UACR. Estimated GFR at baseline was mean 70.4 ml/min/1.73m2, remained stable through week 29 (mean 73.2 ml/min/1.73m2). Proteinuria reduction was sustained in all seven participants who opted to participate in the treatment extension, including four patients treated for over 12 months. There was one treatment emergent serious adverse event not related to study drug. Transient and reversible alanine amino transferase elevations (3-5X fold upper limit normal) without a change in bilirubin were observed in three individuals, who remained on study and completed treatment.CONCLUSIONSSefaxersen inhibited complement alternative pathway activity in patients with IgAN and reduced proteinuria with stable eGFR. Our findings support further evaluation of sefaxersen as a new therapy for IgAN in the Phase 3 IMAGINATION trial.","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"257 1","pages":""},"PeriodicalIF":19.6,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145823875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
INTRODUCTIONC3 glomerulopathy is a rare kidney disease resulting from dysregulation of the complement alternative pathway. The mechanistic diversity of alternative pathway activation, the heterogeneous immunological and clinical profiles limit a comprehensive understanding of the disease.METHODSHere, we characterize mechanisms of complement-mediated immune response within the kidney. We studied a retrospective cohort of 47 patients diagnosed with C3 glomerulopathy and profiled systemic and intra-kidney complement activation and characterized intra-kidney immune infiltrates.RESULTSThe immune infiltrate of the kidney showed distinct compositions between the glomerular and interstitial compartments, with most neutrophils and macrophages in the glomeruli versus a majority of B and T lymphocytes and macrophages in the interstitium. The presence of a neutrophil-rich glomerular infiltrate appeared to be associated with stronger markers of complement activation in both systemic and intra-kidney compartments. However, interstitial immune infiltrates were not associated with a specific complement activation profile. The presence of a neutrophil-rich glomerular infiltrate correlated with a better response of the kidney to treatment and kidney survival, while patients with higher interstitial infiltrate had poor kidney survival.CONCLUSIONOur study highlights a link between the intra-kidney immune response, complement activation profile, and the phenotypic expression of the disease, which contributes to improving our understanding of the disease.
{"title":"Complement activation drives a compartmentalized innate immune response in C3 glomerulopathy contributing to the disease phenotype.","authors":"Marie-Sophie Meuleman,Aurélien de Reyniès,Céline Mayinga,Stéphanie Ngo,Nathalie Rioux-Leclercq,Agathe Vermorel,Jérome Olagne,Diane Giovannini,Arnaud Francois,Anne Croué,Gaëtane Planchard,David Buob,Yahsou Delmas,Marie Courbebaisse,Béatrice Parfait,David Lebeaux,Gérard Friedlander,Marina Avramescu,Benoit Brilland,Hugoline Boulay,Manon Martins,Lubka Roumenina,Véronique Frémeaux-Bacchi,Jean-Paul Duong Van Huyen,Sophie Chauvet","doi":"10.1016/j.kint.2025.12.009","DOIUrl":"https://doi.org/10.1016/j.kint.2025.12.009","url":null,"abstract":"INTRODUCTIONC3 glomerulopathy is a rare kidney disease resulting from dysregulation of the complement alternative pathway. The mechanistic diversity of alternative pathway activation, the heterogeneous immunological and clinical profiles limit a comprehensive understanding of the disease.METHODSHere, we characterize mechanisms of complement-mediated immune response within the kidney. We studied a retrospective cohort of 47 patients diagnosed with C3 glomerulopathy and profiled systemic and intra-kidney complement activation and characterized intra-kidney immune infiltrates.RESULTSThe immune infiltrate of the kidney showed distinct compositions between the glomerular and interstitial compartments, with most neutrophils and macrophages in the glomeruli versus a majority of B and T lymphocytes and macrophages in the interstitium. The presence of a neutrophil-rich glomerular infiltrate appeared to be associated with stronger markers of complement activation in both systemic and intra-kidney compartments. However, interstitial immune infiltrates were not associated with a specific complement activation profile. The presence of a neutrophil-rich glomerular infiltrate correlated with a better response of the kidney to treatment and kidney survival, while patients with higher interstitial infiltrate had poor kidney survival.CONCLUSIONOur study highlights a link between the intra-kidney immune response, complement activation profile, and the phenotypic expression of the disease, which contributes to improving our understanding of the disease.","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"25 1","pages":""},"PeriodicalIF":19.6,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145823906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
INTRODUCTIONRNA modifications regulate the progression of inflammatory diseases. However, the role of N7-methylguanosine (m7G) modification and its regulatory enzyme, methyltransferase-like 1 (METTL1), in inflammatory kidney diseases remains poorly understood. Here, we aimed to investigate the function and underlying mechanisms of METTL1-mediated m7G modification in acute kidney injury (AKI).METHODSKidney tubular epithelial cell (TEC)-specific METTL1 conditional knockout mice were used to evaluate the functional role of METTL1 in multiple AKI mouse models (cisplatin, ischemia/reperfusion and cecal ligation/puncture). Additionally, kidney tissue was obtained from patients with AKI and from the non-tumor kidney tissue of patients with nephrectomy for kidney cancer. RNA sequencing and m7G-methylated RNA immunoprecipitation sequencing were performed to identify downstream targets and elucidate underlying mechanisms.RESULTSBoth m7G modification and METTL1 expression were markedly upregulated in TECs from patients and mice with AKI. TEC-specific deletion of METTL1 significantly attenuated kidney injury and inflammation in the multiple AKI mouse models. Mechanistically, METTL1-mediated m7G modification enhanced the stability of the TEA domain transcription factor 2 (TEAD2) mRNA by the binding protein Quaking. Elevated TEAD2 impaired mitochondrial function by transcriptionally repressing medium-chain acyl-CoA dehydrogenase (ACADM), thereby amplifying proinflammatory responses. METTL1 knockdown mediated by tetrahedral framework DNA nanostructures, as well as pharmacological inhibition with AZD1080, a novel METTL1 inhibitor, effectively alleviated the severity of AKI in mice in prevention and therapeutic approaches.CONCLUSIONSOur findings suggest that targeting the METTL1/TEAD2/ACADM axis may represent a potential therapeutic strategy for inflammatory kidney diseases.
{"title":"The m7G methyltransferase METTL1 promotes acute kidney inflammation by disrupting mitochondrial function.","authors":"Shuai-Shuai Xie,Yu-Hang Dong,Jian Gao,Wei Li,Long Xu,Jia-Nan Wang,Ju-Tao Yu,Chao Hou,Chao Li,Ying-Ying Gao,Ze-Hui Dong,Wen-Xian Ma,Rui Hou,Shuai Sun,Ming-Lu Ji,Ruo-Bing He,Xiao-Guo Suo,Wei-Jian Ni,Jia-Gen Wen,Juan Jin,Qin Yang,Hong Cai,Xiao-Ming Meng","doi":"10.1016/j.kint.2025.11.010","DOIUrl":"https://doi.org/10.1016/j.kint.2025.11.010","url":null,"abstract":"INTRODUCTIONRNA modifications regulate the progression of inflammatory diseases. However, the role of N7-methylguanosine (m7G) modification and its regulatory enzyme, methyltransferase-like 1 (METTL1), in inflammatory kidney diseases remains poorly understood. Here, we aimed to investigate the function and underlying mechanisms of METTL1-mediated m7G modification in acute kidney injury (AKI).METHODSKidney tubular epithelial cell (TEC)-specific METTL1 conditional knockout mice were used to evaluate the functional role of METTL1 in multiple AKI mouse models (cisplatin, ischemia/reperfusion and cecal ligation/puncture). Additionally, kidney tissue was obtained from patients with AKI and from the non-tumor kidney tissue of patients with nephrectomy for kidney cancer. RNA sequencing and m7G-methylated RNA immunoprecipitation sequencing were performed to identify downstream targets and elucidate underlying mechanisms.RESULTSBoth m7G modification and METTL1 expression were markedly upregulated in TECs from patients and mice with AKI. TEC-specific deletion of METTL1 significantly attenuated kidney injury and inflammation in the multiple AKI mouse models. Mechanistically, METTL1-mediated m7G modification enhanced the stability of the TEA domain transcription factor 2 (TEAD2) mRNA by the binding protein Quaking. Elevated TEAD2 impaired mitochondrial function by transcriptionally repressing medium-chain acyl-CoA dehydrogenase (ACADM), thereby amplifying proinflammatory responses. METTL1 knockdown mediated by tetrahedral framework DNA nanostructures, as well as pharmacological inhibition with AZD1080, a novel METTL1 inhibitor, effectively alleviated the severity of AKI in mice in prevention and therapeutic approaches.CONCLUSIONSOur findings suggest that targeting the METTL1/TEAD2/ACADM axis may represent a potential therapeutic strategy for inflammatory kidney diseases.","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"37 1","pages":""},"PeriodicalIF":19.6,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145771441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-15DOI: 10.1016/j.kint.2025.12.004
Alice Shasha Cheng,Linda Xiaoyan Li,Julie Xia Zhou,Peter C Harris,James P Calvet,Xiaogang Li
INTRODUCTIONAutosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common inherited kidney disease with no effective therapy to halt its progression. ALDH1A1, one of the aldehyde dehydrogenases, is the main ALDH1 isozyme known to oxidize 9-cis retinaldehyde into 9-cis retinoic acid, which can regulate the expression of the PKD1 gene. However, the role and mechanisms of ALDH1A1 in ADPKD remains elusive.METHODSTo investigate this, Aldh1A1 was knocked out and ALDH1A1 inhibited with disulfiram (DSF) either alone or together with PD-L1 antibody in Pkd1 mutant mice. The effect of ALDH1A1 on cyst growth, immune response and PKD associated signaling pathways as well as the target genes of ALDH1A1 was determined by immunostaining, Western blot, qRT-PCR, flow cytometry, CUT-Tag analysis, and CHIP assay.RESULTSALDH1A1 was upregulated in ADPKD kidneys, leading to an activation of PKD associated signaling pathways, including AKT, S6, STAT3 and Rb. This was possibly mediated by AURKA, to increase cystic kidney epithelial cell proliferation. Knockout of Aldh1A1 delayed cyst growth in Pkd1 mutant kidneys. ALDH1A1 functions as a transcription factor to target diverse genes as examined by CUT-Tag analysis. Elevated ALDH1A1 regulated the transcription of Pd-l1 and Ccl2 to affect PD-L1 mediated immune surveillance and recruitment of macrophages, respectively. Inhibiting ALDH1A1 with DSF decreased cyst growth in aggressive (Pkd1nl/nl) and mild (Pkd1RC/RC) Pkd1 mouse models. Additionally, targeting ALDH1A1 in combination with PD-L1 antibody had a synergistic effect on delaying cyst growth in Pkd1 mutant mouse kidneys.CONCLUSIONSOur study suggests that DSF is a promising agent for ADPKD treatment and highlights novel therapeutic strategies by the combination of chemotherapy with immunotherapy in ADPKD treatment.
{"title":"Aldehyde dehydrogenase 1 A1 regulates the transcription of PD-L1 and its targeting with disulfiram together with PD-L1 immunotherapy synergistically delays cyst growth in ADPKD.","authors":"Alice Shasha Cheng,Linda Xiaoyan Li,Julie Xia Zhou,Peter C Harris,James P Calvet,Xiaogang Li","doi":"10.1016/j.kint.2025.12.004","DOIUrl":"https://doi.org/10.1016/j.kint.2025.12.004","url":null,"abstract":"INTRODUCTIONAutosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common inherited kidney disease with no effective therapy to halt its progression. ALDH1A1, one of the aldehyde dehydrogenases, is the main ALDH1 isozyme known to oxidize 9-cis retinaldehyde into 9-cis retinoic acid, which can regulate the expression of the PKD1 gene. However, the role and mechanisms of ALDH1A1 in ADPKD remains elusive.METHODSTo investigate this, Aldh1A1 was knocked out and ALDH1A1 inhibited with disulfiram (DSF) either alone or together with PD-L1 antibody in Pkd1 mutant mice. The effect of ALDH1A1 on cyst growth, immune response and PKD associated signaling pathways as well as the target genes of ALDH1A1 was determined by immunostaining, Western blot, qRT-PCR, flow cytometry, CUT-Tag analysis, and CHIP assay.RESULTSALDH1A1 was upregulated in ADPKD kidneys, leading to an activation of PKD associated signaling pathways, including AKT, S6, STAT3 and Rb. This was possibly mediated by AURKA, to increase cystic kidney epithelial cell proliferation. Knockout of Aldh1A1 delayed cyst growth in Pkd1 mutant kidneys. ALDH1A1 functions as a transcription factor to target diverse genes as examined by CUT-Tag analysis. Elevated ALDH1A1 regulated the transcription of Pd-l1 and Ccl2 to affect PD-L1 mediated immune surveillance and recruitment of macrophages, respectively. Inhibiting ALDH1A1 with DSF decreased cyst growth in aggressive (Pkd1nl/nl) and mild (Pkd1RC/RC) Pkd1 mouse models. Additionally, targeting ALDH1A1 in combination with PD-L1 antibody had a synergistic effect on delaying cyst growth in Pkd1 mutant mouse kidneys.CONCLUSIONSOur study suggests that DSF is a promising agent for ADPKD treatment and highlights novel therapeutic strategies by the combination of chemotherapy with immunotherapy in ADPKD treatment.","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"23 1","pages":""},"PeriodicalIF":19.6,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145771442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-08DOI: 10.1016/j.kint.2025.11.005
Tilman B. Drueke, Krzysztof Kiryluk, Robert Unwin
{"title":"Contribution of Genetic Variants to Nephrolithiasis","authors":"Tilman B. Drueke, Krzysztof Kiryluk, Robert Unwin","doi":"10.1016/j.kint.2025.11.005","DOIUrl":"https://doi.org/10.1016/j.kint.2025.11.005","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"10 1","pages":""},"PeriodicalIF":19.6,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145731931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-06DOI: 10.1016/j.kint.2025.10.013
Olivia Lenoir, Pierre-Louis Tharaux
{"title":"When YAP is hyperactivated in podocytes, it persistently 'yaps', disrupting the quiescence of neighbouring glomerular cells.","authors":"Olivia Lenoir, Pierre-Louis Tharaux","doi":"10.1016/j.kint.2025.10.013","DOIUrl":"https://doi.org/10.1016/j.kint.2025.10.013","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"2 1","pages":""},"PeriodicalIF":19.6,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145689182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-06DOI: 10.1016/j.kint.2025.10.014
Divya Bhatia, Mary E. Choi
{"title":"Small but mighty: Hypoxia-responsive tRNA-derived small RNA as a novel regulator of RNA autophagy and kidney protection","authors":"Divya Bhatia, Mary E. Choi","doi":"10.1016/j.kint.2025.10.014","DOIUrl":"https://doi.org/10.1016/j.kint.2025.10.014","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"20 1","pages":""},"PeriodicalIF":19.6,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145689538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-25DOI: 10.1016/j.kint.2025.09.035
Anastasia Hughes , Andrea Matus Gonzalez , Anita van Zwieten , Chandana Guha , Simon Carter , Dale Coghlan , Amanda Dominello , Javier Recabarren Silva , Jonathan C. Craig , Martin Howell , Siah Kim , Karine Manera , Colm O’Reilly , Angela Rejuso , Benedicte Sautenet , Nicole Scholes-Robertson , Amanda Sluiter , Rebecca Wu , Germaine Wong , Mignon McCulloch , Yvonne Farquharson
Life participation is of critical importance to children and adolescents with chronic kidney disease (CKD), their caregivers, and health professionals. However, life participation is assessed and reported inconsistently and uncommonly in trials involving children with CKD. The consensus workshops aimed to describe the perspectives of patients, caregivers, and health professionals on developing a core outcome measure for life participation in children with CKD. Four consensus workshops (1 in-person [English language], 3 online [2 English language and 1 Spanish language]) were held to discuss the relevance of content, appropriateness, and feasibility of a proposed patient-reported core outcome measure. Transcripts were analyzed thematically. A total of 171 participants, including 79 patients and caregivers and 92 health professionals, from 16 countries attended. Four themes were identified. Allowing individual interpretation and valuation of life participation included encapsulating key domains of life participation, recognizing varying degrees of achieving participation in different domains, reflecting personal context and values, emphasizing meaningful participation in activities, acknowledging changes over time, and attributing responses to the intervention. Respecting developmental needs entailed developing age-specific measures, considering literacy, using relevant and clear language, using engaging formats, and establishing an appropriate recall period. Capturing broad perspectives included ensuring universal applicability across settings and allowing for proxy completion. Establishing widespread implementation by reducing the completion burden, validating for all stages and diagnoses of CKD, and enabling comparisons across CKD stages were suggested. A core outcome measure for life participation in children with CKD should be widely applicable and developmentally appropriate, allow patients to interpret life participation in their own context, and be psychometrically robust and feasible to implement. The proposed measure will be revised and validated to be included in all clinical trials in children with CKD. Measuring life participation in a consistent and meaningful way across trials can better support patient-centered decision-making, disease management, and outcomes in children with CKD.
{"title":"Establishing a core outcome measure for life participation in children with chronic kidney disease: a Standardized Outcomes in Nephrology—children and adolescents with chronic kidney disease (SONG-Kids) consensus workshop report","authors":"Anastasia Hughes , Andrea Matus Gonzalez , Anita van Zwieten , Chandana Guha , Simon Carter , Dale Coghlan , Amanda Dominello , Javier Recabarren Silva , Jonathan C. Craig , Martin Howell , Siah Kim , Karine Manera , Colm O’Reilly , Angela Rejuso , Benedicte Sautenet , Nicole Scholes-Robertson , Amanda Sluiter , Rebecca Wu , Germaine Wong , Mignon McCulloch , Yvonne Farquharson","doi":"10.1016/j.kint.2025.09.035","DOIUrl":"10.1016/j.kint.2025.09.035","url":null,"abstract":"<div><div>Life participation is of critical importance to children and adolescents with chronic kidney disease (CKD), their caregivers, and health professionals. However, life participation is assessed and reported inconsistently and uncommonly in trials involving children with CKD. The consensus workshops aimed to describe the perspectives of patients, caregivers, and health professionals on developing a core outcome measure for life participation in children with CKD. Four consensus workshops (1 in-person [English language], 3 online [2 English language and 1 Spanish language]) were held to discuss the relevance of content, appropriateness, and feasibility of a proposed patient-reported core outcome measure. Transcripts were analyzed thematically. A total of 171 participants, including 79 patients and caregivers and 92 health professionals, from 16 countries attended. Four themes were identified. <em>Allowing individual interpretation and valuation of life participation</em> included encapsulating key domains of life participation, recognizing varying degrees of achieving participation in different domains, reflecting personal context and values, emphasizing meaningful participation in activities, acknowledging changes over time, and attributing responses to the intervention. <em>Respecting developmental needs</em> entailed developing age-specific measures, considering literacy, using relevant and clear language, using engaging formats, and establishing an appropriate recall period. <em>Capturing broad perspectives</em> included ensuring universal applicability across settings and allowing for proxy completion. <em>Establishing widespread implementation</em> by reducing the completion burden, validating for all stages and diagnoses of CKD, and enabling comparisons across CKD stages were suggested. A core outcome measure for life participation in children with CKD should be widely applicable and developmentally appropriate, allow patients to interpret life participation in their own context, and be psychometrically robust and feasible to implement. The proposed measure will be revised and validated to be included in all clinical trials in children with CKD. Measuring life participation in a consistent and meaningful way across trials can better support patient-centered decision-making, disease management, and outcomes in children with CKD.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"109 2","pages":"Pages 273-282"},"PeriodicalIF":12.6,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145592840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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