Pub Date : 2026-01-01Epub Date: 2025-09-05DOI: 10.1681/ASN.0000000846
Bo Liang, Fu-Rong Li, Liang Liu, Jing-Hong Zhao
{"title":"Novel Biomarkers in CKD.","authors":"Bo Liang, Fu-Rong Li, Liang Liu, Jing-Hong Zhao","doi":"10.1681/ASN.0000000846","DOIUrl":"10.1681/ASN.0000000846","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"214"},"PeriodicalIF":9.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12807131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-12-01DOI: 10.1681/ASN.0000000965
Ian Michael Rogers, Anupama Bhadwal
{"title":"Toward the Clinical Translation of Adipose-Derived Mesenchymal Stem Cells: Small Molecule Regulation of Thrombomodulin Enhances Therapeutic Efficacy.","authors":"Ian Michael Rogers, Anupama Bhadwal","doi":"10.1681/ASN.0000000965","DOIUrl":"10.1681/ASN.0000000965","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"37 1","pages":"6-8"},"PeriodicalIF":9.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12807175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146010941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-06-13DOI: 10.1681/ASN.0000000791
Stephen Richard Ash
{"title":"The Quest for a Urea Sorbent: From Frustration, to Failure, to the KidneyX Prize.","authors":"Stephen Richard Ash","doi":"10.1681/ASN.0000000791","DOIUrl":"10.1681/ASN.0000000791","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"180-182"},"PeriodicalIF":9.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12807146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144289483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-12-01DOI: 10.1681/ASN.0000000952
Kerri L Cavanaugh, Devika Nair
{"title":"Recognizing Impact of SGLT2 Inhibitor Therapy on Quality of Life for Patients Living with CKD.","authors":"Kerri L Cavanaugh, Devika Nair","doi":"10.1681/ASN.0000000952","DOIUrl":"10.1681/ASN.0000000952","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"37 1","pages":"9-11"},"PeriodicalIF":9.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12807148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146010946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-11-25DOI: 10.1681/ASN.0000000944
Nina Visočnik, Andreas Kronbichler
{"title":"Molecular Signatures as Guide to Kidney Prognosis in ANCA-Associated Vasculitis.","authors":"Nina Visočnik, Andreas Kronbichler","doi":"10.1681/ASN.0000000944","DOIUrl":"10.1681/ASN.0000000944","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"37 1","pages":"12-14"},"PeriodicalIF":9.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12807132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146010962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUNDRenal lipid dysmetabolism contributes to glomerular disease progression, including Alport Syndrome. We recently identified alterations in the apolipoprotein M/sphingosine-1-phosphate/sphingosine-1-phosphate receptor 4 signaling axis in glomeruli from patients with glomerular disease.METHODSWe utilized Col4a3 knockout mice and immortalized podocytes derived from these mice as a mouse model of Alport Syndrome. Mice and podocytes were treated with recombinant apolipoprotein M or the sphingosine-1-phosphate receptor 4 specific antagonist, CYM50358.RESULTSCol4a3-/- glomeruli and podocytes exhibited reduced apolipoprotein M and increased sphingosine-1-phosphate receptor 4 expression and increased sphingosoine-1-phosphate levels, mirroring findings in patients with glomerular disease. Treatment with apolipoprotein M or CYM50358 reduced albuminuria, BUN, and plasma creatinine, and ameliorated glomerulosclerosis, tubulointerstitial fibrosis, podocyte loss and foot process effacement. Both treatments reduced triglyceride and cholesterol accumulation in glomeruli and podocytes. RNA-seq analysis of Col4a3-/- revealed that sphingosine-1-phosphate receptor 4 antagonism upregulated lysosomal and autophagy-related genes. Western blot analysis confirmed increased LC3-II/LC3-I ratios and decreased p62, indicating enhanced autophagic flux. Treated podocytes showed increased lysosome numbers and co-localization with lipid droplets. In contrast, apolipoprotein M had no effect on autophagy but promoted cholesterol efflux. Furthermore, knockdown of APOM or overexpression of S1PR4 was sufficient to cause podocyte cell death.CONCLUSIONSWe found that the apolipoprotein M/sphingosine-1-phosphate axis was dysregulated in Col4a3-/- podocytes. Targeting this pathway through apolipoprotein M supplementation or sphingosine-1-phosphate receptor 4 antagonism improved kidney function and reduced lipid accumulation by enhancing either cholesterol efflux or autophagy, respectively.
{"title":"Modulation of the APOM/S1PR4 Pathway Reduces Podocyte Lipid Overload in Alport Syndrome via Distinct Autophagy and Efflux Mechanisms.","authors":"Matthew Tolerico,Arianna Insenga,Judith Molina,Arianna Carrazco,Rachel Njeim,Alexis Sloan,Anthony Griswold,Makoto Kurano,Armando Mendez,Robin Nathans,Robin Bolek,Sandrine Ettou,Stephen Berasi,Alessia Fornoni,Sandra Merscher","doi":"10.1681/asn.0000000996","DOIUrl":"https://doi.org/10.1681/asn.0000000996","url":null,"abstract":"BACKGROUNDRenal lipid dysmetabolism contributes to glomerular disease progression, including Alport Syndrome. We recently identified alterations in the apolipoprotein M/sphingosine-1-phosphate/sphingosine-1-phosphate receptor 4 signaling axis in glomeruli from patients with glomerular disease.METHODSWe utilized Col4a3 knockout mice and immortalized podocytes derived from these mice as a mouse model of Alport Syndrome. Mice and podocytes were treated with recombinant apolipoprotein M or the sphingosine-1-phosphate receptor 4 specific antagonist, CYM50358.RESULTSCol4a3-/- glomeruli and podocytes exhibited reduced apolipoprotein M and increased sphingosine-1-phosphate receptor 4 expression and increased sphingosoine-1-phosphate levels, mirroring findings in patients with glomerular disease. Treatment with apolipoprotein M or CYM50358 reduced albuminuria, BUN, and plasma creatinine, and ameliorated glomerulosclerosis, tubulointerstitial fibrosis, podocyte loss and foot process effacement. Both treatments reduced triglyceride and cholesterol accumulation in glomeruli and podocytes. RNA-seq analysis of Col4a3-/- revealed that sphingosine-1-phosphate receptor 4 antagonism upregulated lysosomal and autophagy-related genes. Western blot analysis confirmed increased LC3-II/LC3-I ratios and decreased p62, indicating enhanced autophagic flux. Treated podocytes showed increased lysosome numbers and co-localization with lipid droplets. In contrast, apolipoprotein M had no effect on autophagy but promoted cholesterol efflux. Furthermore, knockdown of APOM or overexpression of S1PR4 was sufficient to cause podocyte cell death.CONCLUSIONSWe found that the apolipoprotein M/sphingosine-1-phosphate axis was dysregulated in Col4a3-/- podocytes. Targeting this pathway through apolipoprotein M supplementation or sphingosine-1-phosphate receptor 4 antagonism improved kidney function and reduced lipid accumulation by enhancing either cholesterol efflux or autophagy, respectively.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"30 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005158","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}
Kylie Heitman,Qing Li,Abul Fajol,Matthew Denniff,Dungeng Peng,S Madison Thomas,Brian Czaya,Christopher Yanucil,David Westbrook,Syed Wasiuddin,Glenn C Rowe,Abolfazl Zarjou,Orlando M Gutierrez,Kenneth E White,Jorge L Gamboa,Emma L Watson,Matthew S Alexander,Christian Faul
BACKGROUNDFibroblast growth factor 23 (FGF23) is a hormone that reduces the renal reabsorption of phosphate in response to systemic phosphate elevations. In chronic kidney disease (CKD), serum levels of phosphate and FGF23 reach levels that can harm various tissues. While the bone acts as the main production site for FGF23, bone-specific gene deletion studies in mice suggest the existence of other FGF23 sources. Here, we determine if skeletal muscle produces FGF23 in response to phosphate elevations.METHODSWe studied four mouse models with phosphate elevations, two with CKD (global Col4a3 deletion and adenine-rich diet) and two without CKD (genetic klotho deficiency and high-phosphate diet). Furthermore, we generated a new mouse line with skeletal muscle-specific Fgf23 deletion (KO), which received an adenine-rich or high-phosphate diet. We measured skeletal muscle FGF23 by qRT-PCR, ELISA, and immunohistochemistry as well as serum levels of phosphate, FGF23, and parathyroid hormone (PTH). We determined FGF23 mRNA levels in muscle biopsies from CKD patients, and we studied the effects of phosphate and PTH elevations on FGF23 expression in cultured myotubes isolated from mice and CKD patients. Finally, we studied the effects of acute phosphate loading on urine phosphate levels in Fgf23 KO mice.RESULTSAll four mouse models with phosphate and PTH elevations showed FGF23 expression in skeletal muscle tissue on mRNA and protein level. Phosphate, but not PTH, induced FGF23 expression in cultured myotubes. Furthermore, CKD patients with higher serum phosphate levels expressed more FGF23 in skeletal muscle. Fgf23 KO mice had elevated serum phosphate levels when administered a high-phosphate diet and decreased urine phosphate levels following acute phosphate loading.CONCLUSIONSPhosphate elevations induced FGF23 expression in skeletal muscle, independent of the absence or presence of CKD. Skeletal muscle-derived FGF23 reduced renal phosphate reabsorption.
{"title":"Systemic Phosphate Elevations Induce FGF23 Production in Skeletal Muscle to Reduce Renal Phosphate Reabsorption in Mice.","authors":"Kylie Heitman,Qing Li,Abul Fajol,Matthew Denniff,Dungeng Peng,S Madison Thomas,Brian Czaya,Christopher Yanucil,David Westbrook,Syed Wasiuddin,Glenn C Rowe,Abolfazl Zarjou,Orlando M Gutierrez,Kenneth E White,Jorge L Gamboa,Emma L Watson,Matthew S Alexander,Christian Faul","doi":"10.1681/asn.0000000963","DOIUrl":"https://doi.org/10.1681/asn.0000000963","url":null,"abstract":"BACKGROUNDFibroblast growth factor 23 (FGF23) is a hormone that reduces the renal reabsorption of phosphate in response to systemic phosphate elevations. In chronic kidney disease (CKD), serum levels of phosphate and FGF23 reach levels that can harm various tissues. While the bone acts as the main production site for FGF23, bone-specific gene deletion studies in mice suggest the existence of other FGF23 sources. Here, we determine if skeletal muscle produces FGF23 in response to phosphate elevations.METHODSWe studied four mouse models with phosphate elevations, two with CKD (global Col4a3 deletion and adenine-rich diet) and two without CKD (genetic klotho deficiency and high-phosphate diet). Furthermore, we generated a new mouse line with skeletal muscle-specific Fgf23 deletion (KO), which received an adenine-rich or high-phosphate diet. We measured skeletal muscle FGF23 by qRT-PCR, ELISA, and immunohistochemistry as well as serum levels of phosphate, FGF23, and parathyroid hormone (PTH). We determined FGF23 mRNA levels in muscle biopsies from CKD patients, and we studied the effects of phosphate and PTH elevations on FGF23 expression in cultured myotubes isolated from mice and CKD patients. Finally, we studied the effects of acute phosphate loading on urine phosphate levels in Fgf23 KO mice.RESULTSAll four mouse models with phosphate and PTH elevations showed FGF23 expression in skeletal muscle tissue on mRNA and protein level. Phosphate, but not PTH, induced FGF23 expression in cultured myotubes. Furthermore, CKD patients with higher serum phosphate levels expressed more FGF23 in skeletal muscle. Fgf23 KO mice had elevated serum phosphate levels when administered a high-phosphate diet and decreased urine phosphate levels following acute phosphate loading.CONCLUSIONSPhosphate elevations induced FGF23 expression in skeletal muscle, independent of the absence or presence of CKD. Skeletal muscle-derived FGF23 reduced renal phosphate reabsorption.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"39 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005087","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}
{"title":"Probing Molecular Mechanisms of Proximal Tubular Resilience and Repair.","authors":"Sanjeev Kumar","doi":"10.1681/asn.0000000994","DOIUrl":"https://doi.org/10.1681/asn.0000000994","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"5 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005085","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}
{"title":"Fungal DNA in Circulation: A Sleuth's Clue to Predict Cardiovascular Risk for Hemodialysis Patients.","authors":"Nishank Jain,Parth Dhamelia,John M Arthur","doi":"10.1681/asn.0000000993","DOIUrl":"https://doi.org/10.1681/asn.0000000993","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"10 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005088","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}
BACKGROUNDKidney fibrosis is the final common pathway of chronic kidney diseases. Proximal tubular epithelial cells (PTECs) arrested in G2/M phase of the cell cycle play a pivotal role in kidney fibrosis. Phosphofurin acidic cluster sorting protein 2 (PACS-2) is a multifunctional protein involved in various cellular activities including cell cycle regulation, yet its role in kidney fibrosis remains unclear.METHODSPTEC-specific Pacs-2 knockout mice were generated by utilizing LoxP-Cre recombination system and subjected to unilateral ureteral obstruction (UUO) and aristolochic acid to induce kidney fibrosis. Cultured human and mouse tubular epithelial cells were treated with TGF-β1 to analyze the underlying cellular mechanisms. Co-immunoprecipitation coupled with mass spectrometry (CO-IP/MS), molecular cloning and genetic manipulation were used to investigate PACS-2 interactions and specific binding domains.RESULTSPACS-2 expression was significantly lower in the cortex of fibrotic kidney from UUO mouse. PACS-2 deficiency in PTECs exacerbated G2/M cell cycle arrest and kidney fibrosis in murine UUO and aristolochic acid nephropathy models, two independent models for CKD. In vitro, overexpression of PACS-2 alleviated TGF-β1-induced fibrogenic responses in PTECs through inhibiting cell cycle arrest at G2/M phase. By CO-IP/MS, we identified cyclin-dependent kinase-like 1 (CDKL1) as the key molecule linking PACS-2 to cell cycle progression in PTECs. Knockdown of CDKL1 partially reversed the anti-fibrotic effects of PACS-2 by promoting G2/M cell cycle arrest in TGF-β1-stimulated HK-2 cells. Mechanistically, we demonstrated that PACS-2 interacted with kinase domain of CDKL1 and modulated its kinase activity, thereby regulating cell cycle, rather than affecting its subcellular translocation or protein expression.CONCLUSIONSOur study demonstrates that renal tubular PACS-2 alleviated G2/M cell cycle arrest and kidney fibrosis by interacting with CDKL1 and modulating its kinase activity.
{"title":"PACS-2 Alleviates Kidney Fibrosis by Inhibiting Tubular Epithelial Cell G2/M Arrest through CDKL1 Kinase.","authors":"Chenrui Li,Yan Liu,Hao Zhao,Yiyun Xi,Chongbin Liu,Shilu Luo,Na Jiang,Ming Yang,Yachun Han,Wei Chen,Li Li,Lin Sun","doi":"10.1681/asn.0000000953","DOIUrl":"https://doi.org/10.1681/asn.0000000953","url":null,"abstract":"BACKGROUNDKidney fibrosis is the final common pathway of chronic kidney diseases. Proximal tubular epithelial cells (PTECs) arrested in G2/M phase of the cell cycle play a pivotal role in kidney fibrosis. Phosphofurin acidic cluster sorting protein 2 (PACS-2) is a multifunctional protein involved in various cellular activities including cell cycle regulation, yet its role in kidney fibrosis remains unclear.METHODSPTEC-specific Pacs-2 knockout mice were generated by utilizing LoxP-Cre recombination system and subjected to unilateral ureteral obstruction (UUO) and aristolochic acid to induce kidney fibrosis. Cultured human and mouse tubular epithelial cells were treated with TGF-β1 to analyze the underlying cellular mechanisms. Co-immunoprecipitation coupled with mass spectrometry (CO-IP/MS), molecular cloning and genetic manipulation were used to investigate PACS-2 interactions and specific binding domains.RESULTSPACS-2 expression was significantly lower in the cortex of fibrotic kidney from UUO mouse. PACS-2 deficiency in PTECs exacerbated G2/M cell cycle arrest and kidney fibrosis in murine UUO and aristolochic acid nephropathy models, two independent models for CKD. In vitro, overexpression of PACS-2 alleviated TGF-β1-induced fibrogenic responses in PTECs through inhibiting cell cycle arrest at G2/M phase. By CO-IP/MS, we identified cyclin-dependent kinase-like 1 (CDKL1) as the key molecule linking PACS-2 to cell cycle progression in PTECs. Knockdown of CDKL1 partially reversed the anti-fibrotic effects of PACS-2 by promoting G2/M cell cycle arrest in TGF-β1-stimulated HK-2 cells. Mechanistically, we demonstrated that PACS-2 interacted with kinase domain of CDKL1 and modulated its kinase activity, thereby regulating cell cycle, rather than affecting its subcellular translocation or protein expression.CONCLUSIONSOur study demonstrates that renal tubular PACS-2 alleviated G2/M cell cycle arrest and kidney fibrosis by interacting with CDKL1 and modulating its kinase activity.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"63 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005090","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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