{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:47:10Z","timestamp":1790362030679,"version":"4.1.0"},"reference-count":115,"publisher":"Portland Press Ltd.","issue":"7","funder":[{"DOI":"10.13039\/501100001691","name":"Grants-in-Aid for Scientific Research","doi-asserted-by":"crossref","award":["24K14775 25K03027"],"award-info":[{"award-number":["24K14775 25K03027"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Acute kidney injury (AKI) and chronic kidney disease (CKD) are the two primary forms of kidney disease that significantly contribute to increased mortality and progression to end-stage renal disease. To effectively treat AKI and CKD, elucidating the detailed mechanisms underlying their onset and progression is essential for the development of novel therapeutic strategies. Impaired cellular function resulting from the altered metabolism of energy-producing nutrients, such as fatty acids, glucose, and amino acids, is closely involved in the pathogenesis of both AKI and CKD. Among these nutrients, branched-chain amino acids (BCAAs), such as leucine, isoleucine, and valine, are essential amino acids in humans and animals because they cannot be synthesized de novo. BCAAs play a crucial role in protein synthesis and energy production in various metabolic tissues, including skeletal muscle, liver, brown adipose tissue, pancreas, heart, and the kidney. Maintaining an appropriate balance between BCAA catabolism and anabolism is vital for optimal cellular function. Alterations in BCAA homeostasis have emerged as key contributors to the pathophysiology of several metabolic disorders, including obesity-related insulin resistance, type 2 diabetes, heart failure, kidney disease, and sarcopenia. In the present review, we provide a comprehensive overview of BCAA metabolism, with a particular focus on the molecular mechanisms linking disrupted BCAA homeostasis in proximal tubular cells to kidney disease. We also discuss the potential of targeting BCAA metabolism as a novel therapeutic strategy to suppress kidney disease progression.<\/jats:p>","DOI":"10.1042\/cs20260961","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T11:25:09Z","timestamp":1782300309000},"page":"1455-1471","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Impact of impaired branched-chain amino acid metabolism on kidney disease"],"prefix":"10.1042","volume":"140","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0199-1650","authenticated-orcid":false,"given":"Munehiro","family":"Kitada","sequence":"first","affiliation":[{"name":"1Hamada Medical Clinic, Higashi Takamatsu, Wakayama 641-0052, Japan"},{"name":"3Department of Nephrology, Wakayama Medical University, Kimiidera, Wakayama 641-8509, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sho","family":"Sugahara","sequence":"additional","affiliation":[{"name":"2Department of Diabetes, Endocrinology and Nephrology, Shiga University of Medical Science, Seta-Tsukinowa cho, Otsu, Shiga 520-2192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mako","family":"Yasuda-Yamahara","sequence":"additional","affiliation":[{"name":"2Department of Diabetes, Endocrinology and Nephrology, Shiga University of Medical Science, Seta-Tsukinowa cho, Otsu, Shiga 520-2192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Kume","sequence":"additional","affiliation":[{"name":"2Department of Diabetes, Endocrinology and Nephrology, Shiga University of Medical Science, Seta-Tsukinowa cho, Otsu, Shiga 520-2192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-ichi","family":"Araki","sequence":"additional","affiliation":[{"name":"3Department of Nephrology, Wakayama Medical University, Kimiidera, Wakayama 641-8509, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"2026062407250173400_B1","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1146\/annurev-physiol-020518-114455","article-title":"Branched chain amino acids","volume":"81","author":"Neinast","year":"2019","journal-title":"Annu. Rev. Physiol."},{"key":"2026062407250173400_B2","doi-asserted-by":"publisher","first-page":"417.e414","DOI":"10.1016\/j.cmet.2018.10.013","article-title":"Quantitative analysis of the whole-body metabolic fate of branched-chain amino acids","volume":"29","author":"Neinast","year":"2019","journal-title":"Cell Metab."},{"key":"2026062407250173400_B3","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1146\/annurev-physiol-042222-025000","article-title":"Mitochondrial dysfunction in kidney tubulopathies","volume":"86","author":"Hoogstraten","year":"2024","journal-title":"Annu. Rev. Physiol."},{"key":"2026062407250173400_B4","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/s41581-021-00394-7","article-title":"Kidney physiology and susceptibility to acute kidney injury: implications for renoprotection","volume":"17","author":"Scholz","year":"2021","journal-title":"Nat. Rev. Nephrol."},{"key":"2026062407250173400_B5","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1038\/nm.3762","article-title":"Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development","volume":"21","author":"Kang","year":"2015","journal-title":"Nat. Med."},{"key":"2026062407250173400_B6","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1038\/s41580-019-0199-y","article-title":"mTOR at the nexus of nutrition, growth, ageing and disease","volume":"21","author":"Liu","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2026062407250173400_B7","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1038\/s41581-022-00648-y","article-title":"Nutrient-sensing mTORC1 and AMPK pathways in chronic kidney diseases","volume":"19","author":"Huynh","year":"2023","journal-title":"Nat. Rev. Nephrol."},{"key":"2026062407250173400_B8","doi-asserted-by":"publisher","first-page":"1319","DOI":"10.34067\/KID.0003782020","article-title":"mTOR signaling in kidney diseases","volume":"1","author":"Gui","year":"2020","journal-title":"Kidney360"},{"key":"2026062407250173400_B9","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1146\/annurev-physiol-042222-024724","article-title":"Metabolic rewiring and communication: an integrative view of kidney proximal tubule function","volume":"86","author":"Chrysopoulou","year":"2024","journal-title":"Annu. Rev. Physiol."},{"key":"2026062407250173400_B10","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1007\/s00424-009-0638-2","article-title":"Kidney amino acid transport","volume":"458","author":"Verrey","year":"2009","journal-title":"Pflugers Arch."},{"key":"2026062407250173400_B11","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1007\/978-3-030-45328-2_5","article-title":"Amino acid metabolism in the kidneys: nutritional and physiological significance","volume":"1265","author":"Li","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"2026062407250173400_B12","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1038\/nature05475","article-title":"Essential role for collectrin in renal amino acid transport","volume":"444","author":"Danilczyk","year":"2006","journal-title":"Nature"},{"key":"2026062407250173400_B13","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1007\/BF02977671","article-title":"Reabsorption of neutral amino acids mediated by amino acid transporter LAT2 and TAT1 in the basolateral membrane of proximal tubule","volume":"28","author":"Park","year":"2005","journal-title":"Arch. Pharm. Res."},{"key":"2026062407250173400_B14","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1152\/physrev.00018.2006","article-title":"Amino acid transport across mammalian intestinal and renal epithelia","volume":"88","author":"Br\u00f6er","year":"2008","journal-title":"Physiol. Rev."},{"key":"2026062407250173400_B15","doi-asserted-by":"publisher","first-page":"5109","DOI":"10.1113\/JP280234","article-title":"Tissue-specific deletion of mouse basolateral uniporter LAT4 (Slc43a2) reveals its crucial role in small intestine and kidney amino acid transport","volume":"598","author":"Rajendran","year":"2020","journal-title":"J. Physiol."},{"key":"2026062407250173400_B16","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1681\/ASN.2010030246","article-title":"SGLT2 mediates glucose reabsorption in the early proximal tubule","volume":"22","author":"Vallon","year":"2011","journal-title":"J. Am. Soc. Nephrol."},{"key":"2026062407250173400_B17","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1152\/physrev.00055.2009","article-title":"Biology of human sodium glucose transporters","volume":"91","author":"Wright","year":"2011","journal-title":"Physiol. Rev."},{"key":"2026062407250173400_B18","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1177\/2042018816676239","article-title":"The renal effects of SGLT2 inhibitors and a mini-review of the literature","volume":"7","author":"Andrianesis","year":"2016","journal-title":"Ther. Adv. Endocrinol. Metab."},{"key":"2026062407250173400_B19","doi-asserted-by":"publisher","first-page":"106646","DOI":"10.1016\/j.isci.2023.106646","article-title":"Dynamic cellular changes in acute kidney injury caused by different ischemia time","volume":"26","author":"Shan","year":"2023","journal-title":"iScience"},{"key":"2026062407250173400_B20","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1042\/bj1120149","article-title":"The fuel of respiration of rat kidney cortex","volume":"112","author":"Weidemann","year":"1969","journal-title":"Biochem. J."},{"key":"2026062407250173400_B21","doi-asserted-by":"publisher","first-page":"F207","DOI":"10.1152\/ajprenal.1982.242.3.F207","article-title":"Renal Na-K-ATPase: its role in tubular sodium and potassium transport","volume":"242","author":"Katz","year":"1982","journal-title":"Am. J. Physiol."},{"key":"2026062407250173400_B22","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1085\/jgp.84.4.643","article-title":"Active ion transport in the renal proximal tubule. III. The ATP dependence of the Na pump","volume":"84","author":"Soltoff","year":"1984","journal-title":"J. Gen. Physiol."},{"key":"2026062407250173400_B23","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1146\/annurev-biophys-083012-130429","article-title":"Common folds and transport mechanisms of secondary active transporters","volume":"42","author":"Shi","year":"2013","journal-title":"Annu. Rev. Biophys."},{"key":"2026062407250173400_B24","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1016\/j.kint.2018.05.002","article-title":"A sodium\u2013glucose cotransporter 2 inhibitor attenuates renal capillary injury and fibrosis by a vascular endothelial growth factor-dependent pathway after renal injury in mice","volume":"94","author":"Zhang","year":"2018","journal-title":"Kidney Int."},{"key":"2026062407250173400_B25","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1038\/s12276-024-01263-6","article-title":"The role of BCAA metabolism in metabolic health and disease","volume":"56","author":"Choi","year":"2024","journal-title":"Exp. Mol. Med."},{"key":"2026062407250173400_B26","doi-asserted-by":"publisher","first-page":"988290","DOI":"10.3389\/fonc.2022.988290","article-title":"The mechanism of branched-chain amino acid transferases in different diseases: Research progress and future prospects","volume":"12","author":"Nong","year":"2022","journal-title":"Front. Oncol."},{"key":"2026062407250173400_B27","doi-asserted-by":"publisher","first-page":"4022","DOI":"10.3390\/ijms23074022","article-title":"The critical role of the branched chain amino acids (BCAAs) catabolism-regulating enzymes, branched-chain aminotransferase (BCAT) and branched-chain \u03b1-keto acid dehydrogenase (BCKD), in human pathophysiology","volume":"23","author":"Dimou","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"2026062407250173400_B28","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/S0065-2571(96)00009-X","article-title":"Studies on the regulation of the mitochondrial alpha-ketoacid dehydrogenase complexes and their kinases","volume":"37","author":"Harris","year":"1997","journal-title":"Adv. Enzyme. Regul."},{"key":"2026062407250173400_B29","first-page":"419","article-title":"Regulation of branched-chain amino acid catabolism: nutritional and hormonal regulation of activity and expression of the branched-chain alpha-keto acid dehydrogenase kinase","volume":"4","author":"Shimomura","year":"2001","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"2026062407250173400_B30","doi-asserted-by":"publisher","first-page":"1678","DOI":"10.1172\/JCI38151","article-title":"Protein phosphatase 2Cm is a critical regulator of branched-chain amino acid catabolism in mice and cultured cells","volume":"119","author":"Lu","year":"2009","journal-title":"J. Clin. Invest."},{"key":"2026062407250173400_B31","doi-asserted-by":"crossref","first-page":"S117","DOI":"10.1016\/j.kint.2023.10.018","article-title":"KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease","volume":"105","author":"Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group","year":"2024","journal-title":"Kidney Int."},{"key":"2026062407250173400_B32","doi-asserted-by":"publisher","first-page":"2461","DOI":"10.1016\/S0140-6736(25)01853-7","article-title":"Global, regional, and national burden of chronic kidney disease in adults, 1990-2023, and its attributable risk factors: a systematic analysis for the Global Burden of Disease Study 2023","volume":"406","author":"GBD 2023 Chronic Kidney Disease Collaborators","year":"2025","journal-title":"Lancet"},{"key":"2026062407250173400_B33","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/S0140-6736(25)01942-7","article-title":"Chronic kidney disease","volume":"407","author":"Herrington","year":"2026","journal-title":"Lancet"},{"key":"2026062407250173400_B34","doi-asserted-by":"publisher","first-page":"Itc66","DOI":"10.7326\/AITC201711070","article-title":"Acute kidney injury","volume":"167","author":"Levey","year":"2017","journal-title":"Ann. Intern. Med."},{"key":"2026062407250173400_B35","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1038\/ki.2011.379","article-title":"Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis","volume":"81","author":"Coca","year":"2012","journal-title":"Kidney Int."},{"key":"2026062407250173400_B36","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1056\/NEJMra1214243","article-title":"Acute kidney injury and chronic kidney disease as interconnected syndromes","volume":"371","author":"Chawla","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"2026062407250173400_B37","doi-asserted-by":"publisher","first-page":"2096","DOI":"10.1016\/S0140-6736(10)61271-8","article-title":"Glomerular filtration rate, proteinuria, and the incidence and consequences of acute kidney injury: a cohort study","volume":"376","author":"James","year":"2010","journal-title":"Lancet"},{"key":"2026062407250173400_B38","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1681\/ASN.2007080837","article-title":"Acute kidney injury increases risk of ESRD among elderly","volume":"20","author":"Ishani","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"2026062407250173400_B39","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1681\/ASN.2015030309","article-title":"Progression after AKI: understanding maladaptive repair processes to predict and identify therapeutic treatments","volume":"27","author":"Basile","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"2026062407250173400_B40","doi-asserted-by":"publisher","first-page":"10880","DOI":"10.3390\/ijms231810880","article-title":"From AKI to CKD: maladaptive repair and the underlying mechanisms","volume":"23","author":"Wang","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"2026062407250173400_B41","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1681\/ASN.2015010006","article-title":"Failed tubule recovery, AKI\u2013CKD transition, and kidney disease progression","volume":"26","author":"Venkatachalam","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"2026062407250173400_B42","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.kint.2024.02.025","article-title":"The key role of altered tubule cell lipid metabolism in kidney disease development","volume":"106","author":"Lee","year":"2024","journal-title":"Kidney Int."},{"key":"2026062407250173400_B43","doi-asserted-by":"publisher","first-page":"1580","DOI":"10.3390\/nu13051580","article-title":"Sugar or fat? Renal tubular metabolism reviewed in health and disease","volume":"13","author":"Gewin","year":"2021","journal-title":"Nutrients"},{"key":"2026062407250173400_B44","doi-asserted-by":"publisher","first-page":"5731","DOI":"10.1007\/s00018-021-03892-w","article-title":"The role of metabolic reprogramming in tubular epithelial cells during the progression of acute kidney injury","volume":"78","author":"Li","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"2026062407250173400_B45","doi-asserted-by":"publisher","first-page":"1276217","DOI":"10.3389\/fcell.2023.1276217","article-title":"Energy metabolic reprogramming regulates programmed cell death of renal tubular epithelial cells and might serve as a new therapeutic target for acute kidney injury","volume":"11","author":"Zhao","year":"2023","journal-title":"Front. Cell Dev. Biol."},{"key":"2026062407250173400_B46","doi-asserted-by":"publisher","first-page":"2879","DOI":"10.1007\/s00125-025-06519-y","article-title":"BCKDK accelerates the progression of diabetic kidney disease by regulating leucine-mediated metabolic remodelling in renal tubular cells","volume":"68","author":"Shi","year":"2025","journal-title":"Diabetologia"},{"key":"2026062407250173400_B47","doi-asserted-by":"publisher","first-page":"20583","DOI":"10.1074\/jbc.M114.569251","article-title":"Benzothiophene carboxylate derivatives as novel allosteric inhibitors of branched-chain \u03b1-ketoacid dehydrogenase kinase","volume":"289","author":"Tso","year":"2014","journal-title":"J. Biol. Chem."},{"key":"2026062407250173400_B48","doi-asserted-by":"publisher","first-page":"156037","DOI":"10.1016\/j.metabol.2024.156037","article-title":"Disruption of branched-chain amino acid homeostasis promotes the progression of DKD via enhancing inflammation and fibrosis-associated epithelial-mesenchymal transition","volume":"162","author":"Deng","year":"2025","journal-title":"Metabolism"},{"key":"2026062407250173400_B49","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/j.kint.2025.04.025","article-title":"Restoration of branched chain amino acid catabolism improves kidney function in preclinical cardiovascular-kidney-metabolic syndrome models","volume":"108","author":"Bollinger","year":"2025","journal-title":"Kidney Int."},{"key":"2026062407250173400_B50","doi-asserted-by":"publisher","first-page":"F259","DOI":"10.1152\/ajprenal.00550.2016","article-title":"The critical role of Kr\u00fcppel-like factors in kidney disease","volume":"312","author":"Mallipattu","year":"2017","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"2026062407250173400_B51","doi-asserted-by":"publisher","first-page":"e2024414118","DOI":"10.1073\/pnas.2024414118","article-title":"Kr\u00fcppel-like factor 6-mediated loss of BCAA catabolism contributes to kidney injury in mice and humans","volume":"118","author":"Piret","year":"2021","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026062407250173400_B52","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1016\/j.ebiom.2019.04.005","article-title":"The impact of dietary protein intake on longevity and metabolic health","volume":"43","author":"Kitada","year":"2019","journal-title":"EBioMedicine"},{"key":"2026062407250173400_B53","doi-asserted-by":"publisher","first-page":"E2817","DOI":"10.1073\/pnas.1402352111","article-title":"mTORC1 maintains renal tubular homeostasis and is essential in response to ischemic stress","volume":"111","author":"Grahammer","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026062407250173400_B54","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.bbrc.2005.12.012","article-title":"Inhibition of mTOR signaling with rapamycin attenuates renal hypertrophy in the early diabetic mice","volume":"340","author":"Sakaguchi","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2026062407250173400_B55","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1007\/s00125-016-3925-4","article-title":"A very-low-protein diet ameliorates advanced diabetic nephropathy through autophagy induction by suppression of the mTORC1 pathway in Wistar fatty rats, an animal model of type 2 diabetes and obesity","volume":"59","author":"Kitada","year":"2016","journal-title":"Diabetologia"},{"key":"2026062407250173400_B56","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1681\/ASN.2012050476","article-title":"Rheb\/mTORC1 signaling promotes kidney fibroblast activation and fibrosis","volume":"24","author":"Jiang","year":"2013","journal-title":"J. Am. Soc. Nephrol."},{"key":"2026062407250173400_B57","doi-asserted-by":"publisher","first-page":"22414","DOI":"10.1074\/jbc.M116.732511","article-title":"Amino acids regulate mTORC1 by an obligate two-step mechanism","volume":"291","author":"Dyachok","year":"2016","journal-title":"J. Biol. Chem."},{"key":"2026062407250173400_B58","doi-asserted-by":"publisher","first-page":"4038","DOI":"10.3168\/jds.2016-11973","article-title":"Methionine, leucine, isoleucine, or threonine effects on mammary cell signaling and pup growth in lactating mice","volume":"100","author":"Liu","year":"2017","journal-title":"J. Dairy Sci."},{"key":"2026062407250173400_B59","doi-asserted-by":"publisher","first-page":"484","DOI":"10.3945\/jn.111.152595","article-title":"Isoleucine and leucine independently regulate mTOR signaling and protein synthesis in MAC-T cells and bovine mammary tissue slices","volume":"142","author":"Appuhamy","year":"2012","journal-title":"J. Nutr."},{"key":"2026062407250173400_B60","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1007\/s00726-019-02709-2","article-title":"Regulation of protein synthesis in porcine mammary epithelial cells by L-valine","volume":"51","author":"Zhang","year":"2019","journal-title":"Amino Acids"},{"key":"2026062407250173400_B61","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1093\/biolre\/ioz065","article-title":"Valine increases milk fat synthesis in mammary gland of gilts through stimulating AKT\/MTOR\/SREBP1 pathway\u2020","volume":"101","author":"Che","year":"2019","journal-title":"Biol. Reprod."},{"key":"2026062407250173400_B62","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1126\/science.aab2674","article-title":"Sestrin2 is a leucine sensor for the mTORC1 pathway","volume":"351","author":"Wolfson","year":"2016","journal-title":"Science"},{"key":"2026062407250173400_B63","doi-asserted-by":"publisher","first-page":"F152","DOI":"10.1152\/ajprenal.00260.2024","article-title":"Activation of branched chain amino acid catabolism protects against nephrotoxic acute kidney injury","volume":"328","author":"DiMartino","year":"2025","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"2026062407250173400_B64","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.1056\/NEJMcp0804458","article-title":"Clinical practice. Autosomal dominant polycystic kidney disease","volume":"359","author":"Grantham","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"2026062407250173400_B65","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.kint.2017.01.021","article-title":"Branched-chain amino acids enhance cyst development in autosomal dominant polycystic kidney disease","volume":"92","author":"Yamamoto","year":"2017","journal-title":"Kidney Int."},{"key":"2026062407250173400_B66","doi-asserted-by":"publisher","first-page":"107954","DOI":"10.1016\/j.celrep.2020.107954","article-title":"Proximal tubule mTORC1 is a central player in the pathophysiology of diabetic nephropathy and its correction by SGLT2 inhibitors","volume":"32","author":"Kogot-Levin","year":"2020","journal-title":"Cell Rep."},{"key":"2026062407250173400_B67","doi-asserted-by":"publisher","first-page":"E736","DOI":"10.1152\/ajpendo.00231.2015","article-title":"Alterations of plasma metabolite profiles related to adipose tissue distribution and cardiometabolic risk","volume":"309","author":"Boulet","year":"2015","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"2026062407250173400_B68","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1056\/NEJM196910092811503","article-title":"Plasma amino acid levels and insulin secretion in obesity","volume":"281","author":"Felig","year":"1969","journal-title":"N. Engl. J. Med."},{"key":"2026062407250173400_B69","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.cmet.2009.02.002","article-title":"A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance","volume":"9","author":"Newgard","year":"2009","journal-title":"Cell Metab."},{"key":"2026062407250173400_B70","doi-asserted-by":"publisher","first-page":"1372","DOI":"10.2337\/db11-1355","article-title":"Metabolic signatures of insulin resistance in 7,098 young adults","volume":"61","author":"W\u00fcrtz","year":"2012","journal-title":"Diabetes"},{"key":"2026062407250173400_B71","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1038\/nm.2307","article-title":"Metabolite profiles and the risk of developing diabetes","volume":"17","author":"Wang","year":"2011","journal-title":"Nat. Med."},{"key":"2026062407250173400_B72","doi-asserted-by":"publisher","first-page":"e166956","DOI":"10.1172\/jci.insight.166956","article-title":"Longitudinal trajectories of branched chain amino acids through young adulthood and diabetes in later life","volume":"8","author":"Sawicki","year":"2023","journal-title":"JCI Insight"},{"key":"2026062407250173400_B73","doi-asserted-by":"publisher","first-page":"818","DOI":"10.3389\/fendo.2019.00818","article-title":"Metabolomic assessment reveals alteration in polyols and branched chain amino acids associated with present and future renal impairment in a discovery cohort of 637 persons with type 1 diabetes","volume":"10","author":"Tofte","year":"2019","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"2026062407250173400_B74","doi-asserted-by":"publisher","first-page":"1269633","DOI":"10.3389\/fendo.2023.1269633","article-title":"Serum branched chain amino acids: an effective indicator of diabetic kidney disease","volume":"14","author":"Liu","year":"2023","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"2026062407250173400_B75","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1016\/j.clnu.2024.02.008","article-title":"Association between branched-chain amino acids and renal function in the ELSA-Brasil study","volume":"43","author":"Calice-Silva","year":"2024","journal-title":"Clin. Nutr."},{"key":"2026062407250173400_B76","doi-asserted-by":"publisher","first-page":"299s","DOI":"10.1093\/jn\/136.1.299S","article-title":"Application of branched-chain amino acids in human pathological states: renal failure","volume":"136","author":"Cano","year":"2006","journal-title":"J. Nutr."},{"key":"2026062407250173400_B77","doi-asserted-by":"publisher","first-page":"1660","DOI":"10.1093\/ajcn\/31.9.1660","article-title":"Valine metabolism in normal and chronically uremic man","volume":"31","author":"Jones","year":"1978","journal-title":"Am. J. Clin. Nutr."},{"key":"2026062407250173400_B78","doi-asserted-by":"publisher","first-page":"3345","DOI":"10.3390\/nu14163345","article-title":"Impaired amino acid metabolism and its correlation with diabetic kidney disease progression in type 2 diabetes mellitus","volume":"14","author":"Zhu","year":"2022","journal-title":"Nutrients"},{"key":"2026062407250173400_B79","doi-asserted-by":"publisher","first-page":"1706","DOI":"10.1111\/dom.15475","article-title":"Branched-chain amino acid levels are inversely associated with incident and prevalent chronic kidney disease in people with type 2 diabetes","volume":"26","author":"de Klerk","year":"2024","journal-title":"Diabetes Obes. Metab."},{"key":"2026062407250173400_B80","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1093\/ajcn\/82.2.342","article-title":"Inflammation contributes to low plasma amino acid concentrations in patients with chronic kidney disease","volume":"82","author":"Suliman","year":"2005","journal-title":"Am. J. Clin. Nutr."},{"key":"2026062407250173400_B81","doi-asserted-by":"publisher","first-page":"351","DOI":"10.2337\/db25-0782","article-title":"Urinary branched-chain amino acid excretion and chronic kidney disease progression in patients with type 2 diabetes","volume":"75","author":"Liu","year":"2026","journal-title":"Diabetes"},{"key":"2026062407250173400_B82","doi-asserted-by":"publisher","first-page":"e13856","DOI":"10.1111\/obr.13856","article-title":"Branched-chain amino acid metabolism: Pathophysiological mechanism and therapeutic intervention in metabolic diseases","volume":"26","author":"Mansoori","year":"2025","journal-title":"Obes. Rev."},{"key":"2026062407250173400_B83","doi-asserted-by":"publisher","first-page":"2290458","DOI":"10.1080\/14756366.2023.2290458","article-title":"Identification of putative allosteric inhibitors of BCKDK via virtual screening and biological evaluation","volume":"39","author":"Li","year":"2024","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"2026062407250173400_B84","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1021\/jm301448p","article-title":"Discovery of potent myeloid cell leukemia 1 (Mcl-1) inhibitors using fragment-based methods and structure-based design","volume":"56","author":"Friberg","year":"2013","journal-title":"J. Med. Chem."},{"key":"2026062407250173400_B85","doi-asserted-by":"publisher","first-page":"3508","DOI":"10.1038\/s41467-022-31249-9","article-title":"A randomized placebo-controlled clinical trial for pharmacological activation of BCAA catabolism in patients with type 2 diabetes","volume":"13","author":"Vanweert","year":"2022","journal-title":"Nat. Commun."},{"key":"2026062407250173400_B86","doi-asserted-by":"publisher","first-page":"4812","DOI":"10.1038\/s41467-023-40536-y","article-title":"Small molecule branched-chain ketoacid dehydrogenase kinase (BDK) inhibitors with opposing effects on BDK protein levels","volume":"14","author":"Roth Flach","year":"2023","journal-title":"Nat. Commun."},{"key":"2026062407250173400_B87","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1536\/ihj.20-010","article-title":"Usefulness of plasma branched-chain amino acid analysis in predicting outcomes of patients with nonischemic dilated cardiomyopathy","volume":"61","author":"Kimura","year":"2020","journal-title":"Int. Heart J."},{"key":"2026062407250173400_B88","doi-asserted-by":"publisher","first-page":"102959","DOI":"10.1016\/j.jbc.2023.102959","article-title":"Structural studies identify angiotensin II receptor blocker-like compounds as branched-chain ketoacid dehydrogenase kinase inhibitors","volume":"299","author":"Liu","year":"2023","journal-title":"J. Biol. Chem."},{"key":"2026062407250173400_B89","doi-asserted-by":"publisher","first-page":"2295","DOI":"10.1056\/NEJMoa1811744","article-title":"Canagliflozin and renal outcomes in type 2 diabetes and nephropathy","volume":"380","author":"Perkovic","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"2026062407250173400_B90","doi-asserted-by":"publisher","first-page":"1436","DOI":"10.1056\/NEJMoa2024816","article-title":"Dapagliflozin in patients with chronic kidney disease","volume":"383","author":"Heerspink","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"2026062407250173400_B91","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1056\/NEJMoa2204233","article-title":"Empagliflozin in patients with chronic kidney disease","volume":"388","author":"Herrington","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"2026062407250173400_B92","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1161\/CIRCULATIONAHA.118.037418","article-title":"Evaluation of glomerular hemodynamic function by empagliflozin in diabetic mice using in vivo imaging","volume":"140","author":"Kidokoro","year":"2019","journal-title":"Circulation"},{"key":"2026062407250173400_B93","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1016\/S2213-8587(20)30300-4","article-title":"Effects of canagliflozin on anaemia in patients with type 2 diabetes and chronic kidney disease: a post-hoc analysis from the CREDENCE trial","volume":"8","author":"Oshima","year":"2020","journal-title":"Lancet Diabetes Endocrinol."},{"key":"2026062407250173400_B94","doi-asserted-by":"publisher","first-page":"F969","DOI":"10.1152\/ajprenal.00551.2017","article-title":"SGLT2 inhibition in a kidney with reduced nephron number: modeling and analysis of solute transport and metabolism","volume":"314","author":"Layton","year":"2018","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"2026062407250173400_B95","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1016\/j.cmet.2021.02.016","article-title":"A kidney perspective on the mechanism of action of sodium glucose co-transporter 2 inhibitors","volume":"33","author":"Sen","year":"2021","journal-title":"Cell Metab."},{"key":"2026062407250173400_B96","doi-asserted-by":"publisher","first-page":"4029","DOI":"10.1038\/s41598-018-22229-5","article-title":"Comprehensive renoprotective effects of ipragliflozin on early diabetic nephropathy in mice","volume":"8","author":"Kamezaki","year":"2018","journal-title":"Sci. Rep."},{"key":"2026062407250173400_B97","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1016\/j.kint.2018.04.025","article-title":"Sodium\u2013glucose cotransporter 2 inhibition normalizes glucose metabolism and suppresses oxidative stress in the kidneys of diabetic mice","volume":"94","author":"Tanaka","year":"2018","journal-title":"Kidney Int."},{"key":"2026062407250173400_B98","doi-asserted-by":"publisher","first-page":"1451671","DOI":"10.3389\/fendo.2024.1451671","article-title":"Effects of canagliflozin on kidney oxygenation evaluated using blood oxygenation level-dependent MRI in patients with type 2 diabetes","volume":"15","author":"Mori","year":"2024","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"2026062407250173400_B99","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.3390\/cells10061457","article-title":"Dapagliflozin restores impaired autophagy and suppresses inflammation in high glucose-treated HK-2 cells","volume":"10","author":"Xu","year":"2021","journal-title":"Cells"},{"key":"2026062407250173400_B100","doi-asserted-by":"publisher","first-page":"404.e406","DOI":"10.1016\/j.cmet.2020.06.020","article-title":"SGLT2 inhibition mediates protection from diabetic kidney disease by promoting ketone body-induced mTORC1 inhibition","volume":"32","author":"Tomita","year":"2020","journal-title":"Cell Metab."},{"key":"2026062407250173400_B101","doi-asserted-by":"publisher","first-page":"1706838","DOI":"10.3389\/fendo.2025.1706838","article-title":"Sodium\u2013glucose cotransporter 2 inhibitors-but not insulin-enhance renal branched-chain amino acid catabolism","volume":"16","author":"Sakamoto","year":"2025","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"2026062407250173400_B102","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1007\/s11255-024-04172-9","article-title":"Dapagliflozin restores autophagy and attenuates apoptosis via the AMPK\/mTOR pathway in diabetic nephropathy rats and high glucose-induced HK-2 cells","volume":"57","author":"Ye","year":"2025","journal-title":"Int. Urol. Nephrol."},{"key":"2026062407250173400_B103","doi-asserted-by":"publisher","first-page":"1730","DOI":"10.2337\/db18-0927","article-title":"Targeting BCAA catabolism to treat obesity-associated insulin resistance","volume":"68","author":"Zhou","year":"2019","journal-title":"Diabetes"},{"key":"2026062407250173400_B104","doi-asserted-by":"publisher","first-page":"11348","DOI":"10.1074\/jbc.M109.075184","article-title":"Adipose tissue branched chain amino acid (BCAA) metabolism modulates circulating BCAA levels","volume":"285","author":"Herman","year":"2010","journal-title":"J. Biol. Chem."},{"key":"2026062407250173400_B105","doi-asserted-by":"publisher","first-page":"2038","DOI":"10.1161\/CIRCULATIONAHA.115.020226","article-title":"Catabolic defect of branched-chain amino acids promotes heart failure","volume":"133","author":"Sun","year":"2016","journal-title":"Circulation"},{"key":"2026062407250173400_B106","doi-asserted-by":"publisher","first-page":"H1160","DOI":"10.1152\/ajpheart.00114.2016","article-title":"Defective branched chain amino acid catabolism contributes to cardiac dysfunction and remodeling following myocardial infarction","volume":"311","author":"Wang","year":"2016","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"2026062407250173400_B107","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1186\/s12889-025-25740-3","article-title":"Sarcopenia risk along the cardiovascular-kidney-metabolic syndrome spectrum: synergistic effects of multisystem burden and physical inactivity","volume":"26","author":"Wang","year":"2025","journal-title":"BMC Public Health"},{"key":"2026062407250173400_B108","doi-asserted-by":"publisher","first-page":"2636","DOI":"10.1016\/S0140-6736(19)31138-9","article-title":"Sarcopenia","volume":"393","author":"Cruz-Jentoft","year":"2019","journal-title":"Lancet"},{"key":"2026062407250173400_B109","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1002\/jcsm.13221","article-title":"Sarcopenia and cardiovascular diseases: A systematic review and meta-analysis","volume":"14","author":"Zuo","year":"2023","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"2026062407250173400_B110","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1002\/jcsm.13425","article-title":"Prevalence of sarcopenia in patients with chronic kidney disease: a global systematic review and meta-analysis","volume":"15","author":"Duarte","year":"2024","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"2026062407250173400_B111","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1093\/nutrit\/nuaa011","article-title":"Nutritional interventions to improve muscle mass, muscle strength, and physical performance in older people: an umbrella review of systematic reviews and meta-analyses","volume":"79","author":"Gielen","year":"2021","journal-title":"Nutr. Rev."},{"key":"2026062407250173400_B112","doi-asserted-by":"publisher","first-page":"3811","DOI":"10.1007\/s11255-025-04560-9","article-title":"Anti-sarcopenic effect of leucine-enriched branched-chain amino acid supplementation among elderly chronic kidney disease patients: a double-blinded randomized controlled trial","volume":"57","author":"Sunsandee","year":"2025","journal-title":"Int. Urol. Nephrol."},{"key":"2026062407250173400_B113","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1002\/jcsm.12934","article-title":"Effect of perindopril or leucine on physical performance in older people with sarcopenia: the LACE randomized controlled trial","volume":"13","author":"Achison","year":"2022","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"2026062407250173400_B114","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1007\/s00394-021-02710-0","article-title":"Effects of branched-chain amino acid-rich supplementation on EWGSOP2 criteria for sarcopenia in older adults: a systematic review and meta-analysis","volume":"61","author":"Bai","year":"2022","journal-title":"Eur. J. Nutr."},{"key":"2026062407250173400_B115","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1038\/s43587-024-00797-8","article-title":"Multi-omic profiling of sarcopenia identifies disrupted branched-chain amino acid catabolism as a causal mechanism and therapeutic target","volume":"5","author":"Zuo","year":"2025","journal-title":"Nat. Aging"}],"container-title":["Clinical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/140\/7\/1455\/989435\/cs-2026-0961.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/140\/7\/1455\/989435\/cs-2026-0961.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T11:25:11Z","timestamp":1782300311000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/clinsci\/article\/140\/7\/1455\/237752\/Impact-of-impaired-branched-chain-amino-acid"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,24]]},"references-count":115,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7,15]]}},"URL":"https:\/\/doi.org\/10.1042\/cs20260961","relation":{},"ISSN":["0143-5221","1470-8736"],"issn-type":[{"value":"0143-5221","type":"print"},{"value":"1470-8736","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,7]]},"published":{"date-parts":[[2026,6,24]]}}}