{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:09:58Z","timestamp":1791331798627,"version":"4.3.1"},"reference-count":116,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,1,16]],"date-time":"2019-01-16T00:00:00Z","timestamp":1547596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["NHRI-EX106-10617SI"],"award-info":[{"award-number":["NHRI-EX106-10617SI"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001868","name":"National Science Council","doi-asserted-by":"publisher","award":["105-2628-B-182-009-MY4"],"award-info":[{"award-number":["105-2628-B-182-009-MY4"]}],"id":[{"id":"10.13039\/501100001868","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG3H0131, CMRPG3H0271, and CMRPG3H0841"],"award-info":[{"award-number":["CMRPG3H0131, CMRPG3H0271, and CMRPG3H0841"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Autophagy is a cellular recycling process involving self-degradation and reconstruction of damaged organelles and proteins. Current evidence suggests that autophagy is critical in kidney physiology and homeostasis. In clinical studies, autophagy activations and inhibitions are linked to acute kidney injuries, chronic kidney diseases, diabetic nephropathies, and polycystic kidney diseases. Oxidative stress, inflammation, and mitochondrial dysfunction, which are implicated as important mechanisms underlying many kidney diseases, modulate the autophagy activation and inhibition and lead to cellular recycling dysfunction. Abnormal autophagy function can induce loss of podocytes, damage proximal tubular cells, and glomerulosclerosis. After acute kidney injuries, activated autophagy protects tubular cells from apoptosis and enhances cellular regeneration. Patients with chronic kidney diseases have impaired autophagy that cannot be reversed by hemodialysis. Multiple nephrotoxic medications also alter the autophagy signaling, by which the mechanistic insights of the drugs are revealed, thus providing the unique opportunity to manage the nephrotoxicity of these drugs. In this review, we summarize the current concepts of autophagy and its molecular aspects in different kidney cells pathophysiology. We also discuss the current evidence of autophagy in acute kidney injury, chronic kidney disease, toxic effects of drugs, and aging kidneys. In addition, we examine therapeutic possibilities targeting the autophagy system in kidney diseases.<\/jats:p>","DOI":"10.3390\/cells8010061","type":"journal-article","created":{"date-parts":[[2019,1,17]],"date-time":"2019-01-17T03:02:03Z","timestamp":1547694123000},"page":"61","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":160,"title":["Autophagy in Chronic Kidney Diseases"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6036-6635","authenticated-orcid":false,"given":"Tien-An","family":"Lin","sequence":"first","affiliation":[{"name":"Department of General Surgery, Chang Gung Memorial Hospital, Taoyuan City 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9918-4369","authenticated-orcid":false,"given":"Victor Chien-Chia","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan City 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Yung","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan City 333, Taiwan"},{"name":"Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan 350, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1007\/s00467-015-3134-2","article-title":"Autophagy in renal diseases","volume":"31","author":"Decuypere","year":"2016","journal-title":"Pediatr. Nephrol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1089\/ars.2013.5371","article-title":"An overview of autophagy: Morphology, mechanism, and regulation","volume":"20","author":"Parzych","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1089\/ars.2013.5363","article-title":"Autophagy in kidney health and disease","volume":"20","author":"Wang","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/cr.2013.169","article-title":"Historical landmarks of autophagy research","volume":"24","author":"Ohsumi","year":"2014","journal-title":"Cell. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1056\/NEJMra1205406","article-title":"Autophagy in human health and disease","volume":"368","author":"Choi","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1083\/jcb.119.2.301","article-title":"Autophagy in Yeast Demonstrated with Proteinase-deficient Mutants and Conditions for its Induction","volume":"119","author":"Takeshige","year":"1992","journal-title":"J. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1124\/pr.112.007120","article-title":"Therapeutic targeting of autophagy in disease: Biology and pharmacology","volume":"65","author":"Cheng","year":"2013","journal-title":"Pharmacol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1159\/000374071","article-title":"Autophagy protects renal tubular cells against ischemia\/reperfusion injury in a time-dependent manner","volume":"36","author":"Guan","year":"2015","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Duann, P., Lianos, E.A., Ma, J., and Lin, P.H. (2016). Autophagy, Innate Immunity and Tissue Repair in Acute Kidney Injury. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17050662"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1126\/science.1099993","article-title":"Autophagy in health and disease: A double-edged sword","volume":"306","author":"Shintani","year":"2004","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"C776","DOI":"10.1152\/ajpcell.00507.2009","article-title":"Autophagy in health and disease. 1. Regulation and significance of autophagy: An overview","volume":"298","author":"Mehrpour","year":"2010","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1016\/j.kint.2016.04.014","article-title":"Autophagy in kidney disease and aging: Lessons from rodent models","volume":"90","author":"Lenoir","year":"2016","journal-title":"Kidney Int."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1159\/000363677","article-title":"Autophagy in acute kidney injury and repair","volume":"127","author":"He","year":"2014","journal-title":"Nephron Clin. Pract."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1172\/JCI39492","article-title":"Autophagy influences glomerular disease susceptibility and maintains podocyte homeostasis in aging mice","volume":"120","author":"Hartleben","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"170","DOI":"10.3109\/09637486.2015.1137889","article-title":"Dietary consumption of advanced glycation end products and risk of metabolic syndrome","volume":"67","author":"Angoorani","year":"2016","journal-title":"Int. J. Food Sci. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"34167","DOI":"10.1038\/srep34167","article-title":"Involvement of Endoplasmic Reticulum Stress, Autophagy, and Apoptosis in Advanced Glycation End Products-Induced Glomerular Mesangial Cell Injury","volume":"6","author":"Chiang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/1475-2840-13-78","article-title":"Advanced glycation endproducts trigger autophagy in cadiomyocyte via RAGE\/PI3K\/AKT\/mTOR pathway","volume":"13","author":"Hou","year":"2014","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3640","DOI":"10.1007\/s00018-008-8383-9","article-title":"Cadmium-induced autophagy and apoptosis are mediated by a calcium signaling pathway","volume":"65","author":"Wang","year":"2008","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1016\/j.kint.2016.01.012","article-title":"Podocyte injury and its consequences","volume":"89","author":"Nagata","year":"2016","journal-title":"Kidney Int."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1053\/j.ajkd.2015.05.021","article-title":"Autophagy and the Kidney: Implications for Ischemia-Reperfusion Injury and Therapy","volume":"66","author":"Decuypere","year":"2015","journal-title":"Am. J. Kidney Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1097\/01.ASN.0000054887.42550.14","article-title":"Podocyte Differentiation and Glomerulogenesis","volume":"14","author":"Kreidberg","year":"2013","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2941","DOI":"10.1681\/ASN.2005010055","article-title":"Podocyte depletion causes glomerulosclerosis: Diphtheria toxin-induced podocyte depletion in rats expressing human diphtheria toxin receptor transgene","volume":"16","author":"Wharram","year":"2005","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1159\/000228897","article-title":"Correlation of Autophagy Type in Podocytes with Histopathological Diagnosis of IgA Nephropathy","volume":"76","author":"Sato","year":"2009","journal-title":"Pathobiology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1177\/0963689717743512","article-title":"Acute Kidney Injury as a Condition of Renal Senescence","volume":"27","author":"Andrade","year":"2018","journal-title":"Cell Transplant."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1681\/ASN.2011070690","article-title":"Inhibition of MTOR disrupts autophagic flux in podocytes","volume":"23","author":"Cina","year":"2012","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1097\/TP.0b013e318211d342","article-title":"Sirolimus and proteinuria in renal transplant patients: Evidence for a dose-dependent effect on slit diaphragm-associated proteins","volume":"91","author":"Stallone","year":"2011","journal-title":"Transplantation"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1111\/apha.12852","article-title":"Autophagy in renal tubular injury and repair","volume":"220","author":"Lin","year":"2017","journal-title":"Acta Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"826","DOI":"10.4161\/auto.19419","article-title":"Autophagy plays a critical role in kidney tubule maintenance, aging and ischemia-reperfusion injury","volume":"8","author":"Liu","year":"2012","journal-title":"Autophagy"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1681\/ASN.2013040374","article-title":"New Autophagy Reporter Mice Reveal Dynamics of Proximal Tubular Autophagy","volume":"25","author":"Li","year":"2013","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1681\/ASN.2010070705","article-title":"Autophagy protects the proximal tubule from degeneration and acute ischemic injury","volume":"22","author":"Kimura","year":"2011","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1038\/ki.2012.261","article-title":"Autophagy in proximal tubules protects against acute kidney injury","volume":"82","author":"Jiang","year":"2012","journal-title":"Kidney Int."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1016\/j.kint.2017.06.030","article-title":"AKI on CKD: Heightened injury, suppressed repair, and the underlying mechanisms","volume":"92","author":"He","year":"2017","journal-title":"Kidney Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.redox.2015.01.001","article-title":"Oxidative stress and autophagy: Crucial modulators of kidney injury","volume":"4","author":"Sureshbabu","year":"2015","journal-title":"Redox Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1038\/nm.2507","article-title":"Ischemia and reperfusion--from mechanism to translation","volume":"17","author":"Eltzschig","year":"2011","journal-title":"Nat. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.pharmthera.2011.11.004","article-title":"The cellular and molecular origin of reactive oxygen species generation during myocardial ischemia and reperfusion","volume":"133","author":"Raedschelders","year":"2012","journal-title":"Pharmacol. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Martin, J.L., Gruszczyk, A.V., Beach, T.E., Murphy, M.P., and Saeb-Parsy, K. (2018). Mitochondrial mechanisms and therapeutics in ischaemia reperfusion injury. Pediatr. Nephrol., 1\u20138.","DOI":"10.1007\/s00467-018-3984-5"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1080\/15548627.2015.1135284","article-title":"The yin and yang of autophagy in acute kidney injury","volume":"12","author":"Melk","year":"2016","journal-title":"Autophagy"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.4161\/auto.21211","article-title":"ROS-induced mitochondrial depolarization initiates PARK2\/PARKIN-dependent mitochondrial degradation by autophagy","volume":"8","author":"Wang","year":"2012","journal-title":"Autophagy"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.2353\/ajpath.2010.090594","article-title":"Autophagy is a renoprotective mechanism during in vitro hypoxia and in vivo ischemia-reperfusion injury","volume":"176","author":"Jiang","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.4161\/auto.25418","article-title":"Autophagy protects kidney proximal tubule epithelial cells from mitochondrial metabolic stress","volume":"9","author":"Kimura","year":"2013","journal-title":"Autophagy"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/j.kint.2015.11.021","article-title":"Autophagy in acute kidney injury","volume":"89","author":"Kaushal","year":"2016","journal-title":"Kidney Int."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1681\/ASN.2004070539","article-title":"Chronic kidney disease awareness, prevalence, and trends among U.S. adults, 1999 to 2000","volume":"16","author":"Coresh","year":"2005","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Hill, N.R., Fatoba, S.T., Oke, J.L., Hirst, J.A., O\u2019Callaghan, C.A., Lasserson, D.S., and Hobbs, F.D. (2016). Global Prevalence of Chronic Kidney Disease\u2014A Systematic Review and Meta-Analysis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0158765"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0140-6736(11)60178-5","article-title":"Chronic kidney disease","volume":"379","author":"Levey","year":"2012","journal-title":"Lancet"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/j.bbrc.2018.09.003","article-title":"Activation of autophagy contributes to the renoprotective effect of postconditioning on acute kidney injury and renal fibrosis","volume":"504","author":"Song","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.kint.2016.11.004","article-title":"Recycling to discover something new: The role of autophagy in kidney disease","volume":"91","author":"Leventhal","year":"2017","journal-title":"Kidney Int."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1080\/15548627.2015.1049799","article-title":"Endothelial cell and podocyte autophagy synergistically protect from diabetes-induced glomerulosclerosis","volume":"11","author":"Lenoir","year":"2015","journal-title":"Autophagy"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1159\/000356212","article-title":"Impaired leukocytes autophagy in chronic kidney disease patients","volume":"3","author":"Chen","year":"2013","journal-title":"Cardiorenal Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15548627.2015.1100356","article-title":"Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)","volume":"12","author":"Klionsky","year":"2016","journal-title":"Autophagy"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1093\/ejechocard\/jeq175","article-title":"Left atrial function: Physiology, assessment, and clinical implications","volume":"12","author":"Blume","year":"2011","journal-title":"Eur. J. Echocardiogr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2615286","DOI":"10.1155\/2017\/2615286","article-title":"Research Progress on Mechanism of Podocyte Depletion in Diabetic Nephropathy","volume":"2017","author":"Dai","year":"2017","journal-title":"J. Diabetes Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3560238","DOI":"10.1155\/2017\/3560238","article-title":"Podocyte Autophagy: A Potential Therapeutic Target to Prevent the Progression of Diabetic Nephropathy","volume":"2017","author":"Liu","year":"2017","journal-title":"J. Diabetes Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/j.yexcr.2013.01.018","article-title":"High glucose induces autophagy in podocytes","volume":"319","author":"Ma","year":"2013","journal-title":"Exp. Cell. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1080\/15548627.2015.1115173","article-title":"Emerging role of podocyte autophagy in the progression of diabetic nephropathy","volume":"11","author":"Kume","year":"2015","journal-title":"Autophagy"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"R15","DOI":"10.1530\/JOE-14-0437","article-title":"Autophagy in diabetic nephropathy","volume":"224","author":"Ding","year":"2015","journal-title":"J. Endocrinol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"225","DOI":"10.2337\/diabetes.55.01.06.db05-0894","article-title":"Glucose-Induced Reactive Oxygen Species Cause Apoptosis of Podocytes and Podocyte Depletion at the Onset of Diabetic Nephropathy","volume":"55","author":"Susztak","year":"2006","journal-title":"Diabetes"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1016\/j.metabol.2016.05.015","article-title":"Autophagy protects human podocytes from high glucose-induced injury by preventing insulin resistance","volume":"65","author":"Xin","year":"2016","journal-title":"Metabolism"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"755","DOI":"10.2337\/db15-0473","article-title":"Impaired Podocyte Autophagy Exacerbates Proteinuria in Diabetic Nephropathy","volume":"65","author":"Tagawa","year":"2016","journal-title":"Diabetes"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"908185","DOI":"10.1155\/2011\/908185","article-title":"Dietary restriction ameliorates diabetic nephropathy through anti-inflammatory effects and regulation of the autophagy via restoration of Sirt1 in diabetic Wistar fatty (fa\/fa) rats: A model of type 2 diabetes","volume":"2011","author":"Kitada","year":"2011","journal-title":"Exp. Diabetes Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s11892-017-0879-y","article-title":"Regulating Autophagy as a Therapeutic Target for Diabetic Nephropathy","volume":"17","author":"Kitada","year":"2017","journal-title":"Curr. Diabetes Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1681\/ASN.2012111080","article-title":"Obesity-mediated autophagy insufficiency exacerbates proteinuria-induced tubulointerstitial lesions","volume":"24","author":"Yamahara","year":"2013","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/nature17950","article-title":"Noncanonical autophagy inhibits the autoinflammatory, lupus-like response to dying cells","volume":"533","author":"Martinez","year":"2016","journal-title":"Nature"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.4161\/auto.21212","article-title":"Autophagy in immunity: Implications in etiology of autoimmune\/autoinflammatory diseases","volume":"8","author":"Zhou","year":"2012","journal-title":"Autophagy"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.jaut.2018.08.009","article-title":"Autophagy: A new concept in autoimmunity regulation and a novel therapeutic option","volume":"94","author":"Bonam","year":"2018","journal-title":"J. Autoimmun."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1097\/MAJ.0b013e31827f4ee3","article-title":"Lupus Nephritis and End-stage Kidney Disease","volume":"346","author":"Maroz","year":"2013","journal-title":"Am. J. Med. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1080\/15548627.2017.1309485","article-title":"Autophagy and kidney inflammation","volume":"13","author":"Kimura","year":"2017","journal-title":"Autophagy"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1073\/pnas.0909448107","article-title":"Nuclear location of an endogenously expressed antigen, EBNA1, restricts access to macroautophagy and the range of CD4 epitope display","volume":"107","author":"Leung","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2833","DOI":"10.1038\/sj.onc.1210946","article-title":"The latent membrane protein 1 oncogene modifies B-cell physiology by regulating autophagy","volume":"27","author":"Lee","year":"2008","journal-title":"Oncogene"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.kint.2016.06.001","article-title":"LAPping up dead cells to prevent lupus nephritis: A novel role for noncanonical autophagy in autoimmunity","volume":"90","author":"Leventhal","year":"2016","journal-title":"Kidney Int."},{"key":"ref_70","first-page":"803","article-title":"The novel involvement of podocyte autophagic activity in the pathogenesis of lupus nephritis","volume":"33","author":"Jin","year":"2018","journal-title":"Histol. Histopathol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"25154","DOI":"10.3390\/ijms161025154","article-title":"The Role of Autophagy in Lupus Nephritis","volume":"16","author":"Wang","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.3389\/fimmu.2017.01832","article-title":"Autophagy: A Potential Therapeutic Target for Reversing Sepsis-Induced Immunosuppression","volume":"8","author":"Ren","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1097\/SHK.0b013e318240b52a","article-title":"The decline of autophagy contributes to proximal tubular dysfunction during sepsis","volume":"37","author":"Hsiao","year":"2012","journal-title":"Shock"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.2353\/ajpath.2010.090345","article-title":"Autophagy is a component of epithelial cell fate in obstructive uropathy","volume":"176","author":"Li","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2835","DOI":"10.1681\/ASN.2013101068","article-title":"Autophagy Regulates TGF- Expression and Suppresses Kidney Fibrosis Induced by Unilateral Ureteral Obstruction","volume":"25","author":"Ding","year":"2014","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1080\/15548627.2016.1166317","article-title":"Persistent activation of autophagy in kidney tubular cells promotes renal interstitial fibrosis during unilateral ureteral obstruction","volume":"12","author":"Livingston","year":"2016","journal-title":"Autophagy"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1159\/000488827","article-title":"Mitophagy Plays a Protective Role in Iodinated Contrast-Induced Acute Renal Tubular Epithelial Cells Injury","volume":"46","author":"Lei","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"F777","DOI":"10.1152\/ajprenal.00590.2007","article-title":"Autophagy is associated with apoptosis in cisplatin injury to renal tubular epithelial cells","volume":"294","author":"Yang","year":"2008","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1007\/s10157-009-0254-7","article-title":"Cisplatin-induced macroautophagy occurs prior to apoptosis in proximal tubules in vivo","volume":"14","author":"Inoue","year":"2010","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"384","DOI":"10.3389\/fphar.2018.00384","article-title":"Necrostatin-1 Attenuates Cisplatin-Induced Nephrotoxicity Through Suppression of Apoptosis and Oxidative Stress and Retains Klotho Expression","volume":"9","author":"Ning","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1038\/s41419-018-0374-7","article-title":"Histone deacetylase inhibitors protect against cisplatin-induced acute kidney injury by activating autophagy in proximal tubular cells","volume":"9","author":"Liu","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.ajpath.2011.11.001","article-title":"Autophagy guards against cisplatin-induced acute kidney injury","volume":"180","author":"Takahashi","year":"2012","journal-title":"Am. J. Pathol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"23975","DOI":"10.1038\/srep23975","article-title":"Metformin Protects Against Cisplatin-Induced Tubular Cell Apoptosis and Acute Kidney Injury via AMPKalpha-regulated Autophagy Induction","volume":"6","author":"Li","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"F74","DOI":"10.1152\/ajprenal.00114.2017","article-title":"Autophagy is activated to protect against podocyte injury in adriamycin-induced nephropathy","volume":"313","author":"Yi","year":"2017","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1096\/fj.02-0580fje","article-title":"MAP-LC3, a promising autophagosomal marker, is processed during the differentiation and recovery of podocytes from PAN nephrosis","volume":"17","author":"Asanuma","year":"2003","journal-title":"FASEB J."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.bbrc.2013.12.015","article-title":"The cytoprotective role of autophagy in puromycin aminonucleoside treated human podocytes","volume":"443","author":"Kang","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1002\/path.4382","article-title":"Podocyte autophagic activity plays a protective role in renal injury and delays the progression of podocytopathies","volume":"234","author":"Zeng","year":"2014","journal-title":"J. Pathol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s00441-017-2628-6","article-title":"Role of apoptosis in the development of autosomal dominant polycystic kidney disease (ADPKD)","volume":"369","author":"Peintner","year":"2017","journal-title":"Cell Tissue Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.semnephrol.2013.11.005","article-title":"Polycystic kidney disease: A case of suppressed autophagy?","volume":"34","author":"Ravichandran","year":"2014","journal-title":"Semin. Nephrol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1128\/MCB.01259-08","article-title":"Polycystin-1 regulates extracellular signal-regulated kinase-dependent phosphorylation of tuberin to control cell size through mTOR and its downstream effectors S6K and 4EBP1","volume":"29","author":"Distefano","year":"2009","journal-title":"Mol. Cell. Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1093\/ndt\/gfx262","article-title":"Targeting new cellular disease pathways in autosomal dominant polycystic kidney disease","volume":"33","author":"Chang","year":"2017","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1038\/nm.3092","article-title":"Defective glucose metabolism in polycystic kidney disease identifies a new therapeutic strategy","volume":"19","author":"Rowe","year":"2013","journal-title":"Nat. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"6404","DOI":"10.1074\/jbc.M113.501205","article-title":"Polycystin-1 Negatively Regulates Polycystin-2 Expression via the Aggresome\/Autophagosome Pathway","volume":"289","author":"Cebotaru","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_94","first-page":"158","article-title":"Autophagy activators suppress cystogenesis in an autosomal dominant polycystic kidney disease model","volume":"26","author":"Zhu","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1002\/ar.1092320205","article-title":"Glomerular number and size in relation to age, kidney weight, and body surface in normal man","volume":"232","author":"Nyengaard","year":"1992","journal-title":"Anat. Rec."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"15358","DOI":"10.3390\/ijms150915358","article-title":"The aging kidney: Increased susceptibility to nephrotoxicity","volume":"15","author":"Wang","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1038\/ki.2012.174","article-title":"The effect of increasing age on the prognosis of non-dialysis patients with chronic kidney disease receiving stable nephrology care","volume":"82","author":"Minutolo","year":"2012","journal-title":"Kidney Int."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1159\/000355760","article-title":"Aging and chronic kidney disease","volume":"38","author":"Nitta","year":"2013","journal-title":"Kidney Blood Press Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1080\/15548627.2016.1159376","article-title":"Time-dependent dysregulation of autophagy: Implications in aging and mitochondrial homeostasis in the kidney proximal tubule","volume":"12","author":"Yamamoto","year":"2016","journal-title":"Autophagy"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.kint.2017.02.036","article-title":"Molecular mechanisms of renal aging","volume":"92","author":"Schmitt","year":"2017","journal-title":"Kidney Int."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Boutouja, F., Stiehm, C.M., and Platta, H.W. (2019). mTOR: A cellular regulator interface in health and disease. Cells, 8.","DOI":"10.3390\/cells8010018"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1080\/15384101.2018.1482149","article-title":"Aged kidney: Can we protect it? Autophagy, mitochondria and mechanisms of ischemic preconditioning","volume":"17","author":"Jankauskas","year":"2018","journal-title":"Cell Cycle"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Andrianova, N.V., Jankauskas, S.S., Zorova, L.D., Pevzner, I.B., Popkov, V.A., Silachev, D.N., Plotnikov, E.Y., and Zorov, D.B. (2018). Mechanisms of Age-Dependent Loss of Dietary Restriction Protective Effects in Acute Kidney Injury. Cells, 7.","DOI":"10.3390\/cells7100178"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1038\/nature09076","article-title":"Termination of autophagy and reformation of lysosomes regulated by mTOR","volume":"465","author":"Yu","year":"2010","journal-title":"Nature"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1111\/jcmm.13393","article-title":"Autophagy promotes fibrosis and apoptosis in the peritoneum during long-term peritoneal dialysis","volume":"22","author":"Wu","year":"2018","journal-title":"J. Cell. Mol. Med."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2290","DOI":"10.1038\/cddis.2016.79","article-title":"Activation of salt-inducible kinase 2 promotes the viability of peritoneal mesothelial cells exposed to stress of peritoneal dialysis","volume":"7","author":"Wang","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1111\/ajt.12743","article-title":"Autophagy: Basic principles and relevance to transplant immunity","volume":"14","author":"Bizargity","year":"2014","journal-title":"Am. J. Transplant."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.ejphar.2012.09.010","article-title":"Involvement of autophagy in the pharmacological effects of the mTOR inhibitor everolimus in acute kidney injury","volume":"696","author":"Nakagawa","year":"2012","journal-title":"Eur. J. Pharmacol"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.bjhh.2014.03.010","article-title":"Influence of cyclosporine on the occurrence of nephrotoxicity after allogeneic hematopoietic stem cell transplantation: A systematic review","volume":"36","author":"Secoli","year":"2014","journal-title":"Revista Brasileira de Hematologia e Hemoterapia"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1097\/TP.0b013e31825ace5c","article-title":"Chronic cyclosporine nephropathy is characterized by excessive autophagosome formation and decreased autophagic clearance","volume":"94","author":"Lim","year":"2012","journal-title":"Transplantation"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/j.fct.2018.06.054","article-title":"Mechanism of cyclosporine A nephrotoxicity: Oxidative stress, autophagy, and signalings","volume":"118","author":"Wu","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/ki.2014.18","article-title":"Delayed kidney graft function: From mechanism to translation","volume":"86","author":"Schroppel","year":"2014","journal-title":"Kidney Int."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/nrd3802","article-title":"Autophagy modulation as a potential therapeutic target for diverse diseases","volume":"11","author":"Rubinsztein","year":"2012","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1089\/ars.2017.7234","article-title":"Autophagy in Human Health and Disease: Novel Therapeutic Opportunities","volume":"30","author":"Giampieri","year":"2019","journal-title":"Antioxid. Redox Signal."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"7627329","DOI":"10.1155\/2018\/7627329","article-title":"Chloroquine Protects Human Corneal Epithelial Cells from Desiccation Stress Induced Inflammation without Altering the Autophagy Flux","volume":"2018","author":"Shivakumar","year":"2018","journal-title":"Biomed. Res. Int."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Bullon, P., Cordero, M.D., Quiles, J.L., Ramirez-Tortosa, M.D.C., Gonzalez-Alonso, A., Alfonsi, S., Garc\u00eda-Mar\u00edn, R., de Miguel, M., and Battino, M. (2012). Autophagy in periodontitis patients and gingival fibroblasts: Unraveling the link between chronic diseases and inflammation. BMC Med., 10.","DOI":"10.1186\/1741-7015-10-122"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/8\/1\/61\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:26:39Z","timestamp":1760185599000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/8\/1\/61"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,16]]},"references-count":116,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,1]]}},"alternative-id":["cells8010061"],"URL":"https:\/\/doi.org\/10.3390\/cells8010061","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,16]]}}}