{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T16:25:00Z","timestamp":1782231900745,"version":"3.54.5"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T00:00:00Z","timestamp":1637884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006143","name":"Department of Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006143","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Government of India","award":["EEQ\/2019\/000308"],"award-info":[{"award-number":["EEQ\/2019\/000308"]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["AN372\/30-1"],"award-info":[{"award-number":["AN372\/30-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Klotho is a transmembrane anti-ageing protein that exists in three forms, i.e. \u03b1-Klotho, \u03b2-Klotho and \u03b3-Klotho, with distinct organ-specific expression and functions in the body. Here we focus on \u03b1-Klotho (hereafter Klotho), abundantly expressed by the distal and proximal convoluted tubules of the kidney. A significant decline in systemic and renal Klotho levels is a new hallmark for kidney disease progression. Emerging research portrays Klotho as a promising diagnostic and therapeutic target for diabetic and non-diabetic kidney disease. Even so, the underlying mechanisms of Klotho regulation and the strategies to restore its systemic and renal levels are still lacking.<\/jats:p><jats:p>Angiotensin-converting enzyme inhibitors and\/or angiotensin receptor blockers are the current standard of care for kidney diseases, but the molecular mechanisms for their nephroprotective action are still ambiguous. Moreover, endoplasmic reticulum (ER) stress also plays a crucial role in kidney disease progression. Few studies have claimed that the renin\u2013angiotensin\u2013aldosterone system (RAAS) has a direct relation with ER stress generation and vice versa in kidney disease. Interestingly, RAAS and ER stress modulation are associated with Klotho regulation in kidney disease. Here we focus on how the RAAS and ER stress connect with Klotho regulation in kidney disease. We also discuss Klotho and ER stress in an alliance with the concept of haemodynamic and metabolic overload in kidney disease. In addition, we highlight novel approaches to implement Klotho as a therapeutic target via RAAS and ER stress modulation for the treatment of diabetic and non-diabetic kidney diseases.<\/jats:p>","DOI":"10.1093\/ndt\/gfab340","type":"journal-article","created":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T12:16:49Z","timestamp":1637756209000},"page":"819-825","source":"Crossref","is-referenced-by-count":16,"title":["Klotho in kidney diseases: a crosstalk between the renin\u2013angiotensin system and endoplasmic reticulum stress"],"prefix":"10.1093","volume":"38","author":[{"given":"Ajinath","family":"Kale","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science , Pilani Campus, Pilani, Rajasthan , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Himanshu","family":"Sankrityayan","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science , Pilani Campus, Pilani, Rajasthan , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Joachim","family":"Anders","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine IV, University Hospital of the Ludwig Maximilians University of Munich , Munich , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil Bhanudas","family":"Gaikwad","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science , Pilani Campus, Pilani, Rajasthan , India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,11,26]]},"reference":[{"key":"2023033113133319900_","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1053\/j.ackd.2017.10.011","article-title":"The global epidemiology of diabetes and 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