{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T21:26:01Z","timestamp":1791062761774,"version":"4.1.0"},"reference-count":43,"publisher":"American Physiological Society","issue":"6","funder":[{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)","doi-asserted-by":"publisher","award":["DK092485"],"award-info":[{"award-number":["DK092485"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000724","name":"Foundation for Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000724","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2016,12,1]]},"abstract":"<jats:p>Lithium has been a valuable treatment for bipolar affective disorders for decades. Clinical use of lithium, however, has been problematic due to its narrow therapeutic index and concerns for its toxicity in various organ systems. Renal side effects associated with lithium include polyuria, nephrogenic diabetes insipidus, proteinuria, distal renal tubular acidosis, and reduction in glomerular filtration rate. Histologically, chronic lithium nephrotoxicity is characterized by interstitial nephritis with microcyst formation and occasional focal segmental glomerulosclerosis. Nevertheless, this type of toxicity is uncommon, with the strongest risk factors being high serum levels of lithium and longer time on lithium therapy. In contrast, in experimental models of acute kidney injury and glomerular disease, lithium has antiproteinuric, kidney protective, and reparative effects. This paradox may be partially explained by lower lithium doses and short duration of therapy. While long-term exposure to higher psychiatric doses of lithium may be nephrotoxic, short-term low dose of lithium may be beneficial and ameliorate kidney and podocyte injury. Mechanistically, lithium targets glycogen synthase kinase-3\u03b2, a ubiquitously expressed serine\/threonine protein kinase implicated in the processes of tissue injury, repair, and regeneration in multiple organ systems, including the kidney. Future studies are warranted to discover the exact \u201ckidney-protective dose\u201d of lithium and test the effects of low-dose lithium on acute and chronic kidney disease in humans.<\/jats:p>","DOI":"10.1152\/ajprenal.00145.2016","type":"journal-article","created":{"date-parts":[[2016,5,3]],"date-time":"2016-05-03T17:56:43Z","timestamp":1462298203000},"page":"F1168-F1171","source":"Crossref","is-referenced-by-count":76,"title":["What we need to know about the effect of lithium on the kidney"],"prefix":"10.1152","volume":"311","author":[{"given":"Rujun","family":"Gong","sequence":"first","affiliation":[{"name":"Division of Kidney Disease and Hypertension, Department of Medicine, Rhode Island Hospital, Brown University School of Medicine, Providence, Rhode Island; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Kidney Disease and Hypertension, Department of Medicine, Rhode Island 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