{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T06:44:45Z","timestamp":1793256285190,"version":"4.5.0"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,8]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract.<\/jats:title>\n                    <jats:p>\n                      This study examines the clinical features, pathologic findings, and outcome of 24 patients with biopsy-proven lithium toxicity. The patient population was 50% male, 87.5% Caucasian, and had a mean age of 42.5 yr (range, 26 to 57). Mean duration of lithium therapy for bipolar disorder was 13.6 yr (range, 2 to 25). All patients were biopsied for renal insufficiency (mean serum creatinine 2.8 mg\/dl; range, 1.3 to 8.0), with associated proteinuria &gt;1.0 g\/d in 41.7%. Nephrotic proteinuria (&gt;3.0 g\/d) was present in 25%. Other features included nephrogenic diabetes insipidus in 87% and hypertension in 33.3%. Renal biopsy revealed a chronic tubulointerstitial nephropathy in 100%, with associated cortical and medullary tubular cysts (62.5%) or dilatation (33.3%). All of the renal cysts stained for epithelial membrane antigen, while 51.4% stained with lectin Arachis hypogaea, and only 3.8% stained with Tetragonolobus purpureas, indicating they originated from distal and collecting tubules. The degree of tubular atrophy and interstitial fibrosis was graded as severe in 58.3%, moderate in 37.5%, and mild in 4.2% of cases. There was a surprisingly high prevalence of focal segmental glomerulosclerosis (50%) and global glomerulosclerosis (100%), sometimes of equivalent severity to the chronic tubulointerstitial disease. The significant degree of foot process effacement (mean 34%, five of 14 cases with &gt;50%) suggests a potential direct glomerular toxicity. Focal segmental glomerulosclerosis correlated with proteinuria &gt;1.0 g\/d (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.0014, Fisher exact test). Despite discontinuation of lithium, seven of nine patients with initial serum creatinine values &gt;2.5 mg\/dl progressed to end-stage renal disease (ESRD). Only three patients, all with initial serum creatinine &lt;2.1 mg\/dl, had subsequent improvement in renal function. By Kaplan-Meier survival analysis, the only significant predictor of progression to ESRD was serum creatinine &gt;2.5 mg\/dl at biopsy (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.008). In conclusion, lithium nephrotoxicity primarily targets distal and collecting tubules, with a higher incidence of proteinuria and associated glomerular pathology than recognized previously. Renal dysfunction is often irreversible despite lithium withdrawal, and early detection is essential to prevent progression to ESRD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.v1181439","type":"journal-article","created":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T15:11:40Z","timestamp":1619363500000},"page":"1439-1448","source":"Crossref","is-referenced-by-count":295,"title":["Lithium Nephrotoxicity"],"prefix":"10.1681","volume":"11","author":[{"given":"GLEN S.","family":"MARKOWITZ","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JAI","family":"RADHAKRISHNAN","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"NEERAJA","family":"KAMBHAM","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ANTHONY M.","family":"VALERI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"WILLIAM H.","family":"HINES","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"VIVETTE D.","family":"D'AGATI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/00001751-200008000-00008","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T19:30:10Z","timestamp":1786131010000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/00001751-200008000-00008"}},"subtitle":["A Progressive Combined Glomerular and Tubulointerstitial Nephropathy"],"short-title":[],"issued":{"date-parts":[[2000,8]]},"references-count":0,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2000]]}},"URL":"https:\/\/doi.org\/10.1681\/asn.v1181439","relation":{},"ISSN":["1046-6673"],"issn-type":[{"value":"1046-6673","type":"print"}],"subject":[],"published":{"date-parts":[[2000,8]]}}}