Lithium in Bipolar Disorder: Renal Mechanisms, Nephrotoxicity Phenotypes, and a Shared-Care Pathway for Clinical Practice

Lithium remains a cornerstone mood stabilizer for bipolar disorder, with strong evidence for relapse prevention and a unique association with reduced suicide risk. Its benefit is counterbalanced by renal adverse effects, ranging from impaired urinary concentrating capacity and nephrogenic diabetes insipidus (NDI) to chronic tubulointerstitial nephropathy with progressive loss of glomerular filtration rate in a minority of long-term users. Mechanistically, lithium enters collecting duct principal cells via the epithelial sodium channel, disrupts vasopressin-regulated water handling by downregulating aquaporin-2, and can drive chronic interstitial injury. Risk is amplified by episodes of lithium intoxication, dehydration, interacting medications that reduce renal lithium clearance, longer treatment duration, and comorbid kidney disease. This review integrates psychiatric and nephrologic perspectives on lithium’s indications, mechanisms, renal phenotypes, and prevention strategies, and proposes a practical shared-care pathway for patients with bipolar disorder who develop polyuria, NDI, acute kidney injury, or chronic kidney disease during lithium therapy, emphasizing monitoring, targeted treatment of polyuria, mitigation of toxicity, and structured shared decision-making when renal function declines.