Lithium-Induced Renal Ectasia

“Ms. LK,” a 22-year-old Caucasian woman, was referred to our outpatient psychiatry clinic in January 2011 by Urology for help with her lithium therapy in the setting of new-onset renal tubular ectasia. She has a past medical history of childhood-onset bipolar disorder. Other pertinent medical history includes numerous E. coli urinary tract infections successfully treated with short courses of ciprofloxacin.

LK was referred to urology because of her report of “fragments in my urine.” She denied dysuria, hematuria, and polyuria. Her blood urea nitrogen (BUN) and serum creatinine (SCr) remained stable, at 11 mg/dL and 0.9 mg/dL. Her GFR was >60 ml/min/1.79 m². Her lithium level at this time was 1.32 mmol/L. Previously, she had only one other elevated lithium level, 1.44 mmol/L, in 2006. Otherwise, her lithium levels consistently ranged from 0.3 mmol/L to 0.8 mmol/L. A pelvic exam, cystoscopy, and pelvic ultrasound were negative. A kidney ultrasound revealed increased echogenicity of the periphery of the medullary pyramids, of uncertain etiology, but thought to be most commonly seen in the setting of medullary nephrocalcinosis. However, an X-ray of the kidneys, ureters, and bladder (KUB) was negative for renal calcinosis. A computed tomography (CT) of the abdomen and pelvis revealed renal tubular ectasia. HIV test was negative. She was tapered off lithium, as nephrology thought this was the culprit for the renal ectasia. Two months after this incident, she had a follow-up outpatient visit with nephrology. LK presented to this visit with no urinary complaints. Nephrology ruled out HIV-induced nephropathy with negative HIV antibodies. Therefore, they maintained that lithium caused her renal ectasia and advised her to remain off lithium. Her bipolar disorder is stable and treated with lamotrigine 200 mg daily.

Lithium is filtered by the glomeruli and eliminated from the body almost exclusively by the kidneys.² Approximately 80% of filtered lithium is reabsorbed, mainly by the proximal tubule, with a lesser effect by the loop of Henle and the collecting duct. Factors that affect GFR and proximal tubule reabsorption can influence lithium’s clearance and lead to toxic adverse renal effects. Risk factors for renal toxicity, in addition to chronic therapy, include frequent lithium intoxications, chronic physical illness, age, and drug interactions.³

Hestbech et al., in 1977, conducted the first renal biopsy study to investigate the association between chronic lithium treatment and interstitial nephritis;⁴ 13 of the 14 patients included in this study showed morphological kidney changes, including tubular dilation. Follow-up renal biopsy studies supported these initial findings of structural kidney changes with preservation of the glomerular function in those patients prescribed chronic lithium.^2,5

Morphological kidney changes such as renal tubular ectasia due to chronic lithium treatment may be an unavoidable adverse effect. Clinicians need to be aware of this occurrence and mitigate it through renal-function monitoring and avoidance of risk factors for lithium toxicity.