Lithium toxicity: A double-edged sword

A 62-year-old white male, with a bipolar disorder treated with lithium, a history of type II diabetes mellitus, and hypertension, was referred to the renal clinic for evaluation of nephrotic syndrome and stage IV chronic kidney disease (CKD) ( Modification of Diet in Renal Disease glomerular filtration rate 26 cc/min/1.73m(2)). The patient had a history of bipolar disorder treated for over 10 years with lithium until 2 years ago when a diagnosis of nephrogenic diabetes insipidus and mild CKD was made and lithium discontinued. At that time, he had a urine osmolality of 272mOsm/kg and a serum creatinine of 1.5mg/dl. His medications included lisinopril, atenolol, gemfibrozil, haloperidol, quetiapine, metformin, and bupropion SR. There was no history of polyuria or polydipsia. Review of systems revealed no other significant symptoms. On examination, blood pressure was 133/64mm Hg, heart rate 70 beats per minute, regular rhythm. Lung and cardiovascular examination were unremarkable. Abdomen was soft, nontender with no organomegaly. Extremities revealed trace edema. Urine examination revealed a specific gravity of 1.012, pH 5.5, 3 + protein, negative blood and no casts. His urine albumin creatinine ratio 3 months before was 3.9 g protein per gram creatinine. His laboratory investigations revealed BUN 40mg/dl ( reference range 9-25mg/dl), creatinine 3.0mg/dl (0.7-1.3mg/dl), potassium 5.6mEq/l (3.5-5.0mmol/l), glucose 72mg/dl (5-118mg/dl), HbA1C 4.8 (4.2-5.8%), serum total proteins 6.2g/dl (6-8g/dl), albumin 3.5g/dl (3.7-5.4g/dl), cholesterol 208mg/dl (140-199mg/dl), triglycerides 626mg/dl (35-150mg/dl), low-density lipoprotein 78mg/dl (50-129mg/dl), hemoglobin 13.2g/dl (11.5-16.4g/dl), and hematocrit of 37.7% (36-48%). Complements and other serologic tests were negative. Renal ultrasound revealed bilateral nephromegaly (right kidney 12.6cm and left kidney 12.9cm) with a diffuse increase in echogenicity and innumerable tiny cysts throughout the kidney (cortex and medulla) (Figure 1). There was no evidence of hydronephrosis. A clinical diagnosis of nephrotic syndrome was made and it was decided to proceed to a kidney biopsy.