Lithium toxicity: A double-edged sword

Abstract

CASE PRESENTATION 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/1.73 m 2 ). The patient had a history of bipolar disorder treated for over 10 years with lithium until 2 years ago when a diagnosis of KIDNEY BIOPSY On light microscopy, 16 glomeruli were observed. Seven (44%) were globally sclerosed and two revealed segmental capillary collapse, with hyaline entrapment and adhesion of the tuft to the Bowman's capsule (Figure 2). The remaining glomeruli showed a normal architecture, with mild mesangial hypercellularity associated with diffuse increase in the extracellular matrix. The glomerular basement membranes revealed focal irregularities and short segments with double contours. Tubules revealed extensive atrophy (45%) with thickening of tubular basement membranes. Many micro cysts, ranging in size from 1 to 2 mm, were noted. These were localized in the cortex and along the corticomedullary junction. The lining was of low cuboidal epithelial cells. Pericystic stromal fibrosis was apparent (Figure 3). Focal calcification and protein reabsorption granules were also noted in many tubules. The interstitium showed prominent areas of fibrosis (45%) and interstitial inflammation by mononuclear cells and very rare polymorphonuclear cells. Interlobular arteries and arterioles revealed moderate changes of arteriosclerosis. Congo-red stain was negative. No significant deposits were observed on immunofluorescence microscopy, except for nonspecific trapping of immunoglobulin M and C3 in the mesangial areas. Tubular basement membranes revealed focal deposition of C3 ( þþþ /4 þ ). A single sclerosed glomerulus was observed on semithin sections hence the tissue was not examined at ultrastructural level. A biopsy diagnosis of chronic active interstitial nephritis likely secondary to lithium toxicity was made. The presence of numerous cortical micro cysts and the focal global and segmental glomerulosclerosis (FSGS) were also attributed to lithium.