Chronic progressive renal lesions induced by lithium

Abstract

New Zealand white rabbits, eight fed lithium (Li) (50 to 250 mmole LiCl/kg food) and seven controls (C) had sequential open renal biopsies at zero, one, three, six, and 12 months. A distinctive histological lesion, consisting of cytoplasmic vacuolation and accumulation of glycogen in cells lining distal convoluted tubules and collecting ducts, was present in Li (one, three, six, and 12 months), but was absent in Li prior to lithium (zero months) and in C (zero, one, three, six, and 12 months). Histological changes of chronic focal interstitial nephropathy namely, interstitial fibrosis, (quantitated by point counting), tubular atrophy and cast formation (quantitated by digitization), and glomerular sclerosis (determined as the percent of sclerosed glomeruli) showed significant differences between Li and C from as early as one month (interstitial fibrosis, P < 0.02; tubular atrophy, P < 0.05; casts, P < 0.05), and up to 12 months (glomerular sclerosis, P < 0.05). Distal tubular dilatation and microcyst formation, (quantitated by digitization) was also marked in Li compared with C from one month (P < 0.05). The degree of distal tubular dilatation and other changes of interstitial nephropathy tended to progress with duration of lithium exposure. Macroscopically, Li kidneys (12 months) were pale, granular, and exhibited microcysts. Raised blood urea (P < 0.02) and serum creatinine levels (P < 0.05) were also late features (12 months) of lithium-induced nephropathy. The data support the view that lithium induces chronic renal lesions. The precise relationship between the distinctive distal tubular lesion, distal tubular dilatation and focal interstitial nephropathy remains speculative.