Lithium-induced uraemia in rats: survival and renal function and morphology after one year

Chronic renal failure was induced in Wistar rats by administration of a LiCl-containing (40 mmol/kg) diet from birth until an age of 55-65 weeks. The 55 weeks mortality was 51% in Li-uraemic rats versus 6% in control rats. In surviving rats the mean plasma Li levels were 0.6-0.7 mmol/l after 16 weeks and 1.0-1.1 mmol/l after 48 weeks. The mean plasma urea level was 14 mmol/l after 16 weeks and 22 mmol/l after 48 weeks of treatment compared with 8 mmol/l in the controls rats. In 55 weeks old Li-uraemic rats inulin clearance was reduced by 62% and Li clearance by 39%. Thus, fractional Li excretion was increased (from 20 to 34%) in rats with chronic Li-uraemia. Li-uraemic rats also had polyuria and failed to concentrate their urine in response to exogenous vasopressin. Systolic and mean arterial blood pressures were not significantly changed in rats with Li-uraemia. Morphological examinations of the kidneys showed large cortical cysts formed by dilated distal tubules and collecting ducts and widespread interstitial fibrosis. Proximal tubular mass was reduced by 50% and glomerular volume was also significantly reduced. The results indicate that in rats with Li-induced uraemia renal function and morphology deteriorate during Li-exposure up to an age of one year, associated with increased mortality.