Lithium induced interstitial nephropathy associated with chronic renal failure. Reversibility and correlation between functional and structural changes.

Abstract

We have previously shown that administration of lithium to rats in the first weeks after birth results in a severe interstitial nephropathy. The aim of the present work was to study the relationship between functional impairment and structural lesions and to evaluate whether the nephropathy regresses after withdrawal of lithium. Three groups of animals were studied: 16 weeks-old controls (group A), rats treated with lithium for 16 weeks (group B) and rats treated for 8 weeks followed by 8 weeks without lithium (group C). Plasma urea and renal concentrating ability were determined and one kidney fixed by vascular perfusion with glutaraldehyde for light microscope morphometry. The results show a significant reduction in renal function after lithium treatment. There was a highly significant reduction in proximal tubular length and a pronounced increase in interstitial volume due to severe fibrosis. The total mass of glomerular tufts was also reduced, but not when this parameter was divided by the body weight. Sclerotic glomeruli were not observed. The structural and functional lithium-induced lesions are independent of sex and irreversible, since they persist 8 weeks after withdrawal of lithium. It is proposed that lithium-induced interstitial fibrosis is followed by proximal tubular atrophy with a reduction in the amount of functioning proximal tubules. This leads to a decrease in proximal tubular reabsorption of sodium and a disturbance in the glomerulo-tubular balance resulting in a decrease in glomerular filtration rate.