Functional and structural changes in the rat kidney by long-term lithium treatment.

The relation between functional and structural renal changes induced by lithium was studied in rats during long-term treatment and after withdrawal of lithium. Administration of LiCl in the diet for up to 21 weeks caused marked polyuria associated with a significant lowering of renal concentrating ability assessed by dehydration and vasopressin tests. Plasma creatinine and plasma urea were not significantly changed by the treatment. Upon withdrawal of lithium water intake and concentrating ability were normalized within 4--8 weeks. Lithium caused focal light microscopic changes in the distal convoluted tubule and the collecting duct, consisting of nuclear and cellular polymorphism and, after prolonged treatment, dilatation of tubular lumens with tubular cell atrophy. These changes appeared later than the concentrating defect and persisted when lithium was withdrawn after prolonged treatment. No significant correlation was found between the degree of tubular changes and water intake or concentrating ability. It is concluded that the reversible diabetes insipidus induced by lithium in rats cannot be explained directly by the light microscopical changes observed in the distal part of the nephron, although the structural changes may be secondary to the polyuric state induced by lithium.