Lithium isotopes: differential effects on renal function and histology

Objectives: Reduction in renal concentrating ability has been reported in p atients undergoing chronic lithium treatment. Prior work has demonstrated d ifferences in physiological effects of the stable lithium isotopes, Li-6 an d Li-7. Here, we measured the degree of polyuria, polydipsia and kidney his tological changes induced in rats by equimolar amounts of (LiCl)-Li-6, (LiC l)-Li-7 and the commercially available mixture of both isotopes. Methods: Rats were given 1.0 mEq/kg of either (LiCl)-Li-6, (LiCl)-Li-7 or ' (LiCl)-Li-n' (isotope mixture, 93% (LiCl)-Li-7) by subcutaneous injection t wice daily for up to 49 days. Twenty-four-hour urine volume and water intak e were measured daily. Kidneys from rats treated for 7 days with 1.5 mEq/kg (LiCl)-Li-6, (LiCl)-Li-7 and vehicle were examined under light microscopy and histopathologic changes graded on a 4-point scale of severity. Results: All rats showed loss in renal concentrating ability manifested by increasing urine volume and water intake. Peak effects occurred after 9-13 days treatment, then declined to Stable levels at two to three times pre-tr eatment level. Mean peak effect was significantly greater for (LiCl)-Li-6 t han for (LiCl)-Li-7. Chronic effects of (LiCl)-Li-6 (weeks 3-7 of treatment ) on polyuria and polydipsia were persistently higher than that of (LiCl)-L i-7. (LiCl)-Li-n effect was intermediate. Kidneys from rats treated for 7 d ays with (LiCl)-Li-6 showed more frequently severe lesions in renal tubules than did (LiCl)-Li-7-treated rats. Conclusions: Our current data and prior studies suggest that elimination or reduction of Li-6 from pharmaceutical preparations may merit further evalu ation as a possibly less potentially nephrotoxic form of lithium treatment.