SEVERE FUNCTIONAL AND STRUCTURAL CHANGES CAUSED BY LITHIUM IN THE DEVELOPING RAT KIDNEY

Abstract

Li [used in the treatment of manic-depressive illness] was administered to rats during maternal pregnancy and/or 8 wk postnatally, to study the effects on renal function and structure in the developing kidney. Plasma Li was 0.5-1.0 mmol/l 3 and 8 wk postnatally. Functionally, postnatal Li leads to growth retardation, polyuria with lowering of renal concentration ability, and uremia associated with as much as 80% lowering of the normal glomerular filtration rate (GFR). Prenatal Li alone did not affect the concentrating ability but caused a 20% increase in GFR when evaluated 8 wk postnatally. Postnatal Li caused very severe structural changes, consisting of up to 3-mm cortical cysts (= dilated distal convoluted tubules), extensive interstitial fibrosis with cell infiltration, and atrophy of the cortical collecting ducts. Morphometric measurements showed a significant reduction in the volume of the proximal tubular cells. Prenatal Li caused only slight structural changes, and animals treated both pre- and postnatally were less affected than animals treated postnatally only. The structural changes caused by postnatal Li were unrelated to changes in the concentrating ability but showed a significant correlation with the lowering of the GFR. Apparently, the postnatally developing rat kidney is particularly sensitive to the nephrotoxic effects of Li, which in low concentrations causes impairment of renal function, leading to uremia. Prenatal Li exposure by maternal Li treatment had little effect on renal function and structure when evaluated postnatally.