Effect of chronic lithium treatment upon the Na(+)-coupled cotransporters in renal brush border membranes.

While the most frequent and prominent side effect of the chronic lithium (Li) administration is dysfunction of collecting ducts and polyuric syndrome, some reports also suggest defects in functions of proximal tubules. We determined the transport properties of brush border membranes (BBM) from kidneys of rats chronically fed for four weeks a chow containing Li (60 mmol/kg; Li-rats) and compared them with BBM from placebo-treated controls. BBM from Li-rats did not differ from controls in Na(+)-gradient-dependent transport of 32Pi, D-[3H]-glucose or L-[3H]-proline, but showed a considerable increase in the transport rates of [14C]-citrate (delta + 53%; P < 0.001) and [14C]-succinate (delta + 48%, P < 0.005), and also enhanced the rate of Na(+)-H+ antiport across BBM (delta + 30%, P < 0.05). In contrast, direct addition of 1 mM Li to BBMV in vitro inhibited Na(+)-dependent transports of both citrate and succinate. The Li-rats had higher plasma level of citrate and decreased (delta - 50%) renal clearance of citrate. Our results show that chronic exposure to oral Li in vivo results in increased Na(+)-gradient-dependent transport of polycarboxylic acids and increased Na(+)-H+ antiport in BBM of proximal tubules; these changes are contrary to effects of Li added to isolated BBM in vitro.