Laboratory Investigation

Kidney International (1993) 43, 1074–1080; doi:10.1038/ki.1993.150

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

Ahad NK Yusufi1, Sten Christensen1 and Thomas P Dousa1

1Nephrology Research Unit, Division of Nephrology and Internal Medicine, Departments of Medicine and Physiology, Mayo Clinic and Foundation, Mayo Medical School, Rochester, Minnesota, USA

Correspondence: Thomas P Dousa MD PhD, 921B Guggenheim Building, Mayo Clinic, Rochester, Minnesota 55905, USA.

Received 21 August 1992; Revised 14 December 1992; Accepted 15 December 1992.

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Abstract

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 poly-carboxylic 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.

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