Studies of the urinary acidification defect induced by lithium

Abstract

Experiments were carried out in rats and isolated turtle bladders to study the defect in H+ transport induced by LiCl. After 3-4 days of intraperitoneal LiCl, rats developed urinary findings of "distal" renal tubular acidosis. Proximal tubular fluid pH measured in situ by glass microelectrodes was higher in lithium-treated rats than in acidotic controls. Proximal fluid total CO2 [tCO2] was also higher, and the fraction of tCO2 leaving the proximal tubule was 14 vs. 7% (P less than 0.001). Impaired acidification was also apparent beyond distal convoluted tubules, as judged by normal distal tCO2 reabsorption but increased HCO3(-) in the urine. During NaHCO3 loading, the proximal defect was ameliorated but not the distal. Turtle bladder studies showed that mucosal lithium inhibits H+ secretion secondary to reducing transepithelial electrical potential, presumably by hyperpolarization of the luminal membrane. A similar mechanism may be responsible for lithium's effect on the distal nephron. Inhibition of proximal tubular HCO3(-) reabsorption is probably not attributable to electrical potential changes but might be due to interference of luminal membrane Na+ entry by Li+ and reduced (Na+ + Li+)-H+ exchange.

Effects of chronic lithium administration on renal acid excretion in humans and rats

“…It is important to recognize that the studies in the current report reflect effects of chronic lithium exposure. Numerous studies show that acute lithium exposure is associated with impaired urine acidification and collecting duct proton secretion (Homer and Solomon 1962;Roscoe et al 1976;Nascimento et al 1977;Arruda et al 1980;Bank et al 1982;Dafnis et al 1992). To some extent, these may be related to the effects of lithium in impairing electrogenic, ENaC-mediated sodium reabsorption and thereby decreasing development of the luminal negative voltage necessary for normal rates of proton secretion.…”

The Clinical Spectrum of Renal Tubular Acidosis

“…In amiloride-treated rats, infusion of bicarbonate or phosphate produces only subnormal increases in urinary pC02• Urine pH is also abnormally alkaline after sodium sulfate infusion (29). Lithium therapy probably produces a similar although less severe defect (30). Seme patients with normal aldosterone levels can have a selective resistance to aldosterone, as for example infants with the disorder pseudohypoaldosteronism, who exhibit urinary salt wasting and hypo tension accompanied by mineralocorticoid resistance (14).…”

Relationship between erythrocyte lithium concentration and renal concentrating capacity

“…The earliest manifestations of lithium nephrotoxicity are polyuria and a urinary acidification defect (3–5). Polyuria occurs in 70% of lithium‐treated patients.…”