Analysis of the relation between lithium clearance and sodium clearance in rats

In rats on a normal or high sodium intake, lithium clearance (CLi) is thought to approximate fluid delivery to the end of the proximal tubule (Vprox), whereas in rats on a very low sodium intake CLi is lower than Vprox owing to significant reabsorption of lithium in the distal nephron. This paper examines the relation between CLi and sodium clearance (CNa) in animals adapted to a range of dietary sodium contents (5-300 mmol/kg). Measurements were performed in conscious, unoperated rats with hereditary diabetes insipidus, in which changes in urine flow rate (V) can be used as an index of changes in Vprox; stimulation of distal lithium reabsorption was identified by comparing changes in CLi with the corresponding changes in V. CLi exhibited a curved, positive relation with CNa, with considerable scatter and a sharp decrease of CLi at low values of CNa. Further analysis indicated that this relationship consisted of three elements: (i) an almost unaltered Vprox in response to variations in dietary sodium: taken alone, this would result in a horizontal regression of CLi on CNa. (ii) Distal reabsorption of lithium in rats on very low sodium intakes, bending the curve towards low CLi values at low values of CNa. (iii) Intra-individual variations in Vprox, causing covariation of CLi and CNa; the slopes of the regression lines linking the two depended on the level of sodium intake, but all the regression lines intercepted the CLi axis at a similar (low) value of CLi, making a major contribution to the curved shape of the relationship. It is concluded that observations of greatly reduced values of CLi at low values of CNa cannot be taken as unequivocal evidence, per se, of distal reabsorption of lithium. Nor should measured values of CLi be corrected for differences in CNa.