Small intra- and large inter-individual variability in lithium clearance in humans

We report the inter- and intra-individual variability in fractional lithium clearance (C(Li)), an alleged quantitative index of Na and water delivery from the proximal tubules, in humans (N = 91). The inter-individual variability was large, the variation coefficients at various Na excretion rates ranging between 11% and 19%. The intra-individual variability was small, the relative intra-individual standard deviation for duplicate measurements (N = 33) being 5%. These observations suggest large inter-individual differences in proximal tubular Na reabsorption. To confirm this, we also studied the inter- and intra-individual variability in the maximum urine flow during water diuresis (V(max)), an index of Na delivery to the diluting segment. They were found to be almost identical to the inter- and intra-individual variability in C(Li), and fractional C(Li) and V(max) correlated strongly (r = 0.83, P < 0.001). In addition, the inter-individual variability in the fractional clearance of uric acid (C(UA)), a directional marker of Na reabsorption in the proximal tubules, was large, but the intra-individual variability small. The correlation between fractional C(UA) and C(Li), however, was relatively weak (r = 0.40, P < 0.01). Although our results do not prove the exact, quantitative validity of the lithium clearance concept, we conclude that the variability in C(Li) reflects large inter-individual differences in Na handling in the proximal segments of the nephron. Our observations also have implications for the use of the lithium clearance method. The large inter-individual variability in C(Li) makes the method less suitable to detect subtle differences in C(Li) in small, unpaired groups of subjects. Due to the small intra-individual variability, however, C(Li) is a sensitive tool to detect small changes in tubular Na handling within individuals, provided that Na intake is not altered.