Lithium clearance in mineralocorticoid escape in humans

Lithium clearance (CLi) has been advanced as an indicator of Na delivery from the proximal tubules. We studied CLi in eight healthy males before and after mineralocorticoid escape, a maneuver that may induce suppression of fractional proximal Na reabsorption (FPRNa). FPRNa was also estimated from changes in maximal free water clearance (CH2O). According to the latter method, FPRNa dropped from 85.7 +/- 2.2 to 81.3 +/- 3.4%, whereas inulin clearance rose from 125 +/- 11 to 149 +/- 15 ml/min. The changes in CLi were surprisingly large, from 40.6 +/- 7.6 to 75.8 +/- 18.4 ml/min. If lithium is a valid marker of Na handling in the proximal tubule in humans, this change would imply a fall in FPRNa from 67.5 +/- 3.9 to 49.7 +/- 9.0%, suggesting a much larger shift in tubular Na reabsorption in escape than hitherto suspected. In addition, it would suggest that the inevitable back diffusion of a part of the solute-free water in the distal nephron, and thus overestimation of FPRNa by the CH2O method, increases importantly during escape. Alternately, lithium may not be a good marker of proximal tubular Na handling. For instance, both lithium reabsorption and escape may take place beyond the proximal tubule, or lithium may be excreted in the distal nephron in certain conditions. Present methods do not permit further analysis of these options in the human model.