Distinction between proximal and distal regulations of sodium and potassium excretion in humans

The clearances of creatinine (CCr), lithium (CLi), sodium (CNa), and potassium (CK) were determined during three consecutive 2-hour periods in a large number of physically healthy persons who were in lithium treatment for manic-depressive illness. CLi was used as a measure of the proximal tubular fluid output (Vprox). CLi showed considerable spontaneous variations from one 2-hour period to another, and neither bladder emptying errors nor changes of CCr could account for these. The variations of CLi, which reflected variations of Vprox, resulted in joint variations of CNa and CK. Also the ratios CNa/CLi and CK/CLi, which reflected the distal handling of sodium and potassium, showed considerable spontaneous variations. These were correlated neither with each other nor with variations of CLi. Our study indicates that through the use of CLi as a measure of Vprox it is possible to distinguish between a single joint proximal regulation and two separate distal regulations of sodium and potassium excretion. Further studies concerning the interplay between proximal and distal regulations under normal and pathological conditions may provide deeper insight into the way in which the kidney functions.