Abstract

The mechanism by which the mammalian kidney creates the osmotic gradient necessary for urine concentration remains an open question. We present a brief survey of the give-and-take between theory and experiment on this question over the last half century. We start with the introduction of the countercurrent multiplier paradigm in 1951. We finish with a description of a recent suggestion that the explanation for the enigmatic inner medullary osmotic gradient may reside in the very metabolism of the inner medullary cells, which are required by the region's hypoxia to obtain their ATP largely from anaerobic glycolysis and which thus, by the same token, furnish net osmoles to the medullary interstitium by convering glucose to lactate.