Rex L. Jamison, MD
Professor of Medicine Stanford University School of Medicine
and Veterans Affairs Health Care System
Palo Alto, California 94304
The modern era of research on the concentrating mechanism is character- ized as a stair constructed of a mathematical model step alternating with an experimental step. Kuhn's countercurrent multiplier model began the era in 1951. It had 3 elements: countercurrent flow in adjacent channels of a U-shaped loop; differing permeabilities of the channel walls; and a source of energy to generate the "single effect" (separation of water from solute) that is multiplied to generate an axial gradient. By experiment, Henle's loop has the requisite flows; its limbs differ in permeability properties; and the thick ascending limb (AL) in the outer medulla has a Na pump. But the thin AL in inner medulla (IM) lacks an active pump. Stephenson, Kokko & Rector devised a passive model: Urea added to the IM from the collecting duct extracted water but not Na from the DL to create a transepithelial gradient for passive Na transport from the thin AL. But by experiment, urea entered the DL rather than extracting water in most species. Wexler, Kalaba & Marsh conceived a 3-dimensional model more akin to IM topography that generated an axial gradient; but experiments did not verify key permeability and topographic assumptions. A newer Wang & Wexler model is " still missing some essential feature." Recent findings by Pallone, Sands, Knepper, Verkman and others of urea transporters and water channels in tubules and vessels in the renal medulla add further data to be incorporated into the next model step. But the stair has clearly reached a new level.