Clearance Concept in Renal Physiology

Abstract

In 1928 Donald D. Van Slyke (see Fig. 2) and associates (25) introduced the word “clearance” to indicate the urinary output of urea per minute relative to its concentration in blood, defining it as the volume of blood completely “cleared” of urea per minute when urine flow exceeds 2 ml/min. Fifteen years later Homer W. Smith [see Fig. 6; (42)] wrote: “In my opinion this word has been more useful to renal physiology than all the equations ever written. In recent years,” he added, “it has broken loose from the excretion of urea and, taking conceptual wings, has become a generalized notion applicable to all aspects of renal excretion.” Smith’s admittedly somewhat startling assertion has found its justification in major contributions to our understanding of kidney function that can be ascribed in part to attention focused by an apt and useful term on a potentially effective new methodology and on the body of concepts from which it has emerged. The fundamental concept itself can be traced, in fact, as far back as July 1870 to a meeting of the Physikalisch-Medizinische Gesellschaft in Würzburg at which Professor Adolf Fick (see Fig. 4) presented a very short paper outlining a method of measuring cardiac output in dogs (14a). Fick’s method depended on much the same mathematical formulation introduced by Van Slyke, but it was used for measuring carbon dioxide clearance by the lungs and, in doing so, for evaluating total blood flow (or cardiac output) through the lungs. In this seemingly ambiguous statement, that clearance measures simultaneously an excretion of a solute and a volume of fluid flow, lies a source of some confusion in the understanding and application of the clearance principle.