Renal clearance and isolated kidney perfusion techniques

Abstract

Renal techniques are in essence measurements of input—output relationships of endogenous or exogenous substances in the kidney. When judiciously applied and interpreted, techniques measure whole kidney functions and, therefore, are useful to assess the effects of systemic factors or substances on total kidney function. As such, they are still an indispensable tool in the armamentarium of physiologists, pharmacologists, nephrologists, and clinical investigators. In addition, earlier investigators in the decades spanning the 30s to the 60s applied techniques to gain insights as to nephron sites and mechanisms of transport processes [11. Some of the most brilliant inferences in our field come from such early application of the techniques, and they still serve as inspiration for many of the research efforts of present day investigators. With the advent of more direct techniques at the tubular, cell, membrane and molecular levels, such indirect use of techniques rightfully lost some of its appeal. Nevertheless, because of their simplicity and power, techniques are still useful, on the one hand, to direct the application of more modern technologies and, on the other hand, to integrate the information obtained with the latter into a coherent description of whole kidney function. In the first part of this article, I will present some of the issues regarding the definition, application, and interpretation of techniques without an attempt to cover the field. For a detailed analysis of techniques, the reader is referred to the excellent review articles by Levinsky and Levy [21 and by Schuster and Seldin [31, which also contain extensive bibliographical references. The first issue to be addressed is the definition of the term renal clearance. The term was defined by Moller, McIntosh, and Van Slyke [4], Holten and Rehberg [51, and Homer W. Smith [6], as the ratio of U, . V P, where U, and P,, are the urine and plasma concentrations of a substance and V is the urine flow rate. Conceptually, textbooks also use the two descriptive definitions by Homer W. Smith: clearance is the volume of plasma required to supply the quantity x excreted in urine each minute time or clearance is the virtual volume of plasma completely cleared of that substance in one minute's time [6]. The equation and the first of the above