The isolated perfused kidney: Possibilities, limitations and results

Abstract

Despite its potential interest, the use of isolated perfused kidneys in experimental investigation has been hampered by certain drawbacks such as the impairment of blood circulation. Several of them have been solved. Simple circuits, using the kidneys of small animals and cell free perfusion fluids, have been used successfully for metabolic and pharmacologic studies. A quantitative approach of the regulation of urine secretion requires the use of whole blood. The quality of the results depends upon careful control of many technical details, however small they might appear. Under the best conditions achieved so far, one cannot avoid a progressive loss of vascular tone, some redistribution of intrarenal blood flow, a moderate reduction of glomerular filtration rate, a loss of urine acidification and a progressive impairment of the ability to concentrate the urine. The isolated kidney cannot be considered to be a suitable tool for the study of intrarenal circulation or the regulation of acid base balance. Serious difficulties are the lack of stability of the preparation whose functional indexes undergo progressive changes, and the sometimes unpredictable differences observed between individual experiments. It is, however, possible to solve many of these problems by the simultaneous perfusion of the 2 kidneys of the same pair, by two identical machines with identical blood. One definite index can then be modified on one side, the other side serving as a reference at each corresponding period. Statistical evaluation of the results can be made on the basis of a reasonable number of impaired values, and small differences can be demonstrated with an accuracy which is probably impossible to reach without simultaneous control. The authors believe that the paired experiments represent the best way to get accurate results. There is little doubt but that more extensive use of this technique may help to elucidate some problems such as renal effect, secretion, catabolism or excretion of various hormones. Study of the regulation of urine excretion requires the use of blood perfused kidneys. Two main points should always be kept in mind: on one hand, this preparation practically represents the only possible and logical way to identify autonomous renal mechanisms; on the other hand, even under the best available conditions, there are still several functional abnormalities which may reduce the physiological significance of the results. It might be assumed that, when the behavior of the isolated kidney differs from the behavior of the kidney in situ, the results must be interpreted with caution, albeit the knowledge of the reasons of the differences may be of significance. When the systematic comparison of the results obtained with this technique and in other experimental conditions (in situ or transplanted kidneys) none of which is devoid of its own limitations, gives identical results, then it may be concluded with a reasonably high degree of certainty that the mechanisms involved depend on the kidney itself and are of valuable pathophysiologic significance.