The Utilization of Radioactive Iodinated Hippuran for Determination of Renal Clearance Rates

Abstract
Radioactive tagging of chemicals has given the investigator a means of simplifying tests for many physiologic functions. Quantitative assays of renal function hitherto have been cumbersome, and to some degree hazardous, in view of the possible introduction of infection if bladder catheterization must be employed. Yet greater accuracy in the study of split renal function is now more important than ever, with the increased interest in surgical corrective measures, particularly for renovascular hypertension. With these considerations, a study was undertaken with the following objectives: (a) To determine whether or not a radioactive clearance study technic could be developed which would parallel standard technics. (b) To determine whether or not such a technic could be adapted to human use without subjecting the patient to excessive radiation from large amounts of the labeled compound. (c) To simplify the basic technic to a single intravenous injection, with avoidance of catheterization through the use of external scintillation detector devices over the bladder. (d) To discover if “whole blood” determinations could be substituted for the conventional “plasma” determinations, thus simplifying the laboratory procedure further. Basic Review of Renal Physiologic Mechanisms Involved It has been accepted that filtration of the plasma occurs in the renal glomeruli and that fluid isolated from Bowman's capsule is normally protein-free and has the characteristics to be expected of a simple filtrate in respect to osmotic pressure, electrical conductivity, glucose, pH, sodium, potassium, chloride, phosphate, urea, uric acid, creatinine, phenol red, and inulin. It follows that substances present in the filtrate, but absent from the bladder urine, must be reabsorbed in the tubules and that other substances such as urea and creatinine undergo concentration between the glomerulus and the bladder. Such concentration may result from reabsorption of water or additional excretion by the tubules. Inulin has become the standard for reference for measuring glomerular filtration. Para-amino-hippuric acid (PAH) is almost completely extracted from the plasma in a single circuit, and almost completely handled in the kidney by secretion through the tubules (tubular transport). Hence, PAH clearance is a measure not only of tubular function, but also of renal plasma flow. The extraction ratio is the ratio of any substance in the renal artery (A) less that in the renal vein (V) to the amount in the artery, or: PAH has an average extraction ratio of 0.91, and hence PAH clearance may be taken as an approximate measure of renal plasma flow. Clearance rate of any substance, X, represents the volume of plasma required to supply the quantity of X excreted in the urine in one minute's time. This is expressed as: where C is the clearance rate of X in ml./minute V is urine excreted in ml./minute P is plasma concentration, mg./c.c. (X) U is urine concentration, mg./c.c. (X)