RT Journal Article SR Electronic T1 AN EXPERIMENTAL AND CLINICAL STUDY OF THE FUNCTIONAL ACTIVITY OF THE KIDNEYS BY MEANS OF PHENOLSULPHONEPHTHALEIN JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 579 OP 661 VO 1 IS 6 A1 L. G. ROWNTREE A1 J. T. GERAGHTY YR 1910 UL http://jpet.aspetjournals.org/content/1/6/579.abstract AB In all over two hundred functional tests have been performed on one hundred and fifty different subjects. In normal cases the drug appears in the urine in from five to ten minutes, and 40 to 60 per cent of the 6 mg. dose, the average being about 50 per cent., is recovered in the first hour. From 15 to 25 per cent of the drug administered is recovered in the second hour, making the total recovery for two hours 61 to 85 per cent. We do not consider the time of total elimination as of as much value as the amount of elimination for a definite period. In most of the work done in the past where total renal function [See table in the PDF file] was under estimation, the time for complete elimination has been alone considered. This admits a source of error apparently not hitherto recognized. This error is due to the fact that diseased kidneys tend to work at their maximum. For instance, a normal case will eliminate the largest proportion of indigo-carmine during the first hour, consequently leaving less in the circulation for elimination in the succeeding hours; while the diseased kidneys, though eliminating a smaller proportion for the first hour, will eliminate almost as much in the second and third hours so that the total quantity of drug excreted at the end of three or four hours may be practically the same whether the kidneys are normal or diseased. This error, of course, assumes most importance where the lesser grades of renal involvement exist and in connection with those substances requiring many hours for elimination. The time of appearance of phthalein in the urine is five to ten minutes when the secretion of urine is free, but even in health this may be delayed when the secretion is very scanty. Following its appearance the intensity rapidly increases and reaches its maximum in from fifteen to twenty minutes. At the end of an hour to one hour and a half, as a rule, an appreciable decrease in the density becomes manifest. A tapering diminution occurs from the end of the first hour. At the end of the second hour only a definite pink is obtained on addition of an alkali. In the majority of instances excretion is practically complete at the end of two hours. The application of this test in the various types of nephritis has given the following results: In three cases of acute nephritis no increased permeability of the kidney has been demonstrated, but in two out of the three cases a marked decrease in the amount of elimination has been observed. In eight cases of parenchymatous nephritis with one exception there has been a marked decrease in the amount excreted. In one case only 10 per cent was excreted in two hours. The greatest decrease has been noted in cases where clinically, marked secondary sclerotic changes were considered to be present. In ten cases of chronic interstitial nephritis a low output was encountered in each instance, the decrease being usually proportionate to the degree of severity of the disease as estimated clinically. In two cases only a trace of the drug—less than 1 per cent—was eliminated in the course of an hour. Both cases died of uræmia within two months. The curve of elimination in nephritis differs from the normal in that the maximum intensity is slowly reached, giving a slowly rising curve to the maximum, which is frequently not attained until the second hour. The excretion of the second hour is usually greater than that of the first. Urinary Obstruction. In sixty cases with obstruction in the lower urinary tract, almost all being patients with hypertrophy of the prostate, the elimination of the dye has been studied. It is a difficult proposition to size up the situation in many of these patients. They are frequently the subjects of pyelonephritis, pyonephrosis, pressure atrophy and the resulting changes in functional activity. The urine output, urea, and total solids may be practically normal and yet the patient be on the verge of a renal failure which will be precipitated by any operative interference. The phthalein test has given valuable information in all these cases and has enabled us to differentiate those cases with severe renal damage from those in which the renal involvement is slight. As a rule the test has demonstrated the greatest impairment of function in those cases which have large residual urine and have not been leading a catheter life. Clinically, this type of case is recognized as the most dangerous when operation is undertaken without preliminary treatment. In many instances in which the output of drug was low when the patient was first seen, the adequate régimé described above has resulted in a decided improvement of the kidney function as indicated by the test. When the time of appearance is delayed beyond twenty-five minutes and the output of drug is below 20 per cent for the first hour, operation is postponed regardless of the patient's clinical condition. If, under routine treatment, the output remains low but constant, the renal function is probably in a stable condition and the operation may be undertaken, care being taken to select an anesthetic which will not further depress the renal function. In one instance a successful operation was performed with an output of 8 per cent for the first hour, but this output had remained constant for a period of five weeks. The low output here was ascribed to chronic interstitial changes in tne kidney, and nitrous oxide was accordingly employed. When the residual urine is large and the patient has not been leading a catheter life, even if the output at a single determination is large, operation is deferred in order to determine whether the functional activity is stable, for it has long been recognized that following the relief of retention the function of the kidney is extremely variable. Repeated determinations should be made, and, except when unavoidable, operations should not be performed when the tests indicate a decreasing function. There have been two such cases in our series in both of which operation was followed by death from acute suppression. Again when only a trace of dye is excreted operation should not be attempted, as grave renal changes exist. Two cases excreting only a trace died of uræmia within a short period. In neither case was any operation performed, though clinically at the time of the first test no evidence of uræmia was detected. The application of this test has brought forward new evidence as to the marked improvement in the renal conditions which accrues as the result of the preliminary treatment introduced some years ago by Dr. Young. Many cases in our series which on admission showed a very low output, under this treatment show a progressive increase in the amount eliminated. The output has increased from as low as 8 per cent to practically normal. The test has made it possible to select a time for operation when the kidneys have regained their full functional power and stability. In no case in which the functional test indicated an efficient or stable renal function prior to operation, has any evidence of renal inefficiency become apparent subsequently. Phloridzin has been tried in a number of these cases and has not proven practicable nor reliable. In several cases in which it was used no glycosuria appeared in three hours, though the phthalein test indicated a satisfactory renal function, which was corroborated by the clinical condition and by the absence of evidences of renal inadequacy following operation. Unilateral Cases. It has been demonstrated that the time of appearance and the percentage output is practically the same for the two healthy kidneys. When one kidney only is diseased, the time of the appearance of the drug is delayed on the diseased side and the amount excreted is not only relatively but absolutely decreased. The amount of delay in the time of appearance is comparatively of little value. Reliance is only to be placed upon the quantity excreted during a period of at least one hour. It is possible by using large doses and extending the observations for a period of two hours, each side being collected separately, to demonstrate in some degree the reserve functional ability of each kidney. Although in the majority of these cases of unilateral disease the combined output is equal to that of two normal kidneys, the greater part of the excretion is shown to be performed by the healthy kidney. In proportion to the decrease in function on the diseased side, approximately there is a proportionate increase in the function on the healthy side. In such cases following nephrectomy the remaining kidney eliminates an amount of drug which is normally excreted by two healthy kidneys. In all cases studied the output from the remaining kidney has been greater than the combined output from the two kidneys prior to operation. In one case of pyelitis no disturbance of function was indicated.