Diaper Phenolsulfonphthalein Test in the Newborn Infant*

THE JOURNAL OF UROLOGY

Vol. 91, No. 2 Februaiy 1964 Copyright © 1964 by The Williams & Wilkins Co. Printed 1·n U.S.A.

DIAPER PHENOLSULFO:'.\i'PHTHALEIN TEST IN THE KEWBORN INFANT* LARRY M. BARSOCCHINI

AND

DONALD R. SMITH

From the Division of Urology, University of California School of Medicine, San Francisco, Cal.

Congenital anomalies of the urogenital tract occur in one of every 500 live births. 1 Many of these anomalies remain silent and are detected late when the child is seen with a recurrent urinary tract infection. However, by this time, most of the patients have irreversible hydroureter or hydronephrosis. The lesions usually exist in spite of a normal blood urea nitrogen or creatinine clearance whereas all obstructive urogenital lesions produce decreased phenolsulfonphthalein (PSP) excretion due to the dilution effect of a large volume of residual urine. Thus many of these lesions could be discovered by the PSP test in the newborn period; this test is an inexpensive, easily performed clinical procedure. Our investigation is based upon the clinical experiences of Lyon2 with the diaper PSP test performed in infants. The value of the PSP test in adults for determining kidney function and residual urine has been amply demonstrated by Smith3 and others. However, there has been little investigation of the test in the newborn period. The present study was undertaken to evaluate the diaper PSP test as a screening procedure and to establish a normal range in the immediate neonatal period.

intramuscularly with a tuberculin syringe, 3) the first 100 patients were injected intragluteally and the rest in the anterior thigh. The diapers were applied very loosely in order to facilitate more diffusion of the dye and were removed at 1-hour intervals for the three 1-hourtest periods. The wet diaper was placed in a 3000 ml. pyrex beaker which was marked off at 1 liter. This beaker was filled with tap water to the ½ to ¾ mark and the wet diapers dropped in. After a 5 minute soaking the diaper was thoroughly wrung out, 10 ml. of 5 per cent sodium hydroxide (N aOH) was added, and the beaker was filled to the 1000 ml. mark. As a control, diapers were taken after they were initially wrung out and placed in a filled 1000 ml. beaker. After soaking for an hour, they were again wrung out. About 10 to 15 per cent dye per 5 diapers selected at random was consistently found, that is, an average of 2 to 3 per cent PSP per diaper that was not extracted in the initial wringing out process. This is a source of error but one which is constant and within the limitations of this technique. The percentage of PSP excreted was determined using the Dunning colorimetric kit which has graduated vials in 5 per cent increments.

SUBJECTS AND ME'I'HODS

RESUL'l'S

This procedure was done routinely on days 1-5 in 200 consecutive full-term infants at San Francisco General Hospital. Because of the relative newborn oliguria and the tarry stools of the first and second neonatal days, most of the tests were done on the third day. The procedure was as follows: 1) no attempt was made to hydrate the infants, 2) 6 mg. (1 cc) of PSP* was injected Accepted for publication July 2, l!l63. * Research project carried out by L. M. B. as a senior medical student. Supported by a United States Public Health Service student summer fellowship. 1 Wallace, H. M., Baumgartner, L. and Rich, H.: Congenital malformations and birth injuries in New York City. Pediatrics, 12: 525-534, 1953. 2 Lyon, R. P.: The diaper PSP test. In press. 3 Smith, D. R.: Estimation of the amount of residual urine by means of the phenolsulfonphthalein test. J. Urol., 83: 188-191, 1960. * Obtained from Hynson, Westcott and Dunning, Inc., Baltimore, Maryland; lots 521 and 542.

The average PSP excretion in the first hour was 18.9 per cent (20 per cent), the second hour average sample was 29.1 per cent (30 per cent), the third hour average sample was 26.7 per cent (25 per cent). The results obtained in the 200 PSP tests are shown in figure 1. In the 200 tests which were run, 21 infants (11.5 per cent) did not void in the 3-hour test period. The 3-hour n1ean was 39.3 per cent (40 per cent) and the standard error was ±0.66 per cent. Below 30 per cent PSP excretion in 3 hours was considered abnormal. Seventy-three of the 200 infants (36.5 per cent) did not void during the 2-hour test period. The mean was 29.7 per cent (30 per cent) and the standard error ±0.38 per cent. Because there is a risk of losing some of the PSP when using the intragluteal site (i.e. oozing of the dye from the skin due to subcutaneous injection) the second 100 infants were injected 195

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FIG. 1. A, total 3-hour phenolsulfonphthalein excretion in 200 consecutive full-term newborn infants. B, total 2-hour phenolsulfonphthalein excretion in 200 consecutive full-term newborn infants.

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in the thigh. 4- 5 Figure 2 shows the two curves (intragluteal). The mean was 39.5 per cent (40 per cent) and the standard error was ±1.11 per cent. In group B (thigh) the mean was 39.1 per cent (40 per cent) and the standard error was ±0.34 per cent. Therefore, the site chosen for the injection did not affect the results. DISCUSSION

It has been shown by Rowntree and Geraghty 6 and others that approximately 90 per cent of the injected PSP is reversibly bound to the albumin fraction of the plasma protein and is then secreted by the renal tubules. The rate of excretion thus

4 Gilles, F. H. and French, J. H.: Postinjection sciatic nerve palsies in infants and children. J. Pediat., 58: 195-204, 1961. 10 20 30 40 50 60 5 Combes, M.A., Clark, W. K., Gregory, C. F. and James, J. A.: Sciatic nerve injury in infants; o/o PSP -excRETEO -recognition and prevention of impairment re3 hr. fofal sulting from intragluteal injections. J.A.M.A., 173: 1336-1339, 1960. 6 Rowntree, L. G. and Geraghty, J. T--c: An experimental and_ cli-nical study oLthe -functional FIG. 2. Total-~3-hour pnenolsulfonphthalein ex- ~activity-o-f--tha kidneys by-means-of phenolsulcretion in 200 consecutive full-term newborn in- phonphthalein. J. Pharmacol. Exper. Therap., 1: 579-661, 1910. fants.

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DIAPER PSP TEST IN NEWBORN INFANT

depends on plasma albumin levels, renal blood flow and renal tubular function. PSPtests have been runextensivelyonadults 3 •7 •8 and children. 2 The results obtained are greater, however, than are the results of this present study. ),. number of investigators have studied renal function in newborns 9· 21 and it has been shmvn that the glomerular filtration rate (GFR), renal blood flow (RDF) and maximum tubular excretory capacity (Tpah) are reduced to approximately 30 to 45 JJer cent of the adult level and do not approximate the adult levels until 20 to 40 weeks of life. TheRe reports also indicate that the newborn infant has a greater deficiency of tubular than glomerular tissue, although it is thought that this deficiency might partially be one of vascularization of the kidney tubules rather than tubular deficiency per se. It has 7 Pierce, J. M., Ruzumna, R. and Segar, R.: Standardization of the phenolsulfonphthalein excretion test in clinical practice. J.A.M.A., 175: 711-713, 1961. 8 Smith, D. R.: Personal communication. 9 McCance, R. A. and Widdowson, E. M.: Normal renal function in the first two days of life. Arch. Dis. Child, 29: 488-494, 1954. 10 JVIcCance, R. A. and Widdowson, E. M.: New thoughts on renal function in the early days of life. Brit. Med. Bull., 13: 3-6, 1957. 11 Winberg, J.: The 24-hour true endogenous creatinine clearance in infants and children without renal disease. Acta Paediat., 48: 443-452, 1959. 12 McCance, R. A.: Renal physiology in infancy, Amer. J. Med., 9: 229-241, 1950. 13 Rubin, M. I., Bruck, E. and Rapoport, M.: Maturation of rnnal function in childhood: Clearance studies. J. Clin. Invest., 28: 1144-1162, 1949. 14 Smith, C. A.: The Physiology of the Newborn Infant. Springfield, Ill.: Charles C. Thomas, 1959, 3rd edit. 15 Barnett, H. L., Hare, W. K., JVIcNamara, H. and Hare, R. S.: JVIeasurement of glomerular filtration rate in premature infants. J. Clin. Invest., 27: 691-699, 1948. 16 Calcagno, P. L. and Rubin, M. I.: Water requirements for renal excretion in full-term newborn infants and premature infants fed a variety of formulas. J. Pediat., 56: 717-727, 1960. 17 Edelmann, C. M., Jr. and Barnett, H. L.: Role of the kidney in water metabolism in young infants. J. Pediat., 56: 154-179, 1960. 18 Vesterdal, J. and Tudvad, F.: Studies on the kidney function in premature and full-term infants by estimation of the inulin and para-aminohippurate clearances. Acta Paediat., 37: 429-440, 1949. 19 West, J. R., Smith, H. W. and Chasis, H.: Glomerular filtration rate, effective renal blood flow, and maximal tubular excretory capacity in infancy. J. Pediat., 32: 10-18, 1948. 20 Williamson, R. C. and Hiatt, E. P.: Development of renal function in fetal and neonatal rabbits using PSP. Proc. Soc. Exp. Biol. & Med., 66: 554-557, 1947. 21 Winter, C. C.: Kidney function tests in children. Calif. Med., 94: 127-131, 1961.

also been shown14 that the plasma albumin level is lower in newborns than in adults. For these reasons, that is, reduced plasma protein, RBF and Tpah, it was expected that the newborn infant would have a lower PSP excretion than the adult or child. The total 3-hour value obtained in this study of 40 per cent PSP excretion thus goes very well with the previously mentioned renal function studies. Although the diaper PSP test is usually run as a 2-hour test, the high percentage of "no samples" renders the test useless for routine clinical work and thus the 3-hour test should be used. The average 3-hour PSP excretion of 40 per cent fairly well parallels the 40 cc/min./1.73 m 2 •9 quoted for GFR in the neonatal period. Both figures are greater than the urea clearance figure for newborns which is quoted as 30 cc/min./1.73 m 2 •9 'Whether the GFR and urea clearance can be correlated with the PSP excretion is not known but it certainly bears mentioning for in adults and children the PSP excretion can be empirically correlated with the serum creatinine level and creatinine clearance. We believe that if the PSP test were done as a routine screening procedure on all nursery newborns many silent obstructive lesions could be detected. When this test is carried out as a routine procedure it can be run as a 3-hour, one-sample test and thus the first and second hour samples could be eliminated without sacrificing the information desired. If the infant does not void in the 3-hour test period a repeat test should be done in 2 to 3 weeks when the tubular function has further matured. If the excretion is still abnormal a bacteriologic study of the urine and excretory urograms are difinitely indicated. If the PSP test is used in this manner it can be an invaluable tool in the armamentarium of the pediatrician or urologist. SUMMARY

The diaper PSP test was evaluated in 200 consecutive full-term newborn infants. A 3-hour total of over 30 per cent PSP excretion was considered to be normal and less than this figure was considered abnormal. The running of this test as a 2-hour procedure was found to be inadequate. It was decided that this test could be run as a 3hour, one-sample test as a screening procedure. It was projected that this test could be used as a routine procedure to detect silent urogenital, anomalies in the newborn period.

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