Radioisotope Renography Renal Function Test in Newborn · venous urography showed a close correlation between the two tests, but renography proved to be more sensitive and informative

Archives of Disease in Childhood, 1971, 46, 314.

Radioisotope Renography as a Renal Function Testin the Newborn

B. L. KATHELFrom the Department of Urology, Alder Hey Children's Hospital; and Institute of Child Health, University of Liverpool

Kathel, B. L. (1971). Archives of Disease in Childhood, 46, 314. Radioisotoperenography as a renal function test in the newborn. Isotope renography hasbeen carried out in 32 babies with neurogenic bladder due to spina bifida or withother urological lesions. The tracings can be interpreted according to the standardsapplicable to renography in older children. Comparison of renography and intra-venous urography showed a close correlation between the two tests, but renographyproved to be more sensitive and informative.As renography is easily performed and since the radiation dosage is very small, it

is of value in those patients where frequent assessment of the function and emptyingcapability of each individual kidney is required.

A large amount of work has been done concerningisotope renography as a test of renal function inadults, but relatively little has been recorded aboutthe value of the technique in infancy. The normalrenogram tracing shows three phases. First, thereis a sudden rise in radioactivity, then a slow riseto a peak (second phase) and subsequently a fallaway (third phase) (Fig. 1). From this department,Johnston and Irving (1967) described renogramtracings from normal kidneys in children under 2years of age. These they found to be relativelyflat as compared with those obtained from olderchildren. Winter et al. (1968) on the other handperformed renography in 26 newborn babies withpresumed normal kidney function, and found thatin 19 the tracings were of normal adult type; 7showed a prolonged functional and/or excretoryphase.The present contribution relates to infants

under the age of 2 months. It is concerned withthe analysis of renograms from kidneys with normaland abnormal function, and with the rates of elimi-nation of radioisotope from the blood and of itsaccumulation in the bladder. The results arecompared with the findings on intravenous pyelo-graphy and with biochemical studies. The mainobject of this presentation is to evaluate the test asan index of individual renal function in the newborn.

Received 14 October 1970.

TechniqueLugol's iodine solution (0 2 ml) (17 3 mg total iodine

and 6-6 mg free iodine) is given orally on the nightbefore and on the evening after the test in order toblock the possible uptake of any free radioactive iodineby the thyroid. Renography is carried out 1 hoursafter a feed to obtain a standard level of hydration. Thepatient is bandaged to a crucifix splint in the proneposition, a detector probe is placed over the site of eachkidney, and a third is positioned over the left scapularregion. The probes are connected to ratemeters andrecorders. The meter range employed has been 30and the paper speed 1 25 cm/minute. Hippuran125I 0-3 ,uCi/kg is injected rapidly into a scalp vein.For renography in children over 2 years of age we use adose of 0 25 ,uCi/kg and a meter range of 100. Themodification in technique for newbom infants is neces-sary to obtain sufficient amplitude in the tracing. Ifnecessary, the positions of the kidney probes are read-justed within a few seconds of the start of the test inorder to obtain maximum deflection. The renogramtracings last from 10 to 30 minutes. At the conclusionbladder radioactivity is recorded with the baby in thesupine position. All recordings reproduced by recordersare from right to left-a convention in the renographicfield.The following parameters were measured from reno-

gram curves. (1) The time interval from the injectionto the peak of the tracing (Tm). (2) The time intervalfrom the injection to the point where the curve decaysto 500, of the maximum (TI). (3) The amplitude oftracing is expressed by radioactive counts per second.The parameters were compared with those obtained

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Radioisotope Renography as a Renal Function Test in the Newborn

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FIG. 1.-Normal left and right renograms, blood clearance curve, and bladder radioactivity recorded on 12th day oflife. Slow clearance of tracer is shown. (This recording and those in Fig. 2, 3b, 4a and c, and 5a are to be readfrom right to left.) These have been rescaled in time from the originals to a paper speed of 0 6 cm/min in order to

facilitate publication.

from kidneys in children over 2 years of age. In thelatter group, from our observations of 80 normal reno-

grams, the normal range of Tm is from 2-5 to 5-5minutes, with an average of 4 minutes and the normalrange of Ti is from 8 - 2 to 19 - 9 minutes, with an average

of 14- 0 minutes. The neonatal renograms were

classified as normal, if within these limits, and abnormalif outside the limits.

MaterialTwo groups of patients were studied.(1) 27 newborn infants with neurogenic bladder due

to spina bifida. In these, intravenous pyelographywas carried out within 12 days of birth. In 19 patients,radiology was performed before renography and in 8patients afterwards. Renography was carried outbetween the 9th and 30th days of life.

(2) 5 patients with urinary tract disorders withoutspina bifida. In these, renography was carried outbetween the 30th and 60th days.The weights of the patients in both groups varied

from 2 5 kg to 4-5 kg.

Results

Normal kidneys. The renograms from 41kidneys of normal pyelographic appearance fromGroups 1 and 2 were assessed. In 17 of these,parameters Tm and T' both corresponded withour accepted normal standards (Fig. 1). In 20, a

peak was not defined, therefore Tm was notmeasurable; in these, Ti was normal in 3, pro-longed in 9, and not measurable in 8. In 4 instancesboth Tm and Te were prolonged. In the entiregroup Tm or Ti were prolonged either singly or

together in 13 instances. The details of rangeand average of parameters in minutes are shown inTables I and II.

7

TABLE IAnalysis of 41 Renograms from Pyelographically

Normal Kidneys

Tm (min) Ti (min)

17 Normal range 1 to5-5,average3-2 8 to 19 9, average 13-54 Prolonged 5 75 to 8, average 22 to 37, average 29 5

6 820 Peaks not 9 Prolonged

defined 3 Normal ranger4 showed

8 Not 30% decaymeasur- at 26 minable 4 showed no

Ldecay

TABLE II

Detailed analysis of 17 Normal Renograms fromPyelographically Normal Kidneys

Tm (min) Ti (min)

2 -65 10*42-84 10*43 0 13 02-5 11 025 11 02 -75 16 -754-6 12-54-5 12 04-75 14-65 -5 14-62 -3 12 -253 *0 10 *753 0 13-02 -5 16-55-15 18-753 0 19 91*25 8-0

Weights of the patients varied from 2 * 5 kg to 4 - 5 kg. Renographywas carried out between 9th and 60th days of life.

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TABLE III

Correlation Between Renograms and Intravenous Pyelograms

Agreement False Positive Renogram False Negative Renogram Inter-With IVP Normal IVP Abnormal pretationIVP Renogram Abnormal Renogram Normal Uncertain

41 renograms from pyelographically normal kidneys 33 8 - -

23 renograms from pathological kidneys 18 - 2 3

Total 64 51 8 2 3

Bladder radioactivity in 33 renograms was withinthe normal range of 20 to 30 c.p.s. with an averageof 25 c.p.s. (Fig. 1). In 8 renograms the rangewas from 3 to 15 c.p.s.; these were from the groupin which the third phase was level or was slowlydecaying.

41 comparisons of renograms and normalpyelograms were studied (Table III). The reno-grams and intravenous pyelograms corresponded in33 normal kidneys and did not in 8. In the latter,the renogram showed delayed decay or a level thirdphase. These 4 patients were spina bifida babieswith a raised blood urea and a distended andinexpressible bladder, suggesting urinary stasis eventhough the upper urinary tract was undilated onpyelography.

Pathological kidneys. The renograms of 23abnormal kidneys from Groups 1 and 2 werestudied. Of these, 21 were hydronephrotic, 1 wasmulticystic, and 1 was congenitally dysplastic.4 renograms relating to the multicystic kidney, thecongenitally dysplastic kidney, and 2 of the hydro-nephrotic kidneys corresponded to the bloodbackground, signifying no renal function. In theremaining 19 renograms, the third phase was levelafter the maximum in 7, rising in 5, and there wasonly 30% decay at 26 minutes in 7.The bladder radioactivity ranged from 18 to

30 c.p.s. with an average of 24 c.p.s. in casesof unilateral pathology. With bilateral hydro-nephrosis the range was from 3 to 12 c.p.s. withan average of 7 *5 c.p.s.

23 comparisons of renograms and pyelogramsof abnormal kidneys were studied (Table III).In 18, the renographic and pyelographic findingscorresponded. In 2 the renograms were normalbut the pyelograms showed minor dilatation of thecalyces. In the remaining 3 the interpretation wasdifficult as it was not clear whether the tracingrepresented blood background radioactivity orwhether there was in addition very subnormal renalfunction.

DiscussionIt has long been realized that kidney function

in the neonate differs from that in the older childand the adult. This is probably due mainly toanatomical and physiological differences betweenthe age groups. In the newbom, the proximalconvoluted tubules are still of primitive form andthe loops of Henle are short (Smith, 1951). Inaddition the cuboidal epithelium lining the glomeru-lar capsule which is present in the fetus, maypersist until 2 years of age. In the newborn, thearterial blood pressure and, by presumption, theintraglomerular pressure are relatively low. Bothglomerular and tubular functions are affected.The glomerular filtration rate in the neonate is low(Barnett, 1940), though the precise measurementsdepend upon whether calculation is related tosurface area or to total body water. Edelmann andSpitzer (1969) summarize that low glomerularfiltration rates (GFR) in the neonatal period are dueto incomplete morphological and functional develop-ment of all components involved in the process offiltration. This low GFR limits the capacity ofthe infant to withstand stress of loading. Anadult level of GFR is reached at the age of 9 to 12months. Grotte, Arturson, and Malmberg (1968)believe that glomerular permeability increases withthe development of the nephron. With increasingage, the pore radius of the glomerular membrane,approximately 20 A in the neonatal period, increasesto 40 A in the adult. The defect in tubular func-tion in the newborn is shown by the 30% reductionin extraction of PAH as compared with the adult,by the reduction in the effective renal plasmaflow as indicated by diodrast or PAH clearances,and by the inability of the newborn kidney toproduce a concentrated urine. Calcagno andRubin (1963) demonstrated that this was notdue to a reduction in renal perfusion, which sup-ports the concept of a functionally limited cortex.Our own observations of slow clearance of Hippuran125I from the blood (Fig. 1) favour the aboveconcept. McCance (1948) pointed out that, while

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Radioisotope Renography as a Renal Function Test in the Newborn

FIG. 2.-Renograms recorded on 30th day of life in baby with an afunctional left multicystic kidney. Normal rightrenogram. Flat tracing on left.

kidney function is adequate to maintain homeo-stasis in the normal infant, the kidney has littlereserve capacity and may be unable to compensatefor disturbances in metabolism or waterbalance.

In 17 of the renogram tracings obtained from 41pyelographically normal kidneys in the newborn,the parameters Tm and Ti were within the rangeof normality for older children (Tables I and II).Winter et al. (1968) had a similar correspondencein 19 of 26 neonatal cases. However in 14 normalneonatal kidneys in our series, Tm and/or Ti wereprolonged as compared with tracings from olderchildren. Again Winter et al. (1968) had similarfindings in 7 of 26 neonatal cases. In 20 of ourtracings from normal kidneys, measurement ofTm was not possible, since a clear peak at the endof the second phase was not defined. Winter etal. (1968) did not have this difficulty, probablybecause he used a much slower paper speed.When Tm and Ti are prolonged or when Tmcannot be measured, we believe that the level ofbladder radioactivity is relevant in the interpreta-tion of renal function. If bladder radioactivity iswithin the range of 20 to 30 c.p.s. the overall renalfunction can be assumed to be normal. On theother hand, if bladder radioactivity is below 15c.p.s. renal function can be interpreted as sub-normal provided there is no obstruction in theupper urinary tract. We have not found the bloodclearance curve of tracer to be helpful as an indexof renal function in the newborn since the clearanceis much slower than in older children (Fig. 1).Our recent renogram tracings from newborn

infants differ from those obtained by Johnston andIrving (1967). These authors noted a flat orsubnormal tracing to be an invariable occurrence

in children under the age of 2 years. The reasonfor the different finding is not clear. Johnstonand Irving were, however, using Hippuran 131Iand the babies were examined in the supine posi-tion which may make correct positioning of thelarge 131I probes difficult.

In the pyelographically abnormal kidneys fromGroups 1 and 2, 19 hydronephrotic as a result ofobstruction of varying pathogenesis, renographyshowed that the third phase was rising in 5, waslevel at the maximum in 7, and in the remaining7 there was only 30% decay at 26 minutes. In 4kidneys, where there was no concentration onpyelography, 1 being congenitally dysplastic, 1multicystic, and 2 hydronephrotic, the tracingswere entirely flat (Fig. 2).

64 comparisons between renography and pyelo-graphy were made; 51 renograms correlated closelywith the findings on intravenous pyelography(Table III). False positive renograms, wherethe pyelogram was normal but the parameters ofthe renogram tracing were outside the acceptedlimits, occurred in 8 kidneys in 4 patients. These4 babies were ill, the blood urea was raised andbladder was distended and inexpressible (Fig. 3 aand b), suggesting that renography was a betterindex of renal function and evacuation than pyelo-graphy. The greater prognostic value of reno-graphy as compared with pyelography was shownin the case illustrated in Fig. 4. This spina bifidababy also had a tensely" distended bladder. Anintravenous pyelogram at the age of 28 days showedno upper tract dilatation, but the renogram (Fig.4a) showed some delay in the third phase on theleft side. At the age of 8 months intravenousurography showed well-marked left hydrone-phrosis and hydroureter (Fig. 4b), and at this

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B. L. Kathel

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FIG. 3.-Infant with spina bifida and inexpressible neuro-

genic bladder with urinary retention. (a) Intravenouspyelogram; undilated upper urinary tract. (b) Renogram;bilateral delayed third phase, more marked on left than

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(b) (c)FIG. 4.-Prognostic significance of renography. Infant with neurogenic bladder due to spina bifida. (a) Renogram on

28th day of life; some delay in emptying on left side; at this time the intravenous pyelogram was normal. (b) Intra-venous pyelogram, aged 8 months; marked left hydronephrosis and hydroureter. (c) Renogram aged 8 months; severe

stasis on left side.

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Radioisotope Renography as a Renal Function Test in the Newborn 319

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tid TIME IN MINUTES1FIG. 5.-Infant with spina bifida due to neurogenicbladder. (a) Renograms, aged 12 days, showing bilateral

(II.b) rising third phases. (b) Intravenous pyelogram; gross_ * l| | |'(b) bilateral hydronephrosis and hydroureters.

time the renogram was typical of severe uppertract stasis (Fig. 4c).The correlation between pyelography and reno-

graphy was much closer with pathological kidneys.The renogram tracings were normal in only 2 ofthe 23 pathological kidneys; each of these showedonly a mild degree of hydronephrosis on pyelo-graphy. The behaviour of the third phase of therenogram corresponded closely with the degree ofpelvicalyceal dilatation. Severe dilatation wasassociated with a rising third phase (Fig. 5 a and b),moderate dilatation with a third phase parallel tothe baseline, and mild dilatation with a delayedthird phase. In 8 patients renography was carriedout before intravenous pyelography and the expec-tations were confirmed. On the whole, reno-graphy correlated very well with intravenouspyelography.

Intravenous pyelography has been the principaldiagnostic test of individual kidney function in thenewborn as with older age groups. The test allowsvisualization of anatomical details, but does notmeasure renal function since it is influenced by thestate of hydration of the patient and by the con-centration and the volume of contrast mediumemployed. Relating radiological opacity with renalfunction is not valid with modem contrast mediaand techniques. In addition the results may beinconclusive because of bowel contents obscuringthe kidney on the radiograph. Isotope reno-graphy gives a qualitative index of the tubularfunction and emptying capability of the individualkidney. The correlation with pyelography in the

detection of renal pathology is close. There is nospecial preparation required and the results areobtained quickly. It is a more sensitive test thanpyelography. Renograms in the newborn can beinterpreted by applying the standards from childrenover 2 years of age. The radiation dose withrenography is only about 1/5000 of that requiredfor a single x-ray exposure (Winter, 1963). Thetest can, therefore, be safely and convenientlyrepeated in following the progress of renal functionover a lengthy period of time.The great value of renography lies, in our view,

in the follow-up of children who will requirerepeated and fairly frequent assessment of thefunction and drainage capability of each individualkidney. As such it can be of great use in themanagement and care of the child with neurogenicbladder due to spina bifida.

I am grateful to Mr. J. H. Johnston for his encourage-ment and advice in the preparation of this report.

REFERENCES

Barnett, H. L. (1940). Renal physiology in infants and children.I. Method for estimation of glomerular filtration rate. Proceed-ings of the Society for Experimental Biology and Medicine, 44,654.

Calcagno, P. L., and Rubin, M. I. (1963). Renal extraction of para-aminohippurate in infants and children. journal of ClinicalInvestigation, 42, 1632.

Edelmann, C. M., Jr., and Spitzer, A. (1969). The maturingkidney: a modem view of well-balanced infants with imbalancednephrons. journal of Pediatrics, 75, 509.

Grotte, G., Arturson, G., and Malmberg, P. (1968). Maturationof kidney function. Proceedings of the XIIth InternationalCongress of Pediatrics, Mexico, 3, 32.


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320 B. L. KathelJohnston, J. H., and Irving, I. M. (1967). Experiences with radio-

isotope renography in children. Archives of Disease in Child-hood, 42, 583.

McCance, R. A. (1948). Renal function in early life. PhysiologicalReview, 28, 331.

Smith, H. W. (1951). The Kidney: Structure and Function in Healthand Disease, p. 265. Oxford University Press, New York.

Winter, C. C. (1963). Radioisotope Renography: A Kidney FunctionTest Performed with Radioisotope-Labeled Agents. Williamsand Wilkins, Baltimore.

Winter, C. C., Elliott, J., Grace, D., and Robertson, A. (1968).Radioisotoperenography in the assessment of renal function inthe newborn. Journal of Urology, 100, 99.

Correspondence to Mr. B. L. Kathel, Department ofUrology, Alder Hey Children's Hospital, Eaton Road,Liverpool L12 2AP.


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Radioisotope Renography Renal Function Test in Newborn · venous urography showed a close correlation between the two tests, but renography proved to be more sensitive and informative