OFFICIAL JOURNAL OF THE CALIFORNIA MEDICAL ASSOCIATION

© 1963, by the California Medical Association

Volume 99 OCTOBER 1963 Number 4

RenogramsCorrelation With Renal Arteriography and Intravenous Pyelography

FRED H. MANDRICK, M.D., and MILO M. WEBBER, M.D., Los Angeles

SINCE TAPLIN and coworkers5 first reported on theirexperience with the radioactive renogram, therehave been many studies of this test reported. It is arapid, accurate and easily accomplished test, and isused extensively at UCLA in the study of patientswith overt or suspected renal disease. Our purposeis to determine the degree of correlation of the testwith other radiographic renal examinations. Allpatients coming to the UCLA Medical Center during1962 who had an intravenous pyelogram and aorto-gram in addition to the radioactive renogram wereselected for this study. Our findings as well as casestudies will be presented.

In most of the published reports on the renogram,the qualitative method of analysis was used. Stewartand Haynie published an excellent report on a quan-titative method of analysis and this is the methodused in the present study.4 The maximum normalpeak time (T max) and half time (T 1/2) of thedownslope of the renogram curve were determinedin a study of normal subjects done at UCLA byBrown and coworkers.' By their standards, the nor-mal value for the T max was up to but not includingfour minutes. The normal value of the T 1/2 of thedownslope was up to but not including seven min-utes. In this study any prolongation of either the

This work was partially supported by United Public Health ServiceGrants No. H 6354 and H 7011.

Presented before the Section on Radiology at the 92nd AnnualSession of the California Medical Association, Los Angeles, March24-27, 1963.

* A study was carried out to determine how wellthe information supplied by a radioactive reno-gram correlates with that obtained by renal ar-teriography and intravenous pyelography. In1962 35 patients at the UCLA Medical Centerhad all three studies. This represents a total of70 kidneys (one kidney surgically absent). Wefound the radioactive renogram to be a veryreliable and valuable aid in the diagnosis ofkidney disease. When compared with the resultsof the intravenous pyelogram and aortogram, therenogram had false negative result in 11 per centof cases, and a 14 per cent false positive result.

T max or T 1/2 of the downslope beyond these valueswas considered to be abnormal.

During 1962, 35 patients had the triad of renalpyelography, arteriography and radioactive renogra-phy. This does not include any cases in which oneor more of the studies was done elsewhere than atUCLA. In only one case was a kidney surgicallyabsent, and the study was based on the total numberof kidney sites-that is, 70 (Table 1). Three inter.esting cases will be presented in detail followed by adiscussion of the correlation of the renogram withthe other studies.

METHODS

At present the test substance of choice is 1-131Hippuran.®2,3 6 Hippuran is rapidly excreted by therenal tubules in the manner of para-amino hippu-rate (PAH), and is not picked up by the liver as is

VOL. 99. NO. 4 * OCTOBER 1963 223

1.

TABLE 1.-Comparlson of Information Obtained by Intravenous Pyelogram, by Aortogram and by Renogram In 35 Cases

Intravenous Pyelogram Aortogram RenogramRight Left Right Left Right Left

0 0 0 Constriction proximal +t 0*

2. 03. Small kidney,

delayed excretion4. 0

5. Delayed excretion

6. 0

7. 0

8. Ureteral stricturewith hydronephrosis

9. 0

10. Poor filling11. 0

12. Delayed excretion

13. Congenitalhypoplasia

14. 015. Poor filling

and visualization16. Delayed excretion

17. Poor concentration

18. Calculus renal pelvis19. Poor filling

and visualization20. Calculus

21. Delayed excretion22. 023. Delayed excretion

24. Caliectasis25. O26. 027. 0

28. 029. Ptosis, marked

30. Delayed excretion31. Delayed excretion32. 033. Ptosis, marked

34.35.

00

Small kidney, congenital0

0

0

Delayed excretion

0

0

Surgically absent

Poor fillingBlunting superior calyx

0

0

00

0

0

00

Calculus, contracted kid-ney, delayed excretionDelayed excretionNon visualization

0

Caliectasis000

00

Delayed excretionDelayed excretionPoor calyceal fillingNon functioningsmall kidneyCalculus upper pole

0.

Indicates false negative. tIndicates false positive.

0Constriction artery

Marked narrowingaccessory renal arteryFibromuscularhyperplasiaMinimal narrowingof origin of arteryFibromuscularhyperplasiaSmall artery

Fibromuscularhyperplasia

0

most portion artery0

Constriction butless than on right

0

0

Almost complete occlu-sion 20. Atherosclerosis

0

0

Surgically absent0

Narrow artery Narrow arteryAortic aneurysm

Marked narrowing Minimal irregularityartery mid portion arteryCongenital hypoplasia 0

00

Marked arterio-sclerotic narrowing

0

0Small artery

0

00

Fibromuscularhyperplasia

000

Two arteries, bothwith fibromuscularhyperplasiaConstricted arteryFibromuscular hyper-plasia and ptosis

0000

0Stenosis with 34 mmgradient

O=Negative. + =Positive.

0Minimal narrowingmid portion artery

0

Minimal narrowing atorifice

00

0

Narrowing of arteryNon visualizationFibromuscularhyperplasia

000

Narrowing of singleartery near origin

00

000

Complete obstructionof artery at orifice

0Stenosis with 8 mmgradient

+t +

+ +

+ +t

+ 0

.+ +

0* 0

+ 0

+ +

+ 0*

+ +

+ +

+ +t

0 0

+ +

+ +t

0* 0*

+ 0

+ +t

+ +

0* ++t +

+ +

+ +

0 00 00* +

+ +t

+ 0

+ +

+ ++t +

+ +

+t +

0* +

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Figure 1 (Case 1).-A 2-minute intravenous py-elograni shows delayed appearance of contrast ine-dia on the right. The right kidney is 2 cm smiallerthan the left.A supine aortogram shows pronounced narrow-

ing of the right renal artery for a distance of 1.5ciii. The left renal artery appears normiial.The renogram shows a flattened tubular phase,

prolonged T max and T 1/2 on the right. T Iniax onthe left is normal, but T 1/% is prolonged. The timebetween the vertical lines on the tracing paper is7 1/2 minutes.

the contrast medium Diodrast.® The amount of in-travenously administered 1-131 Hippuran varied be-tween 9 and 15 microcuries depending on the weightof the patient. All cases were done in the hydratedstate with the patient in the sitting position. Theprobes were placed over the kidneys by means ofthe upright pyelogram film, and after injection ofthe 1-131, finer adjustment of probe localization wasdone. Although some investigators have used a smalltest dose and audiometers in placing the probes,our method was satisfactory.The equipment used for detection of the gamma

rays consists of two thallium-activated sodium iodidecrystals l1/2 x 11/2 x 3/4 inches, retracted 6 centi-meters in a lead collimator, the collimator havingan internal diameter of 21/2 inches and an externaldiameter of 5 inches. The crystal-photomultiplierprobes relay the input via ratemeters to rectilinearstripchart recorders. The equipment is calibrateddaily with a standard 1-131 source.

REPORTS OF CASES

CASE 1. A 54-year-old white housewife had ahistory of hypertension for ten years and she hadbeen treated with various drugs without significantsuccess. Her past history was otherwise negativeexcept for a single bout of right flank pain in 1942which had been attributed to appendicitis and hadcleared spontaneously. Her only complaint was ofchronic fatigue and nervousness under stress.On physical examination the patient was noted to

be somewhat thin and nervous. The blood pressurelying was 240/120 mm of mercury. Positive physicalfindings consisted of Grade 1 arteriolar narrowingof the vessels of the fundus, and a bruit in the rightepigastric region. The heart was not significantlyenlarged to percussion, and no murmur was audible.

Results of urinalysis, of electrolyte determinationand of blood cell counts were within normal limits.Serum creatinine was 0.77 mg per 100 ml. No ab-normalities were seen in an x-ray film of the chest.The electrocardiogram showed LVH and ST-T wave

VOL. 99, NO. 4 * OCTOBER 1963 225

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Figure 2 (Case 2).-Two-mninute intr-avenlous pyelo-granti reveals no contrast mtiedia on the righlt. The rightkideiiy is 2.2 ciii smaller than the left, which appearsnorimial.A supine aortogramii shows a constriction of the maid

portioni ol the right renal artery with post stenoticdilatationi. There is also a constriction of the left renalartery that is hiddelfn b)y the curve of the artery, hutwhich w,as visible on the upright study.Renograin shows low amplitude tubular phase with

prolonged T % on the right. T imiax otn the left is nor-mlal, hut T % is slightly prolonged. The vertical col-umtnii of numbers supplies a gauge for (determining(oulntS per iliintite.

changes secondary to LVH and/or myocardialischemia. Split kidney function studies revealed ascanty urine flow from the right kidney, and normalflow from the left.An intravenous pyelogram showed the right kid-

ney to be 2 cm smaller in vertical height than theleft with delayed appearance of the contrast mediaon the right. There was bilateral ptosis of the kid-neys with the patient in the upright position. Anaortogram showed decided narrowing of the proxi-mal right renal artery, apparently arteriosclerotic,for a distance of 1.5 centimeters. This was laterconfirmed at operation. The narrowing was accen-tuated in the upright position. The renogram showeda flattened tubular phase and prolonged peak timewith pronounced delay in emptying on the right.On the left the tubular phase and peak time werenormal, but the half time of the downslope wasslightly prolonged.

CASE 2. The patient was a 42-year-old white house-wife with a history of hypertension of three years

duration. There was no history of renal infectionsor calculi. The patient complained of frequent head-aches, easy fatigability and nocturia. The historywas otherwise unremarkable.On physical examination the patient had a very

asthenic build and was noted to be quite apprehen-sive. Her blood pressure lying was 200/120 mm ofmercury. Other positive physical findings wereGrade 1 retinopathic changes with focal irregulararteriolar narrowing. The heart was not enlarged topercussion. A bruit was heard in the mid and rightepigastric area.No abnormalities were noted on urinalysis. Blood

cell counts were within normal limits. Electrolyteswere also normal except for a slightly low potassiumlevel, 3.46 mEq per liter. Creatinine was 0.9 mg per100 ml.An electrocardiogram and an x-ray film of the

chest were within normal limits. Split function kid-ney studies revealed normal flow from the leftkidney and scanty flow from the right. An intra-

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F'i-gure 3 ( Case 3 'I oi-miniutte imtravenou-yelograI m fiiliti show s siiiall, contracted riiglit

kinthev with pyelectasia and(i poor funetion. T'lheleft kidnlev aippears nor-miial.

Supiune artogtramll reveals small riht renalartery wvithout constrietion. rhe left realil artriya)ppears, niornual.

Renog-rami shows no significamt futnction onitlhe righit. T miiax ont thle' left is normal 1, mlnt r V.is proloigedl.

venous pyelogram showed the right kidney 2.2 cmsmaller than the left in vertical height. At twominutes there was no contrast media on the rightwhile on the left contrast media was easily seen atthat time. Later films at ten and fifteen minutesshowed greater concentration on the right than theleft. The left kidney as visualized by an intravenouspyelogram, was considered normal. An aortogramshowed bilateral constricting lesions, more pro-nounced on the right with accentuation in the up-right position, and accompanied by post stenoticdilatation on the right. This was later confirmed atoperation. The renogram showed a short, low ampli-tude tubular phase with a greatly prolonged halftime of the downslope on the right. On the left thecurve was essentially normal in appearance, but theT ½ of the downslope was slightly prolonged.

CASE 3. The patient was a 49-year-old whitehousewife with a long history of right chronicpyelonephritis. The first episode of pyelitis was in

1933 and she had had catheter drainage of pus fromthe right kidney. In 1941 she had a similar episode,and a total of 27 ureteral dilitations for a "kink" inthe right ureter had been carried out. In 1946 anintravenous pyelogram showed no stricture of theright ureter. From 1941 to the present time she hadnumerous episodes of right flank pain, tendernessand dysuria. In 1960 for the first time she was toldshe had hypertension. When seen at UCLA for thefirst time she complained of "pain in the right sideof my back" of three weeks' duration.On physical examination she was noted to be

obese and hirsutic. The blood pressure lying was170/80 mm of mercury. Other positive physicalfindings were Grade 2 arteriolar narrowing of thefundic vessels with mild AV nicking. The heart wasnot enlarged, but there was a Grade 1 non-radiatingaortic systolic murmur. There was rather pronouncedtenderness to palpation in the right costovertebralangle, the right flank and the right lower quadrantof the abdomen, but no masses were felt.

VOL. 99, NO. 4 * OCTOBER 1963 227

On microscopic examination of urinary sediment,one to two erythrocytes per high power field werenoted, but no leukocytes. The urine was negativefor protein or sugar. A urine culture grew E. coli.Results of blood cell counts and of electrolyte deter-minations were within normal limits, as were anelectrocardiogram and an x-ray film of the chest.Creatinine was 1.16 mg per 100 ml.

Split function kidney studies showed right urineflow to be about one third as much as the left. Anintravenous pyelogram showed a small contractedright kidney with minimal function at two minutes.The left kidney showed good function at two min-utes. Later films showed the calyces to be blunted,with poor filling on the right. An aortogram showedsmall right renal artery without constriction. Theleft renal artery and vascular pattern appeared nor-mal. The renogram showed no significant functionon the right. The tubular phase and peak on the leftwere normal, but again there was minimal delay inemptying, as seen by the increased T 1/2 of thedownslope.

DISCUSSION

Of primary interest in this study is the number orthe proportion of "false negative" renograms, andto a lesser extent the "false positives."

It is difficult to find criteria by which to judgethe renogram. No ultimate test or pathological ex-amination is available on most of these patients.Therefore, it should be clearly understood that theintravenous pyelogram and the aortogram, whichwere used for comparison in this study, have theirown possibility of error; their use does not neces-sarily indicate that they are more valid, superior toor more accurate than the radiorenogram. Becauseof the wide acceptance of the intravenous pyelogramand the aortogram it is of great practical interest todetermine how the renogram correlates with them,and whether it can be used as a screening test. Theterms "false positive" and "false negative" are notmeant to imply that the renogram is necessarily inerror, but rather the type of non-correlation.

In our study of 70 kidney sites there were eightcases in which the renogram was "negative" whileeither the aortogram or the intravenous pyelogramshowed an abnormality. In five of the eight cases thediscrepancy was with the aortogram, which showedsome narrowing of the renal artery or arteries. Theother three cases showed intravenous pyelogramabnormality-delayed visualization and poor fillingor concentration. If the aortogram and intravenouspyelogram are valid, then there is an 11 per centfalse negative index. However, there is controversyas to whether or how much renal artery narrowingproduces renal ischemia and injury or disease of thekidney. If one were to assume that minimal nar-

TA3LE 2.-."False" Results Obtained by Radloactive Renogram.Assuming linformation Obtained by Intravenous Pyelogram or

Aortogram Was Correct

35 Patients (70 Kidneys)

l. False Negatives: 11 Per CentEight negative renograms while either the intravenouspyelogram or aortogram, but not both, showed an abnor-mality.A. Five of eight cases showed aortogram abnormality

of minimal narrowing, fibromuscular hyperplasia etc.of renal artery.

B. Three of eight cases showed intravenous pyelogramabnormality of delayed visualization or poor concen-tration.

II. False Positives: 14 Per CentTen positive renograms while both the intravenous py-elogram and aortograms were negative.A. Renogram abnormality

1. In all ten cases the T A was prolonged.2. In three of the ten cases the T max was also pro-

longed.B. In each of these ten cases the opposite kidney was

diseased as proven by two or more of the otherstudies.1. In five cases all three studies were positive fcr

the other kidney.2. In three cases the aortogram and renogram were

positive for the other kidney with the aortogramshowing minimal to marked narrowing of therenal artery.

3. In two cases the intravenous pyelogram and reno-gram were positive for the other kidney; poorconcentration in one and a renal calculus in theother case.

rowing produces no ischemia, then this would ofcourse reduce the number of our true false nega-tives. Concerning the intravenous pyelogram, webelieve that delayed visualization and poor concen-tration by one kidney as compared with the othercertainly is valid evidence of renal disease, usuallyowing to vascular abnormality. Furthermore webelieve that visualization delayed to five minutesbilaterally is consistent with disease.

There were ten cases in which the renogram was"positive" and the aortogram and intravenous py-elogram "negative." In all ten cases the T 1/2 wasprolonged while in seven of the ten cases the T maxwas within normal limits. In each of these cases theother kidney in the particular individual was dis-eased, as proven by one or more of the other studies.Cases 1 and 3, herein reported, demonstrate thisvery well: There was severe renal disease on oneside, proven by all three studies, and yet the otherkidney was normal on the intravenous pyelogramand aortogram, but abnormal on the renogrambecause of the prolongation of the T 1/2. This leadsone to speculate on the possibility that a "falsepositive" renogram in the presence of proven diseaseof the other kidney may in reality not be a falsepositive, but in some cases may be indicative of

CALIFORNIA MEDICINE228

the presence of minimal disease in the other kidneythat is not yet discernible in an intravenous py-elogram or aortogram. Another possibility is thatbecause of disease in one kidney, activity or functionof the other kidney is impaired in some way, perhapsby hypertension, which commonly accompanies uni-lateral renal disease (Table 2).

Dept. of Radiology, UCLA Medical Center, Los Angeles, Cali-fornia 90024 (Webber).

REFERENCES

1. Brown, F. A., Gelber, R., Youkiles, L., Bennett, L. R.:A Quantitative Approach to the 1-131 Renogram. In press(J.A.M.A.).

2. Meade, R. C., and Shy, C. M.: The evaluation of indi-vidual kidney function using radioiodohippurate sodium,J. Urol., LXXXVI, 163, 1961.

3. Schulz, R. J., and Katz, L.: Observations on the renalclearance of Hippuran 1-131, Radiology, 78:116-117, Jan.1962.

4. Stewart, B. H., and Haynie, T. P.: Critical appraisalof the renogram in renal vascular disease, J.A.M.A., 180:454-459, May 12, 1962.

5. Taplin, G. V., Meredith, 0. M., Kade, H., Winter,C. C.: The radioisotope renogram, an external test for indi-vidual kidney function and upper urinary tract patency,J. Lab. & Clin. Med., 48:886-901, Dec. 1956.

6. Tubis, M., Posnick, E., Nordyke, R. A.: Preparationand use of 1-131 labeled sodium iodohippurate in kidneyfunction tests, Proc. Soc. Exp. Biol. & Med., C 111:497,1960.

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