Renal Venous Renin Determinations in

the Diagnosis of SurgicallyCorrectable Hypertension

By ANNETTE FITZ, M.D.

SUMMARYRenin activity in renal vein plasma was measured in six normal subjects and 59 hyper-

tensive patients. The average renin value in renal venous plasma in normal subjects was

the same as that found in patients with essential hypertension and renal parenchymalhypertension. Renal venous renin levels were markedly elevated in patients with signifi-cant renal lesions who were improved by surgery but were normal in patients withinsignificant renal artery stenosis. We defined an abnormal renal vein renin levelas one which is higher than 4.1 ng/ml of plasma, the highest normal, and which isalso more than twice as great as the level obtained from the opposite kidney. On 19patients who were operated upon for renal hypertension, there were no "false positivetests," and two "false negative tests." One patient with essential hypertension hadabnormal values by these standards. Since occasional "false positive" and "false nega-tive" results occur, we presently recommend that this test be used with, but not to theexclusion of, other tests of renal function in preoperative evaluations. As experience withthe test increases, and as more prospective studies are done, it may prove to be thesingle most useful device to predict surgical success in patients with renal artery andrenal parenchymal hypertension.

Additional Indexing Words:Blood pressure Renal parenchymalRenal vascular hypertension

RENAL LESIONS, particularly stenosisof the renal artery, often cause correct-

able human hypertension. The role of renaldisease in hypertension has been confirmedexperimentally in many animal species. Evi-dence indicates that such experimental hy-

From the Veterans Administration Hospital andthe Cardiovascular Research Laboratories, Depart-ment of Medicine, University of Iowa College ofMedicine, Iowa City, Iowa.Work was supported in part by Grants HE-5367

and Mol FR-59 from the National Institutes ofHealth, U. S. Public Health Service, and the Vet-erans Administration.

Paper was presented in part at the Annual Meetingof the American Federation for Clinical Research,Atlantic City, New Jersey, May, 1966.

For reprints address: Annette Fitz, M.D., G. M. R.Veterans Administration Hospital, Iowa City, Iowa52240.

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Renal artery stenosis

pertension is often accompanied in the earlystages by increased formation and release ofrenin and angiotensin. This increase in reninand angiotensin is thought to occur secon-dary to decreased renal perfusion pressureor renal blood flow. These factors are oftenfound in human renovascular hypertension.

Correctable renal hypertension is frequentlyassociated with detectable increases in periph-eral vein renin, and these determinationshave been advocated for the screening ofhypertensive patients.1 2 Peripheral vein reninlevels, however, are altered by the postureof the patient,5 by sodium balance,4 by con-comitant drug therapy,4 5 and by associatedconditions such as congestive heart failure4cirrhosis of the liver,6 or accelerated hyper-tension.7 Furthermore, some patients with cor-rectable renal hypertension have been report-ed to have normal peripheral vein levels.4' 6, 8

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RENAL VEIN RENIN

Renal Venous E

Normalsubject

no.

123456

Mean

-i

*Pickens methtRight renal X

*:Left renal vei

Table 1 ting patients for surgery. Goorno and Kap-tenin Activity* in Norimal Men lan'0 and McPhaul and associates"' also have

reported success in predicting the significanceRenin (ng/ml) Ratio, Difference, of a renal artery lesion by testing for a pressor

IIRVt LRV* H / L H-L substance found in the renal venous effluent.2.7 - - Nevertheless information on the usefulness

2.4 3.7 1.5 1.34.1 3.5 1.2 0.6 of the various tests of renal venous pressor1.0 2.2 2.2 1.2 activity in evaluating the hypertensive pa-3.3 tient is limited, and we felt that further eval-

2.4 uation of this procedure was warranted. We

2.7 2.9 1.6 1.0 measured the renal venous renin activity in

od. six normal subjects and 59 completely eval-oed. uated hypertensive patients in order to under-

in. stand better the usefulness of this observationin selecting patients for surgery.

Since total body dilution of small increasesin renin secretion might cause the peripheralrenin activity to remain in the normal range,

many investigators have proposed that therenal vein effluent be sampled and measuredfor renin or angiotensin as a diagnostic tool.Judson and Helmer9 reported that differentialrenal vein renin values were of value in selec-

Methods

Fifty-nine carefully studied hypertensive pa-

tients were obtained from the wards and clinicsat the University of Iowa Hospitals and the IowaCity Veterans Administration Hospital. Bothmen and women, ranging in age from 17 to 69years, were included. Six normal male prisonervolunteers with blood pressures below 130/85

Table 2Renal Venous Renin Activity in Patients with Essential Hypertension

Thiazides or BloodPatient Renin (ng/ml)* Ratio, Difference, < 800 mg Na pressure

no. RRV LRV H/L H-L in diet (mm Hg)

1 6.6 6.6 0 0 No 170/1102 1.3 0 1.3 No 145/953 3.7 3.2 1.2 0.5 No 150/904 2.5 - - No 160/1005 1.6 1.3 1.2 0.3 Yes 170/1106 2.8 1.3 2.2 1.5 No 180/1307 - 4.2 - Yes 225/1508 0.7 1.1 1.6 0.4 No 190/1309 1.3 1.7 1.3 0.4 No 140/90

10 4.1 3.8 1.1 0.3 Yes 200/12511 5.0 1.4 3.6 3.6 No 160/11012 1.4 1.3 1.1 0.1 No 140/9013 3.5 3.9 1.1 0.4 No 210/11514 1.3 1.1 1.2 0.2 No 150/10515 1.2 No 160/9016 6.6 - - No 170/11017 1.4 - - No 150/10018 1.4 1.3 1.1 0.1 No 150/11019 14.Ot 18.Ot 1.3 4.0 No 160/110

Mean 2.7 2.3 1.4 0.7

Key: No sample =-*Mean & SE: RRV + LRV = 2.5 + 0.3, Pickens method.tHelmer method: patient had accelerated hypertension.

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Table 3Renal Venous Renin Activity in Patients with Renal Parenchymal Disease (No Operation)

Patientno.

20

21

22

23

2425

26

27

28

Renin (ng/ml) Ratio,Diseased Normal H / L orkidneys kidneys D IN

3.3

1.7

3.92.0

3.52.4

1.1

2.42.63.84.1

29 (Helmer 3.8method) 3.1

Mean & SE 2.8 + 0.3

Difference,H-L orD-N Disease

2.9 1.1 0.4 Unilateralpyelonephritis

0.7 2.4 1.0 Unilateralpyelonephritis

- - Pyelonephritis- - Chronic glomer-

ulonephritis- Pyelonephritis

Chronic glomer-ulonephritis

1.4 0.8 -0.3 Unilateralhypoplasia

1.1 0.2 Hypoplasia &hydronephrosis

Chronic glomer-1.1 0.3 ulonephritis1.2 0.7 Glomerulo-

nephritis

1.3 + 0.4

Renal Venous Renin Activity in Patients withRenovascular Lesions

Table 4Hypertension Improved by Surgery: Significant Renal and

Renin (ng/mi)Diseased Normalkidney kidney

9.025.01.3

1.06.61.5

4.64.4

4.42.85.9

8.1

6.2560.0*212.0*800.0*

0.9

3.0

3.8

1.4127.0*40.0*

PreoperativeRatio, Difference, blood pressureD/N D-N (mm Hg) Lesion

9.0 8.0 210/115 Vascular3.8 18.4 190/120 Vascular0.9 -0.2 150/110 Traumatic

rupture ofkidney

- 190/120 Bilateral- vascular

4.9

2.0

3.5

2.9

200/120185/110160/105

lesionsVascularVascularVascular

stenosis &pheochromo-cytoma

2.1 4.3 180/120 Hydro-nephrosis

4.4 4.8 185/110 Vascular4.4 433.0 188/110 Vascular5.3 172.0 160/105 Vascular

- 160/110 Vascular

2.6 + 0.8 4.1 6.0

Bloodpressure(mm Hg)

130/85

160/120

230/125175/112

150/105150/110

140/90

140/90

180/120

150/100

Patientno.

303132

33

343536

38394041

Thiazides or

< 800 mg Nain diet

YesNoNo

Yes

No

NoNo

Yes

NoNoNoNo

Mean & SE

renin(Pickens) 7.2 + 2.1

*Renin levels, method of Helmer.

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Table 5Renal Venous Renin Activity in Patients with Insignificant Stenosis of Renal Artery NotImproved by Operation

Renin (ng / ml)Patient Diseased Normal

no. kidney kidney

PreoperativeRatio, Difference, blood pressureD/N D-N (mm Hg)

Thiazides or< 800 mg Na

Lesion in diet

42434445464748

1.02.01.62.74.23.46.6

1.01.01.41.02.6

6.6

Mean & SE 3.1 + 0.7 2.3 + 0.9

mm Hg were studied while on the clinical re-

search ward at the University of Iowa Hospitals(table 1). These normal subjects and all hyper-tensive patients had a complete history and physi-cal examination as well as intravenous urogra-phy, radioactive renography, and aortography.Blood pressures in hypertensive subjects aver-

aged more than 140/90 while hospitalized. Sam-ples of renal venous blood were obtained frompatients who were to undergo aortography forevaluation of their hypertension. All but eight ofthe 30 patients with renal artery lesions had splitfunction tests'-2 as well. Serum sodium determina-tions were done by flame photometer with an

internal standard. The serum sodium values were

obtained on admission, prior to therapy, and priorto renal vein sampling.

Nineteen patients were classified as havingessential hypertension after an extensive work-uprevealed no cause for hypertension (table 2).Ten patients with renal parenchymal diseasewere so classified on the basis of a renal biopsyor because of unequivocal evidence of parenchy-mal diseases on intravenous pyelograms and aorto-grams (table 3). Twelve patients were placed inthe group with "significant" renal artery stenosisor renal disease if surgery resulted in a sustained(> 12 months, 11 patients; > 6 months, one pa-tient) fall in mean blood pressure of greater than25 mm Hg without additional drug therapy (ta-ble 4).

In seven patients, blood pressure did not im-prove following adequate surgery. These were

classed as insignificant renal artery stenosis (ta-ble 5). An additional 11 patients were thought tohave insignificant stenosis when intravenous py-elograms, radioactive renograms, split renal func-tion tests and indocyanine-green renal blood flowsindicated equal renal function despite presenceof a renovascular lesion demonstrated by aortog-raphy (table 6).The normal subjects and the majority of pa-

Circulation, Volume XXXVI, December 1967

tients were not restricted in sodium intake andwere not receiving drugs. Exceptions, noted inthe tables, occurred in those patients who were

severely hypertensive and in whom it was feltdiscontinuing treatment would influence adverse-ly their clinical course. Various maneuvers, suchas sodium restriction, Valsalva maneuvers andpostural changes, have been advocated as usefulstimuli to increase the accuracy of the test. Wewished to evaluate the patients, insofar as pos-

sible, in the basal state, and, therefore, avoidedthe use of such stimuli.The method of Pickens and associates13 for

measurement of renin activity in human plasmawith 4-hour incubation was used with slightmodification in all but the five determinations forwhich the Helmer assay (1-hour incubation) was

utilized.14 Samples of blood were obtained whilethe patient was recumbent prior to aortography.Correct catheter placement was determined byinjection of 1 ml of contrast material into therenal vein and by determination of the renal ve-

nous oxygen saturation. Results are recorded as

nanograms (ng) of angiotensin produced by in-cubation per milliliter of plasma. Statistical sig-nificance of the difference between group means

was determined by Student's t test.15 The mean

and standard error of the mean difference were

calculated for all groups.Results were evaluated on the basis of two fac-

tors: (1) the absolute level of renin obtainedfrom a kidney; (2) a comparison of the level ofrenin obtained from the diseased or stenotic kid-ney with that from its normal mate. The lattercomparison was made in two ways: (a) A ratiowas obtained by dividing the renin from the dis-eased kidney by the renin from the normal kidney(D/ N). In normals and patients with essentialhypertension this ratio was obtained by di-viding the higher by the lower value (H/L). Acomparison was also made by subtracting the"normal" value from the value obtained from the

0 02.0 1.01.1 0.22.7 1.71.6 1.6

0 0

1.2 0.8

180/100170/120170/120150/100170/125180/120170/120

VascularVascularVascularVascularVascularVascularVascular

NoYesNoNoNoNoNo

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Table 6Renal Venotus Renin Activity in PatientsOperation

Renin (ng Iml)Patient Diseased Normal

no. kidney kidney

4950515253545556575859

Mean & SE

1.03.32.54.34.32.23.30.84.51.85.0

1.23.83.81.21.92.34.80.72.81.64.0

Ratio,D/N

0.80.90.73.62.31.00.71.11.61.11.2

Difference,D -S

0.20.51.33.12.40.11.50.11.70.21.0

3.0 0.4 2.6 0.4 1.4 + 0.4

stenotic or diseased kidney (D - N). In normalsand in the patients with essential hypertensionthe lower renin was subtracted from the higherrenin value (H L).

Results

In the normals the average renin contentfrom the right kidney was 2.7 ng/ml, slightlylower than the value of 2.9 ng/ml obtainedfrom the left. The average value of reninfrom nine normal kidneys was 2.8 0.32 ng/ml of plasma. The H/L ratio was over 2.2 inone patient, but the actual difference was

small (H - L 1.2). The highest individualnormal value for renin obtained was 4.1 ng/ml of plasma.

Samples were obtained from 33 kidneysin 19 men and women with essential hyper-tension (table 2). Bilateral samples were ob-tained in 14 patients. The mean value forrenin of 2.5 + 0.3 ng/ml of plasma was notsignificantly different from the normal. Therange of renin values in these patients was

greater than that found in the normals; thelowest value (Pickens' method) was 0, thehighest value was 6.6 ng/ml of plasma in a

patient with labile blood pressure. When thecomparison between kidneys was made, twopatients (nos. 6 and 11, table 2) had an

H/L ratio greater than 2.0. Only patient 11

had a marked difference between kidneys

when both proportion (H/L) and absolutedifferences (H - L) are considered.Three patients (nos. 1, 11, and 16, table

2) had renal renin values greater than 4.1ng/ml, the highest value noted in normals.Ten patients (cases 20 to 29) had renal

parenchymal disease and were not operatedupon (table 3). Bilateral samples were ob-tained in six of these patients. Ratios are

recorded as D/N or D-N when unilateraldisease was present, or as H/L and H-Lwhen patients had bilateral disease. In one

patient (no. 21, table 3) the ratio was over

2, but the difference between kidneys was

only 1.0 ng, a normal value. The mean reninfor this group was 2.8 + 0.3 ng/ml, not differ-ent from normal.Twelve patients had significant stenosis or

renal parenchymal disease and were improvedby operation (table 4). Samples in three ofthe patients (nos. 39, 40, and 41) were ob-tained at operation; the Helmer assay wasused. This technique gives higher reninlevels, and these values probably are furtherelevated because they were obtained at oper-

ation. The renin levels from the diseasedkidney in this group of patients are muchhigher than levels noted in normals and es-

sential hypertensives. The mean renin valuefrom the stenotic or diseased kidney usingthe Pickens method was 7.2 2.1 ng/ml of

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with Insignificant Renal Artery Stenosis; No

Bloodpressure(mm Hg)

184/98160/105200/105170/110180/110170/120150/110160/100190/115200/130180/120

Thiazides or< 800 mg Na

in diet

NoNoNoNoNoNoNoNoNoNoYes

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plasma, significantly higher than the mean of2.5 ng/ml in essential hypertensives (P <0.001). In addition, the average D/N ratioof 4.1 in these patients is significantly higherthan the ratio of 1.3 in essential hyper-tensives (P < 0.001). One patient (no. 32)in this group with a ruptured kidney had aratio of less than 2, and also had a value fromthe diseased kidney of less than 4.1 ng/ml.One additional patient had a normal reninconcentration in venous blood obtained fromthe diseased kidney. One patient (no. 33)had severe bilateral stenosis; both values werehigh. One patient (no. 37) with severe uni-lateral hydronephrosis and accelerated hyper-tension also had a high renin level.

Seven patients were considered to haveinsignificant renal artery stenosis, since theirhypertension was not measurably improvedafter operation (table 5). In these patientsthe renin obtained from the stenotic kidney(3.1 ± 0.7 ng/ml) was not different from thevalue obtained from the opposite kidney(2.3 ± 0.9 ng/ml), nor was it different fromlevels found in normals or patients withessential hypertension.

After extensive evaluation including intra-venous pyelography, radioactive renography,aortography, and split renal function testsor tests of renal blood flows by Cardio-Greendilution technique,16 11 patients were classi-fied as having insignificant renal artery stenosis(table 6). The mean renin level of 3.0 ng/ml from the stenotic kidney is not differentfrom the level found in normal patients orpatients with essential hypertension. Thedifferences between the stenotic and non-stenotic kidney were minimal, except in twopatients (nos. 52 and 53) for whom thevalues from the stenotic side were two tothree times that of the nonstenotic side. Fourpatients (nos. 52, 53, and 59) had valuesfrom the stenotic kidney which exceeded thosevalues found in normals. In two of thesepatients (nos. 57 and 59), however, the D/Nratio was below 2.0, and the difference be-tween kidneys (D - N) was not large.

Patients 31 and 37 (table 4) had accel-erated hypertension. In these patients values

Circulation, Volume XXXVI, December 1967

from both renal veins were high; despite thisa marked difference was noted between kid-neys. One patient (no. 48, table 5), not im-proved by operation, had accelerated hyper-tension. In this instance renin levels werehigh, but equal.Two negative split renal function tests by

Stamey criteria12 were found in the patients(nos. 32 and 37) who were improved bysurgery. One patient (no. 43) in the unim-proved group (table 5) had a split functiontest indicative of significant renal arterystenosis.Serum sodium and bilateral renal vein renin

levels were available in 15 normals and pa-tients with essential hypertension. When totalrenal vein renin (from both kidneys) wascorrelated with sodium an insignificant r valueof -0.193 was obtained. A correlation valuewas also calculated for serum sodium andrenin in patients with renal artery lesions.An r value of -0.373 was obtained which wasalso insignificant at the 5% level.

Discussion

The exact role of the renin-angiotensinsystem in the genesis of human renal hyper-tension is uncertain. In animals with hyper-tension secondary to renal artery stenosis theincrease of renin and angiotensin is transientunless malignant hypertension is produced.Despite this, studies in humans show thatperipheral arterial or venous renin or angio-tensin levels are often elevated in the pres-ence of significant renal artery stenosis. Thissuggests that man, unlike the dog, may main-tain high renin levels in chronic renal orrenal vascular hypertension. Since some pa-tients with significant renal artery lesionshave undeniably normal peripheral venousrenin levels, even when standing, it seemeddesirable to develop a test with more dis-criminatory power. Under these circum-stances renal vein renin activity levels mightbe helpful in making the diagnosis of sur-gically correctable renal disease, regardlessof the role renin and angiotensin play in theetiology of hypertension. It is also importantto determine whether renin determinations

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are a good predictive index without additionalmeasures such as manipulation of posture,3reduction of sodium intake4 and hypotension,or simultaneous determinations of renal bloodflow.Our studies indicate that determination of

bilateral renal venous renin activity is oftena good index of surgical success. In the 12patients who have achieved good results fromsurgery, high levels were noted from thestenotic kidney in 10. The average D/N ratioin these patients was usually, but not always,over 2. We eventually defined a "positive"renal vein renin test as one in which therenin from the diseased kidney was greaterthan normal ( >4.1 ng/ml) and which wasmore than twice the level in the oppositekidney (D/N > 2.0). Using these criteria thetest gave no false positive results in the sevenpatients who had unsuccessful renal surgery.Two of the 12 patients who improved aftersurgery had false negative tests. These twopatients are of special interest. Patient 32(table 4), in addition to mild renal arterystenosis, had a nearly functionless kidney asa result of trauma which had occurred yearsearlier. It is conceivable that there was in-sufficient functioning tissue to produce asignificant amount of renin. The other pa-tient (no. 35, table 4) had severe nephroscle-rosis in the nonstenotic kidney, and is unusualin that a good operative result was achieveddespite a renal blood flow of 180 ml/min inthe "normal' kidney. The results also suggestthat differential renal vein renins might beespecially useful when accelerated hyperten-sion is present, since this condition itself,regardless of cause, usually is associated withhigh renin levels in peripheral veins. In thosepatients who had accelerated hypertensionand were improved by surgery, there wasa clear difference in renal venous renin levels.On the other hand, one unimproved patient(no. 48, table 5) with accelerated hyperten-sion had equal, but elevated, renal venousrenin levels.Our observations in patients with essential

hypertension and renal parenchymal diseaseindicate that an occasional abnormal value

and abnormal ratio may occur. This is notsurprising since Baldwin and co-workers17and other workers18 have demonstrated in-equalities in excretory and secretory functionof kidneys in some patients with essentialhypertension. Minor inequalities in renalvenous renin activity represented only by anH/L ratio of 2.0 may occur on occasion.Except in the presence of a surgically sig-nificant renal arterial or renal parenchymallesion, a high renin level, coupled with aratio of 2.0 or greater, is unusual. Such acombination did occur in two patients, nowclassed as having insignificant lesions, andmay represent a real limitation to the proce-dure. On the other hand, this may be a veryearly index of significant stenosis, not in-dicated by other standard tests. Furtherobservation of these patients will be neededto clarify this point.The normal levels of renal venous renin

activity in patients with various renal diseasesis in accord with previous work.19 Only onepatient with a parenchymal lesion, patient37 (table 4) had an elevated renin level.This young man with severe hydronephrosisand accelerated hypertension was improvedby surgery. This supports the idea that anoccasional patient with a parenchymal lesionmay have hypertension on the basis of therenin-angiotensin system. Further study in alarger group of patients with hypertensionand unilateral hydronephrosis and with pye-lonephritis is needed to evaluate this pos-sibility.Brown and co-workers20 have noted a sig-

nificant correlation between peripheral venousrenin and serum sodium concentrations. Wewere unable to establish a good correlationbetween renal venous renin and sodium inour normals and patients with essential hyper-tension. When patients with renal arterystenosis were considered, the values obtainedsuggest that such a relationship may exist,although at a low level of significance.The fact that high peripheral renin levels

are obtained in most patients with significantrenal artery hypertension suggests that reninsecretion is also high. It is possible that high

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peripheral levels might occur because of al-terations in metabolism, rather than overpro-duction. The present study confirms the factthat the concentration of renin in renal veinblood from diseased kidneys of patients withrenal artery hypertension is increased. It doesnot indicate whether total secretion is in-creased, since secretion is also related torenal blood flow, a measurement often re-duced in the kidney behind a renal arterylesion. In addition, the possibility that reninexcretion in the urine may be increased inpatients with significant renal artery lesionsmust be further investigated before this prob-lem can be settled.Many factors, including the degree of

nephrosclerosis,2' the type of medica-tion, 4 5, 22 diet,4 posture,3 glomerulonephri-tis,21 tubular sodium concentration,23 changesin renal perfusion pressure and renal bloodflow,24' 25 and neurogenic stimuli26' 27 havebeen shown to alter juxtaglomerular activityor renin secretion. In view of this it is perhapssurprising that any pattern in renal vein reninactivity can be discerned in these groupsof patients. Despite these variables the onlypatients who consistently differed from thenormals and essential hypertensives were thepatients with significant renal artery stenosis.It is apparent, however, that occasional "falsepositive" and "false negative" tests occur. Forthis reason we recommend presently usingbilateral renal venous renin levels in conjunc-tion with other established methods ofevaluating patients for surgery.

References1. HELMER, 0. M.: Renin activity in blood from

patients with hypertension. Canad Med Ass J90: 221, 1964.

2. GUNNELLS, J. C., JR., GRIM, C. E., ROBINSON,R. R., AND WILDERMANN, N. M.: Plasma ren-in activity in healthy subjects and patientswith hypertension. Arch Intern Med (Chicago)119: 232, 1967.

3. CONN, J. W., COHEN, E. L., AND ROVNER,D. R.: Suppression of plasma renin activity inprimary aldosteronism. JAMA 190: 125,1964.

4. GENEST, J., ET AL.: Role of the renin-angiotensinsystem in various physiological and patholog-ical states. Canad Med Ass J 90: 97, 1964.

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5. Huvox, A., YAGI, S., MANNICK, J. A., AND HOL-LANDER, W.: Stimulation of renin secretionby hydralazine: II. Studies in renovascularhypertension. Circulation 32 (suppl. II): II-1181965.

6. BROWN, J. J., DAVIES, D. L., LEVER, A. F., ANDROBERTSON, J. I. S.: Variations in plasma ren-in concentration in several physiological andpathological states. Canad Med Ass J 90:201, 1964.

7. FITZ, A. E., AND ARMSTRONG, M. L.: Plasmavasoconstrictor activity in patients with renal,malignant, and primary hypertension. Circula-tion 29: 409, 1964.

8. KIRKENDALL, W. M., FITZ, A. E., AND LAW-RENCE, M. S.: Renal hypertension: Diagnosisand surgical treatment. New Eng J Med 276:479, 1967.

9. JuDsoN, W. E., AND HELMER, 0. M.: Diagnosticand prognostic values of renin activity inrenal venous plasma in renovascular hyper-tension. Hypertension 13: 79, 1965.

10. GOORNO, W. E., AND KAPLAN, N. M.: Renalpressor material in various hypertensive dis-eases. Ann Intern Med (Chicago) 63: 745,1965.

11. MCPHAUL, J. J., JR., MCINTOSH, D. A., WIL-LIAMS, L. F., GmrnTi, E. J., AND GROLLMAN,A.: Correlation of the pressor activity of therenal venous effluent with excretory func-tion and other tests in focal, parenchymal,and vascular renal disease. Circulation 33:781, 1966.

12. STAMEY, T. A.: Diagnosis of curable unilateralrenal hypertension by ureteral catheterization.Postgrad Med 29: 496, 1961.

13. PICKENS, P. T., BuImPus, F. M., LLOYD, A. M.,SMEBY, R. R., AND PAGE, I. H.: Measurementof renin activity in human plasma. CirculationResearch 17: 438, 1965.

14. HELMER, 0. M., AND JUDSON, W. E.: Quan-titative determination of renin in the plasma ofpatients with arterial hypertension. Circula-tion 27: 1050, 1963.

15. SNEDECOR, G. W.: Sampling from a normallydistributed population. In Statistical Methods,ed. 5. Ames, Iowa, Iowa State College Press,1956, p. 45.

16. KIoscHos, J. M., KIRKENDALL, W. M., VELENCA,M. R., AND FITZ, A. E.: Unilateral renal hemo-dynamics and characteristics of dye dilutioncurves in patients with essential hypertensionand renal disease. Circulation 35: 229, 1967.

17. BALDWIN, D. S., HULET, W. H., BIGGS, A. W.,GoMBOS, E. A., AND CHASIS H.: Renal func-tion in the separate kidneys of man: II.Hemodynamics and excretion of solute andwater in essential hypertension. J Clin Invest39: 395, 1960.

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18. IIUNT, J. C., MAIIERi, F. T., GCREIENE, L. F., ANDSilEe.s, S. C.: Ftiunctionial characteristics ofthe separate kidlneys in hypertenisive ii1an1.Amer .J Cardiol 17: 493, 1966.

19. Firz, A. E., KiRKENDALL, W. M., AND AIIM-STRONG, M. L.: Plasmia reniin in renal par-enchymal hypertension. Circutlation 32 (suippl.II): 11-84, 1965.

20. BIOWN, J. J., DAVIES, D. L., LEVERi, A. F., ANI)Ro03ERTSON, J. I. S.: Plasma renin concentra-tion in huimtan hypertension: I. Relationshipletween renin, sodium, ancl potassium. BritMed J 2: 144, 1965.

21. TuiR EON, C., ANI) SOIuIERS, S. C.: juxtaglomer11-lar cell counts andl huimlan hlypertension. AmerJ Path 38: 227, 1961.

22. MAnKs, B. H., GARn1E1Ri, B. F., AND McCoY,F. W.: juxtagloiimeruilar apparatus as an1 extra-

adrenal site of ACTI action. Proc Soc ExpBiol Med 105: 593, 1960.

23. VAXND)E1R, A. J., AND MuILLEn, R.: Conitrol of reniiisecretioni in the anesthetized dog. Amier JPhysiol 207: 537, 1964.

24. SKINNER, S. L., MCCUBBIx, J. W., AND PAGE,I. H.: Control of renin secretion. CirculationResearch 15: 64, 1964.

25. TOBIAN, L.: Interrelationship of electrolytes,juxtagloimerular cells and hypertension. Phys-iol Rev 40: 280, 1960.

26. VANDEIR, A. J.: Effect of catecholamines andthe renal nerves on renin secretion in anes-thetized dogs. Amer J Physiol 209: 659, 1965.

27. BUNAG, H., PAGE, I. H., AND MCCUBBIN, J. V.:Neural stimulation of release of renin. Circula-tion Research 19: 851, 1966.

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ANNETTE FITZHypertension

Renal Venous Renin Determinations in the Diagnosis of Surgically Correctable

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