DIAGNOSIS AND RESULTS OF SURGERY IN RENOVASCULAR HYPERTENSION

Saturday

DIAGNOSIS AND RESULTS OF SURGERY IN RENOVASCULAR HYPERTENSION S. S. A. FENTON J. A. LYTTLE * M.B.

M.D. Belf.

Belf., M.R.C.P.I.

RESEARCH FELLOW

RESEARCH FELLOW

J. F. PANTRIDGE M.C., M.D. Belf., F.R.C.P. PHYSICIAN

ROYAL VICTORIA

HOSPITAL,

BELFAST

12

THE frequency with which a unilateral renal lesion is demonstrated in patients who present with systemic

16

July 1966

(Chamberlain and Gleeson 1965, Groden et al. 1966, Rees 1966). We report here our experience in the detection and surgical treatment of renovascular obstruction in patients with hypertension. Patients 130 patients were investigated between 1960 and 1963. Those submitted to surgery have been, with one exception, followed up for a minimum of 21/2 years. Patients selected for investigation had a diastolic pressure greater than 110 mm. Hg. Patients with secondary hypertension from other causes -coarctation of the aorta, endocrine abnormalities, pyelonephritis, and glomerulonephritis-were not included. The patients showed one or more of the following features thought to suggest renal vascular obstruction (Poutasse and Dustan 1957, Birchall et al. 1958, Peart 1959, Connor et al. 1960, Yendt et al. 1960) :

hypertension varies from 2% (Smith 1948, 1956) to 28% (Dustan and Page 1962). Removal of the diseased kidney may cure the hypertension (Butler 1937) but the results of nephrectomy are variable. Smith (1948, 1956) indicated 1. Hypertension appearing under the age of 40. cure of the hypertension in less than 26% of cases, but it 2. Hypertension of recent onset. is likely that in his patients the predominant lesion was 3. Hypertension after an episode of flank pain, after abdominal chronic pyelonephritis. Howard et al. (1954) showed that injury, or in the presence of a source of emboli. 4. Malignant hypertension over the age of 55. the prospect of cure after nephrectomy was better in 5. Non-familial hypertension. patients with extrarenal renal-artery obstruction; and the 6. The presence of an epigastric or flank bruit. investigation of hypertension by renal arteriography was The investigations were undertaken or attempted subsequently advocated (Poutasse 1959). This investiga- in thesefollowing 130 patients : intravenous pyelography, isotope renotion is not without risk (McAfee 1957, Chamberlain graphy, differential renal function studies, and renal arterioand Gleeson 1965) and renal-artery obstruction has graphy. been demonstrated in patients with normal bloodDiagnostic Methods Renal Arteriography pressure (Sutton et al. 1961, Eyler et al. 1962, Holley et al. We used the Seldinger (1953) technique. The renal 1962). Surgical treatment of renovascular obstruction does not always cure the hypertension and, since drug arteries were demonstrated satisfactorily in 118 of the 130 therapy will effectively control the hypertension in most patients examined. Arterial abnormalities were classified patients, doubt has been cast on the necessity for renal as major or minor: definite narrowing of a renal artery was arteriography and on the value of surgical treatment regarded as a major abnormality and intimal irregularity as a minor abnormality. It was thought that narrowing *Present address: National Hospital for Nervous Diseases, Queen Square, of the renal artery might be related to the hypertension. London W.C.1. TABLE I--CLINICAL DATA OF PATIENTS SUBMITTED TO SURGERY

N.R.=Not

7455

* Died suddenly, myocardial infarction, no necropsy. ’)’ = On drug therapy. accurately recorded. T=Thrombosis. F.M.H.=Fibrous or fibromuscular hyperplasia.

0 = Unsuccessful.

118

Abnormality of the main renal arteries or their primary branches was found in 49 of the 118 patients. A major abnormality was demonstrated in 27 patients. 15 patients were submitted to surgery and the diagnosis confirmed in all. Selected details from the records of these patients are shown in table I. The remaining 12 patients with major abnormalities did not come to surgery; 2 of these were considered to have total occlusion of the renal artery by embolism. The only complication of renal arteriography was occasional local hæmatoma at the site of the femoralartery puncture. Clinical Selection in Relation to the Arteriogram Findings The clinical criteria for selection were compared with the arteriogram findings. Table 11 shows the observed number of patients in each category of arterial lesion for each selection criterion-e.g., there were 71 patients under 40 years of age (60% of all patients). Thus, the " this selection criterion were expected " figures for calculated on the assumption that 60% of all patients with major lesions would be under 40. The same assumption was made for those with minor lesions and normal arteriowas

TABLE II-CLINICAL CRITERIA IN RELATION TO RESULTS OF

ARTERIOGRAPHY

Fig. I-U/P ratios for creatinine.

*

Observed

excess

significant (r<001).

grams. A similar

procedure was followed to calculate the expected figures for each of the other selection criteria. An efficient clinical criterion for identifying patients with major renal-artery obstruction would show a significant difference between the observed and expected figures. This only happened with abdominal bruits. It was disappointing to get so little clinical help in the recognition of suitable cases for arteriography, but the value of listening for a bruit is shown. Differential Renal-function Studies Unilateral obstruction of a main renal artery causing hypertension is indicated by reduction in urine volume of 60% or greater, a 50% increase in urine-creatinine, and a 15%o decrease in urinary sodium concentration. In obstruction of a primary branch, changes of less magnitude but with the same qualitative pattern have been found (Howard et al. 1954, Birchall et al. 1958, Connor et al. 1960, Stamey et al. 1961). In 72 of the 130 patients selected for renal arteriography an attempt

was

during a collection period, inadequate urine flow, inconsistent results over several collection periods, and excessive amounts of blood in small amounts of urine. The 6 cases of major renal-artery obstruction subsequently proved at operation, in which the urine volume was accurately known, showed the characteristic pattern described above. Technical difficulties in several of the cases of major arterial obstruction precluded quantitative measurements but the essential alteration in the renal tubular handling of sodium and water was still detected by qualitative differences which were derived as follows. Reduction of urine volume is due to reabsorption of a greater proportion of the filtered water on the affected side. Using creatinine as an index of filtration this may be demonstrated by comparing the urine/plasma (U/P)

made to collect simultaneous bilateral ureteric

samples under conditions suggested by Howard et al. (1954) for measurement of urine volume, urine creatinine, and urine sodium. The procedure was either wholly or partially successful in 50 patients. In the remaining 22 patients it was comThe problems encountered were pletely unsuccessful. inability to place catheters in one or other ureter, leakage of urine around the catheters into the bladder, cessation of urine

2-Combination of the creatinine U/P ratio and urine-sodium concentration.

Fig.

ratios for creatinine on the two sides. This index is shown for patients with arterial abnormalities and those with pyelonephritis in whom differential renal-function studies were availA able (fig. 1). lower urine-sodium also usually occurs on the side of the

119 TABLE III-INTRAVENOUS PYELOGRAM

lesion, because of increased tubular reabsorption of sodium. sodium and creatinine concentrations are changing in opposite directions a more sensitive index may be obtained by dividing the creatinine U/P ratio by the urine-sodium. Fig. 2 shows this index for the same patients. The ellipse has been calculated to represent 95% of the data for the patients with Thus

as

normal renal arteries (Kilpatrick 1966). Proven cases of renal-artery obstruction and 1 " probable case lie outside the ellipse. In contrast, all patients with normal arteriograms or with minor lesions and the few patients with pyelonephritis lie close to the diameter of the ellipse. Several patients with a probable major renal-artery obstruction lie inside the ellipse. They may represent false-negative results but the isotope renography has also failed to detect asymmetry of function. It seems therefore that differential renal-function studies are efficient in the confirmation of major unilateral renal-artery lesions. These investigations are, however, unpleasant for the patient, there are many technical difficulties, and temporary depression of renal function or urinary-tract infection are

possible sequelx. In the presence of more complex situations such as bilateral arterial obstruction or primary-branch lesions the value of the test is less certain (Brown et al. 1960, Dustan et al. 1961), but 90% of lesions are in the main renal artery and 70% of these are unilateral (DeBakey et al. 1964). Initially it was thought that differential renal-function studies might be of value as a screening procedure but it is now felt that their place is in the preoperative assessment of the significance of a lesion demonstrated by renal arteriography.

1 minute in the appearance time of the contrast medium in the minor calyces was considered significant. The bipolar diameter of the kidneys was also measured and a difference of 1 cm. or more was regarded as significant. Pyelography was done without abdominal compression and films were obtained at 1-minute intervals for the first 5 minutes and then 8, 15, and 30 minutes after the intravenous injection of 20 ml. of 50% sodium diatrizoate. Table in shows for each patient grouping the incidence of each of the abnormalities. 21 of the 27 patients with probable or proven renal-artery obstruction showed one or more of these abnormalities, but these abnormalities were also found in 36 of 61 patients with normal arteries. A further feature, not shown in table ill is that in patients who had a second pyelogram because the original did not include pictures taken at 1-minute intervals, the asymmetry of density was reproducible in only 4 of 10 patients with a major renal-artery obstruction and in 3 of 15 patients with a normal arteriogram. Asymmetry of filling was reproducible in 4 of the 6 patients with major renalartery obstruction and was not reproducible in any of the 6 patients with normal renal arteriograms. This suggests that changes in contrast density and filling are too variable to be of value and this is in agreement with the findings of Connor TABLE IV-HIPPURAN RENOGRAMS

Screening Procedures While renal arteriography and differential renalfunction studies will establish the diagnosis of renalartery obstruction, there is need for a simple safe screening procedure to detect disparity in renal function. Both intravenous pyelography and the isotope renography have been suggested for this purpose. Intravenous

Pyelography

Modern contrast media are excreted predominantly by glomerular filtration and are not reabsorbed by the tubules (Woodruff and Malvin 1960). Since renal-artery obstruction causes increased reabsorption of water it might be expected that, in the absence of severe renal damage, the intravenous pyelogram would show an increased density of contrast medium on the affected side. The reduced urine flow will cause the renal calyces and pelvis on the side of the lesion to be less distended and appear " spastic ". Since the rate of accumulation of contrast medium in the calyceal system is a function of the glomerular filtration-rate (Woodruff and Malvin 1960) it might also be anticipated that the pyelogram would show a delay in appearance time of the contrast medium on the side of the lesion. These changes are considered to be of value in the detection of obstruction of a renal artery (Brown et al. 1960, Palubinskas and Wylie 1961, Baker et al. 1962, Maxwell 1962) and were used in the interpretation of the pyelograms of the patients in our series who had successful arteriograms (table ill). A difference of

al. (1960), Scott et al. (1961), Spencer et al. (1961), DeBakey al. (1964), and Maxwell et al. (1964). It has been suggested that differences in pyelogram density are accentuated during the diuresis which follows an oral water load (Brown et al. 1960). Comparison of density of contrast medium is however of necessity subjective and inexact due to differences of kidney position, overlying soft tissue, and gas shadows and other technical artefacts. Maxwell et al. (1964) and Schreiber et al. (1964) claimed that et et

films taken at 1-minute intervals improve the diagnostic precision of the intravenous pyelogram; but this claim is not substantiated in our study. DeBakey et al. (1964) have also found pyelography to be frequently unhelpful as a screening test, indicating the necessity for renal arteriography. The pyelogram, however, gives information about the anatomy of the kidney and thus still has a place in the investigation of hypertensive patients.

Isotope Renogram This test was performed by surface counting of intrarenal radioactivity after intravenous injection of ’Radiohippuran’ 1-labelled hippuran) (Taplin et al. 1956, Winter 1956). Its clinical usefulness is becoming increasingly apparent (Doig et al. 1963, Kaufman and Maxwell 1964, DeBakey et al. 1964, Kennedy et al. 1965). Isotope renography was done in 109 of the 130 patients The procedure selected for investigation (table iv). adopted was similar to that outlined by Hunt et al (1961):

120

the intrarenal radioactivity after a standard 30 .C intravenous injection of radio-hippuran was detected by two directional scintillation counters (modifiedEkco type 559D’) connected via matching rate-meters (’Ekco type 522C ’) to a two-channel 5 mA role-chart recorder. Radioactivity was recorded continuously for 20 minutes after the injection of the isotope and the renogram curves were compared with attention to amplitude, delay in reaching a peak count, and the contour of the excretory

false-positive ever,

109 patients. Renal-

obstruction demonstrated by arteriography in 19 of these patients. In the remaining 25 artery was

patients an adequate for the renogram abnormality Fig. 3-Photomicrograph of fibromuscular was found in 13. A hyperplasia. high proportion of patients with unilateral renal disease have an abnormal renogram, but it is also abnormal in some who have no demonstrable unilateral renal disease. In patients with renal-artery obstruction the test correlated closely with a positive differential renal-function study. It seems that the isotope renogram is a simple and rapid method of selecting those hypertensive patients who may require more complicated and time-consumcause

Radio-hippuran renograms were recorded in the 27 patients in whom major renal-artery obstruction had been demonstrated by renal arteriography. The renogram was abnormal in 14 of the 15 patients in whom the renal-artery obstruction was

ing investigations.

TABLE V-RESULTS FROM SURGICAL CORRECTION OF OCCLUSIVE RENAL VASCULAR LESIONS IN SEVERAL MEDICAL CENTRES

confirmed

at

Results of

Cases of fibromuscular hyperplasia only.

In the one false-negative renogram the the stenosis was 35 mm. Hg and the sp. gr. of urine was 1.012 at the time of the investigation, indicating inadequate dehydration. It has been shown both experimentally and clinically that adequate dehydration is important in the detection of mild renal-artery obstruction (Sharpe et al. 1962, Tauxe 1962). In the presence of a gradient of 50 mm. Hg or less the only constant abnormality was a delay or fall of the excretory slope and this may be reversed by diuresis (Sharpe This feature has been confirmed in 1 of our et al. 1962). a gradient of 50 mm. Hg was recorded at in whom patients

gradient

subsequently

had a negative differential renalfunction study. Thus, the renogram would have indicated the necessity for renal arteriography in 44 of

slopes. A preliminary investigation in 37 controls had suggested that the renogram was reproducible and that differences of 15% in amplitude or 2 minutes in peak time were significant. Striking differences of the contour of the excretory slope which were reproducible in the prone and the sitting position and which were not explained by abnormalities of the renal pelvis as shown on the intravenous pyelogram were also considered to be significant. A full account of the interpretation of the renogram and of the application of isotope renography in the detection of renovascular hypertension will be published elsewhere. Asymmetry of renal function was detected in 44 of the 109 patients studies (table iv).

*

re-

sults. 2 in this second group, how-

operation.

across

’

Surgery

On the basis of the renal arteriogram and differential renal-function studies 15 patients were submitted to surgery. A revascularisation procedure was attempted in 5 patients but in 3 nephrectomy was subsequently carried out either at the time of the operation or later. In the 2 remaining patients renal-artery obstruction and hypertension persist but further operation has been refused. Renal-artery obstruction was confirmed in all cases at operation, the lowest gradient being 35 mm. Hg. With one exception the follow-up period ranges from 21/2 to 6 years (table i). Those in whom the diastolic pressure fell to and remained below 90 mm. Hg without drug therapy have been regarded as cured. Those in whom diastolic pressure fell by 15 mm. Hg or more without drug therapy but in whom normotensive levels were not achieved have been regarded as improved. On this basis, 8 of the 15 patients have been cured and a further 2 improved. There was no operative mortality. The cure-rate of 53% is similar to that of most other workers (table v), is better than the results reported by Chamberlain and Gleeson (1965), Groden et al. (1966),

operation. The renogram was normal in 7 of the 12 patients in whom obstruction was observed on the arteriogram but who were not submitted to surgery. In 4 of these patients with a normal renogram the differential renal-function studies were also negative: these investigations were technically unsuccessful in the remaining 3. It is possible that the normal renogram in these 7 patients related to a small gradient. 71 patients in this study who had normal arteriograms or minor arterial lesions only, also had renograms. In 15 the renogram was abnormal. In 3 patients there was a difference of 1-2-1-5 cm. in the bipolar length of the kidneys, which could account for the asymmetry in the renogram. No cause for the abnormal renogram was determined in the remaining 12. Difference in kidney depth or other geometrical aberration, undetected pyelonephritis or a minor arterial lesion of greater significance than predicted may explain some of these apparent

renal-artery

Fig. 4-Arteriogram demonstrating fibromuscular hyperplasia.

121

and Rees (1966), but falls far short of the 81 % of patients whom DeBakey et al. (1964) report as being normotensive after 2 years. The character of the renal-artery lesions resulted in a high proportion of patients (13 out of 15) requiring nephrectomy. 11 patients had fibrous or fibromuscular hyperplasia. This is hyperplasia of the fibrous tissue in the media resulting in narrowing of the lumen of vessels (fig. 3). The artery changes may be patchy resulting in a beaded appearance on the arteriogram (fig. 4). The process tends to affect the distal two-thirds of the renal artery and may, as in 5 patients in this series, extend into the primary branches of the main renal artery. Reconstructive surgery of distal stenosis is difficult, if not impossible. Spencer et al. (1961) reported 10 of 11 cases and Bernatz et al. (1962) 11 of 19 cases in whom nephrectomy was the only possible procedure. Fibromuscular hyperplasia has been noted as a common cause of renal artery obstruction in young hypertensive patients (Hunt et al. 1962, Wylie et al. 1962). The high incidence in this series is probably a reflection of the selection criteria which tended to exclude the older age-group in whom atheroma is the more usual finding. Although the xtiology of fibromuscular hyperplasia is in doubt (Lyttle and McCaughey 1966) the results of surgery have recently been reported to be better than for atheromatous lesions (DeBakey et al. 1964). Differential renal-function studies, while valuable as diagnostic procedures, did not have reliable prognostic value in relation to the results of surgery. This is contrary In to the view expressed by Howard and Connor (1964). this series only 45%of the patients with a positive differential renal-function study were cured of their hypertension. This observation has also been made by others (Dustan et al. 1961, Maxwell and Prozan 1962). A more accurate prediction of the results of surgery might be achieved by bilateral renal biopsy (Vertes et al. 1964).

Summary Detailed investigation of a selected group of 118 hypertensive patients showed that 27 had major renal-artery obstruction. 15 of these patients had surgical treatment. 14 of those submitted to surgery were followed up for 21/2 to 6 years; 7 were cured and a further 2 obtained a significant improvement in their hypertension. 11 of the 15 patients submitted to surgery had fibrous or fibromuscular hyperplasia of the renal artery. The clinical prediction of renal-artery obstruction in the hypertensive patient was difficult. The only useful clinical feature was an abdominal bruit present in 63% of patients with major renal-artery obstruction. While differential renal-function studies were valuable as a diagnostic procedure, they are technically difficult to perform and of limited prognostic value in relation to the results of surgery. The ’Hippuran ’ renogram proved to be a safe, simple, and reliable screening test for the detection of renalartery obstruction. S. S. A. F. and J. A. L. were in receipt of Royal Victoria Hospital Research grants.

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for

reprints

should be addressed

to

S. S. A. F.

REFERENCES

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" ... Let us not be any more shocked and grieved by what Africans do than by what anyone else does. Let us not, when they act badly, feel so disappointed that, to comfort ourselves, we feel a positive maternal need to declare our faith in them, and any more than we declare faith in Arabs, Asians, or South Sea Islanders after they have toppled a government in a bout of bloodshed. More than that. Let us not condone their misdeeds any more than we condone our own ... As long as we continue to regard Africans as a " special case " to be courted,

flattered, excused, expected-greater-things-from, grieved-over, we will still not have recognised that they and for all, severed the navel cord which used to bind us. And Africans will continue to regard us with that irritation-merging eventually into pity-which marks the attitude of grown-up children to their anxious, ridiculous parents."-RITA HiNDEN, Encounter, May, 1966, p. 59.

explained-away,

have,

once