surgical treatment of unilateral renal vascular disease: prognostic role of vascular changes in...

Surgical Treat:mevit of Unilateral Renal Vasclilar Disease

Prognostic Role of Vascular Changes in Bilateral Renal Biopsies

DONALD G. VIDT, MD FREDRICK M. YUTANI, MD LAWRENCE J. McCORMACK, MD RAY W. GIFFORD, Jr., MD, FACC

BRUCE H. STEWART, MD, THOMAS C. MCLAUGHLIN, MD THOMAS F. MEANEY, MD DAVID A. McEWEN, MD

From The Cleveland Clinic Foundation, Cleveland, Ohio. Manuscript received June 12, 1972, accepted July 14, 1972.

Address for reprints: Donald G. Vidt, MD. the Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, Ohio 44106.

In patients with unilateral renal arterial steno& no distinction could be made between atherosclerotic or fibrous lesions of the main renal artery on the basis of the presence or severity of intrarenal arteriolar sclerosis. The results of bilateral renal biopsies performed at the time of operation support the concept of the “protected kidney,” in which the prevalence and severity of arteriolar sclerosis is greater in the kidney contralateral to the renal arterial stenosis. The presence or absence of arteriolar sclerosis as determined from bilateral renal biopsies was not sufficiently accurate as a prognostic index to justify the hazards of this procedure for patients being considered for surgical treatment of occlusive renal artery disease.

Occlusive disease of the renal arteries is the most common cause of reversible hypertension. Diagnosis of renal arterial stenosis is established by renal angiography; however, the procedure does not permit prediction of the reversibility of hypertension after nephrectomy or a revascularization procedure. Several tests have been used to help predict the success or failure of surgical correction of renal arterial stenosis in alleviating hypertension. 1-3 The value of evidence of hyaline arteriolar sclerosis found by renal biopsy in predicting the results of surgery has been the subject of dispute. Vertes et al.4 advo- cated performance of a bilateral renal biopsy before proceeding with operations to revascularize or remove kidneys because, they contend- ed, the presence of arteriolar sclerosis of the kidneys precluded a good response to operation. They reported comparable degrees of arteriolar sclerosis in kidneys supplied by normal as well as stenotic renal arteries. In contrast, Barajas et a1.,5 LaforeP and Bauer and Forbes7 noted a lesser degree of hyaline involvement in the ipsilateral kidney. In the present study, we report the results of a retrospec- tive analysis of 33 patients with unilateral renal arterial stenosis and hypertension. The relation of renal arteriolar sclerosis to the opera- tive result is assessed.

Materials and Methods

The case histories of 33 patients with unilateral renal arterial stenosis were reviewed. In all patients, bilateral renal biopsies were performed at the time of nephrectomy or revascularization. In all cases the presence of a stenotic lesion of the renal artery was established by renal angiography performed by the Seldinger technique of percutaneous retrograde catheterization by way of the femoral artery.

The degree of occlusion was estimated from angiograms as follows: minimal narrowing, less than 25 percent; mild narrowing, 25 to 50 percent; moderate narrowing, 51 to 75 percent; severe narrowing, greater than 75 *percent; and complete occlusion. Small biopsies, usually needle, were obtained at the time of operation from the contralateral (nonstenotic) as well as the ipsilateral (stenotic) kidney. Specimens for light microscopy were fixed in Zenker’s solution, dehydrated and embedded in paraffin. Sections, 3~ thick, were stained with hematoxylin and eosin and periodic acid-Schiff

December 1972 The American Journal of CARDIOLOGY Volume 30 a27

SURGERY IN UNILATERAL RENAL VASCULAR DISEASE-VIDT ET AL.

FIGURE 1. Hyaline arteriolar sclerosis, grade I I (periodic acid-Schiff X 400, reduced by 28 percent).

stain for histologic evaluation by one of us (L.M.) who was unaware of the clinical case histories.

Histologic grading of arteriolar sclerosis was as follows: grade 0, normal: no significant changes; grade 1, minimal: muscular hyperplasia only; grade 2, mild: less than l/3 narrowing of the arteriolar lumen by hyaline involvement (Fig. 1); grade 3, moderate: l/3 to 213 narrowing of the arteriolar lumen by hyaline involvement (Fig. 2); grade 4, severe: greater than 2/3 narrowing of the arteriolar lumen by hyaline involvement (Fig. 3). The presence of ischemic changes as demonstrated by interstitial scarring and tubular atrophy and the association of these changes with focal infarction were noted. These ischemic changes were not graded for severity because of the small size of the biopsy specimens.

Sections from the renal arterial lesions were available in all cases and were classified histologically according to the presence of atherosclerotic or fibrous disease. Sections with fibrous lesions were further classified as previously described8 according to the following subgroups: intimal fibroplasia, medial fibroplasia with aneurysms, medial hyperplasia or perimedial fibroplasia.

Bilateral renal venous renin assays were obtained in 10 patients. The renal venous renin activity was determined by the method of Pickens et a1.s Most patients were not receiving a low sodium diet before renal venous catheteri- zations.

The pressure gradient across the area of renal arterial stenosis was obtained in 19 patients by direct measurement of pressures in the aorta and in the renal artery dis- tal to the stenotic area. Pressures were measured in all instances at the time of corrective surgery.

The success of operation was graded according to the following criteria:

Excellent: blood pressure “normal” without medication, according to these limits:

Age (yr) Upper Limit of Normal <30 130/90

31 to 50 140195 >50 160/100

Good: diastolic within limits described; systolic above limits, without medication.

Pair: diastolic blood pressure at least 20 mm Hg less than preoperative levels, without medication, but not within normal limits; or diastolic blood pressure within normal limits with smaller doses of medication than required preoperatively; or smaller doses of medication than

FIGURE 2. Hyaline arteriolar sclerosis, grade III (periodic acid-Schiff X 400, reduced by 28 percent).

required preoperatively, although blood pressure not within normal limits.

Poor: no response; same doses of medication as required preoperatively.

Other forms of secondary hypertension were ruled out by appropriate clinical tests.

All patients but 2 were followed up for at least 12 months after operation. One patient died of severe hypertension and bronchopneumonia 8 months after operation. A second patient died of unknown causes 8 months after operation. He, too, had responded poorly to the surgical procedure.

Results

Atherosclerotic lesion vs. fibrous disease of main renal artery: Of the 33 patients 17 had atherosclerotic lesions and 16 had fibrous disease of the main renal artery (Table I). The average age of 17 patients with atherosclerotic lesions was 49.3 years (range 34 to 63 years), and the group com- prised 9 women and 8 men. The average duration of hypertension before operation in patients with atherosclerotic lesions was 28.5 months (range 2 months to 10 years). Of 16 patients with fibrous disease of the main renal artery, the average age was 29.3 years (range 9 to 42 years); 14 were female, and the average duration of hypertension before operation was 23 months (range 1 month to 10 years).

A more favorable response to surgical correction was seen in patients with fibrous disease. Twelve patients with fibrous disease had complete relief from diastolic hypertension, having had an excellent or good response to surgical correction; in 4, the response was considered fair or poor. Eight patients with atherosclerotic lesions had complete relief from diastolic hypertension; 9 had only a fair or poor response. For the purpose of discussion, patients with a fair or poor response are considered to have had no relief from diastolic hypertension, in contrast to the patients with an excellent or good response, who are considered to have had complete relief from diastolic hypertension.

Renal findings: Arteriolar sclerosis was noted in the contralateral kidney in 18 instances, in 9 of 20 patients who had relief from diastolic hypertension

820 December 1972 The American Journal of CARDIOLOGY Volume 30


and 9 of 13 who failed to respond to surgical correction (Table II). Arteriolar sclerosis was moderate to severe in 4 of the former and in 3 of the latter group of patients. The ipsilateral kidney showed minimal to moderate changes of arteriolar sclerosis in only 5 patients, and no patient had severe involvement; in 4 of these 5 patients, atherosclerosis was the basic disorder in the--renal-artery: In 3, the ipsilateral-kidney was, in fact, less involved. No distinction could be made between atherosclerotic or fibrous lesions of the main renal artery on the basis of the presence or severity of intrarenal arteriolar sclerosis.

The degree of stenosis observed radiographically . ranged from moderate (25 to 50 percent narrowing) to complete occlusion. In 15 of 20 patients who ob-

FIGURE 3. Hyaline arteriolar sclerosis, grade IV (periodic acid-Schiff X 400, reduced by 28 percent).

TABLE I

Data in 33 Patients

Case Age (yr) no. & Sex

Preoperative

Duration of

Hypertension Follow-Up

(mo) (mo)

Renal

Arterial

Lesion

Radiographic

Degree of Stenosis

(%I

Pressure

Gradient

(mm Hg)

Arteriolar Sclerosis

(grade)

I C Operation

A. Complete Relief from Diastolic Hypertension

1 52F 2 39F 3 49M 4 54F

5 48M 6 5JF 7 51M

8 50F 9 28F

10 28F 11 26M 12 42F 13 9F

14 12F

15 30F 16 3JF 17 31F 18 40F 19 34F 20 12M

3 16 AS 51-75 2 53 AS 51-75

60 40 AS 75 120 31 AS 75 10 67 AS 75 4 34 AS 75 7 15 AS 75 7 19 AS 75 3 17 PF 75

24 22 PF 51-75 37 37 MF 75 22 24 MF 75 5 13 PF Occluded

2 32 MF 75 3 12 PF 75

60 24 MF 75 12 30 PF 75 1 36 MF 75 8 30 FM 75 3 15 PF Occluded

. . . 50

. . . 130

. . . 100 115

150 51-60

. . .

. . . 60-70

50 95 100 100

0

0 0

0

1 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0

2 3 0 0 2 0 0 0 0 2 4 0 2 0 0 3 1 0 4 0

R

R

R

R R

R

R

R

R

R

R

R N

R

R

R

R R N

N

B. NO Relief from Diastolic Hypertension

21 53F 2 12 AS 75 100 0 0 R

22 45F 14 8 AS 75 115 2 2 R

23 46M 6 80 AS 51-75 120 0 0 R

24 4JM 24 8 AS 2550 . . . 1 3 R 25 52F 52 48 AS 75 . . . 0 3 N

26 34M 48 17 AS 75 21-31 0 2 R

27 5JM 7 64 AS 75 . . . 0 2 R

28 42F 60 13 AS 51-75 40 0 0 N

29 63M 60 37 AS 25-30 . . . 3 0 R

30 29F 48 49 PF 75 100 0 3 R

31 38F 8 34 MF 25-50 . . . 0 2 N

32 31F 12 13 PF 75 95 0 1 R

33 42F 120 19 IF 25-50 70 0 2 R

AS = atherosclerosis; C = contralateral; FM = fibromuscular; I = ipsilateral; IF = intimal fibroplasia; MF = medial fibroplasia; N =

nephrectomy; PF = perimedial fibroplasia; R = revascularization.

December 1972 The American Journal of CARDIOLOGY Volume 30 829


TABLE II

Degree of Arteriolar Sclerosis and Surgical Response of Diastolic Hypertension

were not graded for severity, were also present in the contralateral kidney of 3 patients in this group.

Arteriolar Sclerosis (grade)

0 1 2 3 4

Complete relief

I 18 2 0 0 0

C 11 1 4 2 2

No relief I 10 1 1 1 0

C 4 1 5 3 0

C = contralateral kidney; I = ipsilateral kidney.

Pressure gradients across the area of stenosis of the renal artery were measured in 19 patients at the time of operation. The gradient exceeded 50 mm Hg in all 11 patients who had an excellent or good response after operation. However, the gradients also exceeded 50 mm Hg in 6 of 8 patients who did not derive benefit from the surgical procedure.

Discussion

tained relief from diastolic hypertension, the degree of narrowing was greater than 75 percent; 2 additional patients had complete occlusion. Seven of 13 patients who did not benefit from surgical correction had severe narrowing greater than 75 percent, and none had complete occlusion of the arterial lumen.

Renal venous renin determinations were available in 10 patients (Table III). In 5 of 7 patients who had complete relief from diastolic hypertension after operation, the ratio of renal venous renin activity of the ipsilateral kidney to that of the contralateral kidney was 1.5 or greater. Three patients with a fair or poor response to operation had a renal venous renin ratio of less than 1.5.

Ischemic tubular atrophy without infarction was noted in the ipsilateral kidney of 10 of 20 patients who had complete relief from diastolic hypertension, whereas these changes were present in the contralat- era1 kidney of only 1 patient in this group. Ischemic tubular atrophy without infarction was also noted in the ipsilateral kidney of 9 of 13 patients who did not derive benefit from operation. These changes, which

The average age of patients with atherosclerotic lesions who had complete relief from diastolic hypertension (50 years) differed little from that of patients with atherosclerotic lesions who failed to respond to surgical correction (48.7 years). Sixteen of 20 patients with an excellent or good result but only 7 of 13 patients with a fair or poor response had had hypertension for less than 2 years before operation. Al- though the average age of patients with fibrous disease who had an excellent or good response after operation was somewhat less (27.4 years) than that of patients who had a poor response (35 years), the dif- ference may be attributed to the inclusion of 3 chil- dren in the former group. The younger average age of all patients with fibrous disease is not surprising, having been noted in prior reports. The better over- all response of patients with fibrous disease has also been recognized by others. In our study, 75 percent of patients with fibrous disease of the renal artery had complete relief from diastolic hypertension, whereas only 47 percent of patients with atherosclerotic lesions derived similar benefit. The type of operation performed had little bearing on the outcome in either group of patients. Revascularization was at- tempted in all instances, and nephrectomy was performed only when revascularization was technically unsuccessful or deemed not feasible.

TABLE III

Renal Venous Renin Assays

Case Renal Venous Renin Assays

no. I C I/C Ratio

A. Complete Relief of Diastolic Hypertension

1 60.0 14.5 4.1 7 5.6 3.7 1.5 a 6.4 3.0 2.1

12 4.3 5.0 0.9 13 28.7 4.5 6.4 15 39.2 33.5 1.2 20 51.0 31.6 1.6

B. No Relief from Diastolic Hypertension

26 3.5 2.9 1.2 28 a.8 8.5 1.0 33 5.0 5.2 1.0

C = contralateral kidney; I = ipsilateral kidney.

Prognostic value of changes in ipsilateral vs. contralateral kidneys: The greater degree of arteriolar sclerosis in the contralateral kidneys suggests that the renal arterial stenosis had a protective effect upon the small vessels. When arteriolar sclerosis was present in the ipsilateral kidney, both patients who had relief from diastolic hypertension (Cases 5 and 16) had a more severe degree of hyaline changes in the contralateral kidneys. Similar findings were noted in 1 of the 3 patients (Case 24) who did not get relief from diastolic hypertension. In 1 (Case 22), a comparable degree of hyaline arteriolar sclerosis was noted in the ipsilateral kidney; in another (Case 29), arteriolar sclerosis of moderate severity was noted in the ipsilateral kidney although changes were negligible in the contralateral kidney. We have no good explanation for this single observation which is at odds with findings in other cases. The occur- rence and severity of hyaline arteriolar sclerosis in the contralateral kidney was comparable whether or not patients derived benefit from operation, thus ne- gating this finding as a prognostic guide for surgical treatment of, occlusive renal artery disease.

830 December 1872 The American Journal of CARDIOLOGY Volume 30


Our findings are in agreement with those reported by Barajas and colleagues,5 who also noted that the magnitude of hyaline deposits in the arterioles of the ipsilateral “ischemic” kidney was less than that in the contralateral “nonischemic” kidney. They, too, concluded that the findings of hyaline arteriolar sclerosis did not correlate with the outcome of repair of the stenotic renal artery and, therefore, had no prognostic significance. In reports of selected cases of malignant hypertension associated with unilateral renal arterial stenosis, Bauer and Forbes7 and, later, Laforet6 demonstrated a protective effect of the stenotic main renal arterial lesion on the small vessels of the ischemic kidneys.

In contrast to these findings, Vertes and colleagues,* reporting on a group of 7 patients, concluded that arteriolar sclerosis was not more severe in the contralateral kidney than in the kidney with the stenotic renal arterial lesion. Individual renal func- tion studies performed before operation failed to con- firm a functional abnormality in 5 of their patients.

Barajas and colleagues5 noted an inverse correlation between the degree of ischemic tubular atrophy and interstitial scarring of the ipsilateral kidney and the results of surgical revascularization, and concluded that severe tubular atrophy and interstitial scarring precluded a favorable response from surgical revascularization of the ischemic kidney. Ischemic changes without infarction in the ipsilateral kidney were frequently noted in our series. However, there was no apparent correlation between the presence of ischemic changes, the type of operation peiformed and the results of operation. Although the presence of ischemic atrophy without infarction did not pre- clude a good response to operation, it is possible that nephrectomy rather than revascularization might have improved results in 6 patients with ischemic atrophy in the ipsilateral kidney who did not benefit from the procedure. Three of these patients had a significant pressure gradient across the area of stenosis. However, we have avoided nephrectomy, prefer- ring to preserve functioning renal tissue whenever possible.

The limited afnount of tissue available from both kidneys by the technique employed was insufficient for assessment of either the juxtaglomerular appara- tus or the degree of ischemic changes present. In the design of the study we were primarily interested in determining the prognostic value of bilateral needle biopsy in evaluation of the hypertensive problem. Results clearly demonstrated the absence of any use- ful correlation. Because of the risk involved, we did not consider it desirable to obtain additional specimens of the size necessary to assess adequately all possible morphologic changes.

Prognostic value of renal venous renin assays: Although bilateral renal venous renin assays were available in only 10 patients, an excellent correlation was noted with the results of surgical treatment. As we have previously reported,s a renal venous renin ratio of greater than 1.5 when the ipsilateral kidney is compared to the contralateral kidney appears to correlate well with a favorable response to operation. Thus, the renal venous renin assays were predictive of the surgical result in 8 of the 10 patients in whom assays had been performed. Patients in this study were not prepared with salt-restricted diets or diuretic agents before performance of the renal venous renin assays. It is possible that the correlation might have been even better if all patients had been given a restricted salt diet plus an oral diuretic agent for several days before renal venous catheterization.

Prognostic value of renal arterial pressure gradients: We were surprised by the relatively poor correlation of pressure gradient to surgical response. It had been our impression that a gradient of 50 mm Hg or greater provided an excellent index of hemo- dynamically significant renal arterial stenosis. In our study, the pressure gradient was predictive of the surgical response in only 13 of 19 patients. The measurements were all made directly at the time of operation and did not represent measurements made preoperatively by means of a catheter in the stenotic renal artery. The use of a catheter is not a reliable method of measurement because of artefacts pro- duced by the catheter.

References

1. Hunt JC, Bernatt MD, Harrison EG Jr: Factors determining diagnosis and choice of treatment of renovascular hypertension: influence of location, severity, and type of stenos- ing lesions. Circ Res 21: suppl 2:21 l-223, 1967

2. Kaufman JJ, Lupu AN, Maxwell MH: Renovascular hypertension: clinical characteristics, diagnosis, and treatment. Cardiovasc Clin 1:79-l 12. 1969

3. Vidt DG, Glfford RW Jr: Reversible renal hypertension. Cardiovasc Clin 1: 131-l 56, 1969

4. Vertes V, Grauel JA, Goldblatt H: Studies of patients with renal hypertension undergoing vascular surgery. New Eng J Med 272:188-189.1965

5. Barajas L, Lupu AN, Kaufman JJ, et al: The value of the renal biopsy in unilateral renovascular hypertension. Ne- phron 4~231-247, 1967

8. Laforet EG: Malignant hypertension associated with unilateral renal artery occlusion: three cases. Ann Intern Med 38:667-688,1953

7. Bauer H, Forbes GL: Unilateral renal artery obstruction associated with malignant nephrosclerosis confined to the opposite kidney. Amer Heart J 44:634-638, 1952

8. Harrison EG Jr, McCormack W: Pathologic classification of renal arterial disease in renovascular hypertension. Mayo Clin Proc 46:161-167, 1971

9. Pickens PT, Bumpus FM, Lloyd AM, et al: Measurement of renin activity in human plasma. Circ Res 17:438-448, 1965

10. Hussain RA, Vidt D-G, McCormack W, et al: Unilateral renovascular hypertension: correlation of differential renal vein renin assays and results of corrective surgery (abstr). Amer Sot Nephrol 3rd Ann Meeting, 1969, p 29,

December 1972 The American Journal of CARDIOLOGY Volume 30 831

surgical treatment of unilateral renal vascular disease: prognostic role of vascular changes in...

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