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Renal Functional Changes Following Surgery for Renovascular Hypertension: Preoperative and Long-term Postoperative Results
THE JOURNAL OF UROLOGY
Vol. 90, No. 4 October 1963 Copyright © 1963 by The Williams & Wilkins Co. Printed in U.S.A.
RENAL FUNCTIONAL CHANGES FOLLOWING SURGERY FOR RENOVASCULAR HYPERTENSION: PREOPERATIVE AND LONG-TERM POSTOPERATIVE RESULTS ALBERT N. BREST, CHARLES HEIDER
AND
JOHN H. MOYER
From the Hypertension Renal Unit, Hahneinann Medical College and Hospital, Philadelphia, Pa.
Renovascular hypertension due to occlusive renal arterial disease is a potentially reversible form of diastolic hypertension. In most cases, the offending anatomic lesion consists of narrowing or occlusion of the renal artery or its primary branches by atheromatous plaques. However, renovascular disease may be congenital as well as acquired in origin and may be either bilateral or unilateral in location. 1 Surgical correction is directed toward renal revascularization by means of endarterectomy, angioplasty, resection with end-to-end anastomosis, or bypass graft. 2 - 7 N ephrectomy is performed only when these latter procedures are not technically feasible or when the involved kidney is non-functional. When the clinical findings suggest the presence of renovascular hypertension, the investigation generally includes differential renal excretion studies, radioisotope renograms, and renal angiography. For purposes of renal functional assessment and evaluation of postoperative
results, we have also included bilateral renal clearances of inulin (glomerular filtration rate, GFR) and para-aminohippurate (renal plasma flow, RPF). These studies provide quantitative data concerning the extent of renal functional impairment in the involved and contralateral kidneys. Although either renal revascularization or nephrectomy may result in blood pressure reduction, little information is available regarding renal functional responses in such cases following surgery. In the patients herein reported, longterm observations indicated significant sustained blood pressure reduction in 12 of 15 patients treated by renal artery bypass or nephrectomy This is a report of the changes in renal function in this group of patients who were studied for periods ranging from 10 to 36 months following surgery.
Accepted for publication March 15, 1963. Supported in part by grants from the Hahnemann Cardiovascular Clinical Research Center (Public Health Service, H6368) and the Southeastern Pennsylvania Heart Association. 1 Brest, A. N. and Moyer, J. H.: In: Significance and incidence of renal atherosclerosis in hypertension. In: Hypertension: Recent Advances. Philadelphia: Lea and Febiger, 1961, p. 184. 2 Morris, G. C., Jr., Cooley, D. A., Crawford, E. S., Berry, W. B. and De Bakey, M. E.: Renal revascularization for hypertension. Surgery, 48: 95, 1960. 3 Poutasse, E. F.: Surgical treatment of renal hypertension: Results in patients with occlusive lesions of renal arteries. J. Urol., 82: 403, 1959. 4 Morris, G. C., Jr., De Bakey, M. E., Cooley, D. A. and Crawford, E. S.: Surgical treatment of renal hypertension. Ann. Surg., 151: 854, 1960. 5 Howard, J. E., Berthong, JVI., Sloan, R. D. and Yendt, E. R.: Relief of malignant hypertension by nephrectomy in 4 patients with unilateral vascular disease. Trans. Assn. Am. Phys., 66: 164, 1953. 6 Yendt, E. R., Kerr, W. K., Wilson, D.R. and Jaworski, Z. F.: Diagnosis and treatment of renal hypertension. Amer. J. Med., 28: 169, 1960. 7 Morris, G. C., Jr.: Surgical considerations in renal vascular hypertension. In: Hypertension: Recent Advances. Philadelphia: Lea and Febiger, 1961, p. 221.
Fifteen patients with renovascular hypertension were studied. The presence of occlusive renal artery disease was confirmed in each instance by renal angiography. Two of the 15 patients had bilateral renal artery lesions; the others had unilateral renovascular disease. Nine patients (group 1) had moderate to severe, but nonmalignant, diastolic hypertension, with grade 2 fundoscopic changes.* The remaining 6 (group 2) patients had severe progressive malignant hypertension, with grade 4 fundoscopic findings. Individual renal clearances of inulin (GFR) and para-aminohippurate (RPF) were performed by ureteral catheterization, 3 to 6 weeks prior to surgery, in all but 2 patients. Renal blood flows were calculated from the para-aminohippurate clearance determinations. t These studies were subsequently performed in all 15 patients, 48 hours prior to surgery. The findings are recorded
380
METHODS
* Keith-Wagener classification
t The corrected normal values for GFR and RBF are approximately 55 ± 10 cc and 500 ± 50 cc per minute, respectively, for each kidney.
i
i TABLE
-----c----~---------, -
C2
Cl ,·--1
C2
Cl
z:,.-
I
Blood Pressure mm.Hg. -~-----~-
~
I
----
DZ
DI
a
Renal Blood Flow cc/min.
Glomerular Filtration Rate cc/min. Patient,
;:d
1
[
DZ
Dl
'
I
Cl
I
CZ
Surgical Procedure
zc:,
D2
D1
>-3 H 0
z:,.-
Group 1. 7 patients with non-malignant hupertension ancl unilateral renal artery involvement
,-
, 14
u'lr ujr ulr u r ulr uir ulr uls ,, ,, I21; 31 30 ,2 I ,o 300 I ,, 32,,-I ,,, ,,, 160 36
26 16 28 12 I 22 I 16
54 54 40 34 14 3G 44124 42 48 20 54
1
1 2 3 4 5 6 7
1
38 46 I 42 43 28 40 132 44 36 43 - 38 38 42 30 46 32 56 72 70 64 -
J
I
200 410 I 206 390 274 376: 145 356 210 400 100 446
213 390 238 375 256 3()0 137 373 200 410 140 510
12\JO 286 2()5 380 -
385 335 315 2()5 388 302 345 , 410 6101580 f
-
Dis
Dis
1181214 185
116 124 222 125 211 125 211 127 186 114 194 120
310 1210 408 176 122 324 208 132 392 226 117 350 196 118 730 190 110 622 200 116
s
D
~
c:,
DI
1160 90 1168 98 170 105 176 118 I 156 841160 80 I 180 ()8 1190 104 , 155 ()4 , 152 86 I 160 a0 I 118 112 I 110 841160 80
------Right bypass Left bypass Right bypass Left bypass Left bypass Right nephrectomy Right nephrectomy
I
1
crj
q
P1 :,.-
z
Q
a
U1 crj
0
~
0 ::;J
,:::
z
Q
U1
q
Group 1. 2 patients with non-malignant hypertension ancl bilateral renal artery involvement R
8 ()
R
L
38
46 I 42 36
36 38
L
I
R
40 146 36140
---
I L
IR
52 42 40 I 38
L
R
46 38
L
R
L
320 410 370 400
380 400 360 396
R
L
400 380
480 394
R
L
430 450 354 388
s
170 210
D
I
s
110 · 181 llG j 212
D
I
s
10211,0 122 210
D
I s
a
D
;:d ~
90 1170 ()4 122 170 100
Bilateral bypass Bilateral bypass
I
u
jr ulr ulr u
l-~~1~-1 1 2
3 4 5 G
12 15 18 14 11 14 so 38
·11 1~ '±
10 8 34 24
i
O 36
/020
~u
18
10
1
I
I
U
I
~'±
14 : 21 38 I -
1-
00
20 59
108 140 251 273
63
-54j
crj
0 ;,:I ;,:I
a
'
z
Groiip 2. 6 patients with malignant hypertension with imilateral renal artery involvement
I
;,:I
Q
l~I_ll__ I 100 92 247 200 0 195 0 110
195 175 160
u 145 155 137 500
I
233 200 208
u 280 330 197 701 666
480
s 230 190 2GO 220
l~J
146 172 140
I I
s
D
----
238 188 268 218 270 210
I
156 142 164 146 132 · 150 I
s
D
I s
0
<1 p,
D
140 90 1160 90 160 120 140 64 180 120 I 126 114 160 110 I 104 100 . 192 90 90 j 168
U1
c:,
Left bypass Right bypass Left bypass Left nephrectomy Right nephrectomy Right nephrectom,'
q ~ :,.;,:I
P1
~
cj
a
;:d
>-3
t,,j
z
U1 H
Cl, control period 1 (initial observation) C2, control period 2 (48 hours before surgery) I, involved kidney R, right kidney l:, uninvolved kidney L, left kidney
DI, followup period 1 (3 weeks after surgery) D2, followup period 2 (10-:36 months after surgery) S, systolic blood pressure D, diastolic blood pressme
0
z
Ci.J
co r-'
382
BREST, HEIDER AN"D MOYER Left Renal Artery Stenosis Renal Hemodynamic Response Following Left Renal Artery Bypass Pt A.G. NONMALIGNANT HYPERTENSION 400
Left
383
350
C:
~
Left
300
"
283
262
C)
<.,
"-C)
"
200
Right 100
GFR(cc/min.)
RBF(ccmin.)
Cl=C2 =CONTROLS ( Pre-op) DI= 3 mos. Post-op: D2= !Omos. Post-op GFR=Glomerular Filtration Rote: RBF=: Renal Blood Flow
Fm. 1. Prior to surgery, GFR and RBF were severely diminished in involved kidney. Renal function was reduced to lesser extent in uninvolved kidney. After left renal revascularization, function improved substantially in left kidney whereas rigbt kidney decreased slightly in function. Right Reno/ Artery Stenosis Renal Hemodynamic Response in Left Kidney Following Right Nephrectomy Pt. 0. 8. NON MALIGNANT HYPERTENSION
i3
300
~
"' C)
C;
.,_
Left
200
Left
C)
100~
100
[11_11
446 510 580 622
Mean BP lmmHg) GFR (cc/min.) RBF (cc/min.) c1:c2= Controls (Pre-op) Dt= 3 Months Post-op 02.:: 10 Months Post-op GFR=Glomerulor Filtration Rote ABF= Rena! 6:ocd F!ow
Fm. 2. Following right nephrectorny for right renal artery stenosis, function improved significantly in contralateral kidney. in table 1 as control values (Cl, C2)+. In 13 of the 15 patients, surgery consisted of unilateral renal artery bypass or nephrectomy. Bilateral renal artery bypasses were constructed in 2 cases. Renal clearance studies were repeated in 13 of the 15 patients, 3 weeks to 3 months postoperatively (period Dl) and again, in all patients, 10 to 36 months following surgery (period D2). RESULTS
Control renal clearance studies in the 7 patients in group 1 with unilateral renal artery disease revealed moderate to severe reduction in GFR and RBF in the involved (I) kidneys. In contrast, renal function in the contralateral, uninvolved
(U) kidneys was only slightly reduced. Postoperatively, GFR and RBF in the involved kidney was improved in all 5 patienfa treated by renal artery bypass. The improvement was noted at 3 months (period Dl) and again at 10 months (period D2). However, in the uninvolved kidney, function either did not change or else was slightly reduced after surgery. This renal functional response was consistent in all 5 cases (fig. 1). In the 2 patients in whom nephrectomy was performed, the remaining (uninvolved) kidney showed a substantial increase in function, actually above the expected normal values, 10 months following surgery (see fig. 2). A significant antihypertensive response was obtained in five of the 7 patients.
RENAL FUNCTIONAL CHANGES FOLLOWING SURGERY FOR RENOV ASCULAR HYPERTENSION
388
Left Renal Artery Stenosis Renal Hemodynamic Response Following Left Renal Artery Bypass Pt
EL.
Malignant Hypertension
400
~
300
G
0c
h-
"'
Right
Left
G
"c_
200
Right
Left 193
191 164
C)
143
141
148
;,
Mean BP {mmHg)
GFR (cc/mm)
Cl: C2=Controls (Pre-op) DI:: 3 Wks Post-op GFReGlomerulor Flltrot1on Rote RBF:: Renal Blood Flow
Fm. 3. Prior t.o surgery, GFR and REF were markedly reduced in involved right kidney. Renal function was diminished t.o sii,lilar extent in uninvolved kidney. Ten months after nght renal artery hypass, bilateral renal functional improvement occurred 11lt.hough not to normal levels. Control studies in the 2 patients in group 1 with bilateral renovascular lesions revealed only slight reduction in GFR and RBF in the involved and contralateral kidneys without significant difference on either side. Although bilateral renal artery bypasses were constructed, renal function improved only slightly in 1 patient and showed no significant change in the other. Only one of the 2 patients had a significant antihypertensive response following surgery. All 6 patients in group 2 had unilateral renal artery disease. Control renal clearance studies indicated a marked reduction in GFR and RBF in both kidneys. In 4 cases, there was no substantial difference in renal function between the involved and contralateral kidneys. In 2 patients, however, the involved kidney was completely non-functional. Renal artery bypass was performed in 3 patients and nephrectoniy in the other 3. Three weeks follmYing surgery (period D 1), slight improvement in renal function was noted bilaterally in the 3 patients in whom renal artery bypass was performed; and function studies perforn1ed 10 to 36 months following surgery showed still further improvement (fig. 3). In the 3 patients in whom nephrectorny was performed, the remaining (uninvolved) kidney showed a substantial increase in function, 10 to 36 months following surgery. In the latter patients, function increased to normal or greater levels, despite being reduced initially. All 6 patients in group 2 obtained a significant antihypertensive re~ponse following surgery and the reduction in blood pressure was subsequently maintained without drng therapy.
DISCUSSION
The arbitrary grouping of these patients according to their clinical status, i.e. malignant versus non-malignant hypertension, seerns to point up significant differences in preoperative impairment in renal function and in the renal functional response observed postoperatively. In the malignant group, the reduction in function was severe and bilateral, despite the presence of unilateral renal arterial occlusive disease. Both the involved and contralateral kidneys showed an increase in function following revascularization, although function in both kidneys remained below normal 10 months after surgery. In the nonmalignant group, on the other hand, greater reduction in renal function occurred in the involved kidney; and after revascularization, renal function increased in the involved kidney but tended to diminish slightly on the contralateral side. Nephrectomy in both groups of patients seemed to result in a compensatory increase in function to normal or greater levels in the remaining kidney. The blood pressure response in the 2 group,'3 was similar, although of different magnitude. The differences in initial renal functional irn.pairment and the subsequent changes observed after revascularization, in the 2 groups, may be due to 1) differences in severity of the hypertensive process, perhaps related to the degree and duration of the renal arterial occlusion, or 2) the possible superimposition of occlusive arterial disease upon pre-existent essential hypertension. There is evidence from renal biopsy material in cases of renovascular hypertension to suggest
384
BREST, HEIDER AND MOYER
that although the ischemic kidney is involved in the production of a vasopressor substance, it is actually protected by the occlusive process, from the effects of increased systemic blood pressures. 2 Nevertheless one would anticipate some degree of renal functional impairment in the involved kidney, dependent upon the magnitude of hemodynamic alteration and renal parenchymal atrophy produced by the occlusion. Conversely the contralateral, unoccluded kidney develops arteriolosclerotic changes secondary to the increased blood pressure. These secondary arteriolonephrosclerotic changes are likely responsible, at least in part, for diminution of renal function in the uninvolved kidney, depending on the duration and the severity of the hypertensive process. 8 Revascularization restores the hemodynamics in the involved kidney and allows for potential reversibility of tissue atrophy. On the other hand, the degree of reversibility in the contralateral kidney depends upon the extent of accompanying renal parenchymal damage resulting from arteriolonephrosclerosis. Thus the slight reduction in GFR and RBF observed in the uninvolved kidney after revascularization in patients in group I is probably related to the decrease in systemic pressure, superimposed upon a fixed degree of renal functional damage in the socalled uninvolved kidneys. Similar reduction in function in the uninvolved kidney following surgery has been reported by Morris2 and by Poutasse. 9 In the patients with malignant hypertension, the marked bilateral reduction in renal function in 6 patients prior to surgery and the incomplete renal functional response to revascularization in 3 patients suggest either that unilateral renovascular hypertension resulted in severe secondary changes in both the involved and contralateral kidneys or else that severe bilateral impairment preceded the development of atherosclerotic renal artery disease. With the development of the malignant hypertensive process, the superimposition of intense angiospasm could result in further reduction in renal function. Removal of the vasospastic element may explain the improvement in 8 Moyer, J. H., Heider, C.H., Pevey, J. K. and Ford, R. V.: The vascular status of a heterogeneous group of patients with hypertension, with particular emphasis on renal function. Amer. J. Med., 24: 164, 1958. 9 Poutasse, E. F.: Occlusion of a renal artery as a cause of hypertension. Circulation, 13: 37, 1956.
contralateral renal function in the 3 patients in group 2 following revascularization, in contrast to the absence of such improvement in the contralateral kidneys in patients in group I in whom severe angiospasm presumably does not play an important role. Where unilateral occlusion has resulted in marked atrophy of the involved kidney and severe arteriolosclerotic changes in the contralateral kidney, return to normal function would be impossible because of the presence of irreversible changes. Likewise if the renovascular hypertension were superimposed upon pre-existent essential hypertension with accompanying renal functional impairment in both kidneys, the degree of reversibility would depend upon the extent of prior bilateral arteriolonephrosclerosis. In either event, postoperative improvement in bilateral renal function would be incomplete. In the 5 patients in whom nephrectomy was performed, the functional improvement in the remaining kidney most likely represents compensatory renal parenchymal hypertrophy. In those patients with severe hypertension, however, it is conceivable that improvement in renal function might also result from release of intense renal vasospasm accompanying the postoperative reduction in blood pressure. In 1933, Ellis and Weiss reported similar improvement in urea and creatinine clearances in the contralateral kidney following nephrectomy and they attributed such changes to compensatory hypertrophy. 10 In animal experiments, it has been shown that kidney enlargment following unilateral nephrectomy can be due both to cellular hypertrophy and cellular hyperplasia. 11-13 It is noteworthy that in the 3 cases in group 2, kidney function improved despite evidences of severe renal functional impairment prior to surgery. Although these discussions are speculative, they do seem to explain the renal functional 1o Ellis, L.B. and Weiss, S.: The renal function in persons with one kidney. Amer. J. Med. Sci., 186: 242, 1933. 11 Sulkin, N. M.: Cytologic studies of the remaining kidney following unilateral nephrectomy in the rat. Anat. Rec., 106: 95, 1949. 12 Rollason, H. D.: Compensatory hypertrophy of the kidney of the young rat with special emphasis on the role of cellular hyperplasia. Anat. Rec., 104: 263, 1949. 13 Simpson, D. P.: Hyperplasia after unilateral nephrectomy and the role of excretory load in its production. Amer. J. Phys., 201: 517, 1961.
RENAL FUNCTIONAL CHANGES FOLLOWING SURGERY FOR RENOVASCULAR HYPERTENSION
changes observed. Additional information including renal biopsy specimens and longer postoperative followup reports will be helpful in further defining the renal functional response. In general, however, it appears that the more severe the hypertension and the more depressed the renal function, the less the improvement following revascularization. Nevertheless, from a practical standpoint, it has been demonstrated that some patients will benefit from surgical management, not only with blood pressure reduction but also with renal functional improvement. The latter may occur despite the presence of severe depression in renal function preoperatively. In the present series, some patients seen initially with malignant hypertension and marked reduction in renal function are still alive 36 months following surgery. Almost assuredly these patients would have died had the malignant process not been arrested. In patients with less severe hypertension, the accomplishment of sustained blood pressure reduction and improvement in kidney function following surgery are valid reasons to search
385
diligently for such instances of potentially reversible hypertensive disease. SUMMARY
Fifteen patients with renovascular hypertension are discussed relative to blood pressure response and renal functional changes observed following renal revascularization or nephrectomy. Surgery resulted in significant blood pressure reduction in 12 of the 15 patients. Patients with non-malignant renovascular hypertension had greater reduction in function in the involved kidney. Improvement following revascularization was unilateral and limited to the involved kidney. The patients wit!i malignant renovascular hypertension had seYere bilateral reduction in renal function. Revascularization in such cases resulted in improved function bilaterally, although not to normal levels. Nephrectomy in both groups of patients resulted in a compensatory increase in function to normal or greater levels in the remaining kidney. Explanations for the differences in the postoperative renal functional response are discussed.
Vol. 90, No. 4 October 1963 Copyright © 1963 by The Williams & Wilkins Co. Printed in U.S.A.
RENAL FUNCTIONAL CHANGES FOLLOWING SURGERY FOR RENOVASCULAR HYPERTENSION: PREOPERATIVE AND LONG-TERM POSTOPERATIVE RESULTS ALBERT N. BREST, CHARLES HEIDER
AND
JOHN H. MOYER
From the Hypertension Renal Unit, Hahneinann Medical College and Hospital, Philadelphia, Pa.
Renovascular hypertension due to occlusive renal arterial disease is a potentially reversible form of diastolic hypertension. In most cases, the offending anatomic lesion consists of narrowing or occlusion of the renal artery or its primary branches by atheromatous plaques. However, renovascular disease may be congenital as well as acquired in origin and may be either bilateral or unilateral in location. 1 Surgical correction is directed toward renal revascularization by means of endarterectomy, angioplasty, resection with end-to-end anastomosis, or bypass graft. 2 - 7 N ephrectomy is performed only when these latter procedures are not technically feasible or when the involved kidney is non-functional. When the clinical findings suggest the presence of renovascular hypertension, the investigation generally includes differential renal excretion studies, radioisotope renograms, and renal angiography. For purposes of renal functional assessment and evaluation of postoperative
results, we have also included bilateral renal clearances of inulin (glomerular filtration rate, GFR) and para-aminohippurate (renal plasma flow, RPF). These studies provide quantitative data concerning the extent of renal functional impairment in the involved and contralateral kidneys. Although either renal revascularization or nephrectomy may result in blood pressure reduction, little information is available regarding renal functional responses in such cases following surgery. In the patients herein reported, longterm observations indicated significant sustained blood pressure reduction in 12 of 15 patients treated by renal artery bypass or nephrectomy This is a report of the changes in renal function in this group of patients who were studied for periods ranging from 10 to 36 months following surgery.
Accepted for publication March 15, 1963. Supported in part by grants from the Hahnemann Cardiovascular Clinical Research Center (Public Health Service, H6368) and the Southeastern Pennsylvania Heart Association. 1 Brest, A. N. and Moyer, J. H.: In: Significance and incidence of renal atherosclerosis in hypertension. In: Hypertension: Recent Advances. Philadelphia: Lea and Febiger, 1961, p. 184. 2 Morris, G. C., Jr., Cooley, D. A., Crawford, E. S., Berry, W. B. and De Bakey, M. E.: Renal revascularization for hypertension. Surgery, 48: 95, 1960. 3 Poutasse, E. F.: Surgical treatment of renal hypertension: Results in patients with occlusive lesions of renal arteries. J. Urol., 82: 403, 1959. 4 Morris, G. C., Jr., De Bakey, M. E., Cooley, D. A. and Crawford, E. S.: Surgical treatment of renal hypertension. Ann. Surg., 151: 854, 1960. 5 Howard, J. E., Berthong, JVI., Sloan, R. D. and Yendt, E. R.: Relief of malignant hypertension by nephrectomy in 4 patients with unilateral vascular disease. Trans. Assn. Am. Phys., 66: 164, 1953. 6 Yendt, E. R., Kerr, W. K., Wilson, D.R. and Jaworski, Z. F.: Diagnosis and treatment of renal hypertension. Amer. J. Med., 28: 169, 1960. 7 Morris, G. C., Jr.: Surgical considerations in renal vascular hypertension. In: Hypertension: Recent Advances. Philadelphia: Lea and Febiger, 1961, p. 221.
Fifteen patients with renovascular hypertension were studied. The presence of occlusive renal artery disease was confirmed in each instance by renal angiography. Two of the 15 patients had bilateral renal artery lesions; the others had unilateral renovascular disease. Nine patients (group 1) had moderate to severe, but nonmalignant, diastolic hypertension, with grade 2 fundoscopic changes.* The remaining 6 (group 2) patients had severe progressive malignant hypertension, with grade 4 fundoscopic findings. Individual renal clearances of inulin (GFR) and para-aminohippurate (RPF) were performed by ureteral catheterization, 3 to 6 weeks prior to surgery, in all but 2 patients. Renal blood flows were calculated from the para-aminohippurate clearance determinations. t These studies were subsequently performed in all 15 patients, 48 hours prior to surgery. The findings are recorded
380
METHODS
* Keith-Wagener classification
t The corrected normal values for GFR and RBF are approximately 55 ± 10 cc and 500 ± 50 cc per minute, respectively, for each kidney.
i
i TABLE
-----c----~---------, -
C2
Cl ,·--1
C2
Cl
z:,.-
I
Blood Pressure mm.Hg. -~-----~-
~
I
----
DZ
DI
a
Renal Blood Flow cc/min.
Glomerular Filtration Rate cc/min. Patient,
;:d
1
[
DZ
Dl
'
I
Cl
I
CZ
Surgical Procedure
zc:,
D2
D1
>-3 H 0
z:,.-
Group 1. 7 patients with non-malignant hupertension ancl unilateral renal artery involvement
,-
, 14
u'lr ujr ulr u r ulr uir ulr uls ,, ,, I21; 31 30 ,2 I ,o 300 I ,, 32,,-I ,,, ,,, 160 36
26 16 28 12 I 22 I 16
54 54 40 34 14 3G 44124 42 48 20 54
1
1 2 3 4 5 6 7
1
38 46 I 42 43 28 40 132 44 36 43 - 38 38 42 30 46 32 56 72 70 64 -
J
I
200 410 I 206 390 274 376: 145 356 210 400 100 446
213 390 238 375 256 3()0 137 373 200 410 140 510
12\JO 286 2()5 380 -
385 335 315 2()5 388 302 345 , 410 6101580 f
-
Dis
Dis
1181214 185
116 124 222 125 211 125 211 127 186 114 194 120
310 1210 408 176 122 324 208 132 392 226 117 350 196 118 730 190 110 622 200 116
s
D
~
c:,
DI
1160 90 1168 98 170 105 176 118 I 156 841160 80 I 180 ()8 1190 104 , 155 ()4 , 152 86 I 160 a0 I 118 112 I 110 841160 80
------Right bypass Left bypass Right bypass Left bypass Left bypass Right nephrectomy Right nephrectomy
I
1
crj
q
P1 :,.-
z
Q
a
U1 crj
0
~
0 ::;J
,:::
z
Q
U1
q
Group 1. 2 patients with non-malignant hypertension ancl bilateral renal artery involvement R
8 ()
R
L
38
46 I 42 36
36 38
L
I
R
40 146 36140
---
I L
IR
52 42 40 I 38
L
R
46 38
L
R
L
320 410 370 400
380 400 360 396
R
L
400 380
480 394
R
L
430 450 354 388
s
170 210
D
I
s
110 · 181 llG j 212
D
I
s
10211,0 122 210
D
I s
a
D
;:d ~
90 1170 ()4 122 170 100
Bilateral bypass Bilateral bypass
I
u
jr ulr ulr u
l-~~1~-1 1 2
3 4 5 G
12 15 18 14 11 14 so 38
·11 1~ '±
10 8 34 24
i
O 36
/020
~u
18
10
1
I
I
U
I
~'±
14 : 21 38 I -
1-
00
20 59
108 140 251 273
63
-54j
crj
0 ;,:I ;,:I
a
'
z
Groiip 2. 6 patients with malignant hypertension with imilateral renal artery involvement
I
;,:I
Q
l~I_ll__ I 100 92 247 200 0 195 0 110
195 175 160
u 145 155 137 500
I
233 200 208
u 280 330 197 701 666
480
s 230 190 2GO 220
l~J
146 172 140
I I
s
D
----
238 188 268 218 270 210
I
156 142 164 146 132 · 150 I
s
D
I s
0
<1 p,
D
140 90 1160 90 160 120 140 64 180 120 I 126 114 160 110 I 104 100 . 192 90 90 j 168
U1
c:,
Left bypass Right bypass Left bypass Left nephrectomy Right nephrectomy Right nephrectom,'
q ~ :,.;,:I
P1
~
cj
a
;:d
>-3
t,,j
z
U1 H
Cl, control period 1 (initial observation) C2, control period 2 (48 hours before surgery) I, involved kidney R, right kidney l:, uninvolved kidney L, left kidney
DI, followup period 1 (3 weeks after surgery) D2, followup period 2 (10-:36 months after surgery) S, systolic blood pressure D, diastolic blood pressme
0
z
Ci.J
co r-'
382
BREST, HEIDER AN"D MOYER Left Renal Artery Stenosis Renal Hemodynamic Response Following Left Renal Artery Bypass Pt A.G. NONMALIGNANT HYPERTENSION 400
Left
383
350
C:
~
Left
300
"
283
262
C)
<.,
"-C)
"
200
Right 100
GFR(cc/min.)
RBF(ccmin.)
Cl=C2 =CONTROLS ( Pre-op) DI= 3 mos. Post-op: D2= !Omos. Post-op GFR=Glomerular Filtration Rote: RBF=: Renal Blood Flow
Fm. 1. Prior to surgery, GFR and RBF were severely diminished in involved kidney. Renal function was reduced to lesser extent in uninvolved kidney. After left renal revascularization, function improved substantially in left kidney whereas rigbt kidney decreased slightly in function. Right Reno/ Artery Stenosis Renal Hemodynamic Response in Left Kidney Following Right Nephrectomy Pt. 0. 8. NON MALIGNANT HYPERTENSION
i3
300
~
"' C)
C;
.,_
Left
200
Left
C)
100~
100
[11_11
446 510 580 622
Mean BP lmmHg) GFR (cc/min.) RBF (cc/min.) c1:c2= Controls (Pre-op) Dt= 3 Months Post-op 02.:: 10 Months Post-op GFR=Glomerulor Filtration Rote ABF= Rena! 6:ocd F!ow
Fm. 2. Following right nephrectorny for right renal artery stenosis, function improved significantly in contralateral kidney. in table 1 as control values (Cl, C2)+. In 13 of the 15 patients, surgery consisted of unilateral renal artery bypass or nephrectomy. Bilateral renal artery bypasses were constructed in 2 cases. Renal clearance studies were repeated in 13 of the 15 patients, 3 weeks to 3 months postoperatively (period Dl) and again, in all patients, 10 to 36 months following surgery (period D2). RESULTS
Control renal clearance studies in the 7 patients in group 1 with unilateral renal artery disease revealed moderate to severe reduction in GFR and RBF in the involved (I) kidneys. In contrast, renal function in the contralateral, uninvolved
(U) kidneys was only slightly reduced. Postoperatively, GFR and RBF in the involved kidney was improved in all 5 patienfa treated by renal artery bypass. The improvement was noted at 3 months (period Dl) and again at 10 months (period D2). However, in the uninvolved kidney, function either did not change or else was slightly reduced after surgery. This renal functional response was consistent in all 5 cases (fig. 1). In the 2 patients in whom nephrectomy was performed, the remaining (uninvolved) kidney showed a substantial increase in function, actually above the expected normal values, 10 months following surgery (see fig. 2). A significant antihypertensive response was obtained in five of the 7 patients.
RENAL FUNCTIONAL CHANGES FOLLOWING SURGERY FOR RENOV ASCULAR HYPERTENSION
388
Left Renal Artery Stenosis Renal Hemodynamic Response Following Left Renal Artery Bypass Pt
EL.
Malignant Hypertension
400
~
300
G
0c
h-
"'
Right
Left
G
"c_
200
Right
Left 193
191 164
C)
143
141
148
;,
Mean BP {mmHg)
GFR (cc/mm)
Cl: C2=Controls (Pre-op) DI:: 3 Wks Post-op GFReGlomerulor Flltrot1on Rote RBF:: Renal Blood Flow
Fm. 3. Prior t.o surgery, GFR and REF were markedly reduced in involved right kidney. Renal function was diminished t.o sii,lilar extent in uninvolved kidney. Ten months after nght renal artery hypass, bilateral renal functional improvement occurred 11lt.hough not to normal levels. Control studies in the 2 patients in group 1 with bilateral renovascular lesions revealed only slight reduction in GFR and RBF in the involved and contralateral kidneys without significant difference on either side. Although bilateral renal artery bypasses were constructed, renal function improved only slightly in 1 patient and showed no significant change in the other. Only one of the 2 patients had a significant antihypertensive response following surgery. All 6 patients in group 2 had unilateral renal artery disease. Control renal clearance studies indicated a marked reduction in GFR and RBF in both kidneys. In 4 cases, there was no substantial difference in renal function between the involved and contralateral kidneys. In 2 patients, however, the involved kidney was completely non-functional. Renal artery bypass was performed in 3 patients and nephrectoniy in the other 3. Three weeks follmYing surgery (period D 1), slight improvement in renal function was noted bilaterally in the 3 patients in whom renal artery bypass was performed; and function studies perforn1ed 10 to 36 months following surgery showed still further improvement (fig. 3). In the 3 patients in whom nephrectorny was performed, the remaining (uninvolved) kidney showed a substantial increase in function, 10 to 36 months following surgery. In the latter patients, function increased to normal or greater levels, despite being reduced initially. All 6 patients in group 2 obtained a significant antihypertensive re~ponse following surgery and the reduction in blood pressure was subsequently maintained without drng therapy.
DISCUSSION
The arbitrary grouping of these patients according to their clinical status, i.e. malignant versus non-malignant hypertension, seerns to point up significant differences in preoperative impairment in renal function and in the renal functional response observed postoperatively. In the malignant group, the reduction in function was severe and bilateral, despite the presence of unilateral renal arterial occlusive disease. Both the involved and contralateral kidneys showed an increase in function following revascularization, although function in both kidneys remained below normal 10 months after surgery. In the nonmalignant group, on the other hand, greater reduction in renal function occurred in the involved kidney; and after revascularization, renal function increased in the involved kidney but tended to diminish slightly on the contralateral side. Nephrectomy in both groups of patients seemed to result in a compensatory increase in function to normal or greater levels in the remaining kidney. The blood pressure response in the 2 group,'3 was similar, although of different magnitude. The differences in initial renal functional irn.pairment and the subsequent changes observed after revascularization, in the 2 groups, may be due to 1) differences in severity of the hypertensive process, perhaps related to the degree and duration of the renal arterial occlusion, or 2) the possible superimposition of occlusive arterial disease upon pre-existent essential hypertension. There is evidence from renal biopsy material in cases of renovascular hypertension to suggest
384
BREST, HEIDER AND MOYER
that although the ischemic kidney is involved in the production of a vasopressor substance, it is actually protected by the occlusive process, from the effects of increased systemic blood pressures. 2 Nevertheless one would anticipate some degree of renal functional impairment in the involved kidney, dependent upon the magnitude of hemodynamic alteration and renal parenchymal atrophy produced by the occlusion. Conversely the contralateral, unoccluded kidney develops arteriolosclerotic changes secondary to the increased blood pressure. These secondary arteriolonephrosclerotic changes are likely responsible, at least in part, for diminution of renal function in the uninvolved kidney, depending on the duration and the severity of the hypertensive process. 8 Revascularization restores the hemodynamics in the involved kidney and allows for potential reversibility of tissue atrophy. On the other hand, the degree of reversibility in the contralateral kidney depends upon the extent of accompanying renal parenchymal damage resulting from arteriolonephrosclerosis. Thus the slight reduction in GFR and RBF observed in the uninvolved kidney after revascularization in patients in group I is probably related to the decrease in systemic pressure, superimposed upon a fixed degree of renal functional damage in the socalled uninvolved kidneys. Similar reduction in function in the uninvolved kidney following surgery has been reported by Morris2 and by Poutasse. 9 In the patients with malignant hypertension, the marked bilateral reduction in renal function in 6 patients prior to surgery and the incomplete renal functional response to revascularization in 3 patients suggest either that unilateral renovascular hypertension resulted in severe secondary changes in both the involved and contralateral kidneys or else that severe bilateral impairment preceded the development of atherosclerotic renal artery disease. With the development of the malignant hypertensive process, the superimposition of intense angiospasm could result in further reduction in renal function. Removal of the vasospastic element may explain the improvement in 8 Moyer, J. H., Heider, C.H., Pevey, J. K. and Ford, R. V.: The vascular status of a heterogeneous group of patients with hypertension, with particular emphasis on renal function. Amer. J. Med., 24: 164, 1958. 9 Poutasse, E. F.: Occlusion of a renal artery as a cause of hypertension. Circulation, 13: 37, 1956.
contralateral renal function in the 3 patients in group 2 following revascularization, in contrast to the absence of such improvement in the contralateral kidneys in patients in group I in whom severe angiospasm presumably does not play an important role. Where unilateral occlusion has resulted in marked atrophy of the involved kidney and severe arteriolosclerotic changes in the contralateral kidney, return to normal function would be impossible because of the presence of irreversible changes. Likewise if the renovascular hypertension were superimposed upon pre-existent essential hypertension with accompanying renal functional impairment in both kidneys, the degree of reversibility would depend upon the extent of prior bilateral arteriolonephrosclerosis. In either event, postoperative improvement in bilateral renal function would be incomplete. In the 5 patients in whom nephrectomy was performed, the functional improvement in the remaining kidney most likely represents compensatory renal parenchymal hypertrophy. In those patients with severe hypertension, however, it is conceivable that improvement in renal function might also result from release of intense renal vasospasm accompanying the postoperative reduction in blood pressure. In 1933, Ellis and Weiss reported similar improvement in urea and creatinine clearances in the contralateral kidney following nephrectomy and they attributed such changes to compensatory hypertrophy. 10 In animal experiments, it has been shown that kidney enlargment following unilateral nephrectomy can be due both to cellular hypertrophy and cellular hyperplasia. 11-13 It is noteworthy that in the 3 cases in group 2, kidney function improved despite evidences of severe renal functional impairment prior to surgery. Although these discussions are speculative, they do seem to explain the renal functional 1o Ellis, L.B. and Weiss, S.: The renal function in persons with one kidney. Amer. J. Med. Sci., 186: 242, 1933. 11 Sulkin, N. M.: Cytologic studies of the remaining kidney following unilateral nephrectomy in the rat. Anat. Rec., 106: 95, 1949. 12 Rollason, H. D.: Compensatory hypertrophy of the kidney of the young rat with special emphasis on the role of cellular hyperplasia. Anat. Rec., 104: 263, 1949. 13 Simpson, D. P.: Hyperplasia after unilateral nephrectomy and the role of excretory load in its production. Amer. J. Phys., 201: 517, 1961.
RENAL FUNCTIONAL CHANGES FOLLOWING SURGERY FOR RENOVASCULAR HYPERTENSION
changes observed. Additional information including renal biopsy specimens and longer postoperative followup reports will be helpful in further defining the renal functional response. In general, however, it appears that the more severe the hypertension and the more depressed the renal function, the less the improvement following revascularization. Nevertheless, from a practical standpoint, it has been demonstrated that some patients will benefit from surgical management, not only with blood pressure reduction but also with renal functional improvement. The latter may occur despite the presence of severe depression in renal function preoperatively. In the present series, some patients seen initially with malignant hypertension and marked reduction in renal function are still alive 36 months following surgery. Almost assuredly these patients would have died had the malignant process not been arrested. In patients with less severe hypertension, the accomplishment of sustained blood pressure reduction and improvement in kidney function following surgery are valid reasons to search
385
diligently for such instances of potentially reversible hypertensive disease. SUMMARY
Fifteen patients with renovascular hypertension are discussed relative to blood pressure response and renal functional changes observed following renal revascularization or nephrectomy. Surgery resulted in significant blood pressure reduction in 12 of the 15 patients. Patients with non-malignant renovascular hypertension had greater reduction in function in the involved kidney. Improvement following revascularization was unilateral and limited to the involved kidney. The patients wit!i malignant renovascular hypertension had seYere bilateral reduction in renal function. Revascularization in such cases resulted in improved function bilaterally, although not to normal levels. Nephrectomy in both groups of patients resulted in a compensatory increase in function to normal or greater levels in the remaining kidney. Explanations for the differences in the postoperative renal functional response are discussed.