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Renal Artery Stenosis in Hypertensive Diabetics
rr
Original Articles
r
RENAL ARTERY STENOSIS IN HYPERTENSIVE DIABETICS
I
CHODAPPASETTY MUNICHOODAPPA, JOHN A. D'ELIA,* JOHN A. LIBERTINO, RAYE. GLEASON AND A. RICHARD CHRISTLIEB From the Joslin Clinic and Elliott P. Joslin Research Laboratory Divisions, Joslin Diabetes Foundation, Department of Urology, Lahey Clinic Foundation, Department of Medicine, New England Deaconess and Peter Bent Brigham Hospitals and Harvard Medical School, Boston, Massachusetts
ABSTRACT
The incidence of atherosclerotic renal artery stenosis was compared in consecutive renal angiography of 28 hypertensive diabetics and 104 hypertensive non-diabetics. Mean age and sex distribution were comparable. Angiographic evidence of atherosclerotic renal artery stenosis was present in 10 diabetics (36 per cent) and 50 non-diabetics (48 per cent). Stenosis was considered hemodynamically significant if the renal vein renin ratio of the involved to uninvolved side was 1.4:1.0 or more. A renal vein renin ratio equal to or more than 1.4 was observed in 4 of 7 diabetics (57 per cent) and 31 of 47 non-diabetics (67 per cent). Fibromuscular hyperplasia was not seen in diabetics but was present in 12 per cent of the non-diabetics. Hypertension was treated surgically and improved in 2 of 3 diabetics (67 per cent) and in 17 of 19 non-diabetics (89 per cent) with angiographic and hemodynamic evidence of renal artery stenosis. In this series the incidence of atherosclerotic renal artery stenosis of physiologic consequence was not significantly different in hypertensive diabetics when compared to hypertensive non-diabetics. Within a population of hypertensive patients under investigation for renal artery stenosis a subgroup exists of patients with atherosclerotic renal artery stenosis and diabetes mellitus. 1• 2 We herein present the accumulated experience from a series of diabetic and non-diabetic patients with renal artery stenosis discovered during physical examination for hypertension and compare the incidence of physiologically significant renal artery stenosis in these 2 groups. PATIENTS AND METHODS
Records of all patients with hypertension admitted to our hospital for renal angiography from 1970 to 1975 were reviewed. Patients referred for reconstruction of the renal artery whose angiography and renal vein studies were done elsewhere were not included. Of the 132 patients hospitalized 28 were reported to have had fasting and post-prandial hyperglycemia and were classified as diabetics. The remaining 104 patients, including 2 patients with elevated post-prandial blood glucose levels but normal fasting levels, were classified as non-diabetics. Demographic data for the diabetic and non-diabetic groups were summarized. High grade proteinuria was defined as >2.0 gm. per 24 hours or > 100 mg./100 ml. on a random urine sample. Hypertensive retinopathy included arteriolar narrowing, arteriovenous crossing defects and flame-shaped hemorrhages. Diabetic retinopathy included microaneurysms, dot and blotch hemorrhages, intraretinal microvascular abnormalities and Accepted for publication July 7, 1978. Read at the IX International Diabetes Federation Congress, New Delhi, India, October 31-November 5, 1976. Supported by grant 13368 from the National Heart and Lung Institute. * Requests for reprints: Joslin Clinic, One Joslin Place, Boston, Massachusetts 02215. 555
microvascular proliferation. No patient exhibited papilledema at the time of hospitalization for renal angiography. All patients underwent a rapid-sequence excretory urogram (IVP) as part of the evaluation for hypertension. 3 A right kidney 1.0 cm. smaller than the left kidney was considered normal. If 1 kidney was 1.0 cm. smaller than expected given the normal-sized contralateral kidney, a possible unilateral decrease in kidney size was indicated. A decrement of 1.5 cm. or more was defined as a significant decrease in renal size. Functional abnormalities on hypertensive IVP included delayed appearance or disappearance of radiographic contrast medium with or without decreased concentration. Results of renal angiography were classified into 3 categories: 1) positive with >50 per cent stenosis, 2) positive with <50 per cent stenosis and 3) negative. When renal artery stenosis was detected angiographically catheterization of the renal vein was done after an overnight fast with the patient in the supine position to obtain blood samples for determination of plasma renin activity by radioimmunoassay described previously. 4 A renal artery stenosis was considered to be hemodynamically significant if the renal vein renin ratio (renin level of involved side divided by renin level of uninvolved side) was 2::1.4:1.0. Three diabetics and 2 non-diabetics with angiographically demonstrated renal artery stenosis of <50 per cent did not undergo catheterization of the renal vein. When blood pressure decreased to ::;140/90 without the use of antihypertensive drugs the operation was considered curative. When blood pressure was improved with the same or decreased antihypertensive therapy as needed preoperatively the operation was considered successful. When blood pressure was not improved the operation was considered a failure. Statistical methods used included Student's t test for significance between means and Yates' modification of the chisquare test for testing the significance of qualitative data. 5
556
MUNICHOODAPPA AND ASSOCIATES RESULTS
TABLE
The diabetic and non-diabetic groups did not differ significantly with regard to sex distribution or severity and duration of hypertension (table 1). The mean duration of diabetes was 10 years in the insulin-dependent group and 3 years in the insulin-independent group (p <0.01). The insulin-dependent group had a known mean duration of hypertension of 5 years as compared to 10 years for the insulin-independent group (p >0.1) (table 2). Mean cholesterol, blood urea nitrogen and creatinine levels did not differ significantly between those patients receiving and those not receiving insulin therapy. The results of IVP are shown in table 3. Results of IVP studies in 2 diabetics and 9 non-diabetics studied elsewhere were not included here. Positive IVP results were found in 27 per cent of the diabetics and in 50 per cent of the non-diabetics (p = 0.057). When IVP results were compared to those of angiography obtained from the same patients 3 falsely positive and 1 falsely negative IVPs were noted among the diabetic patients, while 9 falsely positive and 9 falsely negative IVPs were seen in the non-diabetic group (p = not significant). The results of renal angiography obtained on admission to the hospital are summarized (table 4). No significant differences were found between the diabetic and non-diabetic groups in proportion to patients with unilateral (14:35 per cent, p = 0.07), bilateral (21:14 per cent, p = not significant) or the total of unilateral and bilateral (36:48 per cent, p = not significant) atherosclerotic stenosis. In both study groups 18 per cent of the angiograms revealed atherosclerosis of the aorta. Each of the 5 diabetics had only low grade aortic involvement but 12 of 19 non-diabetics had high grade aortic atherosclerotic disease. Angiographic evidence of renal artery TABLE
No. pts.: Male Female Age: Yrs. Range Hypertension: Yrs. Range Blood pressure (mm. Hg) (mean)
1. Hypertensive patient population Diabetic*
Non-Diabetic*
28 17t llt
104 45 59
48 ± 2.8t 21-70
51 ± 1.2 21-70
7 ± l.7t 1-40
6 ± 0.8 1-40
193/115 ± 7.7/4.3t
2. Diabetic hypertensive patients
No. pts.: Male Female Age: Yrs. Range Hypertension: Yrs. mm.Hg Retinopathy (No.) Lt. ventricular hypertrophy by electrocardiogram (No.) Low grade proteinuria (No.) Diabetes: Yrs. Retinopathy (No.) Neuropathy (No.) High grade proteinuria (No.) Laboratory (:it ± SEM): Cholesterol (mg./100 ml.) Blood urea nitrogen (mg./100 ml.) Creatinine (mg./100 ml.)
Insulin-Dependent*
Insulin-Independent*
15 10
13 7
5
6
41 ± 4.lt 21-70t
55 ± 2.7 36-69
5 ± 1.3:t: 188/118 ± 9.3/5.5:j: 1
10 ± 3.3 198/111 ± 13.6/6.9 2
3
4
4
10 ± l.8t
3
3 ± 1.5
5 3 5
0 0 3
227 ± 19:t: 27 ± 4:1:
223 ± 11 22 ± 2
1.7 ± 0.2:J:
1.3 ± 0.1
* Mean ± standard error of mean. t p < 0.01. :j: Not significantly different by Student's t test.
Diabetic* No.(%)
Non-Diabetict No.(%)
4
38
Pos. IVP: Unilat. small kidney: .e:1.5 cm. 1.0-1.4 cm. Totals Bilat. small kidney Unilat. and bilat. Comparison with angiography: Falsely pos. Falsely neg.
3
7
7
45 3
0
7/26 (27):j:
48/95 (51)
3/15 (20)§ 1/9 (11)§
9/45 (20) 9/41 (22)
* Two studies done elsewhere not included. t Nine studies done elsewhere not included. :j: p = 0.057. § Not significantly different by chi-square. TABLE
4. Renal angiography in hypertensive patient populations Diabetic No.(%)
Atherosclerotic stenosis: Unilat.: >50% <50% Totals Bilat.: >50% <50% Totals Unilat. and bilat. Aorta: >50% <50% Totals Fibromuscular hyperplasia: Unilat.: >50% <50% Totals Bilat.: >50% <50% Totals Unilat. and bilat. Aorta
2 2 4 (14)*
Non-Diabetic No.(%)
30 6 36 (35)
2 4 6(21)t 10/28 (36)t
8 6 14 (14) 50/104 (48)
0 5 5/28 (18)
12 7 19/104 (18)
0 0 0 0 0 0 0/28 (O)t 0
3 4 7 0 6 6 13/104 (12) 0
* p = 0.07. t Not significantly different by chi-square.
187/111 ± 3.0/1.6
* Mean ± standard error of mean. t Not significantly different. TABLE
3. IVP in hypertensive patient populations
or aortic atherosclerotic stenosis was distributed equally between insulin-dependent and non-insulin-dependent diabetics. Fibromuscular hyperplasia was not detected among diabetics but accounted for stenosis in 13 non-diabetic patients (p = not significant). Table 5 shows the number and proportion of elevated renal vein renin ratios in patients with angiographically demonstrated renal artery stenosis. The percentage of positive renal vein renin ratios was similar between diabetic and non-diabetic patients. Also, the distribution of positive ratios between insulin-dependent and non-insulin-dependent diabetics was approximately equal. Of 4 diabetics with a positive renal vein renin ratio after positive results on renal angiography 3 eventually underwent an operation. Of these 1 achieved normal blood pressure without drug therapy after arterial bypass, 1 experienced a similar result after nephrectomy and 1 showed improved control of blood pressure with drug therapy after arterial bypass procedures. During the same period of observation 16 bypass procedures and 3 nephrectomies were done in the 31 non-diabetics who demonstrated hemodynamically significant renal artery stenosis of atherosclerotic origin. Of 4 non-diabetics with a positive renal vein renin ratio after angiographic demonstration of fibromuscular hyperplasia 3 also underwent bypass procedures. The operative success rate in the nondiabetics was 89 per cent. The operative mortality for all procedures was O per cent.
557
RENAL ARTERY STENOSIS IN HYPERTENSIVE DIABETICS
5. Elevated renal vein renin ratios in hypertensive patients with angiographically demonstrated renal artery stenosis
TABLE
Diabetic No.(%) Atherosclerotic stenosis: >50% <50% Totals Fibrom uscular hyperplasia: >50% <50% Totals
Non-Diabetic No.(%)
4/4
30/42
0/3 4/7(57)*
31/46 (67)
0/0
0/0 0/0 --------
* Not significantly different by chi-square.
1/4
3/3 1/7 4/10 --~~--~--------
DISCUSSION
in which 20 to 25 per cent of the has known diabetes was reviewed. to diabetics showed a incidence of renal artery stenosis than non-diabetics. results indicated that the incidence of atherosclerotic renal stenosis was not different between diabetics non-diabetics. fo ~u,,~cu;c,a, no c,,r,;,I'{(;,;;;',c difference was found in the incidence of atherosderotic involvement of the aorta between the 2 groups. In in those cornparisons in which differences statistical significance, such as the proportion of IVP (p = 0,057) or those demonstratstenosis (p = the Uv.«U.~s,v.) affected to be in the non-diabetic group. An attempt to control bias in selection was made excluding patients whose angiography was done at a referring institution. Willingness to expose diabetics to the risk of angiographic contrast material-induced acute renal failure also influences selection of patients, i;. 7 Since in this retrospective study no way existed to reconstruct the rationale for clinical decisions on the basis of the mere presence or absence of diabetes alone, the study focused on· that point in the evaluation for vn,e>rta,,,n,rm at which the physician recom•mHL,vuu., sig:.rJ.ificant renal artery the invasive tests u1,c1uec1c,c; ·with renal diabetes. generally were older than the insulin-dependent (p <0.01) and had a longer duration of known hypertension. Aggressiveness in the search for glucose intolerance and strictness in the definition of hyperglycemia determined whether a given patient was assigned to the insulinindependent group or to the non-diabetic group, In this series 2 patients with normal fasting but elevated post-prandial blood sugar levels were in question and they were assigned arbitrarily to the non-diabetic group. Because a majority of insulin-independent diabetics in this series had knovm hyperglycemia for <12 months it is possible that the mechanisms for genesis of atherosclerosis in some instances •Nere more similar between non-diabetics and insulin-independent diabetics than between the 2 types of diabetics. Some patients may have had metabolically detrimental, unrecognized hyperfor since not all were under close before hospitalization for renal angiography. Arbitrary definitions of what is metabolically detrimental hyperglycemia and what is not may be rendered trivial when more is known about the ~-:;,r;..0,2,-c;;-lvo.,c of atherosclerotic macrovascular n,ucut,m.1c:au ,,.,.c,u.,1'~ indicate that duration of correlates with the
as ren1n
response to a volume depletion stimulus, 10 it may be necessary to accept a lower ratio since decreased plasma renin responsiveness has been observed in diabetics with nephropathy. 11 To our knowledge, this is the first report of renal vein renin ratios in hypertensive diabetics with angiographically demonstrated renal artery stenosis. No instances offibromuscular hyperplasia were observed in the diabetic group, whereas 12 per cent of the non-diabetics showed this non-atherosclerotic form of renal artery stenosis, A larger angiographic experience is necessary to clarify the incidence of fibromuscular hyperplasia in diabetics. Although our operative experience with diabetics having renal artery stenosis is small the results suggest that when medical antihypertensive therapy is inadequate selected diabetics can a successful renal tion for a hE:modvrtarn1,caJll, "'""'a.n.,a.u diabetics. 12-- 14 While it is true that advanced atherosclerosis and diabetes ,,a,C>wwanf a Ns'mr,rn,Pcl nt,prvpnt,irnn. 2 the presence alone not prevent correction of renal artery stenosis when medical therapy has failed or when ischemic loss of renal function. is threatened by diminished perfusion. The absence studies on the incidence of hypertension among diabetics, as well as on the incidence of the various causes of hypertension among diabetics, probably reflects in part previously mentioned problems, including arbitrary criteria to define study bias inherent in selection of controls and difficulties groups selected from diverse populations. The method in this study was purely pragmatic. The results suggest that within the limited scope described no significant difference was found in the incidence of angiographic or hemodynamically significant renal artery stenosis among diabetics as compared to non-diabetics. Further studies in this sphere are warranted with particular reference to the question of the concurrence of fibromuscular hyperplasia and diabetes mellitus. REFERENCES
1 2.
3.
4.
5.
6. 7.
A. P., Perez-Stable, E. and Moutsos, S. E.: Coexistence renal arterial hypertension and diabetes mellitus. J.A.M.A., 192: 813, 1965. A. P. Perez-Stable E., Scheib, E. T., Bron, K., S. E., Berg, G. and Misage, J. R.: Renal artery stenosis and hypertension. Observations on current status of therapy from a study of115 patients. Amer. J. Med., 47: 175, 1969. Bookstein, J. J., Abrams, H. L., Buenger, R. E., Lecky, J., Franklin, S.S., Reiss, M. D., Bleifer, K. H., Klatte, E. C. and Maxwell, M. H.: Radiologic aspects of reno vascular hypertension. Part 1. Aims and methods of the radiology study group. J.A.M.A., 220: 1218, 1972. Christlieb, A. R., Munichoodappa, C. and creased response of plasma renin a.ctivity to crnu,sc,ab,~ in diabetic patients with orthostatic hypotension, Diabetes, 23: 835, 1974. Maxwell, A. E.: Analyzing Qualitative Data. New York: John Wiley and Sons, Inc., pp. 21-23, 1961. Weinrauch, L. A., Friedberg, S. R. and D'Eiia, J. A.: Acute renal failure after cerebral arteriography in a diabetic patient. 12: 197, 1977. Weinrauch, L. , R. W., Leland, 0. S. Jr., Goldstein, H. H., Kassissieh, S. Libertino, J. A., F. J. and ,T. A.: Coronary ar't~10.,ra,Jn, and acute renal failure Intern. rvied., 86: 56, 1
1
Steffes, M. W., Sutherland, D. E. R., J. A. F. and Brown, D. M.: Studies of the glomerular lesions in diabetic rats treated pancreatic islet transplantation. Diabetes, 24: 280, 1975. 9. Spiz'o, R. G-,: Biochemistry of the renal glome:rular basement mernbrarr·2 and its alteration in diat,etes ;neHitus, I\Tew. 3ng1. 8.
558
MUNICHOODAPPA AND ASSOCIATES
10. Christlieb, A. R., Assal, J.-P., Katsilambros, N., Williams, G. H., Kozak, G. P. and Suzuki, T.: Plasma renin activity and blood volume in uncontrolled diabetes. Ketoacidosis, a state of secondary aldosteronism. Diabetes, 24: 190, 1975. 11. Christlieb, A. R., Kaldany, A. and D'Elia, J. A.: Plasma renin activity and hypertension in diabetes mellitus. Diabetes, 25: 969, 1976. 12. Draskoczy, S. P., Leland, 0. S., Jr. and Bradley, R. F.: Aorto-
coronary bypass in the diabetic patient. Kidney Int. (suppl.), 1: 37, 1974. 13. Izenstein, B., Libertino, J., Takacs, F., D'Elia, J. and Goldstein, H. H.: Renal transplantation in end-stage diabetic nephropathy. Abstract. Diabetes (suppl. 1), 25: 367, 1976. 14. Wheelock, F. C., Jr. and Filtzer, H. S.: Femoral grafts in diabetics. Resulting conservative amputations. Arch. Surg., 99: 776, 1969.
Original Articles
r
RENAL ARTERY STENOSIS IN HYPERTENSIVE DIABETICS
I
CHODAPPASETTY MUNICHOODAPPA, JOHN A. D'ELIA,* JOHN A. LIBERTINO, RAYE. GLEASON AND A. RICHARD CHRISTLIEB From the Joslin Clinic and Elliott P. Joslin Research Laboratory Divisions, Joslin Diabetes Foundation, Department of Urology, Lahey Clinic Foundation, Department of Medicine, New England Deaconess and Peter Bent Brigham Hospitals and Harvard Medical School, Boston, Massachusetts
ABSTRACT
The incidence of atherosclerotic renal artery stenosis was compared in consecutive renal angiography of 28 hypertensive diabetics and 104 hypertensive non-diabetics. Mean age and sex distribution were comparable. Angiographic evidence of atherosclerotic renal artery stenosis was present in 10 diabetics (36 per cent) and 50 non-diabetics (48 per cent). Stenosis was considered hemodynamically significant if the renal vein renin ratio of the involved to uninvolved side was 1.4:1.0 or more. A renal vein renin ratio equal to or more than 1.4 was observed in 4 of 7 diabetics (57 per cent) and 31 of 47 non-diabetics (67 per cent). Fibromuscular hyperplasia was not seen in diabetics but was present in 12 per cent of the non-diabetics. Hypertension was treated surgically and improved in 2 of 3 diabetics (67 per cent) and in 17 of 19 non-diabetics (89 per cent) with angiographic and hemodynamic evidence of renal artery stenosis. In this series the incidence of atherosclerotic renal artery stenosis of physiologic consequence was not significantly different in hypertensive diabetics when compared to hypertensive non-diabetics. Within a population of hypertensive patients under investigation for renal artery stenosis a subgroup exists of patients with atherosclerotic renal artery stenosis and diabetes mellitus. 1• 2 We herein present the accumulated experience from a series of diabetic and non-diabetic patients with renal artery stenosis discovered during physical examination for hypertension and compare the incidence of physiologically significant renal artery stenosis in these 2 groups. PATIENTS AND METHODS
Records of all patients with hypertension admitted to our hospital for renal angiography from 1970 to 1975 were reviewed. Patients referred for reconstruction of the renal artery whose angiography and renal vein studies were done elsewhere were not included. Of the 132 patients hospitalized 28 were reported to have had fasting and post-prandial hyperglycemia and were classified as diabetics. The remaining 104 patients, including 2 patients with elevated post-prandial blood glucose levels but normal fasting levels, were classified as non-diabetics. Demographic data for the diabetic and non-diabetic groups were summarized. High grade proteinuria was defined as >2.0 gm. per 24 hours or > 100 mg./100 ml. on a random urine sample. Hypertensive retinopathy included arteriolar narrowing, arteriovenous crossing defects and flame-shaped hemorrhages. Diabetic retinopathy included microaneurysms, dot and blotch hemorrhages, intraretinal microvascular abnormalities and Accepted for publication July 7, 1978. Read at the IX International Diabetes Federation Congress, New Delhi, India, October 31-November 5, 1976. Supported by grant 13368 from the National Heart and Lung Institute. * Requests for reprints: Joslin Clinic, One Joslin Place, Boston, Massachusetts 02215. 555
microvascular proliferation. No patient exhibited papilledema at the time of hospitalization for renal angiography. All patients underwent a rapid-sequence excretory urogram (IVP) as part of the evaluation for hypertension. 3 A right kidney 1.0 cm. smaller than the left kidney was considered normal. If 1 kidney was 1.0 cm. smaller than expected given the normal-sized contralateral kidney, a possible unilateral decrease in kidney size was indicated. A decrement of 1.5 cm. or more was defined as a significant decrease in renal size. Functional abnormalities on hypertensive IVP included delayed appearance or disappearance of radiographic contrast medium with or without decreased concentration. Results of renal angiography were classified into 3 categories: 1) positive with >50 per cent stenosis, 2) positive with <50 per cent stenosis and 3) negative. When renal artery stenosis was detected angiographically catheterization of the renal vein was done after an overnight fast with the patient in the supine position to obtain blood samples for determination of plasma renin activity by radioimmunoassay described previously. 4 A renal artery stenosis was considered to be hemodynamically significant if the renal vein renin ratio (renin level of involved side divided by renin level of uninvolved side) was 2::1.4:1.0. Three diabetics and 2 non-diabetics with angiographically demonstrated renal artery stenosis of <50 per cent did not undergo catheterization of the renal vein. When blood pressure decreased to ::;140/90 without the use of antihypertensive drugs the operation was considered curative. When blood pressure was improved with the same or decreased antihypertensive therapy as needed preoperatively the operation was considered successful. When blood pressure was not improved the operation was considered a failure. Statistical methods used included Student's t test for significance between means and Yates' modification of the chisquare test for testing the significance of qualitative data. 5
556
MUNICHOODAPPA AND ASSOCIATES RESULTS
TABLE
The diabetic and non-diabetic groups did not differ significantly with regard to sex distribution or severity and duration of hypertension (table 1). The mean duration of diabetes was 10 years in the insulin-dependent group and 3 years in the insulin-independent group (p <0.01). The insulin-dependent group had a known mean duration of hypertension of 5 years as compared to 10 years for the insulin-independent group (p >0.1) (table 2). Mean cholesterol, blood urea nitrogen and creatinine levels did not differ significantly between those patients receiving and those not receiving insulin therapy. The results of IVP are shown in table 3. Results of IVP studies in 2 diabetics and 9 non-diabetics studied elsewhere were not included here. Positive IVP results were found in 27 per cent of the diabetics and in 50 per cent of the non-diabetics (p = 0.057). When IVP results were compared to those of angiography obtained from the same patients 3 falsely positive and 1 falsely negative IVPs were noted among the diabetic patients, while 9 falsely positive and 9 falsely negative IVPs were seen in the non-diabetic group (p = not significant). The results of renal angiography obtained on admission to the hospital are summarized (table 4). No significant differences were found between the diabetic and non-diabetic groups in proportion to patients with unilateral (14:35 per cent, p = 0.07), bilateral (21:14 per cent, p = not significant) or the total of unilateral and bilateral (36:48 per cent, p = not significant) atherosclerotic stenosis. In both study groups 18 per cent of the angiograms revealed atherosclerosis of the aorta. Each of the 5 diabetics had only low grade aortic involvement but 12 of 19 non-diabetics had high grade aortic atherosclerotic disease. Angiographic evidence of renal artery TABLE
No. pts.: Male Female Age: Yrs. Range Hypertension: Yrs. Range Blood pressure (mm. Hg) (mean)
1. Hypertensive patient population Diabetic*
Non-Diabetic*
28 17t llt
104 45 59
48 ± 2.8t 21-70
51 ± 1.2 21-70
7 ± l.7t 1-40
6 ± 0.8 1-40
193/115 ± 7.7/4.3t
2. Diabetic hypertensive patients
No. pts.: Male Female Age: Yrs. Range Hypertension: Yrs. mm.Hg Retinopathy (No.) Lt. ventricular hypertrophy by electrocardiogram (No.) Low grade proteinuria (No.) Diabetes: Yrs. Retinopathy (No.) Neuropathy (No.) High grade proteinuria (No.) Laboratory (:it ± SEM): Cholesterol (mg./100 ml.) Blood urea nitrogen (mg./100 ml.) Creatinine (mg./100 ml.)
Insulin-Dependent*
Insulin-Independent*
15 10
13 7
5
6
41 ± 4.lt 21-70t
55 ± 2.7 36-69
5 ± 1.3:t: 188/118 ± 9.3/5.5:j: 1
10 ± 3.3 198/111 ± 13.6/6.9 2
3
4
4
10 ± l.8t
3
3 ± 1.5
5 3 5
0 0 3
227 ± 19:t: 27 ± 4:1:
223 ± 11 22 ± 2
1.7 ± 0.2:J:
1.3 ± 0.1
* Mean ± standard error of mean. t p < 0.01. :j: Not significantly different by Student's t test.
Diabetic* No.(%)
Non-Diabetict No.(%)
4
38
Pos. IVP: Unilat. small kidney: .e:1.5 cm. 1.0-1.4 cm. Totals Bilat. small kidney Unilat. and bilat. Comparison with angiography: Falsely pos. Falsely neg.
3
7
7
45 3
0
7/26 (27):j:
48/95 (51)
3/15 (20)§ 1/9 (11)§
9/45 (20) 9/41 (22)
* Two studies done elsewhere not included. t Nine studies done elsewhere not included. :j: p = 0.057. § Not significantly different by chi-square. TABLE
4. Renal angiography in hypertensive patient populations Diabetic No.(%)
Atherosclerotic stenosis: Unilat.: >50% <50% Totals Bilat.: >50% <50% Totals Unilat. and bilat. Aorta: >50% <50% Totals Fibromuscular hyperplasia: Unilat.: >50% <50% Totals Bilat.: >50% <50% Totals Unilat. and bilat. Aorta
2 2 4 (14)*
Non-Diabetic No.(%)
30 6 36 (35)
2 4 6(21)t 10/28 (36)t
8 6 14 (14) 50/104 (48)
0 5 5/28 (18)
12 7 19/104 (18)
0 0 0 0 0 0 0/28 (O)t 0
3 4 7 0 6 6 13/104 (12) 0
* p = 0.07. t Not significantly different by chi-square.
187/111 ± 3.0/1.6
* Mean ± standard error of mean. t Not significantly different. TABLE
3. IVP in hypertensive patient populations
or aortic atherosclerotic stenosis was distributed equally between insulin-dependent and non-insulin-dependent diabetics. Fibromuscular hyperplasia was not detected among diabetics but accounted for stenosis in 13 non-diabetic patients (p = not significant). Table 5 shows the number and proportion of elevated renal vein renin ratios in patients with angiographically demonstrated renal artery stenosis. The percentage of positive renal vein renin ratios was similar between diabetic and non-diabetic patients. Also, the distribution of positive ratios between insulin-dependent and non-insulin-dependent diabetics was approximately equal. Of 4 diabetics with a positive renal vein renin ratio after positive results on renal angiography 3 eventually underwent an operation. Of these 1 achieved normal blood pressure without drug therapy after arterial bypass, 1 experienced a similar result after nephrectomy and 1 showed improved control of blood pressure with drug therapy after arterial bypass procedures. During the same period of observation 16 bypass procedures and 3 nephrectomies were done in the 31 non-diabetics who demonstrated hemodynamically significant renal artery stenosis of atherosclerotic origin. Of 4 non-diabetics with a positive renal vein renin ratio after angiographic demonstration of fibromuscular hyperplasia 3 also underwent bypass procedures. The operative success rate in the nondiabetics was 89 per cent. The operative mortality for all procedures was O per cent.
557
RENAL ARTERY STENOSIS IN HYPERTENSIVE DIABETICS
5. Elevated renal vein renin ratios in hypertensive patients with angiographically demonstrated renal artery stenosis
TABLE
Diabetic No.(%) Atherosclerotic stenosis: >50% <50% Totals Fibrom uscular hyperplasia: >50% <50% Totals
Non-Diabetic No.(%)
4/4
30/42
0/3 4/7(57)*
31/46 (67)
0/0
0/0 0/0 --------
* Not significantly different by chi-square.
1/4
3/3 1/7 4/10 --~~--~--------
DISCUSSION
in which 20 to 25 per cent of the has known diabetes was reviewed. to diabetics showed a incidence of renal artery stenosis than non-diabetics. results indicated that the incidence of atherosclerotic renal stenosis was not different between diabetics non-diabetics. fo ~u,,~cu;c,a, no c,,r,;,I'{(;,;;;',c difference was found in the incidence of atherosderotic involvement of the aorta between the 2 groups. In in those cornparisons in which differences statistical significance, such as the proportion of IVP (p = 0,057) or those demonstratstenosis (p = the Uv.«U.~s,v.) affected to be in the non-diabetic group. An attempt to control bias in selection was made excluding patients whose angiography was done at a referring institution. Willingness to expose diabetics to the risk of angiographic contrast material-induced acute renal failure also influences selection of patients, i;. 7 Since in this retrospective study no way existed to reconstruct the rationale for clinical decisions on the basis of the mere presence or absence of diabetes alone, the study focused on· that point in the evaluation for vn,e>rta,,,n,rm at which the physician recom•mHL,vuu., sig:.rJ.ificant renal artery the invasive tests u1,c1uec1c,c; ·with renal diabetes. generally were older than the insulin-dependent (p <0.01) and had a longer duration of known hypertension. Aggressiveness in the search for glucose intolerance and strictness in the definition of hyperglycemia determined whether a given patient was assigned to the insulinindependent group or to the non-diabetic group, In this series 2 patients with normal fasting but elevated post-prandial blood sugar levels were in question and they were assigned arbitrarily to the non-diabetic group. Because a majority of insulin-independent diabetics in this series had knovm hyperglycemia for <12 months it is possible that the mechanisms for genesis of atherosclerosis in some instances •Nere more similar between non-diabetics and insulin-independent diabetics than between the 2 types of diabetics. Some patients may have had metabolically detrimental, unrecognized hyperfor since not all were under close before hospitalization for renal angiography. Arbitrary definitions of what is metabolically detrimental hyperglycemia and what is not may be rendered trivial when more is known about the ~-:;,r;..0,2,-c;;-lvo.,c of atherosclerotic macrovascular n,ucut,m.1c:au ,,.,.c,u.,1'~ indicate that duration of correlates with the
as ren1n
response to a volume depletion stimulus, 10 it may be necessary to accept a lower ratio since decreased plasma renin responsiveness has been observed in diabetics with nephropathy. 11 To our knowledge, this is the first report of renal vein renin ratios in hypertensive diabetics with angiographically demonstrated renal artery stenosis. No instances offibromuscular hyperplasia were observed in the diabetic group, whereas 12 per cent of the non-diabetics showed this non-atherosclerotic form of renal artery stenosis, A larger angiographic experience is necessary to clarify the incidence of fibromuscular hyperplasia in diabetics. Although our operative experience with diabetics having renal artery stenosis is small the results suggest that when medical antihypertensive therapy is inadequate selected diabetics can a successful renal tion for a hE:modvrtarn1,caJll, "'""'a.n.,a.u diabetics. 12-- 14 While it is true that advanced atherosclerosis and diabetes ,,a,C>wwanf a Ns'mr,rn,Pcl nt,prvpnt,irnn. 2 the presence alone not prevent correction of renal artery stenosis when medical therapy has failed or when ischemic loss of renal function. is threatened by diminished perfusion. The absence studies on the incidence of hypertension among diabetics, as well as on the incidence of the various causes of hypertension among diabetics, probably reflects in part previously mentioned problems, including arbitrary criteria to define study bias inherent in selection of controls and difficulties groups selected from diverse populations. The method in this study was purely pragmatic. The results suggest that within the limited scope described no significant difference was found in the incidence of angiographic or hemodynamically significant renal artery stenosis among diabetics as compared to non-diabetics. Further studies in this sphere are warranted with particular reference to the question of the concurrence of fibromuscular hyperplasia and diabetes mellitus. REFERENCES
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Steffes, M. W., Sutherland, D. E. R., J. A. F. and Brown, D. M.: Studies of the glomerular lesions in diabetic rats treated pancreatic islet transplantation. Diabetes, 24: 280, 1975. 9. Spiz'o, R. G-,: Biochemistry of the renal glome:rular basement mernbrarr·2 and its alteration in diat,etes ;neHitus, I\Tew. 3ng1. 8.
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10. Christlieb, A. R., Assal, J.-P., Katsilambros, N., Williams, G. H., Kozak, G. P. and Suzuki, T.: Plasma renin activity and blood volume in uncontrolled diabetes. Ketoacidosis, a state of secondary aldosteronism. Diabetes, 24: 190, 1975. 11. Christlieb, A. R., Kaldany, A. and D'Elia, J. A.: Plasma renin activity and hypertension in diabetes mellitus. Diabetes, 25: 969, 1976. 12. Draskoczy, S. P., Leland, 0. S., Jr. and Bradley, R. F.: Aorto-
coronary bypass in the diabetic patient. Kidney Int. (suppl.), 1: 37, 1974. 13. Izenstein, B., Libertino, J., Takacs, F., D'Elia, J. and Goldstein, H. H.: Renal transplantation in end-stage diabetic nephropathy. Abstract. Diabetes (suppl. 1), 25: 367, 1976. 14. Wheelock, F. C., Jr. and Filtzer, H. S.: Femoral grafts in diabetics. Resulting conservative amputations. Arch. Surg., 99: 776, 1969.