Treatment of renovascular hypertension using stent implantation in an elderly patient with NIDDM

A 70-year-old man with NIDDM was diagnosed as having renovascular hypertension (RVH), based on a stenosis of the ostial portion of the left renal artery with markedly elevated plasma renin activity (PRA) in both the left renal vein and the peripheral blood, and positive captopril tests. After percutaneous transluminal renal angioplasty (PTRA), his blood pressure (BP) and PRA normalized. However, since restenosis occurred three months later, stent therapy was applied, and consequently BP and PRA normalized immediately after this procedure. During the one-year follow-up, side effects have not been noted. We propose that stent therapy may be feasible for ostial renal artery stenosis in elderly diabetic patients.     

The captopril test for identifying renovascular disease in hypertensive patients

To develop a screening test for identifying renovascular hypertension, the blood pressure and plasma renin activity responses to an oral test dose of captopril were studied in 246 quietly seated hypertensive patients. The following criteria were developed that exploit the hyperresponsiveness of renin secretion in renovascular hypertensive patients: a 60-minute post-captopril plasma renin activity of 12 ng/ml per hour or more and an absolute plasma renin activity increase of 10 ng/ml per hour or more, along with a 150 percent increase in plasma renin activity (or a 400 percent increase if the baseline plasma renin activity was below 3 ng/ml per hour). Retrospectively, the test identified, among 200 hypertensive patients without evidence of renal dysfunction, all 56 patients with proved renovascular disease. In this group, false-positive results occurred only in two of 112 patients with essential hypertension and in six with secondary hypertension. Nine untreated patients had blood pressure levels of less than 160/100 mm Hg. The test was neither as sensitive nor specific in the 46 patients with renal insufficiency. This study demonstrates that the renin response to oral captopril is a useful screening test for identifying patients with unilateral or bilateral renovascular disease. Since the test also characterizes the renin dependency of the hypertension, it may have other diagnostic and therapeutic uses.     

Identification of Potential Regulatory Regions in the Renin Gene

Circadian blood pressure (BP) variation were studied in patients with renovascular hypertension (RVH) and primary aldosteronism (PA). Ambulatory BP (ABP) was monitored every 5 min for 24 hrs in a ward setting in 23 patients with PA and 17 patients with RVH (13 patients with unilateral renal arterial stenosis and 4 with bilateral stenosis). In patients with RVH, ABP was monitored before and after treatment with a converting enzyme inhibitor or percutaneous transluminal angioplasty. Plasma renin activity (PRA) was high before percutaneous transluminal angioplasty in almost all patients with RVH and low in those with PA. Ordinary circadian BP variation, i.e. nocturnal fall and diurnal rise in BP, was confirmed in the patients with unilateral or bilateral renal artery stenosis. Percutaneous transluminal angioplasty successfully normalized both BP and PRA in those with RVH. Normal circadian BP variation was observed in those with RVH before the treatment with a converting enzyme inhibitor or percutaneous transluminal angioplasty as well as during treatment with the former and after treatment with the latter. Circadian BP variation in the patients with RVH was affected by the pathogenesis of renal artery stenosis alone, i.e, fibromuscular hyperplasia and atherosclerosis; with fibromuscular hyperplasia normal circadian BP variation was observed, while with atherosclerosis, nocturnal BP fall was restricted or eliminated. Circadian BP variation in those with PA before and after excision of adrenal adenoma was essentially similar to that in normal subjects and essential hypertensive patients. From these it seems that in patients with RVH or PA, circadian BP variation is not affected by hypertension per se or by pathogenesis of hypertension.     

Platelet-activating factor and anti-platelet-aggregating factor in acute reduction of blood pressure following percutaneous transluminal renal angioplasty in patients with renovascular hypertension

The mechanism of the acute fall of BP following percutaneous transluminal renal angioplasty (PTRA) was studied in four patients with renovascular hypertension caused by fibromuscular dysplasia. One hour after PTRA, systemic blood pressure and plasma renin activity in the ipsilateral renal venous blood decreased significantly (P less than 0.05), but the plasma noradrenaline level in ipsilateral renal venous blood increased significantly (P less than 0.05). At the same time, a platelet-activating factor (PAF) and an unidentified factor that inhibited the aggregation of rabbit platelets induced by PAF, arachidonic acid or ADP were detected in the ipsilateral renal venous blood, but were not found in the contralateral renal venous blood. Plasma noradrenaline level in cubital venous blood decreased significantly (P less than 0.05) after 24 hours as compared with that before PTRA and BP also maintained the normal level. These results suggest that the reduction in plasma renin activity is associated with the acute reduction in BP following PTRA. PAF and an unidentified factor blocking the aggregation of platelets may be involved in ipsilateral renal venous blood following PTRA in patients with renovascular hypertension. The reduction in plasma noradrenaline level is an additional mechanism involved in maintaining normal BP following PTRA in the late stage.     

Successfully treated "accelerated" renovascular hypertension with intravascular stenting.

A 76-year-old man developed progressive renal dysfunction with refractory hypertension. Bilateral renal artery stenosis due to atherosclerosis was revealed. Both the hypertension and renal dysfunction were improved by percutaneous transluminal renal angioplasty with stenting. Based on the rapidly progressive elevation of plasma renin activity and the improvement of both renal dysfunction and hypertension after stenting, this was considered a case of "accelerated" renovascular hypertension. There have been an increasing number of patients with bilateral renal artery stenosis due to atherosclerosis. The present case reminds us that a rapid progression of renal dysfunction suggests, in addition to besides rapidly progressive glomerulonephritis with crescent formation, bilateral renal artery stenosis, the incidence of which is on the rise. In the present case, angioplasty with stenting was effective for blood pressure control and preservation of renal function.     

Congenital solitary kidney with renovascular hypertension diagnosed by means of captopril-enhanced renography and magnetic resonance angiography

A 24 year-old woman had a congenital solitary kidney with renovascular hypertension due to fibromuscular dysplasia. She had been treated as having essential hypertension until she developed preeclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome at 28 weeks of gestation. Plasma renin activity and captopril test results did not indicate any abnormalities. However, renography revealed captopril-induced deterioration. Magnetic resonance angiography was also useful to detect renal artery stenosis. These findings were confirmed by renal angiography. After successful percutaneous transluminal renal angioplasty, her blood pressure and the pattern of captopril renography normalized.     

The value of tests predicting renovascular hypertension in patients with renal artery stenosis treated by angioplasty.

The aim of this study was to evaluate tests predicting renovascular hypertension. This was done by relating the results of renal vein renin tests, the captopril test, and renal scintigraphic tests to the blood pressure outcome 12 months after relief of renal artery stenosis by percutaneous transluminal renal angioplasty in 31 patients. Cure was seen in eight (26%). Improved blood pressure was obtained in 12 patients (39%), and in 11 patients (35%), the result for blood pressure was a failure. The accuracies of the two mathematical models used to analyze the renal vein renin assays were 44% and 60%. The captopril test showed a sensitivity of 36% and an accuracy of 43%. Renal captopril technetium Tc 99m-labeled pentetic acid scintigraphy gave a sensitivity of 60%. Stepwise logistic regression analysis of clinical variables in relation to blood pressure response revealed age as the only factor significantly related to blood pressure outcome. We conclude that the tests used are unfit for helping select patients for percutaneous transluminal renal angioplasty and that age may have an important influence on outcome.     

Captopril-stimulated renin in the diagnosis of restenosis after percutaneous transluminal renal angioplasty

Recurrence of hypertension is reported in a considerable percentage of renovascular hypertensive patients treated by percutaneous transluminal angioplasty (PTRA); among the possible mechanisms for these failures, restenosis of the renal artery is the only correctable one. Since captopril stimulates renin secretion to a greater extent in renovascular than in essential hypertensive patients, we determined if it could be used to unmask significant restenosis in the patients with hypertension recurring after PTRA. Follow-up study was performed in 28 patients treated with PTRA. We found that captopril caused a greater increase in peripheral plasma renin activity in 8 of 8 cases who had recurrence of hypertension and restenosis than in 13 of 15 of the patients who did not. We suggest that the determination of captopril-stimulated renin may provide a useful, simple and economical tool for the detection of restenosis after PTRA.     

Lack of effect of percutaneous transluminal renal angioplasty on nocturnal hypotension in renovascular hypertensive patients

OBJECTIVE: To investigate whether nocturnal blood pressure fall is blunted in renovascular hypertension and can therefore be used as a diagnostic criterion for this condition. METHODS: In 14 renovascular hypertensive patients (age 43.8+/-2.1 years, mean+/-SEM, clinic blood pressure 173.6+/-3.7 mmHg systolic and 109.0+/-2.0 mmHg diastolic) and in 14 age- and blood pressure-matched essential hypertensive controls 24 h ambulatory blood pressure was measured after washout from drug treatment, during angiotensin converting enzyme inhibitor treatment and, in renovascular hypertension, also after percutaneous transluminal renal angioplasty. RESULTS: The 24 h average systolic and diastolic blood pressures were 146.4+/-5.7 and 97.5+/-3.6 mmHg in renovascular and 144.3+/-1.2 and 98.0+/-2.2 mmHg in essential hypertensive patients. The angiotensin converting enzyme inhibitor treatment reduced 24 h average systolic and diastolic blood pressures by 8.5% and 9.7% in the renovascular and by 8.3% and 10.8% in the essential hypertensive group. Greater systolic and diastolic blood pressure reductions (-18.2% and -18.1%) were observed in renovascular hypertensive patients after percutaneous transluminal renal angioplasty. Blood pressure fell by about 10% during the night and the fall was similar in renovascular and in essential hypertensive patients. In the former group, nocturnal hypotension was similar after washout, during angiotensin converting enzyme inhibitor treatment and after percutaneous transluminal renal angioplasty. Similar results were obtained for nocturnal bradycardia. CONCLUSIONS: Nocturnal blood pressure fall is equally manifest in renovascular and essential hypertension. The removal of the renal artery stenosis and blood pressure normalization do not enhance this phenomenon. Nocturnal hypotension seems therefore to be unaffected by renovascular hypertension.     

Use of Captopril in the Diagnosis of Renal Hypertension

Abstract: 1 . The effects of a single 25 mg oral dose of captopril on blood pressure, heart rate and circulating renin, angiotensin I, angiotensin II, bradykinin and catecholamine levels were examined in untreated patients with essential (n = 10, Group I), accelerated (n = 6, Group II) and renal hypertension (n = 8, Group III) studied on a normal sodium diet .
2 . Mean blood pressure fell only slightly in Group I patients, (113 ± 3 to 109 ± 3 mmHg at 60 minutes) but a greater fall was observed in Group II (153 ± 8 to 135 ± 11 mmHg) and a marked fall in Group III, (136 ± 3 to 114 ± 5 mmHg). There were no significant changes in heart rate in any group .
3 . Plasma angiotensin II levels were significantly reduced 30 minutes after captopril in all three groups and returned toward resting values after four hours. The falls in plasma angiotensin II levels were accompanied by reciprocal increases in blood angiotensin I and plasma renin, but blood bradykinin and plasma catecholamine concentrations remained unchanged .
4 . Resting plasma renin levels showed considerable overlap in the three groups and the mean renin values were not significantly different in the three groups. After captopril a marked rise in plasma renin concentration (>2.5 ng/ml/hr) was observed in seven patients in Group III, including all six patients with renovascular disease. In contrast, none of the patients with essential hypertension and only one patient with accelerated hypertension had such an increase. Determination of the acute renin and blood pressure responses to converting enzyme inhibition with a single oral dose of captopril appears to be useful in identifying patients with renovascular hypertension .     

Similar prevalence of renovascular hypertension in selected blacks and whites

Renovascular hypertension is a potentially curable form of high blood pressure that is thought to be extremely rare among blacks. We demonstrate, however, that in a clinically selected population, the prevalence of renovascular hypertension is similar in blacks and whites. We prospectively evaluated 167 hypertensive subjects who had one or more clinical features known to be associated with renovascular hypertension. All subjects had captopril-stimulated peripheral renin measurements and conventional renal arteriography. All significant renal artery stenoses (greater than 50% luminal narrowing) were treated with percutaneous transluminal angioplasty or surgery. Renovascular hypertension was diagnosed if there was a blood pressure response to interventional therapy, according to the criteria established by the Cooperative Study of Renovascular Hypertension. Of the total group evaluated, 24% (39 of 167) had renal artery stenosis and 14% (23 of 167) had renovascular hypertension. Renal artery stenosis or occlusion was found in 27% (26 of 97) of whites and 19% (13 of 67) of blacks (p = 0.27). Renovascular hypertension was diagnosed in 18% (17 of 97) of whites and 9% (6 of 67) of blacks evaluated (p = 0.25). Renovascular hypertension was associated with severe or refractory hypertension and with smoking, but there were no racial differences in these associations. Blacks with renovascular hypertension tended to have low captopril-stimulated peripheral renin activity. We conclude that blacks with clinical features suggestive of renovascular hypertension should be evaluated with angiography. Captopril-stimulated plasma renin may not be useful in detecting blacks with renovascular hypertension, but this and other potential screening tests require further evaluation.     

Percutaneous Transluminal Renal Angioplasty in the Treatment of Renovascular Hypertension in Children

We report five young patients who underwent percutaneous transluminal renal angioplasty (PTRA) for the treatment of hypertension related to renal artery stenosis. Four had fibromuscular disease and one had probable Takajasu's arteritis; two had solitary kidneys. Following PTRA, a prompt decrease in blood pressure was observed in all patients. Further, four of five patients long after PTRA remained normotensive, and in all patients plasma renin levels declined. These results indicate that PTRA can be a safe and effective alternative to surgery in the treatment of renovascular hypertension in childhood.     

Clinical results of angioplasty of the renal arteries in renovascular arterial hypertension. A retrospective study in 113 patients]

The aim of the study was to evaluate the clinical results of percutaneous transluminal renal angioplasty in a population of 113 consecutive hypertensive patients who underwent endoluminal revascularization for angiographically significant renal artery stenosis. Retrospective analysis of the case records of 104 patients showed that systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased significantly 6 months after angioplasty (-20.9 mmHg and -8.4 mmHg respectively; p = 0.0001). This decrease was maintained until 19.8 months after the procedure. In cases with suboptimal revascularization (persistence of a residual stenosis more than 30%), only the SBP decreased significantly at 6 months (from 177 mmHg to 156.1 mmHg; p = 0.0061); when DBP decreased from 91.4 mmHg to 86.1 mmHg (NS) at 6 months, and fell to 80.9 mmHg (p = 0.026) at 19.8 months (after the performance of a second transluminal angioplasty for 41% patients of this group due to restenosis). Twenty-nine patients presented a restenosis of the renal artery 6 months after the initial procedure. In this group, only SBP decreased significantly at 6.1 months and at 18.7 months (from 171.9 mmHg to 156.1 mmHg and 146.5 mmHg respectively; p = 0.0064 and p = 0.0001). DBP decreased significantly only at 18.7 months (-12.6 mmHg; p = 0.0001), after a second renal angioplasty in 23 patients (79%). In the 60 patients without restenosis at 6 months, SBP and DBP decreased significantly at 6.1 and 18.7 months. No significant variation of creatinine levels was observed. These results confirm the utility of percutaneous transluminal renal angioplasty for the treatment of renovascular hypertension.     

Two cases of renovascular hypertension and ischemic renal dysfunction: reliable choice of examinations and treatments.

We experienced two aged patients with atherosclerotic renovascular stenosis associated with hypertension and ischemic nephropathy. Both patients exhibited sudden rise in blood pressure (BP) and progressive aggravation of renal dysfunction. In these patients, the use of contrast medium to screen for renal artery stenosis (RAS) ran the risk of further deterioration of renal function. We therefore used magnetic resonance angiography (MRA), which is less conducive to renal damage, to screen for RAS. One-sided RAS was treated by percutaneous transluminal angioplasty of the renal artery (PTRA) and stenting. As a result, BP decreased in both patients. Serum creatinine (Cr) decreased slightly in one patient, whereas, in the other, serum Cr increased transiently and then decreased and stabilized to pre-treatment levels. Thus, although it is unclear whether the combination of PTRA and stenting is among the best treatments for patients with RAS and moderate-to-severe renal dysfunction, PTRA and stenting are clearly of benefit in selected patients. In addition, recent progress in characterizing the pathophysiology of ischemic nephropathy associated with renovascular hypertension has created interest in the therapeutic potential of angiotensin II receptor antagonists, sympatholytic agents, and antioxidants. Therefore, we discuss the therapeutic utility of PTRA and stenting and the above-mentioned medications in patients with RAS and renal dysfunction.     

Conversion of inactive renin to active renin following acute angiotensin converting enzyme inhibition in essential hypertension and renovascular hypertension

The physiological role of inactive renin, especially the question of whether and how a conversion to active renin takes place in vivo, remains controversial. In order to show the dynamic alterations from inactive to active renin following acute ACE-inhibition, both forms of renin were investigated in both renal veins and the peripheral circulation of 20 patients with essential hypertension and 20 patients with renovascular hypertension before and 1 h after 25 mg of captopril. Active and inactive renin were determined indirectly as plasma renin activity (PRA, unit: ng/ml x h). In vitro activation of inactive renin was achieved with trypsin (1 mg/ml plasma), followed by a further determination of PRA (= total renin). Subtraction of the active renin from the total renin yields the amount of inactive renin. In patients with essential hypertension, the mean values of active renin increase equally in both renal veins (1.4 and 1.3 before, 1.9 and 1.8 after captopril) and the peripheral circulation (0.9 and 1.3) (p less than 0.002), whereas the inactive renin decreases correspondingly. Renal veins: 7.6 and 8.2 before, 7.2 and 7.6 after captopril; peripheral circulation: 7.7 before and 7.0 after captopril (p less than 0.05). In all patients with renovascular hypertension, there is basally a marked lateralization of active renin (6.4 vs 3.5; p less than 0.01) and inactive renin (20.5 and 18.9, p less than 0.03) towards the side of the ischemic kidney. After captopril, the values for total renin and active renin increase (p less than 0.001), and the side difference for active renin becomes still more pronounced (33.0 vs 14.2; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Atenolol improves blood pressure control in patients taking captopril and frusemide

In a double-blind randomised cross-over study atenolol 100 mg daily and matching placebo were given to 14 patients whose blood pressure (BP) was uncontrolled on a fixed dose of captopril and frusemide. Atenolol produced a further reduction in both supine (170/105 mmHg to 163/94 mmHg) and standing (171/114 mmHg to 160/96 mmHg) BP and a significant fall in pulse rate and plasma renin activity (PRA). This fall in BP showed a highly significant correlation with pre-treatment plasma renin levels. No adverse side effects were encountered during the study. Previous suggestions that beta-blockade had no additional hypotensive effect in patients receiving captopril were not substantiated. For patients whose BP was poorly controlled with captopril and a diuretic, a selective beta-blocker is suggested as a useful third line agent.     

The value of the captopril test and the effect of captopril on renal function

We have investigated the use of captopril as a screening test for renovascular hypertension and compared the effects of captopril on renal function in patients with renovascular hypertension and those without renovascular hypertension. The captopril test and kidney gamma scintigraphy were carried out in 50 hypertensive patients, 13 with renovascular hypertension and 37 without. Blood samples were drawn for the determination of plasma renin activity and kidney gamma scintigraphy was done before and 60 minutes after 50 mg oral captopril administration. Results suggesting the diagnosis of renovascular hypertension are the following: a basal and stimulated plasma renin activity of 4 ng ml/hr or more and an absolute increase in plasma renin activity of 3 ng/ml/hr or more if basal plasma renin activity was less than 4 ng/ml/hr. Data from kidney gamma scintigraphy showed that captopril causes a decrease in clearance rate at 20 minutes in patients with renovascular hypertension but not in patients without renovascular hypertension. We conclude that the captopril test can be used to screen for renovascular hypertension, but catopril may impair the renovascular hypertensive patient's renal function.     

Two-kidney, one clip renal hypertension in the marmoset

The purpose of this study was to assess whether two-kidney, one clip (2K1C) renal hypertension can be induced in the marmoset. During the first 3-5 weeks after renal arterial clipping, blood pressure (BP) and plasma renin activity (PRA) increased in approximately one-third of the operated marmosets. However, within 10 weeks after clipping, BP and PRA had returned to control values. There was a significant positive correlation between BP and log PRA 3 and 5 weeks after the operation, but no correlation was observed at 10 weeks. In a selected group of marmosets with the highest values of BP (greater than 140 mmHg; n = 4), the converting enzyme inhibitor, enalapril (2 mg/kg s.c.) lowered BP by 58 +/- 7 (s.e.m.) mmHg when given 3 weeks after clipping. At 18 weeks the response to enalapril was only -17 +/- 6 mmHg. These results demonstrate that unilateral renal arterial clipping in marmosets results in a transient renin-dependent hypertension. Marmosets in this initial hypertensive phase could be useful for investigating the antihypertensive effects of inhibitors of human renin.     

The renin-angiotensin system in malignant hypertension revisited: plasma renin activity, microangiopathic hemolysis, and renal failure in malignant hypertension

BACKGROUND: Malignant hypertension is a renin-dependent form of hypertension. However, the variations in renin-angiotensin system (RAS) activation in malignant hypertension are not completely understood. A proposed mechanism for ongoing RAS activation is the presence of microangiopathic hemolysis resulting in renovascular ischemia. METHODS: We prospectively examined the association between plasma renin activity (PRA), microangiopathic hemolysis, and renal dysfunction in 30 consecutive patients with malignant hypertension (n=18) and severe hypertension (n=12). The PRA and aldosterone were measured in the supine position and before initiating therapy. RESULTS: The PRA was 8.8 ng angiotensin I (AI)/mL/h (interquartile range [IQR] 4.8-20) in malignant hypertensive patients and 2.8 ng AI/mL/h (IQR 0.6-6.3) in patients with severe hypertension (P<.01). Aldosterone was 1.30+/-1.02 nmol/L in patients with malignant hypertension compared with 0.44+/-0.37 nmol/L in those with severe hypertension (P<.01). In malignant hypertension, PRA highly correlated with lactic dehydrogenase (LDH) (r=0.76, P<.001), meaning that 58% of the variations in PRA could be explained by LDH. The PRA positively correlated with serum creatinine values at presentation (r=0.50, P=.007), but adjustment for LDH abolished the effect of PRA on creatinine (P=.24). CONCLUSIONS: The PRA and aldosterone were markedly elevated in patients with malignant hypertension but not in severely hypertensive patients despite small differences in blood pressure (BP). The strong logarithmic correlation between PRA, microangiopathic markers, and renal dysfunction suggests a renin-mediated acceleration of vascular damage and renal dysfunction in patients with malignant hypertension.     

The effect of percutaneous dilatation of renal arterial stenosis on captopril renography in hypertension

BACKGROUND: The clinical effects of percutaneous transluminal renal artery angioplasty (PTRA) in patients with renal vascular stenosis and hypertension is controversial. METHODS: We consecutively recruited all 23 patients referred for evaluation of renovascular hypertension that eventually underwent unilateral PTRA, to be investigated with captopril MAG3 renography (CR), both before and after the endovascular procedure. Data were evaluated on an intention-to-treat basis. RESULTS: We found that the relative MAG3 clearance of the stenotic kidney increased (from 29.9+/-14% to 35.1+/-14%, p=0.01) and that the creatinine levels fell following the intervention (from 110+/-19 to 99+/-17 micromol/l, p=0.0003). Blood pressure levels were also lowered (from 173+/-32/93+/-17 to 158+/-31/86+/-15 mmHg, p<0.006) while the mean number of anti-hypertensive drugs was unchanged following PTRA (2.9+/-1.4 before and 2.8+/-1.3 drugs after the intervention, respectively, p=0.6). CONCLUSION: This prospective trial showed statistically significant improvements of individual kidney function as measured by CR and blood pressure in subjects with suspected renovascular hypertension treated with PTRA. Although the endovascular procedure was found to be safe, the magnitude of the absolute improvements was rather modest.