Transluminal vascular stent for ostial atherosclerotic renal artery stenosis.

We implanted transluminal stents in 24 hypertensive patients with a critical atherosclerotic ostial renal artery stenosis (28 arteries). Immediate revascularisation was successful in all. Follow-up angiography at 6 months, available in 18 patients, revealed restenosis twice. In another patient restenosis was suspected and confirmed by angiography at 2 months. Hence, the total restenosis rate was 3 of 19 patients (16%) and 3 of 23 arteries (13%). Two patients developed renal insufficiency due to cholesterol embolism. In the remaining 22 patients renal function improved (n = 8) or stabilised (n = 14). Although all had to resume antihypertensive treatment, blood pressure normalised in 15 patients, improved in one, remained unchanged in five and worsened in one.

The diuretic effect of calcium entry blockade in normals and hypertensive patients.

Calcium entry blockers have been shown to exert hemodynamic and diuretic effects in the kidney. The diuretic effects can be demonstrated most clearly in the isolated perfused kidney, not influenced by compensatory mechanisms such as a lower blood pressure or changes of hormones. However, they can also be shown in vivo in humans. We studied the renal effects of calcium entry blockade after the first dosage and after continued oral dosages of 20 mg nicardipine tid in patients with essential hypertension and in normotensive controls. Renal function was determined during maximal free water clearance, allowing estimation of changes in "proximal" and "distal" tubular sodium reabsorption. Results showed a natriuretic effect. In the control subjects, clearance results were compatible with a decrease of proximal and distal tubular reabsorption, but in the hypertensive group natriuresis was mainly achieved by an increase of the glomerular filtration rate and a decrease of fractional distal reabsorption. In both groups the natriuresis occurred concomitantly with a lower blood pressure. The ratio plasma renin activity/plasma aldosterone concentration increased, although nicardipine did not inhibit the increase of plasma aldosterone during angiotensin II infusion. Pre-treatment with the calcium entry blocker nitrendipine enhanced the natriuretic effect of atrial natriuretic factor (ANF) in sodium replete normal volunteers. Facilitation of sodium excretion by human ANF may be an additional diuretic mechanism of calcium entry blockers.

Captopril renography and the effect of percutaneous transluminal angioplasty on blood pressure in 94 patients with renal artery stenosis.

We treated 94 patients by percutaneous transluminal angioplasty (PTA) for renal artery stenosis (RAS). Prior to PTA, a renogram during angiotensin converting enzyme (ACE) inhibition with captopril was performed, but the result did not influence the decision to treat. The parenchymal time activity curves were judged by visual interpretation. Of the 94 patients, 51 had unilateral and 43 bilateral RAS. In 17 patients with bilateral RAS, PTA could be performed only in the least affected kidney; because of this the effect of PTA on their blood pressure could not be evaluated. Of the remaining 77 patients, a positive captopril renogram was seen in all 31 cured patients, in 22 of the 27 patients with improvement, and in six of the 19 patients with no change of their blood pressure. The sensitivity of the tests for cure and improvement of the blood pressure was 91% (53/58 patients) for all patients, 95% in patients with unilateral RAS (35/37), and 86% (18/21 patients) in patients with bilateral RAS, bilaterally treated. In 18 patients with a negative captopril renogram the blood pressure improved in five, and did not change in 13 patients. The success of PTA in patients with a negative captopril renogram was so poor that we feel it would have been better not to have performed angiography and PTA at all. In conclusion, captopril renography is a useful investigation in assessing the likelihood of blood pressure reduction after PTA of renal artery stenosis.

Hypertension in the elderly is associated with white matter lesions and cognitive decline.

Forty-two elderly patients (mean age, 66.2 +/- 5.1 yr) with hypertension, treated for an average of 17.3 years (standard deviation, 10.3), and 42 control subjects (mean age, 66.5 +/- 4.8 yr), matched for age, sex, and level of education, were studied with regard to the detection of lesions in the cerebral white matter with magnetic resonance imaging (MRI), particularly with axial T2-weighted images. The assessment of the MRI scans was blinded. Ten hypertensive patients showed confluent lesions in the white matter, versus only 1 control subject (Chi-square test, p = 0.01). The presence of diffuse lesions of the white matter was related to age but not to the known duration of hypertension, nor to the presence of any other cardiovascular risk factors. Cognitive function was measured in 34 hypertensive patients and in 18 control subjects. Results of the Mini-Mental State Examination, the Stroop color-word test, Trailmaking test, and the visual subtest of the Wechsler Memory Scale were worse in patients with confluent lesions of the white matter; there was no difference in mental functioning between hypertensive patients and control subjects with normal white matter or with only small focal lesions. Our findings suggest that long-standing hypertension in some patients may cause not only strokes but also chronic end-organ damage of the brain in the form of demyelination of the white matter, with cognitive decline.

Renovascular hypertension and renal insufficiency treated with left nephrectomy and right autotransplantation.

A patient presented with renal failure and severe hypertension. Arteriography showed a non-functioning kidney due to occlusion of the renal artery. The artery of the other contralateral kidney seemed unaffected. Converting enzyme inhibition resulted in normalization of the blood pressure, but this was accompanied by worsening of the renal failure. This was the clue for the detection of an origostenosis of the artery of the contralateral kidney, which could only be diagnosed by oblique angiograms. A revascularisation procedure by renal autotransplantation was performed. Simultaneously the non-functioning kidney was excised. The procedure resulted in an uneventful recovery of renal function. Diagnostic and therapeutic issues are discussed.

Hemodynamic effects of Ro 23-6152 in patients with essential hypertension.

In a double blind study 8 patients with uncomplicated essential hypertension received in random order single oral doses of placebo and 10, 30 and 80 mg Ro 23-6152, a novel calcium entry blocker, on 4 different days. Patients were assessed 15 min before dosing and at several time intervals over the following 6 h. Ro 23-6152 30 and 80 mg induced a significant decrease (mean maximum 7 mmHg.1-1.min-1) in total peripheral resistance, while cardiac output, stroke volume and heart rate were slightly increased (mean maximum 0.51.min-1, 10 ml, 5 beats.min-1, respectively) but not significantly so. Systolic blood pressure decreased significantly (5 to 10 mmHg) from 0.5 to 6 h after the 80 mg dose. After the 10 and 30 mg doses the decreases in systolic pressure were not significant. Diastolic blood pressure and mean arterial blood pressure were non-significantly decreased (mean maximum 7 mmHg) after all doses. The PQ interval was also non-significantly increased by no more than 20 ms. It appears that the main hemodynamic effect of Ro 23-6152 in hypertensive patients is a decrease in peripheral resistance. The antihypertensive effect, at least in this short term study, was only modest, probably because the fall in peripheral resistance was partly compensated by an increase in cardiac output.

Percutaneous transluminal renal angioplasty: initial and long-term results.

Renal artery stenosis in 201 patients with hypertension was treated with percutaneous transluminal renal angioplasty (PTRA). A total of 213 procedures were performed as treatment of 262 separate stenosis. The stenosis was caused by atherosclerosis in 134 cases and by fibromuscular dysplasia (FMD) in 52 cases; the cause was indeterminate in 27 cases. Of the 213 procedures, 172 were successful or resulted in improvement, for a technical success rate of 80.8%. The initial clinical results could be evaluated in 210 cases; cure or improvement was achieved in 80%. There were 23 cases in which neither technical nor clinical success was achieved. Data on the remaining 187 cases were the basis of this long-term follow-up study. The cumulative patency rate at 5 years was 80% in the atherosclerosis group, 89% in the FMD group, and 74% in the indeterminate group. The mortality was less than 1%. Because spasm occurred in 33 cases, causing an infarction in ten instances, antispasmodic medication seems warranted. These long-term results indicate that PTRA is the treatment of choice in patients with renovascular hypertension.

[Results of percutaneous transluminal angioplasty in renal artery stenosis during the period 1978-1986]. / Resultaten van percutane transluminale angioplastiek bij nierarteriestenosen in de periode 1978-1986.

UNLABELLED: Two hundred and thirteen patients with hypertension and renal artery stenosis were treated with percutaneous transluminal renal angioplasty (PTRA). The angiographic appearance was typical of atherosclerosis in 134 patients and of fibromuscular dysplasia (FMD) in 52 patients, and could not reliably be classified in one of these groups in 27. In these patients 272 renal artery stenoses were treated. In 81% of these patients the PTRA was technically successful. The antihypertensive result in this group of 210 patients was positive (cure or improvement) in 80%. The life-table results after 5 years show cure or improvement in the atherosclerotic group (n = 35) in 80.27%, in the FMD group (n = 20) in 88.83% and in the unclassified group (n = 10) in 74.27%. One patient died from a mesenteric thrombosis and one from a myocardial infarction which both occurred within a few days after PTRA. Accordingly, the mortality was less than 1%. IN CONCLUSION: PTRA appears to be a good treatment of renovascular hypertension caused by atherosclerosis or FMD, with good long-term antihypertensive effects.

Renovascular hypertension: the small kidney updated.

We report the results of treatment in 57 patients with renovascular hypertension associated with one poorly perfused, small kidney with less than 25 per cent of total 131I-hippurate uptake shown by renography. Arteriography in 29 patients demonstrated occlusion of the artery of the small kidney, and in 28 there was stenosis. In addition, 25 patients had stenosis of the artery supplying the larger contralateral kidney. Stenosis of the arteries of the contralateral kidneys was dilated by percutaneous transluminal arterioplasty in all but one of the 25 patients with bilateral disease of the artery, stenosis of the small kidney could be dilated successfully by percutaneous transluminal arterioplasty in 22 of the 28 patients, and cure or improvement of blood pressure was achieved in 12 of them. Percutaneous transluminal arterioplasty of occluded arteries was generally unsuccessful. In 17 patients with unilateral disease not manageable by percutaneous transluminal arterioplasty, nephrectomy of the small kidney improved blood pressure control without significant deterioration of renal function. Renal function improved in 10 patients with bilateral lesions treated by nephrectomy of the small kidney in combination with contralateral percutaneous transluminal arterioplasty. Histological examination of excised kidneys showed large infarcts or several cholesterol emboli whether percutaneous transluminal arterioplasty had been attempted or not. After observation periods ranging from two to 79 months, 48 patients were normotensive (21 without and 27 with medication) and nine patients were still hypertensive even with medication. This study showed that by using percutaneous transluminal arterioplasty initially if possible, supplemented with nephrectomy and/or medication, normotension without loss of renal function or immediate serious complications could be obtained in the majority of these severely hypertensive patients.

Pharmacokinetics of lisinopril in hypertensive patients with normal and impaired renal function.

The pharmacokinetics of lisinopril was studied after administration of single and multiple doses of 5 mg to hypertensive patients with normal and impaired renal function. In patients with severe renal failure the peak concentrations were higher, the decline in serum concentration was slower and the time to peak concentration was extended. Accumulation of lisinopril was highly correlated with the creatinine clearance. The effective half-life was doubled and tripled in patients with mild and severe renal impairment, respectively, as compared to patients with a normal renal function. Lisinopril lowered blood pressure in all three groups over 24 h. It is suggested that smaller doses of lisinopril should be administered to patients with severe renal failure.

Renovascular hypertension identified by captopril-induced changes in the renogram.

Radioisotope renography was performed in 21 patients with hypertension and unilateral renal artery stenosis with and without premedication with 25 mg of captopril, and the results were compared with the effect of percutaneous transluminal angioplasty on the blood pressure, assessed 6 weeks after angioplasty. Angioplasty caused a considerable decrease in blood pressure in 15 of the 21 patients. In 12 of these 15 patients, captopril induced changes in the time-activity curves of the affected kidney only, suggesting deterioration of the excretory function of that kidney, while the function of the contralateral kidney remained normal. After angioplasty the asymmetry in the time-activity curves diminished despite identical pretreatment with captopril. Such captopril-induced unilateral impairment of the renal function was not seen in the six patients with unilateral renal artery stenosis whose blood pressure did not change after percutaneous transluminal angioplasty or in 13 patients with hypertension and normal renal arteries. The functional impairment of the affected kidneys was characterized by a decrease of 99mTc-diethylenetriamine pentaacetic acid uptake and a delay of 131I-hippurate excretion, while the 131I-hippurate uptake remained unaffected. These data are in agreement with a reduced glomerular filtration rate and diuresis during preservation of the renal blood flow, changes that can be expected after converting enzyme inhibition in a kidney with low perfusion and an active, renin-mediated autoregulation of the glomerular filtration rate. These data suggest that functional captopril-induced unilateral changes, shown by split renal function studies with noninvasive gamma camera scintigraphy, can be used as a diagnostic test for renovascular hypertension caused by unilateral renal artery stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of converting enzyme inhibition on the enhanced proximal sodium reabsorption induced by chronic diuretic treatment in patients with essential hypertension.

During chronic chlorthalidone treatment of patients with essential hypertension, distal tubular sodium reabsorption is continuously inhibited. At the same time, sodium balance is maintained by an increase of the proximal tubular sodium reabsorption. In the present study, we investigated whether this increase is caused by a stimulated renin-angiotensin system (RAS). For this purpose, the renal effects of converting enzyme inhibition (CEI) were evaluated in 12 patients with essential hypertension who remained hypertensive despite chronic chlorthalidone treatment. After 6 weeks of chlorthalidone, an intravenous injection of 10 mg enalaprilic acid decreased the mean arterial pressure (MAP) from 110 to 102 mm Hg. The effective renal plasma flow (ERPF) increased. However, glomerular filtration rate (GFR) and the fractional excretions of sodium, lithium and free water did not change significantly. After 2 additional weeks of chlorthalidone combined with enalapril 20 mg b.i.d., MAP fell to 90 mm Hg, ERPF remained elevated and plasma aldosterone concentration decreased. As in the acute study, no significant changes were detected in the GFR and the fractional excretions of sodium, lithium or free water. Extracellular fluid volume was not diminished during these 2 weeks. Fractional proximal sodium reabsorption during chronic chlorthalidone therapy was higher when calculated from free water clearance (91%) than from the lithium clearance (71%), but neither of the two were affected by acute or chronic CEI. The results of this study suggest that during chronic diuretic treatment, maintenance of sodium balance by increased proximal reabsorption is not dependent on the stimulated RAS, or alternatively, that this function of the RAS is exactly counterbalanced by another effect of CEI, possibly by the fall in blood pressure.

Lisinopril in hypertensive patients with and without renal failure.

Lisinopril (MK521), a lysine analogue of enalaprilic acid, the bioactive metabolite of enalapril, has a longer half-life than enalaprilic acid, and is excreted unchanged in the urine. Its kinetic profile and antihypertensive and hormonal effects have been investigated in an open study in 3 groups each of 6 hypertensive patients, with normal, moderate and severe impairment of renal function. Serum drug level, blood pressure, converting enzyme activity (CEA), plasma renin activity (PRA), aldosterone concentration (PAC), and serum potassium and creatinine were measured during 1 week following a single oral dose and subsequently following 8 daily doses of 5 mg lisinopril. Accumulation of lisinopril was found in the severe renal failure group. CEA was suppressed to less than 10% of its initial value from 4 to 24 h after the initial dose in all three groups, and the suppression was more marked and lasted longer in patients with severe renal failure. An inverse correlation was found in all patients between log serum lisinopril concentration and log CEA. Lisinopril lowered blood pressure in all three groups over 24 h. PRA rose and PAC fell similarly in the groups. Serum potassium increased in the renal failure groups and creatinine remained unchanged in all groups. Thus, when lisinopril 5 mg is given daily to patients with severe renal failure it may accumulate. The high serum lisinopril concentration does not cause an excessive antihypertensive effect. In patients with severe renal failure, adjustment of the dose or the dosing frequency to the degree of renal failure is recommended to avoid administration of doses in excess of those required to achieve adequate inhibition of converting enzyme.