Unilateral Renal Artery Stenosis Research Articles

Unilateral Renal Artery Stenosis Seen Initially as Severe and Symptomatic Hypokalemia

Hypokalemia is an uncommon presentation of renovascular hypertension. Although renal artery stenosis has been associated with hypokalemia secondary to hyperreninemic hyperaldosteronism, few reports have actually evaluated the pathophysiologic changes in such a patient with renovascular hypertension. We studied a patient before and after surgical revascularization who presented with severe hypertension and marked, symptomatic hypokalemia. Before surgery, the patient had excessive urinary potassium secretion, markedly increased secretion of renin after captopril stimulation, and mild secondary hyperaldosteronism. Postoperatively, the patient's blood pressure decreased moderately and the serum and urinary potassium values normalized. After revascularization, plasma renin activity both before and after captopril stimulation and serum aldosterone levels decreased markedly. These findings demonstrate that renovascular hypertension may rarely present with symptomatic hypokalemia secondary to excessive aldosterone secretion. Improvement in the renal ischemic state is accompanied by rapid correction of the metabolic disturbances associated with hyperreninemic hyperaldosteronism.

Unilateral acquired renal cystic diseas and neoplasia in a patient with renal artery stenosis

We report a case of a sixty-two-year-old woman with longstanding unilateral renal artery stenosis in whom acquired renal cystic disease (ARCD) and neoplasia developed. ARCD has been frequently reported in the hemodialysis and peritoneal dialysis patients, but rarely reported in the nonuremic patient. To our knowledge it has not been previously reported in a patient with unilateral renal artery stenosis.

Regional angiotensin II production in essential hypertension and renal artery stenosis.

To study regional metabolism and production of angiotensin II, we measured steady-state plasma levels of 125I-angiotensin I and II and endogenous angiotensin I and II in the aorta and the antecubital, femoral, renal, and hepatic veins during systemic infusion of 125I-angiotensin I or II. Extraction of arterially delivered angiotensin II ranged from 30-50% in the limbs to 80-100% in the renal and hepatomesenteric vascular beds both in essential hypertension (n = 13) and in unilateral renal artery stenosis (n = 7). Across the limbs, 20-30% of arterially delivered angiotensin I was converted to angiotensin II in both groups, and there was no arteriovenous gradient in endogenous angiotensin II. No conversion of arterially delivered angiotensin I was detected across the renal and hepatomesenteric beds, and there was net extraction of angiotensin II from the systemic circulation by these beds. Although regional production of angiotensin I at tissue sites made a significant contribution to its level in the veins, little of this locally produced angiotensin I reached the regional veins in the form of angiotensin II, even in the kidney with artery stenosis, where the venous levels of locally produced angiotensin I were particularly high. These results provide no evidence for a source of circulating angiotensin II other than blood-borne angiotensin I and illustrate the high degree of compartmentalization of angiotensin I and II production.

Effect of captopril on the renal veno-arterial gradient of erythropoietin and oxygen in unilateral renal artery disease.

Twenty-nine patients with unilateral renal artery stenosis or occlusion were investigated. The veno-arterial gradient (VA-gradient) of erythropoietin (EPO), haemoglobin oxygen saturation and plasma renin activity (PRA) was determined separately in each kidney before and 1 h after angiotensin converting enzyme inhibition (ACE-inhibition). The VA-gradient of EPO and of hemoglobin oxygen saturation were the same in the affected and unaffected kidney during basal conditions. During ACE-inhibition the VA-gradient of EPO disappeared on the affected side but not on the unaffected side. A fall in s-EPO after ACE inhibition was demonstrated in the renal vein on the affected side (-1.4 U l-1, p < 0.01), in the contralateral vein (-0.8 U l-1, p < 0.01) and in the aorta (-0.6 U l-1, p < 0.01). The O2-gradients were reduced on both sides after captopril, from 10.8-7.5% (p < 0.04) on the affected side and from 10.8-9.0% (p < 0.04) on the contralateral. It is suggested that the stimulated renin-angiotensin system may be important for EPO production in the affected kidney in unilateral renal disease.

Effect of captopril on renal extraction of renin, angiotensin II, atrial natriuretic peptide and vasopressin, and renal vein renin ratio in patients with arterial hypertension and unilateral renal artery disease

Plasma renin activity (PRA) and plasma concentrations of angiotensin II (AngII), atrial natriuretic peptide (ANP) and arginine vasopressin (AVP) were determined in the abdominal aorta and the renal veins before and 1 h after peroral ingestion of captopril 25 mg in 29 patients with arterial hypertension and unilateral renal artery stenosis or occlusion, in order to study the effect of ACE inhibition on single-kidney extraction ratio (ER) of PRA, AngII, ANP, and AVP, and on renal vein renin ratio (RVRR). PRA was increased, AngII and ANP were reduced, and AVP unchanged after captopril. On the affected side the negative ER or PRA (-1.03) and AngII (-0.28) and the positive ER of ANP (0.25) and AVP (0.14) were not significantly changed by captopril. On the non-affected side ER of AngII and ER of ANP were significantly reduced (ER of AngII, 0.41-0.00, ER of ANP, 0.29-0.17), but ER of PRA and ER of AVP were unchanged. RVRR was not significantly changed by captopril. RVRR was greater than 1.5 in 79% of the patients before captopril, in 82% after captopril, and in 93% either before or after captopril. It is concluded that captopril reduces ER of AngII and ER of ANP on the non-affected side but not on the affected side in unilateral renal artery disease with hypertension, and that the use of RVRR both before and after captopril improves the predictive value of RVRR with regard to the diagnosis of unilateral renal artery disease.

Non-invasive ultrasound assessment of renal artery stenosis by means of the Gosling pulsatility index

To gauge the effectiveness of a new Doppler test for renal artery stenosis (RAS), based on the pulsatility index of the blood flow velocity spectrum within several interlobar arteries of both kidneys. Twenty normotensive volunteers and 49 hypertensive patients were investigated with ultrasound. Patients with angiographic signs of RAS underwent bilateral renal vein catheterization for renin measurement. Significant RAS was assumed if lateralization of renal vein renin to the stenotic side was proven. The pulsatility index was higher in the hypertensives without RAS than in normal volunteers. Side differences between both kidneys were within methodological variations with the exception of one case, in whom side difference was > 0.12. The pulsatility index was lower in kidneys with significant RAS than in kidneys without RAS. In most patients with significant unilateral RAS the side difference was < 0.12. In the other patients with a low pulsatility index and a side difference < 0.12 RAS was found to be bilateral upon angiography. Doppler signals were absent in all kidneys with renal occlusion. A side difference of > or = 0.12 predicts unilateral RAS, whereas the absence of parenchymal Doppler signals indicate occlusive RAS. A low pulsatility index combined with normal side difference may, in hypertensive patients, indicate bilateral RAS. Renovascular hypertension was correctly diagnosed in 84% of the patients and the presence of RAS in 94%.

Circadian blood pressure variation in patients with renovascular hypertension or primary aldosteronism.

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.

Plasma erythropoietin concentrations in renal venous blood of patients with unilateral renovascular hypertension.

In 19 patients with unilateral renal artery stenosis and subsequent renovascular hypertension plasma renin activity (PRA), plasma concentrations of atrial natriuretic peptide (ANP), erythropoietin (Epo), H+ and HCO3-, as well as pO2 and pCO2 were assessed in renal venous blood of the 'ischaemic' and normally perfused kidney, both in arterial blood and in the inferior vena cava distally from the orifices of the renal veins. PRA and ANP were significantly elevated in venous blood of the ischaemic kidney as compared with the normally perfused kidney. In contrast to PRA and ANP, plasma concentrations of Epo were similar in blood withdrawn at all vascular sites. pO2 and pCO2, as well as blood H+ and HCO3- concentrations in venous blood of the ischaemic kidney were of the same magnitude as of the normally perfused kidney. From the results presented in this paper it follows that (i) in contrast to plasma renin activity and ANP, unilateral renal 'ischaemia' does not influence plasma concentrations of Epo in renal venous blood, and (ii) chronic haemodynamic alterations do not seem to influence Epo secretion by the kidneys.

26. Verapamil effect on renography and on renal function in unilateral renal artery stenosis

26. Verapamil effect on renography and on renal function in unilateral renal artery stenosis

Changes in renal function induced by ACE-inhibition in the conscious two-kidney, one-clip Goldblatt hypertensive dog.

In order to study why the diagnostic sensitivity of 123I-hippurate renography for a renal artery stenosis is improved by angiotensin converting enzyme (ACE-) inhibition we used the model of the conscious chronically instrumented two-kidney, one-clip Goldblatt hypertensive dog. Urine flow (UV), renal blood flow (RBF), glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured (with constant infusion of 125I-iothalamate and 131I-hippurate, respectively) for both kidneys separately before and after a bolus injection of a mild unilateral renal artery stenosis (approximately 30% reduction of RBF). During ACE-inhibition, there were remarkable falls in poststenotic GFR (from 37 +/- 5 to 4 +/- 2 ml/min, p less than 0.05), ERPF (from 111 +/- 13 to 21 +/- 10 ml/min, p less than 0.05) and UV (from 0.86 +/- 0.15 to 0.075 +/- 0.045 ml/min, p less than 0.05), whereas RBF of the poststenotic kidney slightly increased (from 193 +/- 18 to 237 +/- 27 ml/min, p less than 0.05). The concentration of hippurate and thalamate in the blood remained remarkably constant while the excretion of the tracers by the poststenotic kidney diminished and renal retention of 123I-hippurate was seen on the renogram. In 2 dogs, the experiments were repeated during mannitol infusion. In that situation, there was a much smaller decrease of poststenotic UV and GFR whereas ERPF even showed a small increase comparable to the RBF changes.(ABSTRACT TRUNCATED AT 250 WORDS)

The Mechanism and Diagnostic Value of Angiotensin I Converting Enzyme Inhibition Renography

The effect of angiotensin converting enzyme (ACE) inhibition on the sensitivity of radionuclide renography in the diagnosis of a unilateral renal artery stenosis was tested both in a conscious dog model and in the human situation. ACE inhibition (10 mg enalaprilic acid, intravenously) markedly improved the sensitivity of [123I]hippuran renography in 10 renovascular hypertensive dogs with a mild to moderate unilateral renal artery stenosis from 50 to 100%. This improved sensitivity was due to an ACE-inhibition-induced delayed tracer handling at the stenotic side without an appreciable change in the renographic curve at the contralateral side. A similar phenomenon was observed in 15 hypertensive patients with an angiographically proved unilateral renal artery stenosis. Both [123I]hippuran and 99mTc-diethylenetriaminepentaacetic acid (DTPA) handling was delayed on the stenotic side after oral enalapril treatment. However, only a moderate increase in sensitivity was observed comparing control renograms to ACE-inhibition renograms: from 87 to 93% for hippuran, and from 60 to 86% for DTPA. Eight of these 15 patients underwent either surgery or angioplasty resulting in a successful correction of the stenosis. Hypertension was more or less cured in five patients. Each of these patients had shown an ACE-inhibition-induced change in the renogram at the stenotic side, suggesting that such a response may predict the curability of the hypertension. However, of the three patients that showed no blood pressure change upon successful revascularization, two showed a positive ACE-inhibition renogram. In conclusion, in an ideal setting as obtained in animal experiments, ACE inhibition improves the sensitivity of renographic studies to 100%. However, its value in the clinical setting needs more standardization.

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.

Role of sympathetic efferent nerves in blood pressure regulation and in hypertension.

This article presents some aspects of the role of sympathetic efferent nerves in the regulation of blood pressure in humans. Lessons have been learned from disorders that cause either sympathetic underactivity or overactivity. In chronic autonomic failure, pressor stimuli (mental arithmetic, isometric exercise, or cold) are unable to raise blood pressure, whereas stimuli that normally activate sympathetic efferent nerves to maintain blood pressure (head-up tilt, exercise, and food ingestion) can cause marked hypotension. Recognition of specific defects, such as the inability to synthesize norepinephrine in isolated dopamine beta-hydroxylase deficiency, suggests that sympathetic nerves may influence blood pressure regulation through nonadrenergic mechanisms (dopamine, neuropeptides, and purines). Tetraplegic patients with high cervical cord transection also have sympathetic impairment and postural hypotension, but this is less of a clinical problem because of compensatory hormonal and other mechanisms. Tetraplegic patients are unique as they also may have severe paroxysmal hypertension because of increased spinal sympathetic reflex activity. The pathophysiological mechanisms responsible for this exaggerated response include changes in postsynaptic adrenergic receptor numbers and their sensitivity, the actions of nonadrenergic cotransmitters, and the lack of sympathoneural pathways from the brain that are severed by the lesion. Finally, the putative role of the sympathetic nervous system in hypertension with unilateral renal artery stenosis, which initially is humorally mediated, is discussed. The centrally acting sympatholytic agent clonidine is effective in lowering blood pressure in renovascular hypertension independently of humoral factors when multiple agents have failed.(ABSTRACT TRUNCATED AT 250 WORDS)

The sympathetic nervous system in hypertension due to unilateral renal artery stenosis in man

The contribution of neurogenic mechanisms in maintaining hypertension was investigated in 13 patients with unilateral renal artery stenosis (twelve with normal, one with grossly elevated plasma renin levels) by determining the haemodynamic and hormonal responses to the centrally acting sympatholytic agent, clonidine. The same patients were studied after captopril to determine the dependency of their blood pressure on the direct peripheral effects of angiotensin-II. Sixteen patients with essential hypertension (normal plasma renin) were additionally studied after clonidine. After clonidine, blood pressure fell markedly in patients with renal artery stenosis (17 +/- 3%) and essential hypertension (18 +/- 2%). In both groups, clonidine lowered cardiac output by a reduction in stroke volume and heart rate; forearm vascular resistance was unchanged but digital skin vascular resistance fell. Plasma noradrenaline levels were normal in both groups and fell after clonidine; plasma renin activity and aldosterone levels were unchanged. After captopril, blood pressure fell minimally (5 +/- 3%) in renal artery stenosis patients; cardiac output fell and forearm and digital skin vascular resistance were unchanged. Plasma renin activity rose, plasma aldosterone fell and plasma noradrenaline was unchanged after captopril. In the patient with grossly elevated renin levels, blood pressure fell minimally (6%) after clonidine, but unlike others fell profoundly (37%) after captopril. We conclude that, in the majority of our renal artery stenosis patients, despite the elevated blood pressure, sympathetic nervous activity was not reduced. Central neurogenic mechanisms appear to play an important role in maintaining raised blood pressure. In the same patients the peripheral effects of angiotensin-II did not maintain vascular tone or hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypertension from the nephrologist's point of view

Secondary hypertension represents about 5-10% of all forms of hypertension, renal and renovascular being the commonest forms. Renal artery stenosis is the principal cause of renovascular hypertension due to atheromatous disease or fibromuscular dysplasia. Rapid sequence intravenous pyelogram, isotope renogram, captopril test and digital subtraction angiography or conventional arteriography, are the diagnostic procedures in the diagnosis of renal artery atenosis. Hypertension is also very common in parenchymal renal disease, mainly in chronic renal insufficiency. In this condition, the mechanism is more related to volume dependent factors than in renovascular hypertension which is mainly renin dependent. In the treatment of renal or renovascular hypertension the same type of drugs have been generally used as in essential hypertension although with some specific indications like the use of angiotensin-converting enzyme inhibitors in unilateral renal artery stenosis or furosemide in case of renal insufficiency. Revascularization by angioplasty or surgical bypass, may be indicated in renovascular hypertension.

Norepinephrine overflow and renin pattern of the individual kidney in patients with unilateral renal artery stenosis.

This study was performed to determine divided renal efferent sympathetic nerve activity from kidneys in seven patients with renin-positive, unilateral renal artery stenosis before and 30 minutes after an acute intravenous dose of 1.25 mg enalaprilat. Renal norepinephrine release was calculated from split renal plasma flow, venoarterial plasma concentration gradients across the kidney, and the fractional extraction of tritiated norepinephrine. All patients had unilateral renin secretion, the affected kidney increasing its plasma renin activity gradient 1.7-fold, whereas no statistically significant change was noted on the contralateral side in response to enalaprilat. Total norepinephrine release to plasma and norepinephrine plasma clearance (assessed by isotope dilution) were similar before and after administration of enalaprilat (approximately 400 ng/min and 1.0 l/min), despite a 26% fall in mean arterial pressure (from 125 mm Hg, p less than 0.01). Heart rate remained unchanged. After enalaprilat, norepinephrine venoarterial difference increased in the renin-secreting kidney (from 264 to 396, SED = 57 pg/ml, p less than 0.05), whereas it increased only slightly in the contralateral kidney (from 149 to 256, SED = 72 pg/ml, NS). Tritiated norepinephrine extraction fell approximately 25% (p less than 0.01) in both kidneys. Thus, renal norepinephrine spillover increased from 49 to 62, SED = 9 ng/min (NS) and from 81 to 129, SED = 17 ng/min (p less than 0.05) from the affected and the contralateral kidney, respectively. Hence, in this relatively small study in patients with renovascular hypertension, no evidence for increased renal nerve activity could be observed in the affected kidney, despite its marked renin production.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal artery stenosis: in vivo perfusion MR imaging.

The intravoxel incoherent motion (IVIM) model of perfusion and diffusion imaging was applied to an in vivo canine model of unilateral renal artery stenosis and was compared with relative renal blood flow determination with radioactive microspheres. The percentage relative renal blood flow as determined with radioactive microspheres correlated closely with the percentage apparent diffusion coefficient. If this method can be adapted to human imaging, it may provide a noninvasive means for detecting renal artery stenosis.

Pediatric Renal Artery Dysplasia: A Morphologic Study

Renal arteries from 12 pediatric patients who had stenosis due to renal artery dysplasia (9 surgical resections and 3 autopsy cases) were examined by light microscopy. The patients ranged in age from 15 months to 14 years; the male/female ratio was one. Bilateral renal artery disease was clinically diagnosed in 8 of the 12 patients; 6 of the 8 also had aortic anomalies. All of the lesions were designated as forms of dysplasia, a departure from previous reports in which dysplasia was subclassified as fibroplasia and hyperplasia. The most common lesion was medial fibrous dysplasia (6), followed by perimedial elastic dysplasia (4); intimal fibrous dysplasia (1) and medial muscular dysplasia (1) were the least common. Medial fibrous dysplasia was present as often with bilateral as with unilateral renal artery stenosis, while perimedial elastic dysplasia was seen exclusively in patients with bilateral renal artery disease. Three patients who came to autopsy had extrarenal vascular involvement by a similar dysplastic lesion. The three patients who had neurofibromatosis showed no distinctive histologic type of renal artery dysplasia.

Captopril-stimulated Renal Vein Renin in Hypertensive Patients With or Without Renal Artery Stenosis

To examine the efficacy and usefulness of captopril-enhanced renal vein renin (RVR) measurements in detecting the functional significance of renal artery stenosis found in hypertensives, we compared these values in 22 patients with arteriographically documented renovascular hypertension due to unilateral (URVH: 14 patients) or bilateral renal artery stenosis (BRVH: 8 patients) and 12 patients with high renin essential hypertension (EHT). Before captopril administration, RVR ratio was less than 1.5 in 8 patients (36.4%) with renovascular hypertension and all patients (100%) with EHT. Captopril enhanced the lateralization of renal vein renin in renovascular hypertension; the postcaptopril RVR ratio was greater than 2.0 in 18 patients (81.8%) and greater than 1.5 in all the patients (100%). On the other hand, RVR ratio remained unchanged in most patients with EHT. There was no significant difference in the postcaptopril RVR ratios between URVH and BRVH. However, the postcaptopril RVR ratio was higher in atherosclerosis (10 patients) than in fibromuscular dysplasia (11 patients) (P less than .05). Captopril also elucidated contralateral renin suppression as expressed by a contralateral/peripheral renin ratio of less than 1.0, which was associated with a favorable outcome of unilateral surgical intervention. Captopril-stimulated RVR indices were valuable in detecting the functionally significant renal artery stenosis and predicting surgical curability in renovascular hypertension.

Intrarenal de novo production of angiotensin I in subjects with renal artery stenosis.

To estimate the renal extraction and de novo production of angiotensin I and to assess the contribution of blood-borne renin to renal angiotensin I production, the aortic and renal venous plasma levels of renin and intact [125I]angiotensin I and endogenous angiotensin I during continuous systemic intravenous infusion of monoiodinated [125I]angiotensin I were measured in subjects with unilateral renal artery stenosis (n = 8) who were treated with captopril (50 mg b.i.d.). Results demonstrated that 80% of angiotensin I delivered by the renal artery was extracted both by the affected and the unaffected kidney and that on both sides a major part of angiotensin I in the renal vein was derived from intrarenal de novo production. Production of plasma angiotensin I was in excess over extraction (p less than 0.01) on the affected side, whereas extraction was in excess over production (p less than 0.01) on the contralateral side. The plasma level of de novo intrarenally produced angiotensin I in the renal vein was seven times higher on the affected side than the contralateral side. This difference was by far too big to be explained by a difference in the transit time of blood between the two kidneys, by an augmented production of angiotensin I in the circulating blood passing through the affected kidney due to the higher level of venous plasma renin activity in that kidney, or by the combination of both.(ABSTRACT TRUNCATED AT 250 WORDS)