Renal Vein Renin Ratio Research Articles

Mild Renal Artery Stenosis Can Induce Renovascular Hypertension and is Associated with Elevated Renal Vein Renin Secretion.

Renovascular hypertension is a syndrome which encompasses the physiological response of the kidney to changes in renal blood flow and renal perfusion pressure. Such physiological changes can occur with renal artery occlusion irrespective of the severity of the lesion. We have analyzed hypertensive patients with mild renal artery stenosis and compared them to patients with no stenosis. Renal vein renin sampling from catheterization of the renal vein was performed in all these patients. Patients with mild stenosis had higher renal vein renin ratio (3.01±1.5) than the patients with no stenosis (1.10± 0.29; p=0.002). Patients with mild stenosis were also found to have higher diastolic blood pressure and renal artery resistive indices when compared to patients with no stenosis. We therefore conclude that mild stenosis can precipitate renin-mediated hypertension in renovascular stenosis and also emphasis that parameters pertinent to renal physiology need to be evaluated before considering treatment options in patients with renal artery stenosis and medical management with RAAS blockade is the preferred modality of therapy for patients with renin-mediated hypertension.

Effect of Percutaneous Transluminal Renal Angioplasty on Absolute Split Renal Function in Patients with Renovascular Hypertension. Influence of Age and Other Parameters

Tc99m-dimercaptosuccinic acid renal uptake (DMSA uptake) was examined to assess the changes in split renal function following percutaneous transluminal renal angioplasty (PTRA) in 9 patients with a total of 12 renal artery stenoses and renovascular hypertension (RVH). The results were studied with respect to age, degree of renal artery stenosis, and renal vein renin ratio (RVRR) before PTRA. Although the degree of renal artery stenosis, systolic blood pressure, and peripheral blood plasma renin activity were improved 3 months after PTRA, neither the DMSA uptake of the affected kidneys nor that of the contralateral kidneys improved. Although restenosis occurred during the long follow-up period in one patient, DMSA uptake did not change in parallel with the degree of stenosis or RVRR. The degree of improvement in DMSA uptake, blood pressure, and plasma renin activity after PTRA in patients aged under 70 years was significantly higher than that in patients 70 years or older. Good improvement of renal function was attained in a 4-year-old boy, despite the fact that split renal function prior to PTRA was so poor that nephrectomy had been considered instead of PTRA. These results suggest that several factors before PTRA, such as DMSA uptake, degree of renal artery stenosis, and RVRR, are not absolutely predictive of results after PTRA, and that the effect of PTRA on blood pressure and renal function is greater in younger patients.

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.

Renovascular disease in childhood

Fifty-four children referred for investigation of hypertension had renovascular disease. In eight patients it was associated with neurofibromatosis, in three with idiopathic hypercalcemia of infancy, and in five cases it followed an arteritic illness. Fibromuscular dysplasia was the underlying abnormality in the majority of cases (46%). Twenty-six patients (48%) were first seen with accelerated hypertension; 38 children (70%) had bilateral renal arterial disease, and in 41 (76%), disease of the small intrarenal vessels was found. Renal vein renin ratios indicated unilateral disease in 31 cases; the results correlated with arteriography findings in 32 (62%) of 51 patients. Eleven children also had the middle aortic syndrome, and 9 of 16 patients, investigated by cerebral arteriography because of cranial bruits or focal neurologic signs, had cerebral vascular abnormalities. Twenty patients were treated surgically--10 by reconstructive procedures, 11 by nephrectomy or heminephrectomy, and 6 by transluminal angioplasty. Of these, 9 (45%) are normotensive with no treatment, 10 have a decreased requirement for antihypertensive drugs, and 1 had no improvement. Thirty-four patients were treated medically because of the extent of their disease; two patients have died of hypertensive complications. We conclude that renal vascular disease in children is often widespread, may be associated with intracerebral vascular disease, frequently affects both kidneys, including both intrarenal and extrarenal vessels, and is therefore not always amenable to surgical intervention and cure.

Peripheral and Renal Vein Renin Activity in Patients with Renovascular Hypertension Due to Nonspecific Aortoarteritis

The diagnostic utility of peripheral and renal vein renin estimations in relation to angiographic findings was evaluated in 13 patients with renovascular hypertension and non-specific aortoarteritis (NSAA, Gr I), in comparison with 10 patients with renal artery stenosis due to other causes (Gr II). Plasma renin activity (PRA) was measured by radioimmunoassay. Blood samples were collected after angiography from the femoral vein and renal vein on the affected side followed by sampling from the less affected or unaffected side. Renal vein renin ratio (RVRR) was calculated from renal vein renin values. The effect of captopril (25 mg oral) on blood pressure, PRA, and RVRR was examined in 8 patients from each group. Normotensive volunteers (8) with moderately low salt intake were also included in the study for comparison of twenty-four-hour urinary sodium output, peripheral PRA, and response to captopril. The mean peripheral PRA was high in both groups as compared with normotensive controls; however, the values were lower in patients with NSAA. The rise in PRA in response to captopril was insignificant in Gr I (p greater than 0.05) and RVRR greater than 1.5 was observed in 5 of 13 patients in contrast to 9 of 10 in Gr II (p less than 0.05). A paradoxical ratio, ie, (high renal vein renin levels on the less stenotic side) was noticed in 3 patients of Gr I, whereas none of the patients of GR II showed such a ratio. An improvement in RVRR after captopril was observed in 50% of patients of Gr I as compared with a marked response in all patients of Gr II.(ABSTRACT TRUNCATED AT 250 WORDS)

Suppression of Renal vein Renin Profiles by Mannitol Prophylaxis: Implications in the Evaluation of Renovascular Hypertension

Renal arteriography with concomitant renal vein renin profiling remains the diagnostic standard for evaluating the anatomic and physiologic significance of stenotic renal artery lesions in hypertensive patients. False-negative renal vein renin profiles with failure of lateralization in patients with anatomically apparent high-grade stenosis complicate the diagnostic process. Mannitol is frequently administered prophylactically to minimize the risk of dye nephropathy in these patients. Yet, the potential effects of mannitol on renal vein renin profiling in man have not been previously reported. Seven patients with renovascular hypertension were studied prospectively to determine changes in renal vein renin profiles before and after mannitol prophylaxis. Despite captopril stimulation, all patients demonstrated significant renin suppression leading to the loss of renin lateralization in patients with unilateral renovascular hypertension. In 60% of the patients, renal vein renin ratios fell to below the standard 1.5 to 1 ratio after mannitol infusion. In patients with bilateral renovascular disease, the least stenotic side suppressed completely, while the more stenotic side suppressed partially. Percent suppression analysis showed a mean suppression of 56.8% on the stenotic side versus 8.2% on the noninvolved side (P less than 0.002). In every study, suppression equaled or exceeded 32% on the involved side and was less than this on the noninvolved side. Thus, the degree of renin suppression following mannitol infusion may prove to be an important tool in the diagnosis of clinically significant stenotic lesions. The mechanism of mannitol-induced suppression remains undefined, but appears independent of volume expansions or dilutional effects. The inhibitory effects of mannitol on renin profiles can obscure the diagnosis of underlying renovascular hypertension.

Renal vein renins: inability to predict response to revascularization in patients with hypertension.

To determine whether the captopril-stimulated renal vein renin ratio (CSRVRR) could enable identification of patients with hemodynamically significant renovascular lesions who would respond to revascularization, the authors measured CSRVRRs in 143 consecutive patients with hypertension who had been selected because of clinical features suggestive of renovascular hypertension. All patients underwent conventional renal arteriography. Renovascular hypertension was the final diagnosis if revascularization resulted in cure or improvement in blood pressure. Complete data were available for 133 patients. Twenty patients had renovascular hypertension; CSRVRR was greater than 1.5 in 13 of these 20 patients (sensitivity, 65%). However, it was also greater than 1.5 in 54 of the 113 patients without renovascular hypertension (false-positive rate, 47.8%). The positive predictive value of CSRVRR was 18.6%; the negative predictive value, 89.3%. It is concluded that CSRVRR is not sufficiently sensitive to enable prediction of which patients will respond to revascularization and is not specific enough to exclude patients who do not have renovascular hypertension.

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.

Prospective analysis of strategies for diagnosing renovascular hypertension.

Renovascular hypertension is a potentially curable form of high blood pressure. However, it is unclear how best to select patients who are likely to have renovascular hypertension, what diagnostic strategy to use in these selected patients, and how to predict the hemodynamic significance of a renal artery stenosis. We determined the prevalence of renovascular hypertension in adults who exhibited suggestive clinical features. In these clinically selected patients, we then determined the test characteristics of various diagnostic and potential screening tests. Renovascular hypertension was diagnosed if correction of renal artery stenosis resulted in decreased blood pressure. Of the 66 hypertensive adults evaluated, 11 (16.7%) had renovascular hypertension. Captopril-stimulated peripheral renin activity detected renovascular hypertension with 73% sensitivity, 72% specificity, 38% positive predictive value, and 92% negative predictive value. Less optimal combinations of sensitivity and specificity were found for differential glomerular filtration rate renography, differential effective renal plasma flow renography, and selective renal vein renin ratios, each performed after a single dose of captopril. Intravenous digital subtraction renal angiography detected all patients with renovascular hypertension and was normal in 71% of patients with essential hypertension. To evaluate potential screening tests for renovascular hypertension, we calculated predictive values applied to a low prevalence population. If the observed sensitivities and specificities apply to a population with 5% prevalence of renovascular hypertension, captopril-stimulated peripheral renin would have a positive predictive value of 12% and a negative predictive value of 98%. In 16 patients with known renal artery stenosis, neither the captopril-stimulated renal vein renin ratio nor captopril-stimulated differential renography accurately predicted blood pressure response to correction of the stenosis. We conclude that clinical criteria can identify a subgroup with 16.7% prevalence of renovascular hypertension. In this high prevalence group, intravenous digital subtraction renal angiography will identify virtually all patients with renovascular hypertension, and a normal study will be sufficient to exclude renovascular hypertension. In unselected hypertensive patients, screening with captopril-stimulated peripheral renin activity may be the most useful and efficient procedure for identification of patients with renovascular hypertension. Functional tests do not accurately predict the hemodynamic significance of a renal artery stenosis.

Blood pressure during long-term converting-enzyme inhibition predicts the curability of renovascular hypertension by angioplasty.

Percutaneous transluminal renal angioplasty (PTRA) was performed in 28 hypertensive patients with 50% or more unilateral renal artery stenosis. Prospectively, the study compared the extent to which systolic (SBP) and diastolic (DBP) pressure during long-term converting-enzyme inhibition (CEI) and the ipsi- to contralateral renal vein renin ratio (RVR) predicted success of PTRA, defined as SBP less than 160 mmHg and DBP less than 95 mmHg. Both SBP and DBP after PTRA were positively correlated with pressure during CEI (P less than 0.001) and negatively with RVR (P less than 0.03). In multiple regression these associations were independent and remained statistically significant. In discriminant analysis, a SBP during CEI less than 160 mmHg, a DBP during CEI less than 95 mmHg, and a RVR greater than or equal to 1.5 identified with equal accuracy the success of PTRA. Furthermore, in patients with a SBP during CEI less than 160 mmHg, the demonstration of a RVR greater than or equal to 1.5 increased (P less than 0.05) the prediction of a positive outcome from 50 to 67%. In contrast, in 92% of the patients with a SBP during CEI greater than 160 mmHg, PTRA was not successful. Thus, blood pressure measurements during long-term CEI predict the curability by PTRA of renovascular hypertension and can be employed either alone or in association with the RVR.

Fibromuscular Dysplasia of the Renal Artery-Management and Outcome

Fifty-seven patients (48 women, 9 men) with fibromuscular dysplasia (FMD) of the renal artery were investigated. Mean age at detection of hypertension was 37 years. The diagnosis was established by angiography. Patients with lateralization of renin secretion to the stenotic side had a significantly higher peripheral renin level than those without. The patients were initially treated with surgery (n = 19), percutaneous transluminal renal angioplasty (PTRA) (n = 9), or pharmacologically (n = 29). During a mean follow-up period of 6.2 years, thirteen pharmacologically treated patients were transferred for surgical treatment or PTRA, because of progression of the FMD or inadequate blood pressure control. The long-term effect of surgery (n = 22) on the blood pressure was satisfactory in 91% and that of PTRA (n = 18) in 55%. The low success rate after PTRA seems to be due to an inappropriate selection of patients. Age, duration of hypertension and renal vein renin ratio seem to be important prognostic factors for the outcome of surgery or PTRA.

Ramipril for hypertension secondary to renal artery stenosis changes in blood pressure, the renin-angiotensin system and total and divided renal function

The converting enzyme inhibitor, ramipril, 20 mg once daily, was given to 3 hypertensive patients with unilateral renovascular disease. At 1 month, 24 hours after the last dose of ramipril, blood pressure, plasma angiotensin II and converting enzyme activity remained low, and active renin and angiotensin I high. There was no tendency for converting enzyme inhibition to be overcome during 1 month of ramipril therapy. Ramipril caused slight increases in serum potassium and urea, no change in serum creatinine and no consistent changes in the renal vein renin ratio. Ramipril caused little change in renal plasma flow on the stenotic side, but filtration fraction was reduced in 2 patients. There was no serious deterioration in total or individual glomerular filtration rate during ramipril therapy. The drug was well tolerated and there were no serious side effects. Ramipril, given once daily, is likely to be effective in controlling hypertension with renal artery stenosis.

Experience with percutaneous transluminal renal angioplasty in renovascular hypertension.

Percutaneous transluminal renal angioplasty (PTRA) was attempted in 17 patients with a diastolic blood pressure greater than or equal to 95 mmHg in spite of treatment with two or three antihypertensive drugs in combination and unilateral or bilateral renal artery stenosis with a reduction of vessel diameter to less than 25%. PTRA resulted in a dilatation of the stenosis in 12 patients. After an observation period of at least 6 months 2 patients were cured, 7 improved and 3 unchanged. Renal vein renin ratio (RVRR) was determined in the last 9 of these patients but was unknown when PTRA was done. RVRR was higher than 1.5 in 5 patients of whom one was cured and 4 improved and less than 1.5 in 4 of whom one was improved and 3 unchanged. No persistent complications were observed after PTRA. It can be concluded that PTRA is an effective antihypertensive treatment in several patients with renovascular hypertension, and a RVRR greater than 1.5 suggests a favourable outcome with regard to blood pressure regulation.

Small kidney and hypertension: selection of patients for surgery.

We studied 37 patients with various degrees of hypertension and a small unilateral kidney. Renal vein renin studies were shown to be positive on 19 occasions and negative on 18. Of those positive, 10 had severe and 1 moderate hypertension. Surgery cured 63.3%. In 27% blood pressure improved and 1 patient failed to respond. Eight patients had mild hypertension with a positive renal vein renin ratio (RVRR), but on observation their home blood pressures were normal without medication and they were not considered for surgery. Eighteen patients with mild hypertension and negative RVRR were also not operated. We believe that RVRR is important for a surgical decision, but only in severe and moderate hypertensives. In mild hypertension, measurement of blood pressure at home is normal on most occasions. These are hyperreactive patients and should not have surgery, regardless of the results of their RVRRs.

Renovascular hypertension. Ability to renal vein ratio to predict the blood pressure level 18-24 months after surgery.

Fourteen patients with severe hypertension and renal artery stenosis were treated surgically. One patient died 4 days after surgery due to a cerebral thrombosis. The other 13 patients were followed for 18-24 months. Five were considered cured since the diastolic blood pressure (DBP) was less than or equal to 90 mm Hg without therapy. Five were improved since DBP was less than or equal to 100 mm Hg during treatment with only one or two antihypertensive agents. There were unchanged. Renal vein renin ratio (RVRR) was greater than or equal to 1.5 either before or after furosemide in all patients who were cured or improved and less than or equal to 1.5 in 2 of 3 who were unchanged. It can be concluded that surgical treatment cured or improved 77% of the patients, and that a RVRR greater than or equal to 1.5 is a good predictor of the blood pressure lowering effect of surgery.

Factors affecting renal vein renin ratio in renal artery stenosis. Secretion of inactive renin.

All four factors which theoretically may affect the renal vein renin ratio in unilateral renal artery stenosis--increased renin secretion and diminished renal plasma flow on the stenotic side; suppressed renin secretion and renin extraction on the contralateral side--have been assessed. In a series of patients with unilateral renal artery stenosis, the renal vein ratio of active renin was more closely related to the reduction of renal plasma flow than to renin secretion rate on the affected side. On the contralateral side renin secretion was suppressed while angiotensin II was extracted. During long-term treatment with the converting enzyme inhibitor enalapril, peripheral plasma angiotensin II was lowered, while active renin concentration was markedly elevated, both in arterial plasma and in renal venous plasma of the stenotic kidney; the contralateral kidney became a net extractor of active renin. Thus, all 4 factors which theoretically affect the renal vein renin ratio can operate clinically. Both before and during enalapril, the affected kidney secreted inactive renin.

Renal vein renin in renovascular hypertension: the experience of two Italian centers.

A retrospective analysis of renal vein renin results has been done in 96 patients with renal artery stenosis and hypertension studied in two Italian centers (Sassari and Pisa) with respect to the outcome of either surgery or percutaneous transluminal angioplasty (PTA). In all patients the renal vein renin ratio and the V-A/A ratios for the affected and unaffected kidney were calculated. Each patient underwent surgery (75) of PTA (21): 71 subjects were cured, 17 improved whereas the arterial pressure did not vary after revascularisation procedure in 8 patients. In the Pisa series all 54 patients showed a lateralisation with contralateral renin suppression and 95% of them benefitted from surgery. In the Sassari series 42 patients were submitted to PTA or surgery, not only on the basis of a positive renal vein renin study but taking into account a complete clinical evaluation: 8 of them were cured or improved in spite of negative renal vein renin criteria. In the two series, the better predictive index appeared to be the suppression of the renin secretion from the contralateral kidney while the high/low renin ratio showed a consistent amount of false-positive and false-negative results. Our retrospective study demonstrates that the renal vein test in hypertensive patients with renal artery stenosis is highly predictive of the curability of the disease, particularly when contralateral suppression of renin secretion is present. On the other hand, since patients with negative renin indexes can also take benefit from surgery of PTA, the renin parameters cannot be adopted as the sole criterion in making the decision to operate.

Renovascular Hypertension: Ten Years' Experience in a Regional Centre

In a unit serving a population of three million, 60 hypertensive patients with renovascular disease were identified over a 10-year period. The presence of renovascular disease was usually suggested by intravenous urography (IVU), although this was falsely negative in 21 per cent of cases; isotope renography (IR) was normal in a similar proportion of patients (25 per cent). Eight patients were treated medically and 52 underwent surgical procedures; nephrectomy in 32, autotransplantation in 10, by pass graft in six and percutaneous transluminal angioplasty in four. Twenty-three per cent of patients were cured, 37 per cent improved and 40 per cent unchanged one year after surgery, but the response could not be accurately predicted. Clinical features were of some value in that those patients most likely to benefit from surgery were younger, had less severe hypertension of shorter duration, smoked less, had less severe retinopathy and less cardiomegaly. There was also a trend for those with better renal function and less electrocardiographic evidence of left ventricular hypertrophy to benefit from surgery. The IVU and IR did not predict response to surgery but arteriographic appearances of fibromuscular dysplasia indicated there should be a favourable response. The renal vein renin ratio, basal or stimulated, was of no prognostic value since approximately two-thirds of patients with ratios above or below the threshold value had some benefit from surgery. We conclude that the surgical treatment of renovascular hypertension is worthwhile but the number of patients suitable for surgery is small. Clinical features and the results of simple investigations provided the best guide to surgical outcome in our patients.

Renal vein renin studies in renovascular hypertension--do they really help?

Measurement of the renal vein renin ratio (RVRR) is commonly used to predict the response of blood pressure to surgery in hypertensive patients with unilateral renovascular disease. We have reviewed our experience in 37 such patients in whom renal vein renin levels were measured basally and after stimulation of renin secretion with intravenous diazoxide or tilting. Twenty-four patients were cured or improved. When a basal ratio of greater than or equal to 1.5 (diseased: normal kidney) was taken as a positive test the false positive rate was 39% and the false negative rate 71%, there being little difference in outcome between those with ratios above or below 1.5. No other threshold value of RVRR identified those responding to surgery, and acute stimulation of renin secretion did not increase the value of the test. We conclude that the RVRR is of no prognostic value in the surgical treatment of hypertension due to unilateral renovascular disease.

Renovascular hypertension in childhood: A changing perspective in management

Seventeen children with renovascular hypertension caused by intrinsic renal artery lesions received treatment during the past 10 years. At presentation nine were asymptomatic, four had headaches, and one had epistaxis; three infants had anorexia and failure to thrive. Routine intravenous pyelogram and radionuclide renal scan findings were abnormal in 29% and 31% of patients, respectively. Arteriography showed a branch artery stenosis in seven patients and a main artery lesion in 10. A renal vein renin ratio of greater than or equal to 1.5 between the affected and the contralateral kidney was obtained in 10 of 17 patients. Of 16 patients available for follow-up, 15 are normotensive after a mean follow-up of 3.7 years. Cure was achieved by partial nephrectomy and ligation of a stenosed vessel in two and nephrectomy in five (three having undergone an unsuccessful angioplasty procedure). Autotransplantation or angioplasty was curative in a further six. Transluminal balloon angioplasty was attempted in seven patients but was successful in only two with main renal artery stenoses. With preservation of renal parenchyma as the main goal, medical and surgical therapy can be individualized for each patient.