Rationale and study design for one-stop assessment of renal artery stenosis and renal microvascular perfusion with contrast-enhanced ultrasound for patients with suspected renovascular hypertension.

BACKGROUND: Renal artery stenosis (RAS) is always associated with abnormalities in renal microvascular perfusion (RMP). However, few imaging methods can simultaneously evaluate the degree of luminal stenosis and RMP. Thus, this study will aim to evaluate the feasibility of using contrast-enhanced ultrasound (CEUS) for assessing both RAS and RMP to achieve a one-stop assessment of patients with suspected renovascular hypertension. METHODS: This will be a single-center diagnostic study with a sample size of 440. Patients with chronic kidney disease (CKD) and suspected of having resistant hypertension will be eligible. Patients with Stages 1-3 CKD will undergo CEUS and computed tomography (CT) angiography (CTA). Values obtained by CEUS and CTA for diagnosing low-grade (lumen reduced by <60%) and high-grade (lumen reduced by ≥60%) RAS will be compared. Moreover, all patients will also undergo radionuclide imaging. The diagnostic value for RAS will be assessed by the receiver operating characteristic curve, including the accuracy, sensitivity, specificity, positive predictive values, negative predictive values, and area under the ROC. Pearson correlation analysis will be performed to assess the association between CEUS findings for RMP and glomerular filtration rate measured by a radionuclide imaging method. CONCLUSION: The data gathered from this study will be used to evaluate the feasibility of expanding clinical applications of CEUS for evaluation of patients with suspected renovascular hypertension. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800016252; https://www.chictr.org.cn.

Hemodynamic assessment in a child with renovascular hypertension using time-resolved three-dimensional cine phase-contrast MRI.

Renovascular hypertension (RVH) is an important cause of hypertension in children. It is essential to assess the hemodynamics of RVH lesions in detail. We herein report the case of a 9-year-old female with RVH caused by left renal artery stenosis in which the hemodynamics of the lesions were assessed with time-resolved three-dimensional cine phase-contrast MRI (3D cine PC MRI) with a vastly undersampled 3D radial projection imaging trajectory before and after percutaneous transluminal renal angioplasty (PTRA). The utility of 3D cine PC MRA for diagnosing RVH and evaluating the renal blood flow pre- and post-PTRA is presented.

Non-invasive assessment of cardiac function in a mouse model of renovascular hypertension.

Hypertension continues to be a significant cause of morbidity and mortality, underscoring the need to better understand its early effects on the myocardium. The aim of this study is to determine the feasibility of in vivo longitudinal assessment of cardiac function, particularly diastolic function, in a mouse model of renovascular hypertension. Renovascular hypertension (RVH) was induced in 129S1/SvImJ male mice (n=9). To assess left ventricular (LV) systolic and diastolic function, M-mode echocardiography, pulsed-wave Doppler echocardiography and tissue Doppler imaging were performed at baseline, 2 and 4 weeks after the induction of renal artery stenosis. Myocardial tissue was collected to assess cellular morphology, fibrosis, extracellular matrix remodeling and inflammation ex vivo. RVH led to a significant increase in systolic blood pressure after 2 and 4 weeks (baseline: 99.26±1.09 mm Hg; 2 weeks: 140.90±7.64 mm Hg; 4 weeks: 147.52±5.91 mm Hg, P<0.05), resulting in a significant decrease in LV end-diastolic volume, associated with a significant elevation in ejection fraction and preserved cardiac output. Furthermore, the animals developed an abnormal diastolic function profile, with a shortening in the E velocity deceleration time as well as increases in the E/e' and the E/A ratio. The ex vivo analysis revealed a significant increase in myocyte size and deposition of extracellular matrix. Non-invasive high-resolution ultrasonography allowed assessment of the diastolic function profile in a small animal model of renovascular hypertension.

Ventricular repolarization before and after treatment in patients with secondary hypertension due to renal-artery stenosis and primary aldosteronism.

A prolonged QT interval is a risk factor for ischemic heart disease in hypertensive subjects. Patients with renal-artery stenosis and primary aldosteronism (PA) are at increased risk of cardiovascular events. The objective of the present study was to evaluate the QT interval in patients with renovascular hypertension (RV) and PA before and after treatment. A total of 24 patients with RV and 38 with PA were studied; 89 patients with essential hypertension (EH) served as control group. Corrected QT intervals (QTcH) were measured from a 12-lead ECG. Basal QTcH was longer in RV (429±30 ms) and PA (423±23 ms) compared with EH controls (407±18 ms; P<0.001). The prevalence of QTcH >440 ms was higher in RV (29%) and PA patients (29%) compared with EH controls (4%; P<0.001). QTcH interval was evaluated after treatment in 19 RV and 15 PA patients. QTcH was reduced after renal-artery angioplasty in RV patients (419±14 ms; P=0.02), and after spironolactone or adrenalectomy in PA (403±12 ms; P=0.01). In conclusion, QT interval was prolonged in patients with RV and PA compared with controls with EH. After angioplasty of renal-artery stenosis in RV, and treatment with spironolactone or adrenalectomy in PA, the cardiovascular risk of such patients may be reduced by concomitant blood pressure lowering and QT duration shortening.

Assessment of renal artery stenosis using both resting pressures ratio and fractional flow reserve: relationship to angiography and ultrasonography.

BACKGROUND. Clinical benefit from renal artery revascularization remains controversial, probably because of inaccurate stenosis severity assessment. Objective. The aim of the study was to evaluate resting translesional pressures ratio and renal fractional flow reserve (rFFR) in relation to angiography and Doppler duplex ultrasonography in patients with at least moderate renal artery stenosis (RAS). METHODS. 44 hypertensive patients (48% of males, mean age 65 years) with at least moderate RAS were investigated. Translesional systolic pressure gradient (TSPG), resting Pd/Pa ratio (the ratio of mean distal to lesion and mean proximal pressures) and hyperemic rFFR - after intrarenal administration of papaverine - were evaluated. Quantitative angiographic analysis of stenosis severity was performed including minimal lumen diameter (MLD) and percent diameter stenosis (DS) assessment. Renal/aortic ratio (RAR), resistive index (RI) and deltaRI (side-to side difference) were obtained in Doppler-duplex ultrasonography. The predictive value of selected variables was calculated using receiver-operating characteristics curves. RESULTS. Mean Pd/Pa ratio was 0.86 ± 0.12 and decreased to 0.79 ± 0.13 after papaverine administration. Both Pd/Pa ratio and rFFR strongly correlated with TSPG (r = -0.92, p < 0.0001 and r = -0.88, p < 0.0001, respectively) and moderately with MLD (r = 0.62, p < 0.0001 and r = 0.66, p < 0.0001) and DS (r = -0.63, p < 0.0001 and r = -0.70, p < 0.0001). To identify more than 70% RAS, considered severe, the most predictive cut-off values were 0.93 for Pd/Pa ratio and 0.80 for rFFR. CONCLUSIONS. Mean Pd/Pa ratio and rFFR strongly correlated with angiographic data and in less pronounced manner with ultrasound parameters reflecting intrarenal blood flow. The best accuracy cut-off points for severe RAS predicting were 0.93 and 0.80, respectively.

Limitations of angiography for the assessment of renal artery stenosis and treatment implications.

Renovascular hypertension due to atherosclerotic renal artery stenosis is the most common cause of secondary hypertension. Percutaneous catheter-based renal artery revascularization has been increasingly utilized for the treatment of renal artery stenosis. Renal artery stenting has a high technical success rate, but the rate of improvement in hypertension is somewhat less than expected with this technique. Misinterpretation of angiographic images may play a role in these unfavorable clinical results. We present a case in which the diagnosis of severe renal artery stenosis was not apparent by angiography. Intravascular ultrasound and translesional pressure gradient measurements during arteriography can help to determine the precise severity of stenosis and may augment the clinical results of percutaneous renal artery stent placement.

Assessment of renal artery fibromuscular dysplasia: angiography, intravascular ultrasound (with virtual histology), and pressure wire measurements.

Fibromuscular dysplasia (FMD) of the renal arteries is classically associated with secondary hypertension in younger individuals, which may be treatable and even curable by percutaneous transluminal renal angioplasty. Angiography of these renal arteries often displays "beaded" luminal abnormalities. The angiographic findings, however, may not accurately reflect the severity or precise location of the intraluminal obstruction. We present a case of an older individual with longstanding hypertension and FMD, in whom the use of a coronary pressure wire and intravascular ultrasound enabled precise localization and treatment of the hemodynamically significant stenosis. Virtual histology of FMD in the renal vasculature is also reported.

Angiotensin-converting enzyme inhibitor-enhanced MR renography: repeated measures of GFR and RPF in hypertensive patients.

This study aims to assess the feasibility of a protocol to diagnose renovascular disease using dual MR renography acquisitions: before and after administration of angiotensin-converting enzyme inhibitor (ACEi). Results of our simulation study aimed at testing the reproducibility of glomerular filtration rate (GFR) and renal plasma flow demonstrate that for a fixed overall dose of 12 ml gadolinium-based contrast material (500 mmol/l), the second dose should be approximately twice as large as the first dose. A three-compartment model for analyzing the second-injection data was shown to appropriately handle the tracer residue from the first injection. The optimized protocol was applied to 18 hypertensive patients without renovascular disease, showing minimal systematic difference in GFR measurements before and after ACEi of 0.8 +/- 4.4 ml/min or 2.7 +/- 14.9%. For 10 kidneys with significant renal artery stenosis, GFR decreased significantly after ACEi (P < 0.001, T value = 3.79), and the difference in GFR measurements before and after ACEi averaged 8.3 +/- 6.9 ml/min or 26.2 +/- 43.9%. Dual-injection MRI with optimized dose distribution appears promising for ACEi renography by offering measures of GFR changes with clinically acceptable precision and accuracy.

Assessment of renal artery stenosis: side-by-side comparison of angiography and duplex ultrasound with pressure gradient measurements.

AIMS: A ratio of distal renal pressure to aortic pressure (P(d)/P(a)) <0.90 can be considered a threshold for defining a significant renal artery stenosis (RAS). The aim of this study was to compare renal angiography (QRA) and colour duplex ultrasound (CDUS) to pressure measurements in assessing RAS. METHODS AND RESULTS: In 56 RAS, percent diameter stenosis (DS(angio)), minimal luminal diameter (MLD), Doppler-derived peak systolic velocity (PSV), end-diastolic velocity (EDV), and renal-to-aortic ratio (RAR) were obtained and compared with the P(d)/P(a) measured with a 0.014" pressure wire. P(d)/P(a) correlated with angiography- and CDUS-derived parameters. The best correlation was observed with EDV (R = -0.61). To identify stenosis associated with a P(d)/P(a) < 0.90, the diagnostic accuracy of DS(angio) > 50%, MLD < 2 mm, PSV > 180 cm/s, EDV > 90 cm/s and RAR > 3.5 were, respectively, 60%, 77%, 45%, 77% and 79%, yet, with a high proportion of false positives (38%, 15%, 55%, 11% and 15%, respectively) indicating an overestimation of the severity of the RAS by both QRA and CDUS. New cut-off values for QRA- and CDUS-derived indices were proposed. CONCLUSION: Generally accepted QRA and CDUS-derived indices of RAS severity overestimate the actual severity of RAS. This 'overdiagnosis' is likely the main cause of the disappointing results of renal angioplasty for renovascular hypertension.

Assessment of renal artery stenosis severity by pressure gradient measurements.

OBJECTIVES: The purpose of this study was to define "significant" renal artery stenosis (i.e., a stenosis able to induce arterial hypertension). BACKGROUND: The degree of renal artery stenosis that justifies an attempt at revascularization is unknown. METHODS: In 15 patients, transstenotic pressure measurements were obtained before and after unilateral stenting. After stenting, graded stenoses were created in the stented segment by progressive inflation of a balloon catheter. Stenosis severity was expressed as the ratio of distal pressure (P(d)) corrected for aortic pressure (P(a)). Balloon inflation pressure was adjusted to create 6 degrees of stenosis (P(d)/P(a) from 1.0 to 0.5, each step during 10 min). Plasma renin concentration was measured at the end of each step in the aorta and in both renal veins. RESULTS: For a P(d)/P(a) ratio >0.90, no significant change in plasma renin concentration was observed. However, when P(d)/P(a) became <0.90, a significant increase in renin was observed in the renal vein of the stenotic kidney, finally reaching a maximal increase of 346 +/- 145% for P(d)/P(a) of 0.50 (p = 0.006). These values returned to baseline when the stenosis was relieved. In addition, plasma renin concentration increased significantly in the vein from the non-stenotic kidney (p = 0.02). CONCLUSIONS: In renal artery stenoses, a P(d)/P(a) ratio of 0.90 can be considered a threshold value below which the stenosis is likely responsible for an up-regulation of renin production and, thus, for renovascular hypertension. These findings might contribute to better patient selection for renal angioplasty.

Usefulness of translesional pressure gradient and pharmacological provocation for the assessment of intermediate renal artery disease.

OBJECTIVE: We sought to determine the hemodynamic significance of intermediate RAS by measuring translesional systolic pressure gradients (TSPG), using a pressure-sensing guidewire at baseline and after acetylcholine (ACh) induced hyperemia, following selective renal artery angiography. BACKGROUND: Renal artery stenosis (RAS) is a cause of reversible hypertension and nephropathy. Stenting effectively relieves RAS, however improvement in blood pressure control or renal function is variable and unpredictable. Hemodynamic significance is usually present with RAS when diameter stenosis is >75%, but is less predictable in intermediate (30%-75%) RAS. METHODS: Twenty-two patients (26 renal arteries) with uncontrolled hypertension underwent invasive hemodynamic assessment because of intermediate RAS, defined as radiocontrast angiographic diameter stenosis (DS) between 30% and 75% (quantitative DS was measured prospectively). Translesional pressure gradients were measured using a 0.014" pressure-sensing wire. Hyperemia was induced by administration of intrarenal ACh. RESULTS: Visual and measured angiographic lesion severity did not correlate with TSPG either at baseline (visual DS, R(2) = 0.091, P = 0.13; measured DS, R(2) = 0.124, P = 0.07) or with hyperemia (visual DS, R(2) = 0.057, P = 0.24; measured DS, R(2) = 0.101, P = 0.12). Baseline and maximal hyperemic gradient did correlate (R(2) = 0.567; P < 0.05). Pharmacological provocation produced a significant increase in TSPG (mean; baseline, 18 +/- 21 vs. hyperemia, 34 +/- 41 mm Hg; P < 0.05). A hemodynamically significant lesion (TSPG > 20 mm Hg) was found in 14/26 (54%) arteries (13 patients); 13 (60%) patients subsequently underwent renal artery stenting for hemodynamically significant RAS. At follow-up (at least 30 days), there was a significant decrease in systolic blood pressure (mean; 167 +/- 24 vs. 134 +/- 19 mm Hg; P < 0.001). CONCLUSIONS: Intrarenal administration of ACh induces hyperemia and can be used to unmask resistive renal artery lesions. Gradient measurement and induced hyperemia may be warranted in the invasive assessment of intermediate renal artery stenoses, rather than relying on stenosis severity alone. Further study is needed to determine whether translesional pressure gradients and pharmacological provocation predict clinical benefit after renal artery stenting.

[Assessment of feasibility of using indices for heart rate variability in the differential diagnosis of renal parenchymal arterial hypertension]. / Otsinka mozhlyvosti vykorystannia pokaznykiv variabel'nosti rytmu sertsia v diferentsial'nii diahnostytsi hipertonichnoï khvoroby ta renoparenkhimnoï arterial'noï hipertenziï.

24-hr monitoring of the heart rate variability (HRV) was instituted in 72 patients with essential hypertension (EH) and 68 patients with chronic glomerulonephritis (CGN) to establish differential-diagnostic criteria for EH and CGN. Clear-cut differences have been ascertained in changes in HRV in EH and CGN as evidenced by the results obtained.

Functional testing: ACEI renography.

Angiotensin-converting enzyme inhibition (ACEI) renography is the only imaging examination that tests directly for the presence of renovascular hypertension (RVH); other imaging examinations test only for the presence of renal artery stenosis (RAS). Consensus panels have recommended that ACEI renograms be interpreted as low, intermediate, or high probability for RVH. ACEI renography is highly accurate in patients with normal renal function and suspected RVH. In this patient population, the sensitivity and specificity of ACEI renography for RAS are approximately 90%; as an initial approach, angiography is not cost effective. Data from 10 studies evaluating cure or improvement in blood pressure in 291 patients undergoing revascularization showed the mean positive predictive value of ACEI renography to be 92%. When azotemic patients present with suspected RVH, as many as 50% of patients may have an intermediate probability ACEI renogram and the sensitivity of detecting RVH falls to approximately 80% even when intermediate and high probability tests are combined.

Noninvasive assessment of renal artery stenosis: current imaging protocols and future directions in ultrasonography.

Doppler ultrasound is one of many modalities that have been evaluated for the detection of renal artery stenosis. The lack of standardization in examination protocols and diagnostic criteria, as well as the wide differences in reported accuracy among different laboratories have, however, prevented universal acceptance of this technique as a reliable screening test for renal artery stenosis. The recent introduction of ultrasound contrast agents has substantially expanded the potential of color Doppler ultrasound. The use of microbubble echoenhancers in combination with harmonic Doppler imaging has been shown to improve diagnostic confidence by improving the operator's ability to visualize the renal arteries, and to significantly reduce the number of equivocal examinations. Moreover, contrast-enhanced Doppler ultrasound can provide functional information through analysis of renal time-intensity wash in/wash out curves. State-of-the-art contrast-enhanced Doppler ultrasound seems to have the potential to become a useful screening test for patients at risk from renovascular hypertension.

Renovascular disease in blacks: prevalence and result of operative management. Consortium of Southeastern Hypertension Control.

Hypertension in blacks differs in a quantitative sense from hypertension in whites; it occurs in blacks with greater frequency and severity and at a younger age when compared with whites. In addition, elevated blood pressure at any level is associated with increased cardiovascular morbidity and mortality in black patients. Several mechanisms have been suggested to account for this form of hypertension, implying that hypertension in black patients is intrinsically different from that in whites. Although these mechanisms remain unproven, it has generally been accepted that correctable renovascular disease and renovascular hypertension (RVH) occur infrequently in blacks; the authors, however, will review preliminary population-based data which suggest that the presence of renal artery disease is not determined by race or ethnicity. In addition, the prevalence of renovascular disease in a large group of consecutive hypertensive subjects will be presented. Finally, the blood pressure and renal function response after surgical renal artery repair in blacks will be compared with whites treated at the authors' institution. Taken collectively, these data and clinical experience support the search for and treatment of renal artery disease in properly selected hypertensive blacks.

Angiotensin II release from rabbit intrarenal arteries: a critical assessment.

A microdissected rabbit intrarenal arterial network (IAN) perfused at constant flow with Krebs-bicarbonate solution was employed to determine whether this network, which has a high renin content, releases angiotensin II (AII) either spontaneously or during beta-adrenergic stimulation. Six groups of experiments were conducted in which samples of the vascular effluent were collected on Sep Paks before and during intraluminal infusion of L-isoproterenol (1.1 to 11 microg/min). Separation and assay of AII were by combined HPLC and RIA. For an accurate estimation of the quantity of AII released, it was important to subtract the Krebs and isoproterenol blanks, 19 and 23 pg, respectively, from the basal and isoproterenol-induced AII release. In Groups 1 and 2, AII release was determined before and during isoproterenol infusion (5.5 microg/min). Basal release of AII was insignificant in Groups 1 to 5. In Group 1, infusion of isoproterenol caused AII release from IAN before and after removal of glomeruli (glomerulectomy), but with variability between experiments. An even higher infusion rate of isoproterenol (11 microg/min) in Group 2 caused no significant AII release. Similarly, in Group 3, in which a longer collection period was imposed, isoproterenol (5.5 microg/min) failed to cause significant AII release. In Groups 4 and 5, Goldblatt hypertensive and salt-restricted rabbits, respectively, isoproterenol caused AII release, but the effect was statistically significant only in Group 4. Supplying renin substrate in Group 6 caused only a small spontaneous AII release. We conclude that under these conditions of complete isolation from the intact circulation, the IAN despite a high renin content, releases little locally generated AII.

Assessment of renal resistance index after captopril test by Doppler in essential and renovascular hypertension.

Ultrasonic duplex scanning has been validated as a noninvasive method to evaluate the kidney arteries and hemodynamic characteristics of renal blood flow in patients with renal artery stenosis. The purpose of our study was to assess the changes in renal vascular impedance in 22 patients with renovascular hypertension, as compared with 45 essential hypertensives and 15 normotensives, by using the Doppler parameter resistance index (RI) before and after a captopril oral test. After the captopril test the delta RI decreased significantly in the stenotic artery (P < 0.05). Univariate analysis showed that PRA values after captopril correlated inversely with the changes of RI only in the stenotic artery (P < 0.05). Thus, our findings suggest that the application of the captopril test to renal echo-Doppler may represent a feasible, noninvasive, and inexpensively useful tool in the screening studies aimed at diagnosing renovascular hypertension.

Estenosis de arteria renal: características angiográficas en 210 casos / Stenosis or the renal artery: angiographic characteristics in 210 cases

Se presentan 210 casos de enfermos portadores de lesiones estenosantes de arteria renal, estudiados en el Departamento de Angiología del Hospital de Especialidades del Centro Médico Nacional, durante un periodo de 29 años (1963-1992), documentados angiográficamente. La indicación del estudio fue la hipertensión arterial severa y las manifestaciones de insuficiencia arterial crónica de miembros inferiores, así como enfermedad aortoiliaca. De estos casos, 92 correspondieron al sexo femenino y 118 al masculino. La edad varió de 9 a 76 años. En cuanto a la localización de la lesión de la arteria renal, en 58 casos, fue en el ostium y/o en el tercio proximal y, en 50 de ellos, la lesión fue bilateral y estaba asociada a otras lesiones del territorio aórtico y correspondieron a mujeres jóvenes los cuales se consideraron de etiología inflamatoria (artritis). En otros 75 casos, la lesión se localizó en el tercio medio con estenosis única o múltiple, y extensión al tercio distal, en la mayoría fue unilateral y solamente en 15 casos, la lesión estaba presente en forma bilateral. Estos casos predominaron en el sexo masculino, entre la tercera y cuarta década de la vida y correspondieron a discplasia fibromuscular. En cambio en los 65 casos restantes, la lesión estenosante se presentó en personas de la sexta década de la vida predominando también en el sexo masculino, donde la angiografía mostró lesiones muy importantes del eje aortoiliaco y se consideraron de origen ateroscleroso. En 12 casos, la estenosis estuvo en relación a otras patologías. Algunos de estos casos fueron sometidos a procedimientos quirúrgicos, del tipo de las derivaciones arteriales, angioplastia transluminal y en los últimos años al autotrasplante renal (descenso renal), con excelentes resultados

[Color-Doppler ultrasonography and hypertension. Functional assessment of the renal region]. / Eco color Doppler e malattia ipertensiva. Valutazione funzionale del distretto renale.

Color-Doppler US can be used for the morphofunctional assessment of most arterial districts. In hypertension, color-Doppler US can be used to study the renal arteries for both the diagnosis of renovascular hypertension and better physiopathologic assessment of renal arterial blood flow in essential hypertension. To this purpose, we studied renal flow characteristics with the resistive index in both basal conditions and after pharmacologic stimulation with angiotensin-converting enzyme inhibitors. The resistive index was seen to rise in parallel with hypertension severity, as measured by mean arterial pressure; the change was statistically significant (p < 0.05). Values rose step by step from 57.4 (+/- 4.96) in the right renal artery and from 56.6 (+/- 4.18) in the left one in controls, up to 62.2 (+/- 6.6) in the right and 62.3 (+/- 7) in the left renal arteries of severe hypertensives. After pharmacologic stimulation in controls and in mild hypertensives, resistive index values rose significantly (+2.32 +/- 2.1 and +3.5 +/- 5.2, respectively), while in more advanced stages of the disease this index remained unvaried from a statistical point of view (+0.5 +/- 1.7 in moderate and -0.2 +/- 2.1 in severe hypertensives). These data can be explained by reduced capability of renal blood flow autoregulation, as a consequence of a defined vascular damage. In the follow-up of more severe stages of the disease, although pharmacologic treatment had been optimized and mean arterial pressure values reduced (109.08 vs. 118.25 mmHg), even after a prolonged therapeutic wash-out, an abnormal RI response persisted in controls (-1.79 +/- 2.62 vs. -0.94 +/- 1.64), due to persistent arteriolar damage. To date, it is still to be defined if our studies can be applied not only to populations but also to single patients.