Branch renal artery repair with cold perfusion protection.

PURPOSE: This retrospective review describes the use and clinical outcome of cold perfusion protection during branch renal artery (RA) repair in 77 consecutive patients. METHODS: From July 1987 through November 2006, 874 patients had open operative RA repair to 1312 kidneys. Seventy-seven patients (62 women, 15 men; mean age, 44 +/- 17 years) had branch RA reconstruction using ex vivo or in situ cold perfusion protection for 78 kidneys. Demographic data and surgical technique were examined. Blood pressure response and renal function were estimated. Patency of repair was determined by angiography and renal duplex ultrasound (RDUS) imaging. Primary RA patency was estimated by life-table methods. RESULTS: Seventy-eight RAs were repaired using ex vivo (49 kidneys) or in situ (29 kidneys) cold perfusion protection. Bilateral RA repair was performed in eight patients, with 13 repairs to solitary kidneys. RA disease included aneurysm (RAA) in 50, fibromuscular dysplasia (FMD) in 37, atherosclerosis in 5, and arteritis in 2; 16 patients had both FMD and RAA. Hypertension was present in 93.5% (mean blood pressure, 184 +/- 35/107 +/- 19 mm Hg; mean of 1.9 +/- 1.1 drugs). RA repair included bypass using saphenous vein in 69, hypogastric artery in 3, polytetrafluoroethylene (PTFE) in 2, composite vein/PTFE in 2, cephalic vein in 1, or aneurysmorrhaphy in 1. The eight bilateral RA repairs were staged. One patient required bilateral cold perfusion protection. One planned nephrectomy was performed at the time of contralateral ex vivo reconstruction. No primary nephrectomies were required for intended reconstruction. Each RA reconstruction required branch dissection and reconstruction (mean of 2.8 +/- 1.6 branches were repaired). Mean cold ischemia time was 125 +/- 40 minutes. Each kidney was reconstructed in an orthotopic fashion. Five early failures of repair required three nephrectomies and one operative revision. Based on postoperative angiography or RDUS, or both, primary patency of RA repair at 12 months was 85% +/- 5%; assisted primary patency was 93% +/- 4%. Among patients with preoperative hypertension, 15% were cured, 65% were improved, and 20% were considered failed. Early renal function was improved in 35%, unchanged in 48%, and worse in 17%. Four patients had perioperative acute tubular necrosis. No patient progressed to dialysis-dependence. CONCLUSION: Both ex vivo and in situ cold perfusion protection extend the safe renal ischemia time for complex branch RA repair and avoid the need for nephrectomy.

Renovascular disease in children and adolescents.

PURPOSE: This retrospective review describes the surgical management of renovascular disease in 25 consecutive children and adolescents with severe hypertension. METHODS: Patients 95 th percentile systolic or diastolic pressure adjusted for gender, age, and height). RA repair comprised 25 bypasses (73%) consisting of 28% saphenous vein, 60% hypogastric artery, and 12% polytetrafluoroethylene; 2 patch angioplasties (6%), and 7 reimplantations (21%). Branch RA exposure was required in 28 kidneys (88%), and branch reconstruction was required in 61%. Warm in situ repair was used in 53%, in situ cold perfusion in 24%, and ex vivo cold perfusion in 23%. Of six bilateral RA repairs, one was staged and two patients are awaiting a staged repair. Combined aortic reconstruction was required in three patients. No unplanned nephrectomy was performed. There were no perioperative deaths. Hypertension was cured in 36%, improved in 56%, and failed in 8% at mean follow-up of 46.4 +/- 7.8 months. The mean calculated glomerular filtration rate increased from 82.0 mL/min/1.73 m 2 preoperatively to 98.2 mL/min/1.73 m 2 postoperatively. The postoperative patency of 30 RA reconstructions was evaluated by angiography, RDS scanning, or both. At mean follow-up of 32.8 months (median, 21.2 months), primary RA patency was 91%. No failures were observed after 2 months follow-up. Estimated survival was 100% at 60 months, with one death 9 years after surgery. CONCLUSIONS: Renovascular hypertension in children and adolescents was caused by a heterogeneous group of lesions. All patients had RA repair, with arterial autografts in most of the RA bypasses. Cold perfusion preservation was used in half of the complex branch RA repairs. These strategies provided 91% primary patency at mean follow-up of 32.8 months, with beneficial blood pressure response in 92%. Surgical repair of clinically significant renovascular disease in children and adolescents is supported by these results.

Renovascular disease and the risk of adverse coronary events in the elderly: a prospective, population-based study.

BACKGROUND: Renovascular disease is a cause of secondary hypertension and renal insufficiency and is suspected to contribute to morbidity and mortality of coronary heart disease. This investigation prospectively examined associations between renovascular disease and adverse coronary events among a population-based sample of elderly Americans. METHODS: The Cardiovascular Health Study is a prospective, multicenter cohort study of cardiovascular disease risk factors, morbidity, and mortality among Americans older than 65 years. Renal duplex sonography was performed on 870 individuals between January 1995 and February 1997. Renovascular disease was defined as any focal peak systolic velocity of 1.8 m/s or greater (renal artery stenosis) or the absence of a Doppler-shifted signal from an imaged artery (renal artery occlusion). Adverse coronary events were defined as hospitalized angina, fatal or nonfatal myocardial infarction, and coronary revascularization. RESULTS: During a mean follow-up of 14 months, 68 participants experienced incident or recurrent adverse coronary events. The presence of renovascular disease demonstrated a significant relationship with adverse coronary events (hazard ratio, 1.96; 95% confidence interval, 1.00-3.83; P = .05) that remained after controlling for the effects of coexisting atherosclerotic risk factors and prevalent cardiovascular disease. The relationship between renovascular disease and adverse coronary events was not dependent on the effects of increased blood pressure. CONCLUSIONS: The presence of renovascular disease was associated with an increase in the risk of adverse coronary events in this sample. The increment in risk was not dependent on the effects of associated atherosclerotic risk factors, other prevalent cardiovascular disease, or increased blood pressure.

Surgical management of renal artery aneurysms.

PURPOSE: This retrospective review describes the surgical management and clinical outcome for renal artery aneurysms (RAAs) in 62 consecutive patients. METHODS: From January 1987 through July 2003, 804 patients had operative renal artery (RA) repair involving 1206 kidneys at our center. A subgroup of 62 patients (42 women, 20 men; mean age 46 +/- 18 years) received repair of 72 RAAs. Demographic data, comorbidity, and surgical technique were examined. Blood pressure and renal function response were determined. Patency of repair was evaluated by renal duplex sonography. Primary patency and patient survival were estimated by life-table methods. Tests of association were performed using chi(2) and the Student t tests. RESULTS: Seventy-two RAs were repaired for RAA with a mean diameter of 2.6 cm (range, 1.3 to 5.5 cm). Bilateral RAAs were present in 21 patients. Associated conditions included fibromuscular dysplasia, atherosclerosis, and arteritis in 54%, 35%, and 7%, respectively. Hypertension was present in 89% (mean blood pressure, 171 +/- 35/95 +/- 19 mm Hg; mean medications, 2.2 +/- 1.2 drugs) and renal insufficiency was present in 8% (mean serum creatinine, 1.9 +/- 0.6 mg/dL). RAA repair included bypass (67%), aneurysmorrhaphy (15%), or a combination (17%). One planned nephrectomy (1%) was performed for un-reconstructable disease. Branch RA reconstruction in 78% used ex vivo cold perfusion in 50%, in situ cold perfusion in 29%, and warm in situ repair in 21%. Of 9 bilateral RAA repairs, 7 (78%) were staged and 2 (22%) were simultaneous. Combined aortic reconstruction was required in 6 (10%) patients. Perioperative death occurred in 1 patient (1.6%), and significant morbidity was observed in 8 patients (12%). Hypertension was considered improved in 54%, cured in 21%, and unchanged in 25% at mean follow-up of 48 months (range, 1-156 months). Among patients with renal insufficiency, renal function was improved in 3 (60%), unchanged in 1 (20%), and declined in 1 (20%). Follow-up patency (mean, 33 months; range, 1-118 months) was determined for 64 (91%) RA reconstructions. Product-limit estimate of primary patency at 48 months was 96%. Product-limit estimate of survival was 91% at 120 months. CONCLUSION: RAAs were repaired with low morbidity and mortality. Complex branch RAA repair using cold perfusion preservation and ex vivo techniques resulted in no unplanned nephrectomy, with an estimated primary patency of 96% at 48 months. Beneficial blood pressure response was observed in the majority of hypertensive patients. These results support selective surgical management of RAA.

Associations between renovascular disease and prevalent cardiovascular disease in the elderly: a population-based study.

Atherosclerotic renovascular disease (RVD) is a suspected contributor to the morbidity and mortality of cardiovascular disease (CVD) through its potential effects on blood pressure and excretory renal function as well as through its associations with other forms of CVD. However, population-based data regarding the associations between the presence of RVD and prevalent CVD are lacking. The Cardiovascular Health Study (CHS) is a prospective, multicenter cohort study of CVD among elderly Americans. As part of an ancillary study, participants in the Forsyth County, North Carolina, cohort of the CHS were invited to undergo renal duplex sonography (RDS) to establish the presence or absence of RVD (defined as any focal peak systolic velocity >/= 1.8 m/second or the absence of a Doppler-shifted signal from an imaged artery). Demographic, risk factor, and prevalent CVD data were obtained from the CHS coordinating center and matched with ancillary study participants. Eight hundred thirty-four CHS participants (including 525 women [63%], 309 men [37%], 194 African-Americans [23%], and 635 Caucasians [76%]) with a mean age of 77.2 +/-4.9 years underwent RDS examination. RVD was present in 57 participants (6.8%). Overall, clinical and/or subclinical manifestations of CVD were present in 603 participants (72.3%) at the time of RDS. Participants with RVD demonstrated a significantly greater prevalence of angina (p = 0.002), previous myocardial infarction (p < 0.001), >/= 25% diameter-reducing internal carotid artery stenosis (p = 0.010), increased carotid intimal medial thickness (p = 0.003), and major electrocardiographic abnormalities (p = 0.013). Following adjustment for demographics and cardiovascular risk factors, the presence of RVD demonstrated a significant and independent association with prevalent coronary artery disease but not with prevalent cerebrovascular or lower extremity vascular disease. These results suggest important population-based associations between RVD and both clinical and subclinical manifestations of CVD, especially coronary artery disease.

Relationships between renovascular disease, blood pressure, and renal function in the elderly: a population-based study.

BACKGROUND: The purpose of this study is to examine the associations between renovascular disease (RVD) and cross-sectional measures of blood pressure and renal function among participants in the Cardiovascular Health Study (CHS). METHODS: The CHS is a prospective cohort study of cardiovascular disease among elderly Americans. As part of an ancillary study, participants in the Forsyth County, NC, cohort of the CHS were invited to undergo renal duplex sonography (RDS) to define the presence or absence of RVD (defined as any focal peak systolic velocity > or = 1.8 milliseconds or the absence of a Doppler shifted signal from an imaged artery). Demographic, risk factor, blood pressure, and serum creatinine data were obtained at the time of RDS and from the annual CHS examination. RESULTS: Eight hundred thirty-four CHS participants (including 525 women [63%], 309 men [37%], 194 African Americans [23%], and 635 Caucasians [76%]) with a mean age of 77.2 +/- 4.9 years underwent successful RDS. RVD was present in 57 participants (6.8%). When examined according to the presence or absence of RVD, significant univariate differences were observed in the prevalence of clinical hypertension (72% versus 50%; P = 0.001), systolic blood pressure (145 versus 136 mm Hg; P = 0.001), and renal insufficiency (16% versus 8%; P = 0.041). Multivariate analyses showed significant and independent associations for the presence of RVD with increasing systolic blood pressure (P = 0.034), clinical hypertension (odds ratio, 2.68; 95% confidence interval, 1.44 to 4.99; P = 0.002), increasing serum creatinine level, and renal insufficiency (odds ratio, 2.21; 95% confidence interval, 1.02 to 4.79; P = 0.043). A significant interaction was observed between the presence of RVD and increasing systolic blood pressure in association with increasing serum creatinine levels (P = 0.041). CONCLUSION: These results suggest important population-based associations between RVD and cross-sectional measures of blood pressure and renal function. Furthermore, the observed relationship between RVD and increasing serum creatinine level was influenced strongly by increasing blood pressure.

Prevalence of renovascular disease in the elderly: a population-based study.

PURPOSE: The purpose of this investigation was to estimate the population-based prevalence of renovascular disease (RVD), defined as > or = 60% diameter-reducing renal artery stenosis or occlusion, and to define its associations with age, gender, race, and other potential risk factors among participants in the Cardiovascular Health Study (CHS). METHODS: The CHS is a multicenter, longitudinal cohort study of cardiovascular disease risk factors, morbidity, and mortality among free-living adults of more than 65 years of age. As part of an ancillary investigation, participants in the Forsyth County cohort of the CHS were invited to undergo renal duplex sonography (RDS) to define the presence or absence of RVD. RVD was defined as stenosis with a focal renal artery peak systolic velocity exceeding 1.8 m/s in the main renal artery and defined as occlusion when an imaged renal artery lacked a Doppler signal. Demographic and atherosclerotic risk factor data were gathered as part of the baseline CHS examination. Univariable tests of association were performed with chi(2) and Student t tests and logistic regression analysis. Multivariate associations were examined with logistic regression analysis. RESULTS: Eight hundred seventy CHS participants underwent RDS. Of these examinations, 834 (96%) were technically adequate to define the presence or absence of RVD. The RDS study cohort had a mean age of 77.2 +/- 4.9 years and consisted of 63% women and 37% men. Participant race was 76% white and 23% African American. The overall prevalence rate of RVD was 6.8%. Among the 57 patients with RVD, 50 (88%) had unilateral disease and seven (12%) had bilateral disease. Seven cases were seen of renal artery occlusion, including one case with contralateral renal artery stenosis. The mean ages of patients with and without RVD were 78.7 +/- 5.7 years and 77.1 +/- 4.9 years (P =.018). RVD was present in 5.5% of women and 9.1% of men (P =.053). RVD was present in 6.9% of white participants and 6.7% of African American participants (P =.933). Multivariate analysis revealed increasing participant age (P =.028; odds ratio, 1.34; 95% CI, 1.03, 1.73), high-density lipoprotein cholesterol levels of less than 40 mg/dL (P =.003; odds ratio, 2.63; 95% CI, 1.40, 4.93), and increasing systolic blood pressure (P =.007; odds ratio, 1.44; 95% CI, 1.10, 1.87) to be significantly and independently associated with the presence of RVD. CONCLUSION: This investigation provides the first population-based estimate of the prevalence of RVD among free-living, elderly black and white Americans. RVD was present in 6.8% of the study cohort. RVD showed no association with ethnicity. However, its presence was significantly and independently associated with increasing age, low high-density lipoprotein cholesterol levels, and increasing systolic blood pressure.

Vasopeptidase inhibition and Ang-(1-7) in the spontaneously hypertensive rat.

BACKGROUND: Omapatrilat, a new vasopeptidase inhibitor, inhibits the activity of angiotensin-converting enzyme (ACE) and neutral endopeptidase 24.11 (NEP). Because these two enzymes participate in the degradation of the vasodilator and natriuretic peptide, angiotensin-(1-7) [Ang-(1-7)], we assessed whether omapatrilat treatment is associated with changes in the plasma and urinary excretion rates of the angiotensins. METHODS: We investigated in spontaneously hypertensive rats (SHR) (0.24 kg body weight) the effect of omapatrilat on plasma and urinary concentrations of angiotensin (Ang) I, Ang II and Ang-(1-7) during 17 days of administration of either the drug (N = 15, 100 micromol/kg/day) or vehicle (N = 14) in the drinking water. Hemodynamic and renal excretory function studies were associated with histological examination of the expression of Ang-(1-7) in the kidneys of both vehicle and omapatrilat-treated SHRs. RESULTS: Omapatrilat induced a sustained lowering of systolic blood pressure (-68 mm Hg) without changes in cardiac rate. The mild positive water balance produced by omapatrilat did not cause natriuresis or kaliuresis, although it was associated with a significant decrease in urine osmolality. Blood pressure normalization was accompanied by increases in plasma Ang I (2969%), Ang II (57%), and Ang-(1-7) (163%) levels, paralleling pronounced increases in urinary excretion rates of Ang I and Ang-(1-7) but not Ang II. Detection of Ang-(1-7) immunostaining in the kidneys of five other SHR exposed either to vehicle (N = 3) or omapatrilat (N = 2) ascertained the source of the Ang-(1-7) found in the urine. Intense Ang-(1-7) staining, more pronounced in omapatrilat-treated SHR, was found in renal proximal tubules throughout the outer and inner regions of the renal cortex and the thick ascending loop of Henle, whereas no Ang-(1-7)-positive immunostaining was found in glomeruli and distal tubules. CONCLUSIONS: Omapatrilat antihypertensive effects caused significant activation of the renin-angiotensin system associated with increases in urinary excretion rates of Ang I and Ang-(1-7). Combined studies of Ang-(1-7) metabolism in urine and immunohistochemical studies in the kidney revealed the existence of an intrarenal source, which may account for the pronounced increase in the excretion rate of the vasodilator heptapeptide. These findings provide further evidence for a contribution of Ang-(1-7) to the regulation of renal function and blood pressure.

Surgical management of atherosclerotic renovascular disease.

OBJECTIVE: This review describes the clinical outcome of surgical intervention for atherosclerotic renovascular disease in 500 consecutive patients with hypertension. METHODS: From January 1987 to December 1999, 626 patients underwent operative renal artery (RA) repair at our center. A subgroup of 500 patients (254 women and 246 men; mean age, 65 plus minus 9 years) with hypertension (mean blood pressure, 200 plus minus 35/104 plus minus 21 mm Hg) and atherosclerotic RA disease forms the basis of this report. Hypertension response was determined from preoperative and postoperative blood pressure measurements and medication requirements. Change in renal function was determined with estimated glomerular filtration rates (EGFRs) calculated from serum creatinine levels. Proportional hazards regression models were used for the examination of associations between selected preoperative parameters, blood pressure and renal function response, and eventual dialysis-dependence or death. RESULTS: Two hundred three patients underwent unilateral RA procedures, 297 underwent bilateral RA procedures, and 205 patients underwent combined renal and aortic reconstruction. After surgery, there were 23 deaths (4.6%) in the hospital or within 30 days of surgery. Significant and independent predictors of perioperative death included advanced age (P <.0001; hazard ratio [HR], 3.23; 95% confidence interval [CI], 1.85 to 5.70) and clinical congestive heart failure (P =.013; HR, 3.05; 95% CI, 1.26 to 7.34). Among the patients who survived surgery, hypertension was considered cured in 12%, improved in 73%, and unchanged in 15%. For the entire group, renal function increased significantly after operation (preoperative versus postoperative mean EGFR, 41.1 plus minus 23.9 versus 48.2 plus minus 25.5 mL/min/m(2); P <.0001). For individual patients, with a 20% or more change in EGFR considered significant, 43% had improved renal function (including 28 patients who were removed from dialysis-dependence), 47% had unchanged function, and 10% had worsened function. Preoperative renal insufficiency (P <.001; HR, 2.35; 95% CI, 1.86 to 2.98), diabetes mellitus (P =.007; HR, 2.14; 95% CI, 1.15 to 3.97), prior stroke (P =.042; HR, 1.50; 95% CI, 1.02 to 2.22), and severe aortic occlusive disease (P =.003; HR, 1.69; 95% CI, 1.19 to 2.31) showed significant and independent associations with death or dialysis during the follow-up examination period. After operation, blood pressure cured (P =.014; HR, 0.52; 95% CI, 0.30 to 0.88) and improved renal function (P =.011; HR, 0.40; 95% CI, 0.19 to 0.81) showed significant and independent associations with improved dialysis-free survival rate. All categories of function response and time to death or dialysis showed significant interactions with preoperative EGFR. CONCLUSION: The surgical correction of atherosclerotic renovascular disease resulted in blood pressure benefit and retrieval of renal function in selected patients with hypertension. The patients with cured hypertension or improved EGFR after operation showed increased dialysis-free survival as compared with other patients who underwent surgery.