Misra, Sanjay

Background— Atherosclerotic renal artery stenosis (ARAS) is known to reduce renal blood flow, glomerular filtration rate (GFR) and amplify kidney hypoxia, but the relationships between these factors and tubulointerstitial injury in the poststenotic kidney are poorly understood. The purpose of this study was to examine the effect of renal revascularization in ARAS on renal tissue hypoxia and renal injury. Methods and Results— Inpatient studies were performed in patients with ARAS (n=17; >60% occlusion) before and 3 months after stent revascularization, or in patients with essential hypertension (n=32), during fixed Na + intake and angiotensin converting enzyme/angiotensin receptors blockers Rx. Single kidney cortical, medullary perfusion, and renal blood flow were measured using multidetector computed tomography, and GFR by iothalamate clearance. Tissue deoxyhemoglobin levels ( R 2 *) were measured by blood oxygen level–dependent MRI at 3T, as was fractional kidney hypoxia (percentage of axial area with R 2 *>30/s). In addition, we measured renal vein levels of neutrophil gelatinase–associated lipocalin, monocyte chemoattractant protein-1, and tumor necrosis factor-α. Pre-stent single kidney renal blood flow, perfusion, and GFR were reduced in the poststenotic kidney. Renal vein neutrophil gelatinase–associated lipocalin, tumor necrosis factor-α, monocyte chemoattractant protein-1, and fractional hypoxia were higher in untreated ARAS than in essential hypertension. After stent revascularization, fractional hypoxia fell ( P <0.002) with increased cortical perfusion and blood flow, whereas GFR and neutrophil gelatinase–associated lipocalin, monocyte chemoattractant protein-1, and tumor necrosis factor-α remained unchanged. Conclusions— These data demonstrate that despite reversal of renal hypoxia and partial restoration of renal blood flow after revascularization, inflammatory cytokines and injury biomarkers remained elevated and GFR failed to recover in ARAS. Restoration of vessel patency alone failed to reverse tubulointerstitial damage and partly explains the limited clinical benefit of renal stenting. These results identify potential therapeutic targets for recovery of kidney function in renovascular disease.

Purpose: To determine the factors that affect mean absorbed dose and fluoroscopic times during renal artery stent placement. Materials and Methods: After institutional review board approval, the HI-IQ database was queried for patients undergoing renal artery stent placement only from January 2007 to June 2010. Procedures that were performed as part of other procedures such as iliac artery stents were excluded. The HI-IQ data included fluoroscopy time ( f) and radiation dose (mGy). Demographic, medical history, procedural details, and advanced preprocedural renal artery stent imaging were obtained. Variables (number of stents, average body mass index , number of stents placed per year and number of years’ service of an interventional physician, pre-procedural imaging, and use of embolic protection device) were analyzed using a t test after log transformation and testing for variance with an F test. Results: A total of 134 patients (75 males, 70.6 ± 10.5 years old) underwent the placement of 177 renal artery stents (unilateral [n = 95], average stent per patient = 1.3). Mean fluoroscopy time was 15.6 minutes and mean absorbed dose to the patient was 1729 mGy. The average fluoroscopic time and absorbed dose was significantly higher with bilateral stent placement compared to unilateral placement (13.8 vs 19.7 minutes, P = .002; 1803 vs 2380 mGy, P = .03). The average fluoroscopic time was significantly higher in patients undergoing abdominal aortogram prior to renal artery selection and stent placement. Conclusion: The placement of more than 1 stent with an abdominal angiogram prior to renal artery stent placement results in increased fluoroscopic time and mean absorbed dose.

Purpose: To compare the clinical outcomes in patients with chronic renal insufficiency (CRI) and renal artery stenosis (RAS) following renal artery (RA) stent placement with and without embolic protection device (EPD) usage. Materials and Methods: Eighteen patients who had RA stent placement with EPD were matched to control patients (RA stent only). Blood pressure, number of hypertensive medications, and estimated glomerular filtration rate (eGFR) at 3 months before the procedure and after 12 months were determined. An increase of ≥ 20% in eGFR at 12 months from baseline was defined as “improvement,” decrease of ≥20% as “deterioration,” and an eGFR change between those values as “stabilization” at 12 months. Results: At 12 months, stage 4 patients treated with EPD had significantly higher eGFR than controls ( P = .01). There was no statistical difference in blood pressure outcomes between the 2 groups. Conclusions: Patients with stage 4 CRI did significantly better with EPD than those treated without it.

Atherosclerotic renal artery stenosis has a range of manifestations depending on the severity of vascular occlusion. The aim of this study was to examine whether exceeding the limits of adaptation to reduced blood flow ultimately leads to tissue hypoxia, as determined by blood oxygen level dependent MRI. We compared 3 groups of hypertensive patients, 24 with essential hypertension, 13 with “moderate” (Doppler velocities 200–384 cm/s), and 17 with “severe” atherosclerotic renal artery stenosis (ARAS; velocities >384 cm/s and loss of functional renal tissue). Cortical and medullary blood flows and volumes were determined by multidetector computed tomography. Poststenotic kidney size and blood flow were reduced with ARAS, and tissue perfusion fell in the most severe lesions. Tissue medullary deoxyhemoglobin, as reflected by R2* values, was higher as compared with the cortex for all of the groups and did not differ between subjects with renal artery lesions and essential hypertension. By contrast, cortical R2* levels were elevated for severe ARAS (21.6±9.4 per second) as compared with either essential hypertension (17.8±2.3 per second; P <0.01) or moderate ARAS (15.7±2.1 per second; P <0.01). Changes in medullary R2* after furosemide administration tended to be blunted in severe ARAS as compared with unaffected (contralateral) kidneys. These results demonstrate that severe vascular occlusion overwhelms the capacity of the kidney to adapt to reduced blood flow, manifest as overt cortical hypoxia as measured by blood oxygen level–dependent MRI. The level of cortical hypoxia is out of proportion to the medulla and may provide a marker to identify irreversible parenchymal injury.

The neurotransmitter dopamine and its dopamine receptor D2 (D2DR) agonists are known to inhibit vascular permeability factor/vascular endothelial growth factor (VEGF)-mediated angiogenesis and vascular permeability. Lung injury is a clinical syndrome associated with increased microvascular permeability. However, the effects of dopamine on pulmonary edema, a phenomenon critical to the pathophysiology of both acute and chronic lung injuries, have yet to be established. Therefore, we sought to determine the potential therapeutic effects of dopamine in a murine model of lipopolysaccharide (LPS)-induced acute lung injury (ALI). Compared with sham-treated controls, pretreatment with dopamine (50 mg/kg body wt) ameliorated LPS-mediated edema formation and lowered myeloperoxidase activity, a measure of neutrophil infiltration. Moreover, dopamine significantly increased survival rates of LPS-treated mice, from 0–75%. Mechanistically, we found that dopamine acts through the VEGF-VEGFR2 axis to reduce pulmonary edema, as dopamine pretreatment in LPS-treated mice resulted in decreased serum VEGF, VEGFR2 phosphorylation, and endothelial nitric oxide synthase phosphorylation. We used D2DR knockout mice to confirm that dopamine acts through D2DR to block vascular permeability in our lung injury model. As expected, a D2DR agonist failed to reduce pulmonary edema in D2DR−/− mice. Taken together, our results suggest that dopamine acts through D2DR to inhibit pulmonary edema-associated vascular permeability, which is mediated through VEGF-VEGFR2 signaling and conveys protective effects in an ALI model.

Background: Transradial access for coronary intervention is associated with reduced access complications compared with transfemoral. Transradial access for renal artery intervention has been less well studied. Safety compared with transfemoral access is undetermined. Methods and Results: We evaluated the feasibility of transradial renal intervention (n = 11 patients) and compared safety parameters with a matched group of transfemoral controls (n = 44). All transradial interventions were successful with no complications. Femoral crossover was required in one due to insufficient guide length. Compared with transfemoral, there were fewer access complications in the transradial group (0 of 11 vs 3 of 44, P = .06) but no differences in fluoroscopy time or contrast volumes (25.3 ± 14.4 vs 29.0 ± 25.1 minutes, P = .47; 83.0 ± 43.7 vs 82.6 ± 35.2 cc, P = .97). At follow-up (median 6 months), radial patency was 100%. Creatinine and systolic blood pressure had decreased (mean 1.4 ± 0.5 to 1.2 ± 0.5, P = .06; 160 ± 25 to 135 ± 17, P = .009). Conclusions: Elective transradial renal intervention is feasible and safe. Radial–renal distance is a limitation with available guides.

We present the midterm clinical outcomes and predictors of balloon angioplasty and stent placement in atherosclerotic femoropopliteal (FP) arterial disease. Between January 2002 and August 2006, 155 patients (men = 56%; 71.4 ± 10.5 years) underwent 171 FP angioplasty or stent for claudication (n = 82, 54%) or critical limb ischemia ([CLI] n = 70, 46%). Follow-up was obtained through September 30, 2009. The average follow-up was 3.25 ± 1.73 years. In claudicants versus CLI, the 12-month patency for TransAtlantic InterSociety Consensus II (TASC II) classification (TASC A/B) was 93% versus 80%, respectively, and TASC C/D 83% versus 80%. At 3 years, TASC A/B was 82% versus 80%, respectively, and TASC C/D was 56% versus 80%, respectively. The predictor of clinical failure in claudicants was chronic renal insufficiency (CRI) and in CLI, the predictor of amputation was hyperlipidemia.

Atherosclerotic renal artery stenosis reduces blood flow and perfusion pressures to the poststenotic kidney producing renovascular hypertension and threatening glomerular filtration rate. Little is known regarding regional tissue oxygenation in human renovascular disease that develops slowly. We compared stenotic and contralateral kidneys regarding volume, tissue perfusion, blood flow measured by multidetector computed tomography, and blood oxygen level–dependent magnetic resonance values in the cortex and medulla in 14 patients with unilateral stenosis (mean: 71% by quantitative computed tomography) and in 14 essential hypertensive patients during 150 mEq/d of sodium intake and renin-angiotensin blockade. Stenotic kidney volume was reduced compared with the contralateral kidney (118.6±9.9 versus 155.4±13.7 mL; P <0.01), as was total blood flow (269.7±42.2 versus 383.7±49; P =0.02), mainly because of reduced cortical volume. Tissue perfusion was similar but lower than essential hypertension (1.5 versus 1.2 mL/min per milliliter; P <0.05). Blood oxygen level–dependent MR at 3 T confirmed elevated R2* values (a measure of deoxyhemoglobin) in deep medullary regions in all 3 sets of kidneys (38.9±0.7 versus cortex 17.8±0.36 s −1 ; P <0.0001). Despite reduced blood flow, R2* values did not differ between atherosclerotic and essential hypertensive kidneys, although furosemide-suppressible fall in medullary R2* was reduced in stenotic kidneys (5.7±1.8 versus 9.4±1.9 s −1 ; P <0.05). Renal venous oxygen levels from the stenotic kidney were higher than those from essential hypertensives (65.1±2.2 versus 58.1±1.2; P =0.006). These data indicate that, although stenosis reduced blood flow and volume, cortical and medullary oxygenation was preserved under these conditions.