Patient Selection Indications for Renal Intervention Joseph C. Babrowicz, Jr., M.D. Georgetown University Hospital Division of Vascular Surgery

DISCLOSURES Joseph C. Babrowicz, MD Honoraria Endologix

Scope of the Problem Screening DUS suggested RAS (>60%) in 6.8% of Medicare population (mean age 77yrs) (White & Olin, Nat Clin Prac Card Med 2009;6:176-190) Clinically manifested RAS in medicare pts 0.5% overall and 5.5% with CKD (Dworkin, NEJM 2009;361:1972-1978)

Risk Factors for RAS Late onset Hypertension (age > 55yrs) Malignant, refractory, resistant HTN Declining renal function with ACE-I or ARB Atrophic kidney, size discrepancy >1.5cm Unexplained renal dysfunction Flash pulmonary edema Multivessel CAD Symptomatic PAD White & Olin, Nat Clin Prac Card Med 2009;6:176-190

Prevalence of RAS in ASCVD Stroke Carotid Art Disease Coronary Art Disease MI AAA Lower extremity PAD 10% 19% 6-40% 12% 20-38% 21-49% Prog Card Dis 2009;52: 238-242

Rates of Adverse CV Events With RAS per 1000 pt years Without RAS per 1000 pt yrs ASHD 303.9 73.5 PVD 258.6 52.2 CHF 194.5 56.3 CVA or TIA 175.5 52.9 Death 166.3 63.3 Prog Card Dis 2009;52:238-242

Evaluation – Screening Suspicion Onset Stage 2 HTN (BP>160/100 mmHg) after age 50yr or in absence of family history HTN associated with renal insufficiency (esp if worsens with ACE-I or ARB) HTN with repeated admit for CHF Drug resistant HTN ( at least 3 drugs) Dworkin, NEJM 2009;362:1972-1978

Evaluation - Imaging Test Advantage Disadvantage Duplex ultrasound Noninvasive Technician dependent, obesity, bowel gas CTA Contrast nephropathy, radiation MRA NSF in CKD DSA Best anatomical info Invasive, CIN, radiation Dworkin, NEJM 2009;362:1972-1978

Evaluation – Adjuncts Resistance Index PSV/EDV in cortical parenchyma Indication of small vessel renal disease Possibly predicts response to renal intervention Data are conflicting Radermacher et al., NEJM 2007;344:410-417

Evaluation - Biomarkers Renin Levels altered by many meds Suppressed by volume expansion Unreliable in clinical practice Brain Natriuretic Peptide Animal study BNP upregulated after cliping renal artery Silva et al (Circ 2005;111:328-333) showed decrease BNP after renal artery stenting More investigation needed White et al., 2009 NCPCardMed; 6:176-90

Evaluation - Invasive Catheter Angiography Variability in estimating degree of stenosis Hemodynamic effects develop between 75% and 85% luminal occlusion Detectable lateralization of renal vein renins at greater than 80% stenosis Somewhat difficult to define “significant lesion” by imaging only Textor et al., Prog Card Dis 2009:52,3:220-228

Figure 4 Treatment of renal artery stenosis with balloon angioplasty and stenting White CJ and Olin JW (2009) Diagnosis and management of atherosclerotic renal artery stenosis: improving patient selection and outcomes Nat Clin Pract Cardiovasc Med doi:10.1038/ncpcardio1448

Evaluation - Invasive Translesional Pressure Gradient AHA consensus suggests peak systolic gradient at least 20mmHg or mean gradient at least 10mmHG Absolute thresholds questioned Dependent on catheter diameter, aortic pressure, distal vascular bed, renal venous pressure Perfusion pressure distal to the gradient more important Pressure wires may provide better information

Fractional Flow Reserve Effective renal perfusion is related to the absolute pressure distal to a stenosis and not the gradient itself Flow across an artery is proportional to the pressure across the vascular bed and inversely proportional to the resistance of the vascular bed FFR = Pressure distal/pressure proximal measured after maximal renal hyperemia using a pressure wire Baseline normal FFR > or = 0.8 White, Prog Card Dis 2009;52:229-237

Fractional Flow Reserve 17 patients with refractory HTN and unilateral RAS treated with renal stenting 7 pts FFR < 0.8 10 pts normal FFR at baseline 3 month follow up 86% with abnormal FFR had improved HTN compared to 30% for normal FFR group BP improvement after renal stenting significantly more likely if baseline FFR<0.8 Mitchel et al., Cath Card Int, 2007;69:685-689

Management for HTN Randomized Trials DRASTIC Trial (NEJM 2000 342 1007-1014) Scottish Newcastle Group (J Hum Hypertension 1998;12:329-335) EMMA Group (Hypertension 1998;31:823-829) ASTRAL Study (NEJM 2009;361:1953-1962) Mostly negative results for BP control – 0nly 70% with improved BP, very few cures Problems - Underpowered, poorly defined medical management, selection biases, crossover, some nonhemodynamically significant lesions, PTA alone

Management – Ischemic Nephropathy Meta-analysis of 10 studies showed serum creatinine levels improve in 25%, no change in 50%, and worsen in 25% ASTRAL study designed to evaluate renal function showed no worthwhile clinical benefit from revascularization Some small studies have shown improved renal function Improvement is best for patients with rapid recent decline in renal function White et al., Nat Clin Pra Card Med 2009;6:176-190

Management – Cardiac Disturbance RAS can exacerbate coronary ischemia and CHF and make medical management (ACE and ARB) difficult Khosla et al. (Am J Card 1997;80:363-366) 48 patients with CHF or ACS had renal stent or renal stent and PCI 88% decreased BPs and/or improved symptoms Renal stent alone had similar outcomes to renal stent/PCI patients suggesting that renal stent was the major factor

Management – Cardiac Disturbance Gray et al. (Vasc Med 2002;7:275-279) 39 patients renal stent for control of CHF BP improved in 72% Renal function improved in 51% Mean number of hospitalizations for CHF fell form 2.4+/-1.4 to 0.3+/-0.7 77% had no further admission at 21 months Related to decreased renin –angiotensin production and ability to administer ACE and ARB meds

Conclusions RAS is an independent predictor of adverse CV events Percutaneous revascularization for hemodynamically significant RAS and accelerated, resistant, or malignant HTN is reasonable Percutaneous revascularization is reasonable for RAS and progressive decline in renal function Percutaneous revascularization is indicated for significant RAS and cardiac disturbance syndromes Defining significant RAS is difficult and adjuncts like FFR and BNP may improve ability to select good responders