Does this patient have flash pulmonary oedema? Philip A Kalra Professor of Nephrology, Salford Royal Hospital and University of Manchester, UK 73 yr old lady; type 2 Diabetes 1 yrs; PVD; hypertension Acute presentation with 3 day history of pulmonary oedema and anuria (April 2) Creatinine 712 mol/l (e 3 ml/min), K 6.1 mmol/l Needed urgent haemodialysis Renal U/S : no obstruction, left K 1 cm Suspected diagnosis : acute left RA occlusion Case 1 mol/l 1 8 6 4 2 9.4 1.4 Serial Creatinine Measurements 1.4 11.4 11.4 13.4 Date Stented 19.4 2.4 2 21.4 4. 12.8 Creatinine British Society for Heart Failure Hypertension/renovascular disease Fibromuscular disease (FMD) Fibromuscular disease (FMD) Up to 1% of all renovascular disease Greatest incidence in women (9:1) aged < 3 years (but also elderly Pascual, AJKD 2) 7% have renal involvement, bilateral in 3%; 3% have renal impairment Associated with pathology in other arterial systems eg carotids (1%) Familial clustering Prevalence : data from angiography in kidney donors (3181 patients in 3 studies) range 3.8%-6.6% (average 4.4% : Cragg et al. 1989; Neymark et al. 2; Andreoni et al. 22) FMD : management Atherosclerotic renovascular disease () CVS co-morbidity and Clinical presentation usually : hypertension (may be accelerated ) + preserved renal function Lesions tend not to progress over time Hypertension cure rate of 1-3% with angioplasty (Slovut & Olin 24), but no RCT comparing medical therapy Angioplasty recommended for young FMD diagnosed soon after hypertension onset malignant hypertension renal impairment bilateral disease Other patients : renin angiotensin blockade + low dose aspirin (Olin & Sealove 211; Plouin et al 27) 4% 4% 3% 3% 2% 2% 1% 1% % % CAD CCF PVD AAA CVA Harding MacDowall Choudri Olin AmJ Med Kuroda JASN 199 Lancet 1998 BMJ 199 Stroke 2 199 % with RAS 1
Other CKD Survival non-dialysis CKD (e 33 ml/min in both groups) 216 : prognosis still very poor Survival after haemodialysis start Other CKD Why would we consider renal revascularization in? Cardiac Flash pulmonary oedema Improve congestion (cardio-renal disease) Pre-coronary or carotid surgery Blood pressure Control of severe hypertension Renal Acute kidney injury Prevention of severe RAS RAO Rapid deterioration in renal function Patients who need RAA blockade but are intolerant Case 2 6 yr old lady with 3 episodes of acute pulmonary oedema in 12 months BP 22/88 on 3 agents Echo moderate to severe systolic dysfunction (EF 3%) and LVH Claudication; right carotid stenosis but no history of IHD from 6 to 22 ml/min in 1 months MRA bilateral 8-9% RAS; right kidney 9 cm, left 11cm (ml/min) 3 3 2 2 1 1 Changes in isosk- and cardiac MR parameters Left Right Pre Post Prerevasc EF (%) 42 3 LVEDV (ml) LV mass (g) 4 months 2 16 21 133 Case 3 : 76 yrs old male Bilateral 9% RAS 2 x attempts at revascularization yrs earlier by cardiologists in London referred with deteriorating renal function BP 127/3 on verapamil, candersartan, indapamide Urine PCR 2 g/mol USS kidneys : right 9.cm, left 1 cm creatinine e 46 2 yrs earlier 147 May 211 23 31 August 219 26 Case 3 : Renal revascularization August 211 ml/min 4 4 3 3 2 2 1 1 29 Aug-11 e Case 4 Randomised into ASTRAL : Successful revascularization Case 4 : Follow-up Male aged 3 Hypertension (17/9) Serum creatinine 18 mol/l Kidney sizes : L 9.8cm; R 11.3cm Angiogram : L 8% RAS; R normal Feb 21 March 21 April 21 May 21 June 21 29 mol/l 369 mol/l 3 mol/l 997 mol/l commenced dialysis 2
Renal revascularization : RCTs in Level 1 evidence now derived from the following RCTs in : - EMMA study (49 patients) Plouin et al, 1998 - DRASTIC (16) Van Jaarsfeld et al, 2 - Scottish and Newcastle () Webster et al, 1998 - STAR (16) Beutler et al, 29 - ASTRAL (86) N Eng J Med, 29 - CORAL (947) N Eng J Med, 213 Many single and multi-centre prospective and retrospective studies showing benefit of revascularization in a proportion of patients New England Journal of Medicine 29; 361 : 193-62 PATIENT CHARACTERISTICS BY RANDOMISED TREATMENT Revasc. Medical P-value Mean age (range) 7 (42 86) 71 (43 88).7 Male 63% 63%.9 Ex-smoker 2% %.3 Current smoker 2% 22%. Diabetes 31% 29%. CHD 49% 48%.2 PVD 41% 4%.7 Stroke 18% 19%.4 Dialysis %.3%. SCr (μmol/l) 88 μmol/l = 1 mg/dl LABORATORY and BP DATA BY RANDOMISED TREATMENT Revasc. Medical P-value 179 (66 1) 178 (64 7).9 Average RAS = 76%; 2% non-compliance with revascularization Change in renal function Macrovascular events Rapid increase in SCr 12% 12%.9 (ml/min) 4.3 (.4 124.) 39.8 (7.1 121.7).7 Albumin:Creatinine ratio 7.2 ( 274) 71.7 ( 2466).9 Systolic BP (mm Hg) 149 (87 27) Diastolic BP (mm Hg) 76 (4 12) Cholesterol (mmol/l) 4.68 (.1 14.8) 12 (9 241) 76 (46 13) 4.71 (1.9 9.6).7.6.8 Change in Systolic blood pressure Survival A Randomized Multicenter Clinical Trial of Renal Artery Stenting in Preventing Cardiovascular and Renal Events: Results of the CORAL Study Christopher J. Cooper, M.D., Timothy P. Murphy, M.D., Donald E. Cutlip, M.D., Kenneth Jamerson, M.D., William Henrich, M.D., Diane M. Reid, M.D., David J. Cohen, M.D., M.Sc., Alan H. Matsumoto, M.D., Michael Steffes, M.D., Michael R. Jaff, D.O., Martin R. Prince, M.D., Ph.D., Eldrin F. Lewis, M.D., Katherine R. Tuttle, M.D., Joseph I. Shapiro, M.D., M.P.H., John H. Rundback, M.D., Joseph M. Massaro, Ph.D., Ralph B. D Agostino, Sr., Ph.D., and Lance D. Dworkin, M.D., on behalf of the CORAL Investigators CORAL : Inclusion criteria and primary outcome measure INCLUSION CRITERIA Clinical Syndrome: Hypertension 2 anti-hypertensive medications, OR Renal dysfunction defined as Stage 3 or greater CKD -AND- Atherosclerotic Renal Artery Stenosis: Angiographic: 6% and < 1%, OR Duplex: systolic velocity of >3 cm/sec, OR Core lab approved MRA, OR Core lab approved CTA PRIMARY OUTCOME Composite of major cardiovascular or renal events: Cardiovascular or Renal Death Stroke Myocardial Infarction Heart Failure Hospitalization Progressive Renal Insufficiency Permanent Renal Replacement Therapy 3
Results: Primary Endpoint Clinical Events Stent plus medical therapy Medical therapy Stent + Medical Therapy 3.1%, 3-years Medical Therapy 3.8%, 3-years HR.94 [.76-1.17], p =.8 RR 1.4 1.2 1.8.6.4.2 US Medicare : Trends in revascularization 1992-21 1992 1994 1996 1998 2 22 21 ASTRAL published In 24 approx 3, renal stent procedures performed annually in US What have we learned from the RCTs? Revascularization does not improve outcomes in majority of unselected patients with These conclusions only apply to the patient phenotype included in the studies Some patients do benefit from revascularization who are they and can we reliably identify them? Don t forget the benefits of medical therapy But at least no more drive-by shootings! Selection of cases for renal revascularization Haemodynamically significant RAS with: 2 Recurrent unexplained congestive heart failure (Class I, evidence level B) Resistant / malignant hypertension (Class IIa, evidence level B) Progressive CKD and bilateral RAS (Class Iia, evidence level B). Am J Kid Dis 214; 63(2) : 186-97 Effect of renal revascularization in patients with RAS > 7% :control versus high-risk* D Vassallo et al; BMC Nephrology (in Press) Control n=144; 43 PTRAS (3%) P value High-risk n=131; PTRAS (43%) P value Death 1.2 (.61-2.38).6.64 (.33-1.26).2 ESKD 1. (.6-1.66) 1..64 (.37-.96).3 CVE 1.6 (.6-1.72).82.66 (.42-1.4).7 Any outcome 1.12 (.69-1.82).6.7 (.4-1.9).12 Techniques to detect responders to PTRAS Pressure wire studies Fractional flow reserve (FFR) Duplex ultrasound MR perfusion imaging Volume : BOLD imaging Pressure wire criteria Flash pulmonary oedema : HR for death with PTRAS.38 (.1-.96; p=.4) Deteriorating renal function : HR for ESKD with PTRAS.44 (.24-.82; p=.1) *High risk = flash pulmonary edema, rapid deterioration in function or severe hypertension 4
MR perfusion imaging - Parenchymal Volume (PV) : SK- of stented kidneys PV:isoSK- characteristics in improvers (>1% improvement in isosk-) and nonimprovers as compared to normal vessel or insignificant RAS group, *P <.. Number Mean PV : SK- SD Range Deteriorated (>1% Deterioration renal function) Stable (-1 to 1%) Improved (>1% Improvement renal function) 4.86 1.1 3.7-.8 18 6.38 2. 3.6-12.7 7 17.49 1.2 6-4.4 Cheung C M et al. Nephrol. Dial. Transplant. 21;2:1133-114 High grade proteinuria = bad outcome in (>.6 g/day) The Author 29. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org 3 main considerations prior to possible revascularization Where are we now in the management of Renal Artery Stenosis? Does the patient have a key clinical phenotype (eg FPE, declining function, severe hypertension)? Is the RAS physiologically or haemodynamically significant? What is the state of the kidney beyond the RAS? Renal atrophy (< 7 cm) Significant proteinuria = severe parenchymal disease Determine kidneys with greatest ischaemic stress yet viable tissue ( Hibernating kidney tissue) Medical therapy Important : ACE-I/ARB Statins Anti-platelet also all effective Beta-blockers With β-blocker No β-blocker Patients with atherosclerotic RVD have very high CVS risk They should all receive comprehensive vascular protective medication (statin, ACE-I/ARB, antiplatelet) An important minority of patients will benefit from renal revascularization : it is important to identify them Revascularization in atherosclerotic RAS is NOT for all but it should be for some.. Definite indications Severe or dialysis dependent AKI Patients who require/would benefit from Renin angiotensin blockade but who are intolerant Recurrent acute heart failure Possible indications Very severe hypertension (eg SBP > 18 on 4+ drugs) Rapidly deteriorating renal function : individual case basis If rapidly deteriorating renal function and severe hypertension occur together Emerging indications Patients with hibernating renal parenchyma? Chronic heart failure? Preventing renal atrophy long term?