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Recent advances in renal hypertension

Recent advances in renal hypertension . Scope. Renal hypertension Introduction Causes ARAS, FMD Pathophysiology Clinical features Diagnosis Imaging Management Conclusions. Renovascular hypertension (RVH). Renal Hypertension or RVH: Defined as

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Recent advances in renal hypertension

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  1. Recent advances in renal hypertension

  2. Scope • Renal hypertension • Introduction • Causes • ARAS, FMD • Pathophysiology • Clinical features • Diagnosis • Imaging • Management • Conclusions

  3. Renovascular hypertension (RVH) • Renal Hypertension or RVH: • Defined as • The presence of systemic hypertension due to a stenotic or obstructive lesion within the renal artery • Form of secondary hypertension, accounting for an estimated 0.5% to 4% of cases in unselected hypertensive patients US Nephrology 2009;5(2):56–59, Proc (Bayl Univ Med Cent) 2010;23(3):246–49

  4. RVH: Introduction • The simultaneous presence of renal artery stenosis (RAS) and systemic hypertension should not lead to the conclusion that • The patient has RVH; • Strictly speaking, the definitive diagnosis of RVH can only be made retrospectively • When hypertension improves upon correction of the stenosis US Nephrology 2009;5(2):56–59, Proc (Bayl Univ Med Cent) 2010;23(3):246–49

  5. RVH: Introduction (Contd) • In practice, obtaining complete “reversal” of hypertension is rarely possible • Important to recognize that renovascular disease • Often accelerates preexisting hypertension, • Can ultimately threaten the viability of the post-stenotic kidney and • Impair sodium excretion in subjects with congestive heart failure Med Clin North Am. 2009 May ; 93(3): 717, available in PMC 2010 May 1.

  6. RVH: Causes • The two most common causes of RVH are 1. Atherosclerotic renal artery stenosis (ARAS) 2. Fibromuscular dysplasia (FMD) Med Clin North Am. 2009 May ; 93(3): 717, available in PMC 2010 May 1.

  7. ARAS • Most common and problematic cause of RVH • 90% of cases of RVH due to ARAS • Mainly in older men • Lesion at the ostium or proximal third of the renal artery as an extension of an aortic plaque • Bilateral in approx. 1/3 of cases Med Clin North Am. 2009 May ; 93(3): 717, available in PMC 2010 May 1.

  8. ARAS (Contd) Aortogram demonstrating high-grade stenosis affecting the left renal artery Quantitative measurements indicated more than 86% lumen obstruction Med Clin North Am. 2009 May ; 93(3): 717, available in PMC 2010 May 1.

  9. ARAS (Contd) • Risk factors • Identical to those associated with systemic atherosclerosis, i.e., • Advanced age, male sex, smoking, • Diabetes mellitus, hypertension, • Positive family history, and • Dyslipidemia US Nephrology 2009;5(2):56–59, Proc (Bayl Univ Med Cent) 2010;23(3):246–49

  10. ARAS (Contd) • Generally believed that • ARAS slowly progresses over time, but the rate of progression is variable • Atherosclerotic renovascular disease is associated with accelerated and more severe target organ injury than essential HT US Nephrology 2009;5(2):56–59, Proc (Bayl Univ Med Cent) 2010;23(3):246–49 HT- Hypertension

  11. FMD • 10% of cases of RVH are due to FMD • Mainly in younger women • Bilateral renal artery involvement with extension into the distal portion of the artery and its branches is common US Nephrology 2009;5(2):56–59, Proc (Bayl Univ Med Cent) 2010;23(3):246–49

  12. RVH: Pathophysiology Safian & Textor. NEJM 344:6;

  13. RVH: Pathophysiology (Contd) • Widely believed that • The obstructing lesion in the renal artery has to reach a “critical level” of about 75% to cause any clinically significant hemodynamic effects US Nephrology 2009;5(2):56–59, Proc (Bayl Univ Med Cent) 2010;23(3):246–49

  14. RVH: Pathophysiology (Contd) US Nephrology 2009;5(2):56–59, Proc (Bayl Univ Med Cent) 2010;23(3):246–49

  15. RVH: Pathophysiology (Contd) • Bilateral RAS, or unilateral RAS in a functionally impaired or absent contralateral kidney, • The increased renin produced by both kidneys is responsible for the increased salt and water retention and subsequent HT US Nephrology 2009;5(2):56–59, Proc (Bayl Univ Med Cent) 2010;23(3):246–49

  16. RVH: Pathophysiology (Contd) • Unilateral RAS with a normal contralateral kidney, • HT is caused by the increased renin produced in the ischemic kidney while • The nonischemic kidney has its renin production suppressed US Nephrology 2009;5(2):56–59, Proc (Bayl Univ Med Cent) 2010;23(3):246–49

  17. RVH: Diagnosis • Mere presence of RAS and hypertension does not establish the diagnosis of RVH • Three-step approach to the diagnosis of RVH has been suggested Curr Cardiol Rep 2005;7(6):405–11.

  18. RVH: Diagnosis (Contd) • First step: • An appropriate selection of patients who are more likely to have RVH • Second step: • The patients’ renal arteries are imaged to demonstrate RAS • Third step: • Resolution or improvement in blood pressure control occurs with reversion of the stenosis Curr Cardiol Rep 2005;7(6):405–411.

  19. RVH: Diagnosis (Contd) • Clinical findings associated with RVH N Engl J Med 2001;344(6):431–42.; Curr Cardiol Rep 2005;7(6):405–11; Kidney Int 2006;70(9):1543–1547

  20. RVH: Diagnosis (Contd) • Clinical findings associated with RVH(Contd) ACE: angiotensin-converting enzyme; ARBs: angiotensin II receptor blockers; RAS: renal artery stenosis N Engl J Med 2001;344(6):431–42.; Curr Cardiol Rep 2005;7(6):405–11; Kidney Int 2006;70(9):1543–1547

  21. RVH: Diagnosis (Contd) • Clinical findings associated with RVH (Contd) AAA: abdominal aortic aneurysm; CAD, coronary artery disease; PAD:peripheral arterial disease N Engl J Med 2001;344(6):431–42.; Curr Cardiol Rep 2005;7(6):405–11; Kidney Int 2006;70(9):1543–47

  22. RVH: Imaging • Intra-arterial angiography • The gold standard • Invasive and carries the risk of contrast-induced nephropathy • Not used routinely unless • Concurrent therapy with angioplasty, with/without stenting, is being considered

  23. RVH: Imaging (Contd) • Digital subtraction angiography (DSA) • Uses less dye than a conventional arteriogram but is still invasive • The quality of images with DSA is not as good as with conventional angiogram

  24. RVH: Imaging (Contd) • Captopril-enhanced renography and scintigraphy • Noninvasive test and the ability to assess renal functional status • Use is limited in patients with bilateral RAS and in patients with significant renal insufficiency • Provide a basis for functional, not anatomical, diagnosis of RAS, as there is no direct visualization of the renal arteries

  25. RVH: Imaging (Contd) • Duplex ultrasound imaging • Direct visualization of the renal vascular tree while assessing blood flow velocity and pressure wave forms • Limitations include interoperator variability and the need for expertise in obtaining and interpreting the images

  26. RVH: Imaging (Contd) • Spiral computed tomography angiography • Enables a three-dimensional reconstruction of the vascular tree • Excellent sensitivity and specificity to visualize RAS • However, requires up to 150 cc of iodinated contrast, which may be nephrotoxic

  27. RVH: Imaging (Contd) • Magnetic resonance angiography (MRA) • Noninvasive imaging technique and results in excellent visualization of the renal vasculature • Gadolinium is used as the radio-contrast in the phase contrast technique • Drawbacks • High cost • Potential for nephrogenic systemic fibrosis in patients with renal insufficiency

  28. RVH: Management • Treatment options include • Pharmacological therapy with various antihypertensive medications, • Percutaneous angioplasty with or without stent placement, and • Surgical revision of RAS

  29. RVH: Management (Contd) • Availability of potent antihypertensive drugs and the advances in endovascular techniques, as well as stents, have made surgical treatment rarely necessary

  30. RVH: Management (Contd)

  31. RVH: FMD Management • FMD • Percutaneous angioplasty is the treatment of choice, • Often resulting in relief of the stenosis and marked improvement (or cure) of the hypertension • Stents may be used • In patients with suboptimal results with angioplasty alone • Surgery is considered to be the last option, particularly • For patients for whom endovascular procedures have failed

  32. RVH: FMD Case • CT angiogram obtained in a 45 y.o. woman presenting with new onset RVH • Aneurysmal dilation and vascular occlusion beyond a fibromuscular lesion is present in the right kidney associated with loss of perfusion to the entire upper pole of the kidney • Antihypertensive therapy in this instance can be achieved using agents that block the RAS • While such cases are unusual, they underscore the broad range of lesions that can produce the syndrome of RVH

  33. Fibromuscular Dysplasia, before and after PTRA Atherosclerotic RAS before and after stent Safian & Textor. NEJM 344:6;

  34. RVH: ARAS Management • ARAS • No general consensus among physicians on the ideal therapy for this condition • Numerous randomized prospective studies have found no evidence of improvement in BP control in patients undergoing angioplasty over medical therapy alone

  35. RVH: ARAS Management (Contd) • One of the largest trials, • The Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) study, • 806 renal failure patients (mean serum creatinine approximately 2 mg/dL) with atherosclerotic renal vascular disease included • Randomized to receive either revascularization and medical therapy or medical therapy alone N Engl J Med 2009;361(20):1953–1962

  36. RVH: ARAS Management (Contd) • ASTRAL Study (Contd) • On average, patients had 75% RAS • At 1-year follow-up there were no differences in the change in serum creatinine level (it rose by 0.2 mg/dL in both groups) or in rates of renal events, including acute renal failure N Engl J Med 2009;361(20):1953–1962

  37. RVH: ARAS Management (Contd) • Currently, at least three major studies are under way to help decipher optimum treatment for patients with ARAS • 1. STAR • 2. RAS-CAD • 3. CORAL

  38. RVH: ARAS Management (Contd) • STAR study • The STent placement and blood pressure and lipid-lowering for the prevention of progression of renal dysfunction caused by Atherosclerotic ostial stenosis of the Renal artery (STAR) study aims to compare • The effects of renal artery stent placement together with medication versus medication alone on renal function in 140 ARAS patients • Medication consists of statins, antihypertensive drugs, and antiplatelet therapy Ann Intern Med 2009;150(12):840–848

  39. RVH: ARAS Management (Contd) • RAS-CAD • A trial looking at cardiac endpoints, the stenting of Renal Artery Stenosis in Coronary Artery Disease (RAS-CAD), • Randomized study aiming to recruit 168 patients • Designed to study the effect of medical therapy alone versus medical therapy plus renal artery stenting on • left ventricular hypertrophy progression (primary endpoint), and • cardiovascular morbidity and mortality (secondary endpoints), in patients affected by ischemic heart disease and RAS J Nephrol 2009;22(1):13–16

  40. RVH: ARAS Management (Contd) • CORAL • The Cardiovascular Outcomes with Renal Atherosclerotic Lesions (CORAL) study is a National Institutes of Health–funded multicenter trial testing the hypothesis that • Stenting atherosclerotic RAS in patients with systolic hypertension reduces the incidence of cardiovascular and renal events • The CORAL study has completed enrollment with over 900 patients, but results will not be available for some time Available at http://www.clinicaltrials.gov/ct/show/NCT00081731

  41. RVH: ARAS Management (Contd) • At this time, there is no clear benefit of revascularization for ARAS, • Especially in patients for whom BP can be controlled easily and who have no evidence of ischemic nephropathy • The risks of the procedure may outweigh any potential benefits • Angioplasty with or without stenting may be of benefit in • Patients with HT that is difficult to control in the setting of decreased renal perfusion, because uncontrolled hypertension is a major cardiovascular risk factor • Accordingly, aggressive treatment of hypertension with medications is recommended

  42. RVH: ARAS Management (Contd) • Antihypertensive treatment may also include • ACE inhibitors and ARBs provided that • Renal function is stable and that close follow-up is available • Medical therapy should also include • Statins to prevent further progression of atherosclerotic plaques in the renal arteries and • Cardiac prophylaxis with lowdose aspirin • Smoking should be strongly discouraged

  43. Conclusions • RVH is potentially remediable cause of HT • ARAS and FMD are common causes of RAS • Appropriate treatment continues to evolve, but control of hypertension is imperative • Role of angioplasty is well accepted in FMD but is not so clear in ARAS

  44. Thank You!

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