1. 55 세 남자 Serum creatinine 2.0 mg/dL BP 160/100 mmHg Urinalysis: protein +/- RBC 2-5 /hpf

2. Acute or rapidly progressive renal failure Chronic renal failure Acute nephritis Nephrotic syndrome Asymptomatic urinary abnormality Urinary tract infection Tubulointerstitial diseases Hypertension Renal vascular diseases Nephrolithiasis Urinary tract obstruction

3. Acute or rapidly progressive renal failure Chronic renal failure Acute nephritis Nephrotic syndrome Asymptomatic urinary abnormality Urinary tract infection Tubulointerstitial diseases Hypertension Renal vascular diseases Nephrolithiasis Urinary tract obstruction

4. Hypertension Primary HT Renal parenchymal HT Renovascular HT Adrenal –Primary aldosteronism –Cushing’s syndrome –Pheochromocytoma

5. In patients with long-standing hypertension, microhematuria, & moderate proteinuria –arteriolosclerosis, chronic nephrosclerosis, & interstitial fibrosis in the absence of immune deposits. Hypertensive nephrosclerosis

6. Sympathetic nervous system Renin-angiotensin system Total body sodium Patient 1 Patient 2 Patient 3 B. Waeber, March 2007 Blood Pressure has multiple regulatory pathways + Endothelial dysfunction

7. Joossens JV. Dietary salt restriction: the case in favour. R Soc Med Ser, 1980 소금 섭취와 고혈압

8. Salt and BP Sodium homeostasis Neuro-hormonal changes (RAS↓ 、 NP↑ 、 PG↑ 、 etc) GFR↑ Na reabsorption↓ Na excretion↑ BP↑ Pressure natriuresis Salt intake↑ (meal) Increased Ca ++ entry  vasoconstriction & HT

9. Hall JE, Hypertension 2003;41:625 Basic renal-body fluid feedback mechanism for long-term regulation of BP & body fluid volumes Guyton AC, Coleman TG. Circ Res. 1969 Pressure natriuresis curve

10. Pathogenesis of hypertension Two phases 1.Early hypertension (Salt-resistant hypertension) Renal vasoconstriction Hyperactive SNS, Renin-dependent Arteriolar disease (-) Intermittent initially renal-independent

11. Pathogenesis of hypertension Two phases 2.Late hypertension (Salt-sensitive hypertension) Subtle renal changes Tubulointerstitial Inflammation & Oxidative Stress Renal-dependent Volume-dependent Hypertensive kidney & normal Na handling Persistent

12. Hypertension Primary HT Renal parenchymal HT Renovascular hypertension –Atherosclerotic

13. 고혈압의 2-5% 1. 동맥경화증 atherosclerotic (ARAS) 60-70% 고령, 흡연, 말초 죽상 동맥경화증, 고혈압, 당뇨병에서 호발 common (age >65; 6.8%) 2. 섬유근육성 이형증 fibromuscular dysplasia 30-40% 젊은 여성 15-50 세 3. Takayasus aortitis 젊은 동양 여성  Ischemic nephropathy or Azotemic renovascular disease Renal artery stenosis

14. Atherosclerotic renal artery stenosis (ARAS) 12%-14% of patients reaching ESRD with no other identifiable primary renal disease: occult, bilateral RAS Patients starting dialysis therapy, spiral CT angiography –41% identified ARAS (>50% lumen occlusion) –16% bilateral (up to 27% of patients with new ESRD) United States Renal Data System data for patients >67 yrs starting dialysis: 7.1-11.1% renovascular disease 16%-22% of medically treated patients with ARAS progress to more advanced renal dysfunction over 3-5 yrs.

15. [ 증례 ] 55 세 남자, 혈압 180/110, SCr 2.0 mg/dL

16. Rt 신장위축

17. Before angioplastyAfter angioplasty [ 증례 ] 28 세 여자, 혈압 150/90 “string-of-beads” appearance

18. [ 증례 ] 17 세 여자, 혈압 230/150, 복부 잡음 (bruit)

19. Atherosclerotic ARAS Coronary Stroke PVD Some degree of RAS can be identified in 20%-45% of patients undergoing vascular imaging for other reasons. More than 70% of older patients with ARAS > 60% occlusion have clinical manifestations of cardiovascular disease.

20. 고혈압의 합병증

21. 병태생리 Critical levels of stenosis  reduction in perfusion pressure below the range of autoregulation  activates RAS and sympathetic adrenergic system and reduces sodium excretion  systemic hypertension  accelerated target organ injury (LVH, renal fibrosis)

22. Goldblatt kidney model Angiotensin II-dependent HT

23. RAS  rise in systemic arterial pressure  restoration of renal perfusion pressure  If advanced, the cycle of reduced perfusion & rising BP recurs  malignant-phase hypertension develops.

24. % stenosis Degree of stenosis Between 70% and 80% of lumen obstruction must occur before measurable changes in blood flow or pressure across the lesion can be detected. A pressure gradient of at least 10 to 20mmHg between the aorta and the poststenotic renal artery is required before measurable release of renin develops. De Bruyne B, J Am Coll Cardiol, 2006

25. Systolic BP in mice in experimental two-kidney–one-clip renovascular HT (2K1C) ARB no AT 1A receptorintact angiotensin 1A receptor Cervenka L, Hypertension 2002

27. Reduced blood flow and GFR when poststenotic pressures fall below the range of autoregulation.  This process can be reversible if pressure is restored and/or the vascular lesion is removed. At some point, both inflammatory and fibrogenic mechanisms appear to no longer respond with recovery of renal function. −cortical hypoxia, microvascular rarefaction, interstitial inflammation, tubular atrophy, and irreversible fibrosis. Perfusion pressure Reversible changes Irreversible changes

28. Reduction of blood flow to the kidney activates numerous pathways of vascular and tissue injury, including increased angiotensin II, endothelin release, and oxidative stress.

29. Contralateral kidney Later, removal of RAS no longer leads to reduction in arterial pressure. –Microvascular injury to the contralateral kidney sustains hypertension (Nephrosclerosis).

30. Volume-dependent HT

31. Syndromes associated with renovascular hypertension 1. Early- or late-onset hypertension ( 50 yrs) 2. Acceleration of treated essential HT 3. Deterioration of renal function in treated essential HT 4. Acute renal failure during treatment of hypertension 5. Flash pulmonary edema 6. Progressive renal failure 7. Refractory congestive heart failure

32. Clinical features Clinical features predictive of RAS –older age –recent progression –other vascular disease (e.g., claudication) –an abdominal bruit –elevated serum creatinine level

33. 1. Doppler ultrasonography Initial screening test, operator-dependent renal a. velocity(>200 cm/s), renal resistive index (RI)  2. Captopril-enhanced renography Captopril-mediated fall in filtration pressure amplifies differences in renal perfusion. Strong negative predictive value Normal study excludes renovascular hypertension. 고혈압과 SCr<2.0 mg/dL 환자의 일측신 진단. 우수한 noninvasive screening test & 기능검사 진단

34. RAS blocker reduces efferent arteriolar resistance sufficient to lower transcapillary filtration pressures, which is central to the benefits in “hyperfiltration” states. In the presence of renovascular disease ? the fall in glomerular filtration beyond a stenotic lesion can be observed despite relatively preserved plasma flows.

35. 3. Magnetic resonance angiography less often used (Gadolinium: nephrogenic systemic fibrosis) 4. Contrast-enhanced CT angiography with vascular reconstruction excellent vascular images and functional assessment a small risk of contrast nephrotoxicity 5. Intra-arterial angiography: gold standard simultaneous with planned intervention hazard of atheroemboli, contrast toxicity & dissection

36. 1. Medical treatment only 2. Revascularization therapy (angioplasty with stent placement) 3. Surgical intervention * Goal −Blood pressure control −Preservation or salvage of renal function Treatment of RAS

37. Blockade of RAS, statins, aspirin, cessation of tobacco Many patients can be managed well without revascularization for many years. − Rates of progression of renovascular disease are moderate and occur at widely varying rates. * Factors favoring medical therapy − Controlled BP with stable renal function − Stable RAS without progression on surveillance studies − Very advanced age and/or limited life expectancy − Extensive comorbidity that make revascularization too risky − High risk for or previous exercise with atheroembolic disease − Other concomitant renal parenchymal diseases that cause progressive renal dysfunction Medical treatment only

38. 20.8% 11.7% 5.5% Cumulative incidence of renal atrophy stratified according to baseline renal artery stenosis Kidney Int 53: 735,1998

39. Angioplasty with stent placement Young patients with fibromuscular dysplasia Atherosclerotic lesion: high re-stenosis rates Indications: 1) Progressive decline in GFR during treatment of hypertension 2) Failure to achieve adequate BP control with medical therapy 3) Rapid or recurrent decline in GFR in ass with a reduction in BP 4) Decline in the GFR during therapy with ACE inhibitors or ARBs 5) Recurrent CHF in a patient with adequate LV function 6) Recent deterioration of kidney function or hypertension Complication: atheroembolism, dissection, capsular perforation, hemorrhage

40. Revascularization versus Medical Therapy for Renal-Artery Stenosis (ASTRAL) 806 patients with atherosclerotic RAS

41. Kaplan–Meier Curves for Overall Survival Serious complications associated with revascularization: 23 patients (2 deaths and 3 amputations of toes or limbs) Conclusions: We found substantial risks but no evidence of a worthwhile clinical benefit from revascularization in patients with atherosclerotic renovascular disease.

42. Stenting & Medical Therapy for Atherosclerotic RAS (CORAL)

43. Randomized clinical trials: PTRA with stenting versus medical therapy alone for renal function and/or CV outcomes with ARVD

44. Predictors of least likely benefit regarding renal revascularization (Practical) Advanced renal insufficiency, usually characterized by serum creatinine levels >3.0mg/dL Small kidneys (length <8cm), particularly when little function can be identified on radionuclide renography. Elevated resistance index (>0.8) was a marker of poor outcomes in both GFR and BP. Recent deterioration of kidney function or hypertension portends more likely improvement with revascularization.

46. Take Home Message Pressure natriuresis and role of the kidney RAS: Ag II-dependent or volume-dependent Suspicion: acceleration of treated essential HT deterioration of renal function Treatment of RAS: medical or intervention –Recent progression of hypertension, deterioration of renal function, and/or pulmonary edema remain among the most consistent predictors of improved BP after intervention.