고혈압과 azotemia를 동반한

68세 남자 환자

000 (M/68)

Adm : 2002-9-24

Chief complaint

Fatigue Onset) 3 weeks ago

Present illness

- 2년전 고혈압을 진단받았으나 특별한 치료 없이 지내던 환자

로 내원 3주전부터 fatigue, anorexia 발생하여 개인병원 방문

후 creatinine 상승된 소견 관찰되어 전원됨.

Past medical historyDM / HTN / Hepatitis / TB (-/+/-/+) : no medication

Drug Hx (-)

Op Hx (-)

Family historyunremarkable

Personal history

Alcohol (+) : 소주 1병/d weekly

Smoking (+) : 1 pack/d x 40 years

Review of Systems

General : fatigue(+) sweating(-) polydipsia(-) wt loss(-)

H & Neck : headache(-) stiffness(-)

Respiratory : cough(-) sputum(-) dyspnea(-)

Cardiac : chest pain(-) orthopnea(-) palpitation(-)

GI : anorexia(+) nausea(-) vomiting(-) diarrhea(-)

Urinary : dysuria(-) nocturia(-) frequency(-)

Musculoskeletal : numbness(-) pain(-)

Physical Examination

Vital sign: 180/90 mmHg – 78회/min – 20회/min – 36.5 °C

B.W : 62kg Ht. : 172cm BMI 21.0 kg/m2

General appearance

- Alert mentality

- Acute ill-looking appearance

Head & Neck

- No neck vein engorgement

- No palpable cervical mass

Chest- Clear breath sound without crackle or wheezing

- Regular heart beats without murmur

Physical Examination

Abdomen

- Soft and flat abdomen

- Tenderness / Rebound tenderness (-/-)

- No palpable abdominal mass

- Abdominal bruit (+) : Rt

Back & Extremity

- CVA Tenderness (-/-)

- Pretibial pitting edema (-/-)

Neurology

- Motor, sensory : intact

- Babinski (-/-)

Q1. 의심되는 질병은 무엇인가?

Initial Lab Finding (02-9-24)

CBC/DC

8600/mm3 –13.2 g/dl – 38.7 % - 332000/mm³ ( seg. 61.3%)

INR : 1.0 % aPTT : 34.5 sec

Chemistry

T-chol/TG 210/349 mg/dL

TB/DB 0.7/0.1 mg/dL

T-protein/albumin 8.1/4.0 g/dL

AST/ALT 24/26 U/L

ALP/GGT 102/18 U/L

BUN/Cr 31/2.0 mg/dL

Na/K/Cl 135/4.3/96 mmol/L

Ca/P/Mg 9.4/4.4/2.4 mg/dL

CRP <0.5 mg/dL

U/A

RBC 0~1/HPF WBC 0~1/HPF

SG : 1.015 PH : 6.5 protein(-) glucose(-)

Chest X-Ray (02-9-24)

Lab Finding

24hr urine collection

protein 153mg/d

creatinine 1088mg/d

CrCl = 37.8ml/min

ANA 1+, nucleolar

C-ANCA negative

P-ANCA negative

PRA >20 ng/ml/hr (0.8~1.36)

Serum Aldosterone 150 pg/ml (50~194)

Lab Finding

Serologic marker

IgG 1910 mg/dL (694~1618) C3 135 mg/dL (88~201)

IgA 245 mg/dL (68~378) C4 20 mg/dL (15~45)

IgM 194 mg/dL (60~263)

IgE 2200 IU/ml (<100)

ANA(Qual) nucleolar RF < 20 IU/ml (<20)

C-ANCA negative

P-ANCA negative

Anti ds-DNA ab negative

Anti phospho IgM 9.14 MPL/ml (<10)

Anti phospho IgG 4.97 GPL/ml (<10)

Anti Sm-Ab negative

Abdominal US (02-9-25)

Rt kidney : 9.4 cm Lt kidney : 10.9 cm

Renal Doppler US (02-9-26)

Rt kidney Lt kidney

Main a

ITLlower

DTPA Captopril Renal Scan (02-9-27)

Q2. 어떤 치료를 선택할 것인가?

Renal Angiography (02-10-1)

Renal Angiography (02-10-1)

Renal Angiography (02-10-1)

F/U Renal Doppler US (02-11-4)

Rt kidney : 10.5 cm Lt kidney : 10.5 cm

2002-9-26 2002-10-4

Main a

ITLlower

F/U Renal Doppler US (02-10-4)

F/U DTPA Captopril Scan (02-10-4)

Q3. 치료는 과연 종료되었는가?

120

140

180160

150

160170180

7070

100100

80

1009090

0

20

40

60

80

100

120

140

160

180

200

9/24 9/25 9/26 9/27 9/28 9/30 10/2 10/4

SBP

DBP

02-10-1

Angioplasty

9/24 : Cr 2.0 10/2 : Cr 1.9

Clinical Course (1)

Felodipine 5mg

Atenolol 50mg

Irbesartan 75mg

1.41.31.31.2

1.92.0

1.4

0

0.5

1

1.5

2

2.5

3

3.5

4

02-9-24 02-10-2 2002 11

월

2002 12

월

2003 01

월

2003 07

월

2003 11

월 day

Cre

atin

ine

(mg

/dL

)

Cr

Clinical Course (2)

Irbesartan 75mgFelodipine 5mgAtenolol 50mg

Thiazide 12.5mgAspirin 100mg,Atorvastatin 10mg

1.81.7

1.81.71.9

1.51.6

0

0.5

1

1.5

2

2.5

3

3.5

4

2004 03

월

2004 06

월

2004 10

월

2004 12

월

2005 06

월

2005 08

월

2005 11

월 day

Cre

atin

ine

(mg

/dL

)

Cr

Clinical Course (3)

Irbesartan 75mgFelodipine 5mgAtenolol 50mg

Thiazide 12.5 mgAspirin 100mg,Atorvastatin 10mg

F/U Renal Doppler US (06-2-20)

Rt kidney : 7.4 cm Lt kidney : 11.7 cm

F/U Renal Doppler US (06-2-20)

2002-9-26 2002-10-4

Main a

2006-2-20

Clinical Course (4)

2 0 0 6 - 3 2006-11 2 0 0 7 - 1 2 0 0 7 - 8 2007-12 2008-4

Creatinine

(mg/dL)

2.1 1.9 1.9 1.9 2.0 2.04

BP

(mmHg)

1 3 5 / 8 0 1 2 0 / 7 0 1 1 5 / 6 0 1 2 5 / 7 0 1 2 0 / 6 5 135 /75

Irbesartan 75mg

Efonidipine 40mg

Aspirin 100mg EOD

Simvarstatin 20mg

Q4. 이 환자의 혈압과 신기능의 유지에 도움

이 된 주된 치료는 과연 무엇인가?

1. angioplasty

2. intensive medical treatment

3. both

RVHT is an important correctable cause of secondary hypertension.

Cause

Atherosclerosis m/c, older

Fibromuscular dysplasia, uncommon, young aged wemen

Transplant RAS : 10% after KTP, usually in 1 year after surgery

The frequency – variable

< 1 % of mild to moderate elevations in BP

10 to 45 % of acute (even if superimposed upon a preexisting elevation in blood pressure), severe, refractory hypertension

Renovascular hypertension(RVTH)

Pathophysiology of RVHT

Unilateral renal a stenosis Bilateral renal a stenosis

Ang II dependent HTN Volume dependent HTN

Pathophysiology of RVHT

AT II

ACEi,ARBintraglomerular pressure↓

GFR↓

AT II

Angiotensin II

Diagnosis of RVHT : arteriography

Gold standard for Diagnosis

Complications)

Atheroembolism, Contrast induced ARF

But, variety of less invasive tests have

been evaluated for screening purposes.

Vascular studies to evaluate renal a.

MR angiography

Spiral CT

Doppler US

Other studies

Plasma renin activity

Captopril renogram

Diagnosis of RVHT : Doppler Sono

Sensitivity 85~99 % , specificity 92~97 %

Advantage : both anatomic and functional assessment of the renal

a.

Disadvantage

time-consuming , technically difficult, highly operator-dependent

Peak systolic renal artery velocity (Vr)

Vr >180 cm/s

ratio of the Vr / Vaorta ≥ 3.5 Pulsus parvus et tardus

Prolonged AT (> 0.07sec)

RI < usually 0.56 (Normal <0.7)

RI >0.8 : extremely poor outcomes after revascularization

high RI may indicate irreversible intrarenal vascular disease

Diagnosis of RVHT : MR angiography

Sensitivity 100 %, specificity 71 % for 50 ~75 % ASO stenosis

Non-nephrotoxic

Clear image of prox. Renal a, but may miss distal renal a

CIx : claustrophobia , metallic implant, pacemaker or aneurysm clip

GFR<30ml/min : gadolinium nephrogenic systemic fibrosis risk ↑

fibrosis of the skin and connective tissues

prevent bending and extending joints

may cause death

Diagnosis of RVHT : CT angiography

sensitivity and specificity

77 and 94 % for ASO stenosis ≥50 %

28 and 99 % for fibromuscular disease

62 and 90 % for all lesions ≥70 %

sCr > 1.7mg/dL accuracy is lower due to reduced renal blood

flow

Contrast induced ARF

Diagnosis of RVHT : renin activity

Sensitivity 75~100% and specificity 60~95%

In RAS, ↑renin in ischemic kidney, ↓renin in contralateral kidney

Baseline PRA is elevated in only 50 to 80 % in RVHT

1 hour after administration of 25 to 50 mg of captopril

exaggerated increase in PRA.

Lateralizing renal vein renin ratio (affected/contralateral) >1.5

90% predicting value for response to revascularization

But false negative 50~60%, some false positive

need to discontinue antihypertensive medications

Diagnosis of RVHT : Captopril scan

DTPA, hippurate ,MAG3

Oral captopril (25 to 50 mg) is given 1 hour before the isotope is

injected

positive finding

Decreased relative uptake with one kidney < 40 % of total

GFR.

Delayed uptake on affected side

Delayed washout on affected side

Negative finding essentially excludes functionally significant

stenosis

But limited in GFR<20ml/min, bilateral RAS

Goal of Treatment

Improved blood pressure control

Preservation of renal function

Treatment of RVHT

Medical therapy

Revascularization

Percutaneous transluminal renal angioplasty

with or without stent placement

Surgery

Treatment of RVHT : Medical

Antihypertensive drug

ACE inhibitor or an ARB, often in combination with diuretic.

CCB and βB are also effective

Normalization of BP may be associated with reduced renal

perfusion, pressures, and renal function may deteriorate

Control of risk factors for atherosclerosis

Aspirin

Cessation of smoking

antidyslipidemic therapy

In diabetes, glycemic control

Progression of atherosclerotic stenosis may occur in one

third of patients

Treatment of RVHT : revascularization

Indications:

Uncontrolled BP despite maximal therapy

Progressive rise in SCr

Intolerance to ACE-I/ ARB (>30% in SCr or severe

hyperkalemia)

Recurrent pulmonary edema, CHF, or volume overload

Prerequisites:

Experienced operator

Presence of two kidneys

RI < 0.80 in target kidney(s)

Percutaneous transluminal renal angioplasty (PTRA)

Young patients with fibromuscular dysplasia

better outcome than atherosclerosis,

Atherosclerotic lesion: high re-stenosis rates

poor outcome in bilateral RAS

Complication 5~20%

Hematoma, renal artery dissection, renal artery thrombosis or

perforation

Atheroembolic event (maybe irreversible)

ARF d/t radiocontrast agent (maybe reversible)

Stent migration and/or thrombosis

Restenosis 14~18%

Major determinant of risk : vessel size <5mm

Treatment of RVHT : angioplasty

Outcome of therapy

Angioplasty and STent for Renal Artery Lesions (ASTRAL)

750 patients , in the United Kingdom

Changes in BP and renal function during the first year of follow-up are

small, and no major differences requiring study termination

CORAL trial

66 patients with creatinine<2.0

intensive medical therapy VS stent

after 21mo of follow-up, no differences in BP or serum creatinine

Study to evaluate the safety and effectiveness of Palmaz balloon

expandable stent In the REnal artery (ASPIRE-2)

renal artery stenting for failed angioplasty

19.7% major adverse event rate during a 24-mo

In patients with diffuse atherosclerosis, the complication rate with

revascularization is relatively high. Medical therapy may be preferred.

Effect of renal artery revascularization versus

medical treatment alone on clinical outcomes

ASN NephSAP 7(2) March 2008

Revascularization for

atherosclerotic renal artery stenosis

: the treatment of choice?