Renovascular Hypertension Workup

00Overview

Renovascular hypertension (RVH) 是 secondary hypertension 中最常見的可矯正原因，佔所有 hypertension 的 1-5%。影像任務核心是：(1) 篩檢 renal artery stenosis (RAS) 的存在與嚴重度；(2) 區分 atherosclerotic RAS 與 fibromuscular dysplasia (FMD)；(3) 評估 functional significance（是否真正造成 renin-mediated hypertension）以決定是否 revascularization。最容易出錯的地方：偵測到解剖上的 RAS 即建議 intervention，忽略了 functional assessment — 解剖性 stenosis 不一定等於 hemodynamically significant RVH。

01Critical concepts

• 解剖 stenosis ≠ functional significance：> 50% RAS 很常見（尤其老年 + atherosclerosis），但不一定都造成 renin-mediated hypertension → 功能性評估（captopril renogram / renal vein renin sampling）是決策關鍵
• 兩大病因（age-stratified）：atherosclerotic RAS 在整體 RAS 族群佔約 90%（older patients, ostial / proximal）；FMD 在整體佔約 10%，但在年輕女性（< 50y）以 RVH 表現者，FMD 比例可達 30-50% → 不可用「90% vs 10%」直接套到所有族群
• CORAL trial 結論：atherosclerotic RAS + medical therapy vs stenting → 無顯著差異 → 強化藥物治療是 first-line；只有特定 clinical scenarios（flash pulmonary edema, refractory HTN, progressive ischemic nephropathy）才考慮 intervention
• Captopril renogram 的原理：ACE inhibitor 阻斷 angiotensin II 的 efferent arteriole constriction → stenotic kidney 的 GFR 下降 → 放射性藥物排泄延遲 → asymmetry with contralateral normal kidney

01正常 anatomy / 常用 modality

正常 renal artery 從 aorta 起源，位於 SMA 下方約 1 cm，right renal artery 較長（pass behind IVC）。正常 renal artery diameter 5-7 mm，peak systolic velocity (PSV) < 180 cm/s。Accessory renal arteries 出現率 20-30%。

常用 modality：

• Doppler ultrasound：first-line screening — 直接 sign：PSV > 180-200 cm/s、renal-to-aortic ratio (RAR) > 3.5；間接（intrarenal）sign：tardus-parvus waveform（distal interlobar/segmental artery acceleration time > 70 ms、acceleration index < 3 m/s²）、intrarenal RI 兩側差 > 0.05；RI > 0.8 提示 parenchymal disease，預後較差
• CT angiography (CTA)：gold standard for anatomy — stenosis grading、FMD beading、accessory arteries
• MR angiography (MRA)：alternative to CTA（no radiation, no iodinated contrast）；gadolinium-enhanced or non-contrast（arterial spin labeling、3D SSFP）
• Captopril renogram (ACE-inhibitor renography)：functional test — 首選 Tc-99m MAG3（高 protein binding、tubular secretion，在 impaired GFR 仍有良好 extraction，影像品質佳）；DTPA（純 GFR tracer）僅在 normal renal function 時 acceptable，CKD 病人 SNR 差
  • Patient prep：hydration（10 mL/kg PO water 30-60 min pre-scan）、空腹 4 hr、ACEI 須先 washout（captopril 2-3 天、長效 ACEI/ARB 3-7 天）、停用 diuretics 數天以避免 false positive
  • ACEI protocol：oral captopril 25-50 mg（crushed, with water）→ wait 60 min；或 IV enalaprilat 40 µg/kg（max 2.5 mg）over 3-5 min → wait 15 min；監測 BP（pre, q15min × 1 hr，captopril 可能誘發 hypotension）
  • Tracer dose：MAG3 5-10 mCi (185-370 MBq) IV；DTPA 10-15 mCi (370-555 MBq) IV；dynamic acquisition 20-30 min（1-2 sec/frame × 60 sec flow，後續 20-30 sec/frame）
  • Two-day vs one-day protocol：抽象上 two-day（baseline 與 captopril 分天做）較準；one-day 可先做 captopril，若 normal 即可結束
• Catheter angiography：diagnostic gold standard + simultaneous intervention（angioplasty ± stenting）；可同時量 translesional pressure gradient
• Renal vein renin sampling：lateralizing test — renin ratio > 1.5 on affected side confirms functional significance

02常見 pattern 分類

Ostial / proximal atherosclerotic stenosis

• Definition：renal artery ostium 或 proximal 1-2 cm 處的 calcified plaque causing lumen narrowing，常為 aortic atherosclerotic plaque 的延伸
• Why it matters：最常見的 RAS 形式（90%），但 CORAL trial 提示 stenting 不優於 optimal medical therapy in most cases
• What it points toward：atherosclerotic disease（與 coronary、cerebrovascular、peripheral artery disease 同屬 systemic atherosclerosis）
• Common trap：ostial calcification 可在 CTA 上造成 blooming artifact → overestimate stenosis severity → 需用 soft tissue kernel + narrow window verification

Mid-to-distal "string of beads" pattern

• Definition：renal artery mid-to-distal segment 呈現交替的 dilation + stenosis（beading pattern），不含 calcification，vessel wall thickening
• Why it matters：是 FMD（medial fibroplasia type，佔 FMD 80-90%）的 pathognomonic sign — young women（20-50y）為主
• FMD subtypes 與影像表現：
  • Medial fibroplasia（最常見）：classic "string of beads"，beads 直徑 > parent artery
  • Intimal fibroplasia（< 10%）：focal concentric smooth stenosis 或 long tubular stenosis；可發生於 proximal segment → 易誤判為 atherosclerotic
  • Perimedial (subadventitial) fibroplasia：focal beading，beads 直徑 < parent artery；progressive，常需 intervention
• What it points toward：FMD → angioplasty（without stenting）效果佳（cure rate 50-70%）；需 screen for FMD in other vascular beds（carotid, iliac, intracranial aneurysm）
• Common trap：subtle FMD beading 在 CTA 上可被 missed → catheter angiography 仍是 definitive（higher spatial resolution）

Asymmetric kidney size

• Definition：one kidney significantly smaller than the other（> 1.5 cm length difference），with smooth contour
• Why it matters：chronic RAS 導致 ischemic nephropathy → kidney atrophy；atrophic kidney 的 revascularization benefit is limited
• What it points toward：chronic hemodynamically significant RAS → ischemic atrophy；unilateral renal artery thrombosis old infarction → focal scar with overall atrophy
• Common trap：asymmetric kidney size has multiple causes（congenital hypoplasia, reflux nephropathy, prior pyelonephritis）→ 不能直接等同於 RVH → 需 vascular imaging confirmation

Positive captopril renogram pattern

• Definition：post-captopril scan 顯示 affected kidney 的 tracer uptake 延遲、時間-活性曲線的 peak time 延長、或 20-min uptake retention 增加，contralateral kidney 正常
• Quantitative interpretation criteria（Taylor/SNM consensus + Fommei grading）：
  • Tmax (time to peak) 延長 > 2 min vs baseline，或 absolute Tmax > 11 min（MAG3）/ > 5 min（DTPA）
  • 20-min/peak ratio (residual cortical activity) 增加 → MAG3 20/3 min ratio > 0.3、DTPA 20/peak > 0.3
  • GFR (DTPA) 或 ERPF (MAG3) split function 改變 ≥ 10% vs baseline
  • Renogram curve grade（Fommei 0-3）：grade 0 正常；grade 1 mild delay (Tmax 延長 < 2 min)；grade 2 marked delay 但仍下降；grade 3 rising curve（無 washout）
  • Probability interpretation：normal baseline + normal post-captopril → low (< 10%)；significant change post-captopril → high (> 90%)；abnormal baseline 但無變化 → intermediate
• Why it matters：confirms hemodynamic significance → RAS 確實造成 renin-dependent hypertension → revascularization likely effective
• What it points toward：functionally significant RAS → candidate for angioplasty / stenting
• Common trap：bilateral RAS 可使 captopril renogram 呈 bilateral abnormal → 失去 lateralizing ability → 此時 renal vein renin sampling 更有用；CKD (eGFR < 30) 與 dehydration 也會造成 false positive

03Top common diagnoses

• Atherosclerotic RAS：老年、systemic atherosclerosis、ostial/proximal、progressive；medical therapy first-line
• FMD：young women、mid-to-distal、non-progressive in most cases（medial type）；angioplasty curative in many
• Renal artery aneurysm：可合併 RAS 或 independent 發現；> 2 cm 考慮 intervention（pregnancy 計畫者 threshold 更低）
• Takayasu arteritis involving renal artery：young Asian women、aortitis + branch stenosis → renal artery involvement（"middle aortic syndrome"）；CTA/MRA 可見 vessel wall thickening + delayed enhancement
• Neurofibromatosis type 1 (NF1) with renal artery stenosis：childhood hypertension + café-au-lait spots → NF1-related vascular dysplasia

04Cannot-miss diagnosis / emergency

05高頻 mimics 與 discriminators

Atherosclerotic RAS vs FMD

• Why they get confused：both cause RAS → hypertension，both visible on CTA/MRA
• Most useful discriminators：(1) age/sex — atherosclerotic in older males + risk factors；FMD in young females；(2) location — atherosclerotic is ostial/proximal；FMD（medial type）is mid/distal；(3) morphology — atherosclerotic is eccentric plaque with calcification；FMD is "string of beads"（無 calcification）；(4) associated disease — atherosclerotic has CAD/PAD；FMD may have carotid/iliac involvement 與 intracranial aneurysm；(5) treatment response — FMD responds well to angioplasty alone（無需 stent）
• Common trap：intimal FMD（rare subtype）involves proximal artery as smooth focal stenosis → looks like atherosclerotic stenosis 但無 calcification → angiography needed

Anatomic RAS vs hemodynamically significant RAS

• Why they get confused：> 50% stenosis on CTA 直接 report 為 "significant RAS"
• Most useful discriminators：(1) Doppler — PSV > 180-200 cm/s + RAR > 3.5 → hemodynamically significant；(2) captopril renogram positive → functional significance confirmed；(3) translesional pressure gradient > 20 mmHg (systolic) 或 mean > 10 mmHg；(4) clinical features — resistant hypertension（≥ 3 drugs）, flash pulmonary edema, unexplained AKI → higher pre-test probability；(5) kidney size symmetry — asymmetric size suggests chronic functional effect
• Common trap：不要對每個 > 50% RAS 都建議 stenting → most cases benefit from optimal medical therapy（CORAL trial evidence）；ostial lesion 的 PSV 會被 aortic jet 假性抬高 → 高 aortic PSV（如 aneurysm、coarctation 上游）可使 RAR 假性偏低，反之 low cardiac output 使 PSV 假性偏低 → 此時需用 acceleration time、intrarenal RI 等次級 sign 輔助

Essential hypertension vs renovascular hypertension

• Why they get confused：> 95% of hypertension is essential（primary）→ most patients with hypertension do NOT have RVH
• Most useful discriminators：(1) RVH clues — onset < 30 or > 55y、abrupt worsening、refractory to ≥ 3 drugs、AKI after ACEI/ARB、flash pulmonary edema、abdominal bruit；(2) essential HT — gradual onset、family history、responsive to standard medications
• Common trap：screening for RAS in uncomplicated essential hypertension has very low yield and is inappropriate → screen only with clinical clues

06Next step / protocol / appropriateness

影像 protocol 選擇：

• Initial screening（clinical suspicion of RVH）：Doppler US of renal arteries → PSV, RAR, RI, acceleration time → if suspicious → CTA or MRA
• Anatomic confirmation：CTA renal arteries（arterial phase 25-30 sec post-injection, 0.625-1 mm slice, coronal/sagittal MIP + curved planar reformat）→ stenosis grading + plaque morphology
• Functional significance assessment：captopril renogram（MAG3 preferred；hydration + ACEI washout + captopril 25-50 mg PO or enalaprilat 40 µg/kg IV）→ pre/post-captopril comparison → lateralizing abnormality
• Pre-intervention：catheter angiography → pressure gradient measurement（> 20 mmHg systolic = significant）→ simultaneous angioplasty ± stent
• FMD screening：if renal FMD confirmed → screen carotid（CTA/MRA/US，含 vertebral）+ iliac arteries + intracranial（MRA brain for aneurysm，~7-12% 發生率）

07Pitfalls / normal variants

• Accessory renal artery stenosis：20-30% 有 accessory renal artery，其 stenosis 也可 contribute to RVH → CTA 必須報告所有 renal arteries
• Renal artery origin variation：renal artery 可從 iliac artery 起源（pelvic kidney）或 low aortic origin → 非 standard CTA field 可能 miss
• RI > 0.8 predicts poor revascularization outcome：elevated RI in affected kidney suggests established parenchymal disease → stenting unlikely to improve BP or renal function
• Captopril renogram false negative in bilateral RAS：bilateral disease → no lateralization → false negative → renal vein renin sampling needed
• Captopril renogram false positive：dehydration、recent ACEI/ARB 未停藥、severe CKD（eGFR < 30）、urinary obstruction
• Ostial PSV pitfall：ostial stenosis 的 Doppler PSV 受 aortic flow velocity 干擾 → 高 aortic PSV 時 RAR 失準 → 依賴 intrarenal tardus-parvus 與 acceleration time
• Normal variant early branching：renal artery early branching（before hilum）can mimic stenosis on Doppler → CTA confirms anatomy