Casemeet and review of literature on fibromuscular dysplasia and renovascular hypertension

1. Clinical Case Meet: Renovascular Hypertension
Presented by : Dr R.Rajesh
Moderator: Dr Sanjay D’ Cruz

2. • Name: KK
• Age: 29/F
• CR no: 2303*******
• Address: Dhablai khurd Punjab
• OPD
Patient Details

3. Chief Complaints
 Now presented with abdomen pain since 1 year

4. History of Presenting illness
• Abdomen pain since 1 year
 For 1 year
 Bilateral lumbar region
 Mild to moderate intensity
 Through out day
 Not much relief with pain killers

5. History of Past illness
• 2018 pregnancy had high BP recordings

6. Background history
• 2022 April
• Went to PVT hospital i/v/o right lumbar pain and both Lower Limb swelling
• BP recordings 160 sys
• Evaluated for young HTN
• Renal Artery Doppler : waveforms are normal but RI is mildly decreased
bilaterally
• CT Renal Angio: multi focal short segments of luminal narrowing with dilated
intervening segments in both renal arteries

7. CT angio followed by PTRA in April 2022

8. General Physical Examination
• Conscious obeying commands
• BP 130/80 mmHg in both UL.
• Pulse 78 beats per minute all peripheral pulses palpable
• Systolic bruit over right carotid artery and left femoral artery

9. Systemic examination
• CVS- S1S2 heard no added sounds. No S4
• RS- Bilateral air entry equal without crepitations/wheeze
• Abdomen- soft No organomegaly, no tenderness. NO BRUIT
• CNS - no FND Fundus grade 1 hypertensive retinopathy

10. Blood Investigations
18/04/22 21/4/22 06/3/23
UREA 39 25 25
CREAT 0.9 0.7 0.8
HB 10.7 10.4 9.9
TLC 7.2 7.1 7.0
PLT 253 261 307
NA+ 137 136
K+ 4.3 4.0

11. Other Investigations
Urine Routine 06/3/23
Protein Nil
Sugar Nil
Pus cells 2-4
Others nil
Hepatitis B Negative
Hepatitis C Negative
Serum Iron 21
TIBC 452
HsCRP 15

12. Radiology March 2023

13. What are we dealing with?
Young female with HTN
CTRA FIBRO MUSCULAR DYSPLASIA

14. • APPROACH TO YOUNG HYPERTENSION
• RENOVASCULAR HYPERTENSION
Points of Discussion

15. Etiology
Young
Hypertension
Secondary(10%) Primary(90%)
1)Mangena P, Saban S, Hlabyago KE, Rayner B. An approach to the young hypertensive patient. S Afr Med J. 2016 Jan;106(1):36-8.
2)National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents (2004) The fourth report on the
diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 114:555–576
• Primary HTN is more common even in younger population also. (1)
• Associated with family history, obesity, tobacco, diabetes, cocaine
• Other mechanisms proposed are low birth weight. (Barker Brenner Hypothesis)
• Secondary hypertension is a type of hypertension with an underlying identifiable
and potentially correctable cause.
• The probability of secondary hypertension is inversely proportional to age of
patient.(2)

16. Evaluation of a patient
• Correct BP measuring
technique ( correct
cuff, resting, home,
repeat )
• Look for risk factors
• Look for end organ
damage ( HF, Stroke,
CKD, PVD, retina)
• Look for secondary
causes in history and
examination.

17. Secondary HTN Causes
1. Renal parenchymal diseases, obstructive uropathy, renin producing
tumors, cystic diseases
2. Endocrine: Thyroid associated, adrenal
3. Vascular: Aortic coarctation, Takayasu, RENOVASCULAR
4. Neurogenic: Psychogenic, diencephalic syndrome, familial dysautonomia,
polyneuritis, raised ICP, acute spinal cord section.
5. OSA
6. Pre eclampsia, Eclampsia
7. Drug induced

18. Workup for HTN
• BASIC : urine analysis, FBS, Hematocrit, Serum Na, K, Ca, Creat, lipid
profile
• Ultrasound KUB and adrenals
• Renal Doppler, CTA if indicated
• Advanced : Dexamethasone suppression test, 24hr urinary
metanephrines, thyroid and parathyroid hormones, Aldosterone
Renin Ratio, sleep study

19. Reno vascular HTN
• Definition:
Syndrome of elevated BP (systolic and/or diastolic) produced by any condition that
leads to reduced perfusion of the kidneys.
Decrease of atleast 60% in luminal diameter, pressure gradient of 20 mmHg across
stenotic area during angiography corresponding to 70% stenosis is usually
considered to be of hemodynamic significance!
• Prevalance:
India PGI study: 3% of young HTN (1)
UK based study: 3/4th of secondary HTN (2)
1) Sharma BK, Sagar S, Chugh KS, Sakhuja V, Rajachandran A, Malik N. Spectrum of renovascular hypertension in the young in north India: a hospital
based study on occurrence and clinical features. Angiology. 1985;36(6):370-378.
2) 2) Little MA, O'Brien E, Owens P, et al. A longitudinal study of the yield and clinical utility of a specifically designed secondary hypertension
investigation protocol. Ren Fail. 2003;25(5):709-717.

20. Normal Anatomy
• Renal artery is 3 to 7 mm in diameter.
• Generally single artery to each kidney.
• The incidence of multiple RAs is about 31%, with
bilateral supernumerary arteries in 11%.
• Right RA pass behind IVC.
• Collateral supply

21. Etiology:
Renovascular
Hypertension
Barbara A and Kausik U. Renovascular hypertension and Ischemic Nephropathy.
Comprehensive Clinical Nephrology. 6th ed. China; 2019. 482-501

22. Pathogenesis
• Some degree of Renal Artery stenosis is
present in 25 to 45% of normal
population, found during vascular
imaging done for other purpose.
• Reduction in renal perfusion pressures
activates the release of renin from
juxtaglomerular cells in the affected
kidneys.

23. Pathogenesis

24. Pathogenesis

25. Pathogenesis
Stephen C, Renovascular Hypertension and Ischemic Nephropathy. The Kidney ed 11, 2020:1580-1621.

26. Atherosclerosis
• Atherosclerosis is most common cause
of RVH in age > 50yrs. Mostly men.
• Risk factors : smoking, CKD, CAD, HTN,
DM, Dyslipidemia.
•Lesions progress with Age. Regress with
Statins. Renal atrophy developed in 21%
of cases with stenosis >60%.
• Lesions are predominantly near to
Ostium
Caps MT et al Circulation 1998;98:2866

27. Fibro muscular dysplasia
• Non atherosclerotic, non inflammatory vascular disease that most
often affects small to medium arteries characterized by smooth muscle
proliferation and fibrosis.
• Predominantly(90% cases) in female population of age group 20 to 40.
• Etiology : unknown , ?collagen related genes
• Renal(65 to 80%) and cerebral arteries(42%) are commonly involved.
B/L renal artery involvement in 35% of adult cases.
• Lesions are typically away from origin.

28. Clinical features of FMD

29. Some of these lesions gradually progress to aneurysms

30. TAKAYASU ARTERITIS
• Inflammatory and stenotic disease of medium- and large-sized
arteries characterized by a strong predilection for the aortic arch
and its branches.
• Age group 10 to 40yrs, female – thoracic aorta, male abdominal
aorta
• Panarteritis followed by fibrotic phase
• C/F: fever, night sweats, arthralgias, anorexia, and weight loss
• SIGNS: Absent Pulses, Carotidynia, Arterial bruit, Discrepant BP
between limbs, Hypertension, Signs of AR, Heart Failure, PAH, Limb
Ischemia.

31. TAKAYASU ARTERITIS
• Involvement : subclavian(93) >
carotid(58) > abd Aorta(47) >
renal(38)
• Renal : renal artery stenosis >
glomerular involvement
• Inflammatory markers are raised
• Vessel wall thickening/
thrombosis/ aneurysms on
radiological investigations.

33. Variable Fibro muscular dysplasia Atherosclerosis Takayasu arteritis
Age 20 to 40 yr > 50 yr 10 to 40 yr
Gender Female Male Female
Risk factors Genetic/ collagen
disorders.
Smoking, dyslipidemia Genetic /microbial
Clinical features Hypertension, flank pain,
head ache, neck pain
Myocardial infarction,
stroke, peripheral
vascular disease
Fever, night sweats,
weight loss, absent pulse,
claudication
Lesion location Middle to distal Proximal Proximal

34. Clinical features of RVH
• Occlusion can be incidental finding.
• “nondipper”/ uncontrolled HTN
• Have more severe target organ
manifestations LVH.
• Occlusion increases BP gradually or may
cause a rapid increase in BP, that
precipitates a hypertensive emergency
like “flash pulmonary/cerebral edema”
• Activate sympathetic nervous system.

35. Clinical features of RVH
• RAAS EFFECTS: Hypokalemia, dipsogenic hyponatremia with hypertension
• Slow progression to CKD.
• When RA stenosis is bilateral or unilateral in the patient with a single functioning
kidney, progression to total occlusion can present as oligoanuric AKI, sometimes
associated with a hypertensive emergency.
• AKI after start of ACEI in bilateral Renal artery thrombosis.
• Abdominal bruit, carotid/subclavian bruit, absent peripheral pulses
• Other organ involvement because of atherosclerosis, Takayasu arteritis.

36. Diagnosis
• Laboratory Findings:
• Low serum K+ ± low Na+ level
• USG-Unilateral small (atrophic) kidney size
• Raised plasma renin level
• Renal vein renin ratio
• Secondary aldosteronism
• Proteinuria, usually mild
• ± Raised serum creatinine level
• Increase in serum creatinine by more than 20% after ACEI/ARB

37. Doppler
• Inexpensive, widely available, operator dependent.
• Suspect RVH if asymmetry in kidney size: L>R 2 cm,
R>L 1 cm
• Positive findings are
1. PSV > 180 cm/sec
2. Relative velocity in comparison to aorta > 3.5
times
3. Post obstruction: parvus and tardus waves
4. Renal arterial resistivity Index (PSV- EDV)/ PSV
difference between 2 kidneys- 0.06 to 0.08
Granata A, Zanoli L, Clementi S, Fatuzzo P, Di Nicol`o P, Fiorini F. Resistive intrarenal index: myth or reality?.
Br J Radiol 2014;87:20140004

38. Renal vein renin measurements
• It may help predict the BP response to renal revascularization.
• Previous studies indicated that lateralization of renal vein levels.
(>1.5 : 1 stenotic-non stenotic kidney ratio) predicts a favorable BP
response for more than 90% of patients.
• Some clinicians use these measurements to verify the role of a
pressor kidney before undertaking nephrectomy.

39. CT and MR angiography
• Sensitivity 98% for CT
• 97% for MR

40. Comparing Non invasive tests

41. Captopril enhanced
Renogram
• Renal scintigraphy
performed with Tc DTPA,
Hippuran or TcMAG
• HIGH negative
predictive value

42. Renal Angiogram
Gold standard

43. Treatment
MEDICAL MANAGEMENT
Renal revascularisation with PTRA
Surgical revacularisation

44. OPTIMISE Medical Therapy
• Stop smoking
• Lifestyle modification
• Control metabolic syndrome
• High dose statin therapy
• BP control
1. ACE inhibitors/ ARBs/ Renin inhibitors
2. Diuretics
3. Calcium Channel Blockers

45. • RAAS blockade is considered fundamental.
• Successful renal revascularization rarely leads to withdrawal of all
antihypertensive drugs.
• Risk of AKI/ worsening eGFR after initiation of ACEI/ARBs to be
monitored by creatinine at 2 and 4 weeks. Usually can recover.
• Caution in cases of bilateral stenosis, solitary stenosed renal artery
and critical artery stenosis.

47. • No statistically significant difference in serum creatinine or in cardiovascular or
renal adverse events between the balloon angioplasty and medical treatment
arms.
• There was a small improvement in diastolic BP and a small reduction in the
number of antihypertensive drugs required in the angioplasty group
• There is a non-significant trend towards a reduction in cardiovascular and renal
adverse events in the angioplasty group
• A small number of procedural complications of balloon angioplasty were
reported, peri-procedural deaths (0.4%)). No side effects of medical therapy were
reported.
• Larger trials with increased power are required to address this issue.
Cochrane Database Syst Rev 2014;CD002944.

48. Endovascular Treatment versus Medical Therapy for Hypertensive
Patients with Renal Artery Stenosis: An Updated Systematic Review
Piaggio et al. Annals of Vascular Surgery 2019

49. Renal revascularization for FMD
• Currently most centers treat hypertension associated with FMD with
percutaneous transluminal renal angioplasty (PTRA) without stenting. (I B)
• “Complete cure,” defined as normal arterial pressure without medications, occurs
in 35% to 50% of cases.
• Although primary technical success rates for PTRA are high (>90%) for FMD,
restenosis from either inadequate initial treatment or recurrent fibrosis has been
reported in up to 34% of cases.
• Endovascular management of RA aneurysms sometimes can be achieved by
use of “covered” stent grafts to exclude the aneurysm.
Alhadad A, Mattiasson I, Ivancev K, et al. Revasularisation of renal artery stenosis caused by fibromuscular dysplasia: effects on blood pressure during 7-year follow-up are
influenced by duration of hypertension and branch artery stenosis. J Hum Hypertens. 2005;19:761–767.

50. Atherosclerotic Disease: Endovascular Stents
• Primary endovascular RA stenting has become standard for the interventional
treatment of atherosclerotic RA stenosis in most centers. ( 1 B )
• With current techniques, target vessel patency rates regularly exceed 95%.
• Short-term use of platelet inhibitors (e.g., clopidogrel) for several weeks to prevent
vessel occlusion is standard.
• BP control rates were improved in 50%, with 68% of patients experiencing
“stabilization” or “improvement” in renal function over a mean of 17 months.

51. For Takayasu arteritis
• Takayasu arteritis: prednisolone, methotrexate, toclizumab.
• After active state resolves
• PTRA by balloon dilation or stenting

52. Indications for interventions
• Hemodynamically significant RAS with recurrent CHF/Flash pulmonary
edema (I B)
• RAS with accelerated/ resistant/ malignant hypertension (II B)
• RAS in hypertension with unilateral small kidney (II B)
• Progressive decline in renal function (II B)
• Patients intolerant to medications (II B)
• Hemodynamically significant RAS with unstable angina (II B )
Recommendations are based on 2005/2017 ACC/AHA guidelines

53. Predictors of poor outcomes after
revascularization
• Patients with nearly or completely occluded vessels
• Ultrasound evidence of high resistive indices ≥ 0.8
• Marked renal atrophy (size <7 cm)
• Absent function measured by split nuclear scan
• Significant albuminuria

54. Complications after PTRA/ Stenting
Most frequent : groin hematoma.
Others:
1. Hemorrhage
2. Femoral artery pseudoaneurysm
3. Stent thrombosis
4. Cholesterol/ distal embolism
5. Dissection of aorta, iliac artery
Mortality attributed to procedure : 0.5%

55. Surgical Revascularization
• Surgical intervention for renovascular disease is reserved for
patients
1. Whom endovascular therapy fails
2. Who have associated aortic disease that is not amenable to
endovascular therapy. ( I )
3. FMD with large (>1.5cm) aneurysms and obstruction ( I )
4. Ostial lesion greater than 10mm i.e total occlusion

56. • Despite these caveats, successful surgical revascularization in well- selected
cases provides durable restoration of kidney blood supply and long-term
survival.
• Overall, the effects of surgical revascularization on BP and renal function
response in patients with ASRVD mirrors those for endovascular therapy.
• Various surgical techniques are endarterectomy, bypass graft, resection
and reanastomosis, auto transplantation.
• When considerable renal atrophy with poor function and RVH refractory to
optimal medical therapy are present, nephrectomy of the ischemic kidney
may improve BP control with minimal impact on total GFR.
Surgical Revascularization

57. Take Home Message
• OPTIMISE Medical Therapy
• No statistically significant difference in serum
creatinine or in cardiovascular or renal adverse
events between the balloon angioplasty and
medical treatment arms.
• Intervention in special circumstances