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OTHER: RENAL HYPERTENSION

Renovascular hypertension

Background
- Definition of renovascular hypertension: hypertension due to renal ischemia from partial or complete occlusion of one or both renal arteries
- Most common form of secondary and potentially curable hypertension
  - Although renal artery disease affects only a small proportion of hypertensives [majority are primary hypertension], it may be the cause of renal failure in as many as 10-20% of patients with ESRD
Epidemiology

Prevalence similar in Caucasians and African-Americans

Etiology of renal artery occlusion:

Adults (2):
1. Atherosclerosis
2. Fibromuscular dysplasia
  - Second most common cause in adults (20-40% of all cases)
  - Usually involves the more distal segments of the renal arteries
Children (4):
1. Fibromuscular dysplasia
2. Vasculitis
3. Neurofibromatosis
4. Neuroblastoma

Pathophysiology of renal hypertension
- Two-Kidney, One-Clip Model (2K1C) i.e. vasoconstrictor hypertensive model
  - Because of the ischemia induced by the unilateral stenosis, renin secretion is increased from the juxtaglomerular apparatus of the ischemic kidney and suppressed in the normal contralateral kidney.
  - As a consequence of the activation of the renin-angiotensin-aldosterone system (RAAS) and an increased production of angiotensin II, there is peripheral vasoconstriction and hypertension
  - This form of hypertension may be managed with (3):
    1. Reversal of the RAAS (or unclipping of the “clipped kidney”)
    2. ACE inhibitors
    3. Angiotensin receptor blockade
- One-Kidney, One-Clip (1K1C) Model i.e. volume hypertensive model
  - There is [an initial] activation of the RAAS similar to that seen in the 2K1C model. However, in contrast to the 2K1C kidney, the absence of a normal contralateral kidney prevents an ensuing natriuresis and diuresis. Thus, there is volume expansion, and renin secretion is suppressed in the clipped kidney because of feedback inhibition. Volume expansion remains, and there is sustained hypertension in spite of the decreased vasoconstriction associated with the now suppressed RAAS.
  - 1K1C model is driven by volume expansion and sodium retention with normal circulating levels of angiotensin II.
Pathophysiology of Ischemic Nephropathy
- In addition to hypertension, renal artery stenosis (RAS), when hemodynamically significant, affects the entire renal functioning parenchyma and causes ischemic nephropathy
- The degree of stenosis necessary to produce a hemodynamically significant effect (reduction in RBF > 40%) has been estimated at 70-80%, and thus this percent of stenosis is referred to as a “critical stenosis”
- Renovascular hypertension is more likely to be observed when (2):
  1. ≥ 70% stenosis in one or both renal arteries
  2. 50% stenosis with post-stenotic dilatation
Diagnosis and Evaluation

History and Physical Exam
- Most patients with renovascular hypertension present with moderate to severe hypertension
- Signs and symptoms of underlying possible renovascular disease and need for further evaluation if warranted (8):
  1. Severe or refractory hypertension with evidence of grade III or IV hypertensive retinopathy (particularly in Caucasians)
  2. Abrupt onset of moderate to severe hypertension, particularly in a normotensive or previously well-controlled hypertensive
  3. Onset of hypertension before age 20 (early onset) or after age 50 (late onset), particularly in those without a family history of hypertension
  4. Unexplained worsening of renal function (with or without hypertension) in association with the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) or with a reduction of blood pressure to the current accepted norm with the use of other antihypertensive agents
  5. Paradoxic worsening of hypertension with the use of diuretics
  6. Unexplained recurrent episodes of heart failure—“flash” pulmonary edema
  7. The presence of a systolic-diastolic abdominal bruit that radiates to both flanks
  8. The presence of diffuse vascular disease and/or evidence of cholesterol embolization
Imaging
- Screening Tests
  - The screening tests that provide the highest sensitivity and specificity are (3):
    1. Magnetic resonance angiography (MRA)
    2. Computed tomography angiography (CTA)
    3. Duplex Doppler US
    - Renal scintigraphy is no longer recommended as a screening test to establish the diagnosis of RAS.
    - CTA and MRA do not visualize the distal renal arterial tree well
    - A transient deterioration of renal function is not infrequently seen following a contrast load in patients with significant RAS and limited renal function
  - MRA with Gadolinium
    - May be used as a highly sensitive and specific non-invasive test to assess the functional significance of a renal vascular lesion; both the RBF and the GFR can be determined by the study digital subtraction angiography (DSA)
    - Concerns regarding the possibility of gadolinium-induced nephrogenic systemic fibrosis have diminished its utility in those with unstable or reduced renal function (GFR <30 mL/min). In these patients, a non-contrast MRA study may be performed, but this shows far less sensitivity and positive predictive value than a gadolinium-enhanced study
  - CTA
    - Limited in those with renal insufficiency because both the sensitivity and specificity declines in the presence of renal insufficiency (serum creatinine >1.7 mg/dL), and the risk of dye-induced nephrotoxicity increases
  - Duplex Doppler US
    - The most important indicator of renal artery stenosis is increased peak systolic velocity (PSV > 180cm/sec)
    - Similar to MRA, duplex Doppler US provides both anatomic and functional information.
    - Disadvantages:
      - Time-consuming
      - Highly operator dependent
      - Technically difficult test to perform
    - The sensitivity of this technique may be further increased when ACE inhibition is used

Confirmatory test
- Angiography
  - Despite a negative screening test, renovascular disease may still be present, particularly if the lesion is in the distal or intrarenal portion of the artery.
  - Both conventional renal angiography and intra-arterial digital subtraction angiography remain the gold standard for diagnosing renovascular disease and are indicated if the clinical index of suspicion is high and intervention is contemplated, regardless of the outcome of the screening tests

Fibromuscular Dysplasia (FMD)

More often seen in younger Caucasian women
Usually bilateral [think two-clip]
Most common presenting symptoms: hypertension, headache, and pulsatile tinnitus
Subtypes (4):
1. Multifocal
  1. Medial fibroplasia
2. Focal
  1. Perimedial fibroplasia
  2. Intimal fibroplasia
  3. Medial hyperplasia

Multifocal
- Medial fibroplasia
  - Most common type of FMD (70-80%)
  - Occurs almost exclusively in women between age 25-50
  - Lesions involve the distal half of the main renal artery and may extend into the branches
  - Unlikely to progress to complete occlusion or loss of renal function

Right renal arteriogram demonstrating web-like stenosis with interposed segments of dilatation (large beads) typical of medial fibroplasia (“string-of-beads” lesion)

Source: Wikipedia

Focal
- Intimal fibroplasia
  - Most common type of focal FMD§
  - May result in dissection, arterial wall hematoma, and renal infarction
  - Likely to progress to loss of renal function without intervention
  - See Figure 117-4
    - Renal arteriogram demonstrates a localized, highly stenotic, smooth lesion involving the distal renal artery, from intimal fibroplasia
- Perimedial fibroplasia
  - 10-25% of FMD cases
  - Occurs almost exclusively in women but they are younger (age 5-15) than medial fibroplasia
  - The stenosis occurs classically in the midrenal artery
  - Likely to progress to loss of renal function without intervention
- Medial hyperplasia
  - Rare
  - Likely to progress to loss of renal function without intervention

Duplex Doppler ultrasound surveillance of kidney length and cortical thickness should be done once or twice a year.

Management of Renovascular Hypertension

May not always be able to reliably assess the significance of a renal arterial lesion before intervention; may need to assume a causal relationship between the lesion and the presence of hypertension
Options for BP control (3):
1. Medical therapy
2. Percutaneous transluminal renal angioplasty (PTRA) (with or without stenting)
3. Surgery

Medical Therapy
- Medical therapy alone may achieve BP control in > 90% of patients with renovascular hypertension
- Although all classes of antihypertensives may be used, drugs that inhibit angiotensin II production (ACE inhibitors) or block its receptor site (ARBs) have been shown to be particularly efficacious because the hypertension is often the result of activation of the renin-angiotensin system
  - ACE inhibitors act on both afferent and efferent arteriole but more on efferent
  - ACE inhibitors are contraindicated in bilateral renal artery stenosis
- Despite BP control with medical therapy, atherosclerotic renal artery lesions may progress with time.
- Medical therapy may reduce BP below a critical level and induce ongoing renal ischemia; renal function should be closely monitored whenever such antihypertensive agents are used in patients with renovascular hypertension
- If blood pressure cannot be well controlled medically or there is very rapid deterioration of renal function, percutaneous angioplasty or surgical intervention may be indicated
Percutaneous Transluminal Renal Angioplasty (PTRA) and Stenting for Hypertension
- Can be successful in treating fibromuscular dysplasia; although successful, a restenosis rate of up to 27% may be seen
- Unlikely to be successful in treating atherosclerotic RAS
  - Recent trials have shown in patients with atherosclerotic RAS, no significant difference between medically treated patients and those treated with PTRA
    - CORAL trial
      - Showed only a 2 mm Hg difference in BP between groups. This did not translate into a significant decrement in clinical events and it exposed the patients to the potential risks of angiography.
      - Patients with accelerated hypertension flash pulmonary edema and malignant hypertension were not included in this trial. Therefore, conclusions regarding these patients cannot be drawn from this or other studies.
Percutaneous Transluminal Renal angioplasty (PTRA) and Stenting for Preservation of Renal Function
- See CW11 Figure 45-8 for management of patients with arteriosclerotic renal artery stenosis algorithm
- Non-ostial lesions:
  - PTRA shows a success rate similar to that of surgical revascularization and poses a lower risk of morbidity and mortality
- Ostial lesions
  - Comprise the vast majority (80-85%) of atherosclerotic RAS
  - PTRA without stenting is far less successful and effective; thus, most PTRA for atherosclerotic RAS are performed with endovascular stent placement
Surgical Revascularization for Renal Artery Stenosis
- See CW11 Figure 45-9 for management of patients with fibromuscular dysplasia algorithm
- Indications for surgical treatment of RAS (5):
  1. Concomitant aortic aneurysmal or occlusive disease; however; renal artery correction and aortic aneurysm correction need not be done simultaneously
  2. Macroaneurysms of the renal artery associated with stenosis
  3. Malignant or accelerated hypertension (with or without acute renal failure) that did not respond or cannot tolerate medical therapy
  4. >75% occlusion occurs either bilaterally or in a solitary kidney
  5. Those in whom PTRA is technically impossible
- The traditional criteria that will ensure the best outcome of surgical revascularization of a renal artery are (5):
  1. Kidney > 8 cm in length; < 8 cm cannot be successfully revascularized because it has reached end-stage
  2. Retrograde filling of the distal renal artery by collateral vessels on radiographic or scintigraphic imaging studies
  3. Patency of the distal renal artery
  4. Viability of the involved kidney on isotopic renography
    - With severe renal loss (serum creatinine > 4 mg/dL), the likelihood of renal recovery is substantially reduced and revascularization is not recommended.
  5. Minimal glomerular sclerosis and well-preserved tubules on renal biopsy; widespread glomerular hyalinization indicates irreversible ischemic renal injury and suggests little benefit from relief of renal artery obstruction
- Extensive atherosclerotic disease precludes renal revascularization
- When the aorta is severely diseased, renal revascularization on the left may be accomplished with a splenorenal bypass, and on the right with a hepatorenal bypass or a supraceliac lower thoracic aorta renal bypass
Renal denervation for resistant hypertension
- Endovascular radiofrequency ablation (RFA) of the renal artery results in destruction of the renal sympathetics and is being increasingly utilized for management of pharmacologically resistant hypertension.
  - Sympathetic innervation to the kidneys run in the adventitial wall of the renal arteries. Stimulation of the renal sympathetics results in a decrease in renal blood flow, an increase in renin secretion, retention of sodium and water, and hypertension.
  - Ablation of the renal sympathetics results in dilation of the renal efferent arteries, decreased plasma renin activity, and increased renal blood flow
  - Renal artery RFA has no effect on parasympathetic nerve activity
  - It has been associated with rare intimal dissections of the renal artery and renal artery aneurysms that may require emergent nephrectomy
- Recently shown to be unsuccessful (SIMPLICITY trial)

Renal artery aneurysm

See Pediatrics Upper Urinary Tract Anomalies Chapter Notes

Questions

Answers

References

Wein AJ, Kavoussi LR, Partin AW, Peters CA (eds): CAMPBELL-WALSH UROLOGY, ed 11. Philadelphia, Elsevier, 2015, chap 45