Two8 86 Renal Physiology and Pathophysiology including Renovascular Hypertension

• Sodium 
• - PCT - 65%, NaK-ATPase 
• - ascending limb of LOH - 25-35% - Loop diuretics 
• - DCT - 5% - Thiazides 
• - Collecting tubules - minimal - aldosterone act

• Potassium - PCT, collecting duct 
• -

• 
• Loop diuretics bind with NKCC2 - decrease NaCl reabsorption - diuresis

• Reduce or block the effect of angiotensin 
• Vasodilatation of efferent arterioles 

• These are collecting duct cells 
• Principal cells are the main Na+ reabsorbing cells and the site of action of aldosterone, K+-sparing diuretics, and spironolactone. [@ principAL cells - ALdosterone] 
• Type A intercalated cells mediate acid secretion and bicarbonate reabsorption.
• Type B intercalated cells mediate bicarbonate secretion and acid reabsorption

[@ BAU - type B basification, type A - Acidification of Urine] 

• 
• Aquaporin 2 is exclusively expressed in principal cells - is predominant vasopressin regulated water channel. In obstruction, these channels are reduced. N-acetylcysteine upregulate AQP2 expression.

• History 
• Volume status 
• Urinary sodium - in hyponatremia, low urinary sodium is expected. If high, (>20mEq/l) - then renal source should be suspected

• 
• H+ secreted - binds to bicarbonate -  forms H2O and CO2 - diffuse passively - inside PCT - again changes to H+ and HCO3- - Bicarbonate is absorbed to vessels through sodium coupled transporter - H+ secreted in lumen

Acetazolamide, CA inhibitor - reduces bicarbonate reabsorption and sodium and water excretion

Hypertensive crisis is an umbrella term for hypertensive urgency and hypertensive emergency.

Hypertensive Urgency - Elevated BP without evidence of acute end organ damage

• Hypertensive Emergency -  Elevated BP with evidence of acute end organ damage
• - Malignant hypertension - retinal hemorrhages, exudates, and papilledema, nephrosclerosis
• - Accelerated hypertension - similar to malignant HTN but papilledema is absent, better prognosis than malignant HTN

[@ CUEMA]

Current AAP guidelines now distinguish between children 1 to 13 years of age and adolescents older than 13 years of age, with normal blood pressure defined as less than the 90th percentile for children and less than 120/80 mmHg for adolescents. 

Hypertension in the pediatric population is defined as blood pressure on repeat measurements greater than the 95th percentile for age, gender, and height in comparison to normative population-based data.

• It can be 
• - Primary (essential) 
• - Secondary - when specific etiology is identified

• AKI 
• Azotemia 
• Chronic GN
• Hypersensitivity nephropathy 
• Nephrosclerosis 
• Renovascular HTN 
• Uremia

The increase in the prevalence in pediatric hypertension in recent years is closely linked to increasing obesity rates in children.

VUR has long been held as the primary cause of significant hypertension in children. Arterial derangements in the renin-angiotensin system and sodium-potassium adenosine triphosphatase activity may be involved, though the precise pathophysiologic process is not clear.  

Indeed, removal of renal segments verified by selective renal vein sampling of arteriolar or segmental vessel renin levels has provided durable normalization of blood pressure in carefully selected patients.

Renovascular hypertension is a clinical syndrome marked by a rise in arterial pressure with or without associated ischemic and hypertensive renal injury. Its most common cause is renal artery stenosis (RAS), defined as narrowing of the renal artery by more than 50% of its natural luminal diameter. 

• Asymptomatic 
• Renovascular HTN
• Ischemic nephropathy 
• Accelerated Cardiovascular  disease - congestive heart failure, stroke, secondary aldosteronism

• Normally, the pressure of aorta should be reflected in the renal artery. There should be no pressure gradient.
• Any gradient more than 10-20 mmHg is significant (70% occlusion)

If there is no gradient, then even if there is narrowing in the renal artery, that is not be significant.  All narrowings seen on routine imaging need not be dealt with.

• To cause decrease in renal perfusion - >50% of diameter should be occluded 
• To cause hypertenion - >70% of diameter should be occluded

We should not look only on DTPA finding - we should also see the parenchyma of the kidney - some of the kidneys can be regainded after vascularization ?

• Atherosclerosis
• - 60-80%, MC in older age 
• - proximal third of the renal artery is usually involved
• - in 70% to 80% of the patients there is an aortic plaque  impinging on the renal ostium, whereas the remaining 30%  exhibit non-ostial narrowing usually 1 to 3 cm distal to the renal artery ostium

• Fibromuscular dysplasia
• - in young age  

• Takayasu arteritis
• - left subclavian artery is involved, BP cannot be measured

Sequence from most common to least common

• Medial fibroplasia
• - distal renal artery
• - most common type
• -  characteristic “string of beads” appearance on angiography  - aneurysms are larger than the renal artery, because of weakening of media, the aneurysm bulge out beyond the diameter of the renal artery 
• -  not likely to progress to complete occlusion, nor are they likely to experience a decrease in their overall renal function

• Perimedial fibroplasia
• - midrenal artery
• - aneurysm is always smaller than the renal artery 
• - Similar to medial fibroplasia, angiography may demonstrate a string of beads. However, unlike medial fibroplasia, the  aneurysmal “beads” in perimedial fibroplasia that never exceed the diameter of the main renal artery

• Intimal fibroplasia
• - Proximal part of the artery 
• -  may be complicated by disruptions of the internal elastic lamina and hence may result in dissection, arterial wall hematoma, and renal infarction

• Medial hyperplasia
• - is least common,

• [@ Medial is mild, does not cause renal damage
• Perimedial and intimal - PeIn - PaIn - can cause renal damage

Distal - midrenal artery - Proximal renal artery in sequence of medial, perimedial and intimal]

• Renovascular hypertension should be suspected in the presence of the following signs and symptoms (Working Group on Renovascular Hypertension, 1987):
• 1. Severe or refractory hypertension with evidence of grade III or IV hypertensive retinopathy
• 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 or in association with the use of ACE inhibitors or angiotensin II receptor blockers (ARBs) or with a reduction of blood pressure (BP) 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

Note - Suspect renovascular hypertension in patients with severe or abrupt-onset hypertension who otherwise have no risk factors for high blood pressure

Goldblatt 1 - two kidney, one clip model, RAAS dependent - if you can correct RAAS, then there is chance to cure this kidney 

Goldblatt 2 - One kidney, one clip model - renin increase is transient -  it is not renin mediated HTN, its fluid mediated HTN.

• MR angiography is the investigation of choice in most center 
• CT angiography is a good alternateive for patients who cannot have MRI and is also useful in the follow up of patients who have renal artery stents 
• Main role of USG is in the investigation of transplant renal artery stenosis

Clinical entity that encompasses flash pulmonary edema (FPE) in the settings of bi- lateral. renal artery stenosis (RAS)

• Control of BP may be achieved in more than 90% of patients with medical therapy alone
• Medical therapy may reduce BP below a critical level and induce ongoing renal ischemia distal to the arterial lesion, resulting in tubular atrophy, interstitial fibrosis, glomerulosclerosis, and progressive loss of function in the affected kidney(s). Although these changes are more likely to be observed with antihypertensives that inhibit angiotensin or block its receptors than with others, this is not uniformly seen in clinical practice. In addition, with the exception of medial fibromuscular dysplasia, all forms of RAS can progress in severity despite medical therapy. Therefore renal function should be closely monitored whenever antihypertensive
• agents are used in patients with renovascular hypertension, particularly when they are combined with diuretic.
• In addition to monitoring the serum creatinine concentration and estimated GFR or creatinine clearance, renal sizes and cortical blood flow velocity by duplex scanning should be assessed, because they may more quickly provide evidence of irreversible nephron loss. ACE inhibitors and ARBs, particularly in the setting of volume contraction, may also result in acute (usually reversible) renal failure in 10% to 20% of those with either bilateral RAS or RAS affecting a solitary kidney.

• Progressive decline in GFR during treatment of hypertenion 
• Failure to achieve adequate blood pressure control despite optimal medical therapy 
• Rapid or recurrent decline in GFR associated with reduced systemic blood pressure 
• Decline in GFR associated with ACE inhibitors/ARB
• Recurrent congestive heart failure out of proportion to left ventricular dysfunction

• Angiographic technique by which stenotic renal arteries are dilated with a balloon-tipped catheter.
• Lesions that are most amenable to PTRA
• - < 10 mm in length
• - partially occluded
• - do not involve the ostium

There appears to be a “window of opportunity” period defined by a serum creatinine level between 1.5 mg/dL and 3 mg/dL

Even when technically successful, the restenosis rate after PTRA is significant (30% for nonostial and 50% for ostial lesions) and may occur shortly after the procedure (15% to 30% within 2 years)

• PTRA - in children, stenting has high occlusion rate 
• PTRA with stenting - in adults, PTRA should be associated with stenting, because they are associated with atherosclerosis

Although the results of many earlier studies suggest that PTRA with stenting may cure or improve control of hypertension, three more recent randomized studies raise questions about the effectiveness of revascularization with stenting for BP control

• STAR trial
• - either renal artery stenting and medical therapy or medical therapy alone
• - result - no difference in the degree of BP control

• Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) trial
• - revascularization and medical therapy or medical therapy alone
• - result - no difference in BP control between the two groups

• Cardiovascular Outcomes and Renal Atherosclerotic Lesions (CORAL) study
• - medical therapy alone vs medical therapy plus renal artery stenting
• - Result - similar outcome
• - Drawback of study - Patients with accelerated/malignant hypertension, Flash pulmonary edema were not included in this trial

These studies raise the question of whether the risk of stenting for RAS is worth the potential benefit regarding BP control or prevention of renal failure, although many believe that a subset of patients may benefit from endovascular intervention

• With the advent of ACE inhibitors, ARB, statins, and PTRA, the need for surgical revascularization and reconstruction of the renal artery has diminished. Indication for surgical intervention include
• - Patients with RAS with concomitant aneurysmal or occlusive aortic disease in which surgery is indicated
• - macroaneurysms of the renal artery associated with the stenosis because rupture of these lesions may occur if they are larger than 4 cm
• - Malignant/accelerated or uncontrollable hypertension, who do not tolerate medical therapy, or who show rapid deterioration of renal function (1 to 6 months before presentation) with serum creatinine remaining between 1.5 and 3.0 mg/dL

• Kidney greater than 8 cm in length;
• Retrograde filling of the distal renal artery by collateral vessels on radiographic or scintigraphic imaging studies;
• Patent distal renal artery;
• Viability of the involved kidney on isotopic renography; and
• Minimal glomerular sclerosis and well-preserved tubules on renal biopsy

Aortorenal bypass – when the abdominal aorta is not diseased.



Alternative techniques for renal arterial bypass

• Splenorenal bypass for left
• Hepatorenal bypass for right arterial lesions,
• Ileorenal bypass,
• Bench surgery with autotransplantation of the involved renal unit,
• Use of the supraceliac or lower thoracic aorta for the bypass
• Some surgeons advocate performing unilateral revascularization to decrease morbidity

Ace inhibitor contraindicated, Unilateral drug of choice is ace inhibitor ? ref