Renal Hypertension

An abnormal activation of the renin-angiotensin-aldosterone system (RAAS) is a significant cause of hypertension in children. Intrinsic renovascular hypertension (RVH), which arises from a disturbance of the circulation to one or both kidneys, is considered the prototypical lesion leading to renin-mediated hypertension. However, other renal diseases associated with the obliteration of blood vessels within the renal parenchyma also are associated with renin-mediated hypertension, the most common of which is the hypertension caused by renal scarring that results from reflux and recurrent pyelonephritis. Renin-mediated hypertension also may be seen as a complication of renal vein thrombosis, renal dysplasia or hypoplasia, polycystic kidneys, obstructive uropathy, and radiation nephritis. Nephroblastomas, hamartomas, and arteriovenous malformations also can compress the renal artery, leading to ischemia and renin-mediated hypertension. Rarely, juxtaglomerular cell tumors and nephroblastomas may produce renin directly and cause hypertension without affecting the renal circulation.

PATHOPHYSIOLOGY

The importance of the RAAS in blood pressure control has been known since the 1930s, when experiments demonstrated that occlusion of the renal artery caused chronic hypertension. The decrease in renal perfusion caused by arterial occlusion leads to increased secretion of renin. Renin acts on the prohormone angiotensinogen and converts it to angiotensin I. Angiotensin I is converted by the lungs to the potent vasoconstrictor angiotensin II by the action of angiotensin-converting enzyme (ACE).

The acute hypertension seen from the increase in angiotensin II is a direct result of its vasoconstrictive properties. In addition, angiotensin II enhances secretion of aldosterone. Aldosterone acts on the distal nephron to promote sodium, chloride, and water reabsorption. Chronic elevation of angiotensin II leads to vascular smooth muscle hypertrophy. The combination of volume expansion and decreased vascular compliance results in the chronic renin-mediated hypertension. Recent studies in animal models and patients suggest that endothelial dysfunction, specifically impaired nitric oxide-mediated vasodilation, contributes to both acute and chronic RVH.

RENOVASCULAR HYPERTENSION

RVH is the second most common cause of surgically remediable hypertension in children. Obstruction of blood flow to the kidneys is either intrinsic (Box 339.1) or extrinsic (e.g., from paraaortic tumors, paraaortic lymph nodes). Of the intrinsic lesions, fibromuscular dysplasia occurs most often in children. Fibromuscular dysplasia often is limited to the renal arteries, but it has been known to occur in other locations. Renal artery stenosis has been associated with many connective tissue, inflammatory, and neuroendocrine disorders, including Marfan syndrome, Williams syndrome, abdominal coarctation of the aorta, Takayasu arteritis, Moya Moya, tuberous sclerosis, and neurofibromatosis. Clinically significant atherosclerotic vessel disease, the most common cause of RVH in adults, is a rare finding in children.

Clinical Manifestations

Box 339.2 lists clinical clues that suggest the presence of RVH. RVH should be considered in any severe case of hypertension
(typically greater than 50 mm Hg systolic blood pressure or greater than 30 mm Hg diastolic blood pressure above the 95 percentile blood pressure) in a child whose condition is refractory to vasodilatory agents. An abdominal bruit, signs of secondary hyperaldosteronism (hypokalemia, mild alkalosis), and retinopathy suggest the presence of a chronic hypertensive disorder and should lead to a consideration of RVH. Finally, hypertension associated with a unilateral small kidney and an excellent response to ACE inhibitors is highly suggestive of RVH.