IV. Hypertension

A.Definitions

1.Normal blood pressures during childhood depend on the child’s age, sex, height, and weight. Standards are based on upper arm blood pressures (blood pressures in the legs are generally higher than in the arms).

2.Normal systolic and diastolic blood pressures are defined as blood pressure less than the 90th percentile.

3.Prehypertension is between the 90th and 95th percentiles for age.

B.Classification. Hypertension is divided into categories based on severity and etiology.

1.Hypertension is defined as the average of three separate blood pressures that are greater than the 95th percentile for age.

2.Stage 1 hypertension is defined as systolic or diastolic blood pressures between the

95th and 99th percentiles + 5 mm Hg.

3.Stage 2 hypertension is defined as systolic or diastolic blood pressures > 99th percentile + 5 mm Hg.

4.Malignant hypertension is hypertension associated with evidence of end organ damage, such as retinal hemorrhages, papilledema, seizures, and coronary artery disease (in adults).

5.Essential hypertension is defined as hypertension without a clear etiology.

6.Secondary hypertension is hypertension that has a recognizable cause (e.g., renal parenchymal disease, coarctation of the aorta). Most hypertension in childhood is secondary hypertension.

C.Measurement

1.Blood pressure cuff size

a.It is critical to use the proper size cuff. A cuff that is too small will give factitiously elevated blood pressures, and a cuff that is too large will give falsely depressed blood pressures.

b.The cuff bladder should measure two-thirds of the length of the arm from the shoulder to the elbow.

2.Position

a.Blood pressure in infants should be measured in the supine position.

b.Blood pressure in children and adolescents should be measured in the seated position with the fully exposed right arm resting on a supportive surface at heart level.

D.Etiology (Table 11-1). The causes of hypertension vary with the child’s age.

1.In neonates and young infants, the most common causes include renal artery embolus after umbilical artery catheter placement, coarctation of the aorta, congenital renal disease, and renal artery stenosis.

2.In children 1–10 years of age, the most common causes include renal diseases and coarctation of the aorta.

3.In adolescents, the most common causes include renal diseases and essential hypertension.

E.Clinical features. Clinical presentations of hypertension also vary with the child’s age. Some children, like some adults, are asymptomatic.

1.Infants may present with nonspecific signs and symptoms including irritability, vomiting, failure to thrive, seizures, or even CHF if the hypertension is severe.

2.Children with malignant hypertension, especially of acute onset, may develop headaches, seizures, and stroke.

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3.Children with chronic hypertension may have growth retardation and poor school performance.

F.Evaluation. Because most children with hypertension have secondary hypertension, the cause of the hypertension is usually identified through a careful history (including family history and birth history), physical examination, and diagnostic testing. Testing is guided by the most likely causes of hypertension on the basis of the child’s age and clinical presentation.

1.Physical examination

a.All children should undergo an assessment of growth and careful, accurate measurements of four-limb blood pressures to evaluate for coarctation of the aorta (see Chapter 8, section III.F). In coarctation, hypertension is usually noted in the right arm with lower blood pressures in the legs.

b.In children, a careful fundoscopic examination may show retinal hemorrhages, papilledema, or in long-standing hypertension, arteriovenous nicking.

c.Other important physical findings include signs of CHF, café-au-lait spots as seen in neurofibromatosis, abdominal masses, abdominal bruits, and ambiguous genitalia.

2.Laboratory evaluation and imaging

a.Initial evaluation should include a complete blood count (CBC), electrolyte panel, blood urea nitrogen (BUN) and creatinine, urinalysis, plasma renin and aldosterone levels, thyroid panel, chest radiograph, and renal ultrasound. A urine microalbumin/creatinine ratio is useful in detecting early glomerular injury from the hypertension as a sign of end organ damage. (Note that the microalbumin/creatinine ratio is a very sensitive test for detecting proteinuria and is used to detect early glomerular proteinuria in hypertension. The protein/creatinine ratio becomes positive when a patient has more overt proteinuria and is therefore an indicator for more severe damage.)

b.If the initial evaluation is suggestive, further studies may include plasma catecholamines, measurement of plasma and urinary steroids, and echocardiography. Computer tomography (CT) angiography, especially in the setting of discrepant kidney sizes, can be performed to rule out renal artery stenosis.

c.Ambulatory blood pressure monitoring is very useful to rule out anxiety (“white coat hypertension”) before embarking on more expensive or invasive diagnostic testing.

G.Management. The treatment of hypertension should be aimed at curative therapies, whenever possible. In chronic hypertension, the ultimate goal is to maintain the child’s blood pressure below the 90th percentile for age.

1.If a specific, treatable cause of hypertension is identified, directed management, such as surgical correction of a coarctation of the aorta, treatment of hyperthyroidism, or removal of a catecholamine-secreting tumor, is performed as a cure.

2.If the child appears to have essential hypertension, the initial approach is conservative through implementation of a diet with no added salt, and if appropriate, weight loss. This approach requires frequent monitoring and encouragement.

3.If the child has underlying renal disease or more significant hypertension (e.g., stage 2), or if conservative hypertension treatment has failed, antihypertensive medications are used.

4.Hypertensive emergencies (e.g., seizures, severe headache, stroke, fundoscopic changes, CHF) require prompt therapy with IV antihypertensives.

Table 11-1

Etiology of Hypertension in Children

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Renal diseases

Glomerulonephritis

Reflux nephropathy

Renal dysplasia

Polycystic kidney disease

Renal trauma

Obstructive uropathy

Hemolytic uremic syndrome

Renal vascular lesions

Renal artery stenosis or embolus

Renal vein thrombosis

Vasculitis

Neurofibromatosis

Cardiac disease

Coarctation of the aorta

Endocrine disorders

Neuroblastoma

Pheochromocytoma

Congenital adrenal hyperplasia

Hyperthyroidism

Hyperparathyroidism

Hyperaldosteronism

Cushing syndrome

Drug-related causes

Corticosteroids

Illicit drugs (e.g., amphetamines, cocaine, PCP)

Anabolic steroids

Cold remedies

Oral contraceptives

Genetic causes

Liddle syndrome

Gordon syndrome

Apparent mineralocorticoid excess syndrome

Glucocorticoid remediable

Aldosteronism

Miscellaneous causes

Wilms tumor

Blood pressure cuff too small

Anxiety

Pain

Fractures and orthopedic traction

Hypercalcemia

*Essential hypertension is rare in young children. All children with hypertension should have a careful evaluation to determine the cause of the hypertension.

PCP = phencyclidine.

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V.Glomerulonephritis

A.Definition. Glomerulonephritis refers to a group of diseases that cause inflammatory changes in the glomeruli.

B.Etiology. Causes are varied but generally involve immune-mediated injury to the glomerulus. Various antigens can stimulate immune complex deposition or formation within the glomerulus.

C.Classification

1.Primary glomerulonephritis refers to a disease process limited to the kidney.

2.Secondary glomerulonephritis refers to a disease process that is part of a systemic disease (e.g., systemic lupus erythematosus [SLE]).

D.Clinical features. The presentation of glomerulonephritis is variable.

1.Some patients present with an acute “nephritic” syndrome which is characterized by gross hematuria, “cola-colored” urine, hypertension, and occasionally signs of fluid overload from renal insufficiency.

2.Some patients may present with glomerulonephritis associated with nephrotic syndrome with heavy proteinuria, hypercholesteremia, and edema.

3.Some patients may be relatively asymptomatic, in whom glomerulonephritis is only detected as part of the evaluation of microscopic hematuria, proteinuria, or hypertension.

E.Laboratory evaluation. Laboratory studies should be performed promptly to avoid missing key transient abnormalities (e.g., transient decrease in serum complement is seen in poststreptococcal glomerulonephritis [PSGN]).

1.Initial evaluation should include urinalysis (to look for casts and to evaluate RBC morphology), urinary TP/CR (to quantify proteinuria), blood chemistries (including electrolyte panel, BUN, creatinine, serum albumin, liver enzymes, and cholesterol), serum complement components, antibody testing (antinuclear antibody [ANA], antineutrophil cytoplasmic antibody panel [ANCA], antistreptolysin O [ASO] and antiDNase B [ADB]), and an IgA level if IgA nephropathy is suspected.

2.Additional evaluation, should the history be suggestive, may include human immunodeficiency virus (HIV) testing and hepatitis C and hepatitis B serologies to evaluate for causes of postinfectious glomerulonephritis.

F.Common types of glomerulonephritis in children

1.Post-Streptococcal Glomerulonephritis (PSGN)

a.Epidemiology. PSGN is the most common form of acute glomerulonephritis that occurs in school-age children. (Note that some of the other less common causes of postinfectious glomerulonephritis include malaria, HIV, hepatitis B and C, and congenital syphilis.) PSGN is rare before 2 years of age.

b.Clinical features

1.PSGN typically develops 8–14 days after an infection of the skin or pharynx with a nephritogenic strain of group A β-hemolytic streptococcus. The latency period after impetigo may be as long as 21–28 days.

2.Hematuria (often gross hematuria), proteinuria (rarely of nephrotic proportion), and hypertension with signs of fluid overload (e.g., edema) are common clinical features.

3.Low serum complement (C3) is present but transient and normalizes within 8–12 weeks.

4.The degree of impairment of renal function is variable and usually normalizes within 6–8 weeks. Severe renal failure is rare.

c.Diagnosis. Diagnosis is on the basis of clinical features and laboratory findings,

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including evidence of prior streptococcal infection.

1.Detection of prior streptococcal infection

a.ASO titer is positive in 90% of children after streptococcal pharyngitis, but is positive in only 50% of patients with impetigo.

b.ADB titer is reliably positive after respiratory or skin infections with streptococcus.

2.Other diagnostic tests should include urinalysis, serum complement levels, renal ultrasound, tests of renal function, serum albumin, and serum cholesterol if the serum albumin is depressed.

3.Renal biopsy is indicated only if the patient has significant renal impairment

or nephrotic syndrome, or if the serum complement fails to normalize within 12 weeks. Biopsy typically shows mesangial cell proliferation and increased

mesangial matrix, as well as very large subepithelial deposits (humps) on electron microscopy, and C3 and IgG deposits on immunofluorescent microscopy.

d.Management. Treatment is supportive in most cases and includes fluid restriction, antihypertensive medications, and dietary restriction of protein, sodium, potassium, and phosphorus, as dictated by the level of renal functional impairment.

e.Prognosis is excellent with complete recovery in most patients.

f.Prompt antibiotic treatment of infections with nephritogenic strains of group A β-hemolytic streptococcus does not reduce the risk of PSGN, although it will reduce the risk of rheumatic fever (see Chapter 16, section VI and Chapter 7, section IX.A.5.f).

2.IgA nephropathy (Berger disease)

a.Epidemiology

1.IgA nephropathy is the most common type of chronic glomerulonephritis worldwide. It typically presents in the second or third decade of life.

2.It is more prevalent in Asia and Australia and in Native Americans, and it is rare in African Americans.

b.Etiology. The cause is poorly understood but may relate to abnormal clearance and formation of IgA immune complexes containing IgA molecules that are abnormally glycosylated.

c.Clinical features. Clinical findings classically include recurrent bouts of gross hematuria associated with respiratory infections. However, not all patients experience gross hematuria. Transient acute renal failure may occur in some patients. Microscopic hematuria is present in between the bouts of gross hematuria. The presence of heavy proteinuria and elevated serum creatinine are poor prognostic signs.

d.Diagnosis. Renal biopsy, which shows mesangial proliferation and increased mesangial matrix on light microscopy, is the basis of diagnosis. Immunofluorescent microscopy reveals mesangial deposition of IgA as the dominant immunoglobulin. Approximately 50% of patients have elevated serum levels of IgA. In more advanced cases there may be crescents, glomerular scarring, and tubular atrophy.

e.Management. Treatment is supportive and includes regular follow-up for the development of hypertension. Hypertension may eventually worsen proteinuria and renal function. Medications (angiotensin-converting enzyme [ACE] inhibitors, steroids, and immunosuppressants such as mycophenolate mofetil) are usually recommended for patients with associated pathologic proteinuria, renal insufficiency, or more significant glomerular inflammation on renal biopsy.

f.Prognosis is variable. Twenty to forty percent of patients eventually develop end-

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stage renal disease (ESRD).

3.Henoch–Schönlein purpura (HSP) nephritis (see Chapter 16, section I)

a.Definition. HSP is an IgA-mediated vasculitis characterized by nonthrombocytopenic “palpable purpura” on the buttocks, thighs, and lower arms, in addition to abdominal pain, arthritis or arthralgias, and gross or microscopic hematuria.

b.Clinical features. Clinical findings related to renal involvement include the following:

1.In the majority of patients, the renal features of HSP are self-limited with complete recovery within 3 months. One to five percent of patients develop chronic renal failure.

2.If proteinuria and marked hematuria are present, there may be severe glomerular inflammation. Renal biopsy is indicated for significant proteinuria or if there is an elevated serum creatinine.

3.The renal biopsy in HSP nephritis is indistinguishable from that of a patient with IgA nephropathy.

4.Membranoproliferative glomerulonephritis (MPGN)

a.Definition. MPGN is a term used for three forms of histologically distinct glomerulonephritis that share similar features. MPGN is characterized by lobular mesangial hypercellularity and thickening of the glomerular basement membrane.

b.Clinical features

1.Patients typically present with acute nephritic syndrome or with nephrotic syndrome accompanied by microscopic or gross hematuria.

2.Hypertension is common.

3.Seventy-five percent of patients have low serum complement levels.

4.Clinical course is variable, although most patients ultimately develop ESRD.

c.Management. There is no standardized treatment for MPGN, although some patients may respond to corticosteroids or mycophenolate mofetil. ACE inhibitors may slow disease progression.

5.Membranous nephropathy (MN) is a rare form of glomerulonephritis in young children, although it may be seen in children and adolescents. MN presents with heavy proteinuria and may progress to renal insufficiency. MN is the most common cause of nephrotic syndrome in adults in the United States. It is an autoimmune disease sometimes associated with hepatitis B infections and SLE.

6.SLE nephritis (see Chapter 16, section IV.D.8)

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