VIII. Hereditary Renal Diseases

A.General concepts. Because many inherited renal diseases present in childhood, a careful family history is critical in all children with renal disease.

B.Alport syndrome

1.Definition. Alport syndrome is a form of progressive hereditary nephritis that is secondary to defects in the side chains of type IV collagen within the glomerular basement membrane.

2.Etiology. Inheritance is usually X-linked dominant, although autosomal dominant and autosomal recessive variants exist.

3.Clinical features

a.Renal manifestations initially include hematuria, often gross hematuria, and sometimes hypertension. ESRD often occurs in males with X-linked Alport syndrome as early as adolescence, but the age of onset of ESRD differs between kindreds. Women who carry the gene are less likely to develop ESRD, but it may occur. Autosomal dominant and autosomal recessive Alport syndrome may also lead to ESRD.

b.Hearing loss typically begins in childhood and progresses; approximately 50% of adults have some loss of hearing, ranging from mild to severe.

c.Ocular abnormalities involving the lens and retina occur in 25–40% of patients.

4.Management. Therapy includes treatment of hypertension, use of ACE inhibitors (even in patients who have proteinuria without hypertension), sometimes with the addition of an angiotensin receptor blocker to slow the progression of renal disease, and eventually renal transplantation.

C.Multicystic renal dysplasia. This condition is the most common cause of a renal mass in the newborn, occurring in 1 in 4300 live births, and is most often unilateral. The inheritance is not clear, but it appears to be a sporadic occurrence. See section XII.D.2 for more details.

D.Autosomal recessive polycystic kidney disease (ARPKD) or infantile polycystic kidney disease

1.Epidemiology. ARPKD is uncommon, occurring in approximately 1 in 10,000–40,000 live births.

2.Clinical features

a.The most severely affected infants have a maternal history of oligohydramnios secondary to nonfunctioning or poorly functioning kidneys in utero. This leads to pulmonary hypoplasia, which may be incompatible with life.

b.Greatly enlarged cystic kidneys

c.Severe hypertension is common.

d.Liver involvement of variable clinical severity is a constant finding, including cirrhosis with portal hypertension.

3.Prognosis. Although the degree of renal insufficiency in infancy may range from mild to severe, ARPKD is progressive and ultimately all patients require renal transplantation.

E.Autosomal dominant polycystic kidney disease (ADPKD) or adult polycystic kidney disease

1.Epidemiology. ADPKD is a common genetic disorder (affecting about 1 in 500 individuals) that usually presents in adulthood (20–40 years of age). There are two gene mutations that cause ADPKD; ADPKD1 mutations are more common and cause an earlier onset of disease than ADPKD2 mutations.

2.Clinical features. Clinical findings are variable and include abdominal pain, flank masses, urinary tract infection (UTI), gross or microscopic hematuria, hypertension, or

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renal insufficiency. Associated cerebral aneurysms may occur, with early death.

3.Prognosis. Most patients develop severe hypertension and renal insufficiency, eventually requiring transplantation.

F.Medullary sponge kidney. This condition occurs sporadically or may have autosomal dominant inheritance. Patients may be asymptomatic or have hematuria, UTI, or nephrolithiasis.

G.Nephronophthisis. This is a ciliopathy that occurs in several forms. The infantile, juvenile, and adolescent forms are autosomal recessive and lead to ESRD in childhood or young adulthood, and there are often significant associated extrarenal manifestations in 10–15% of patients, including retinal degeneration, cerebellar vermis hypoplasia, occipital encephalocele, hepatic fibrosis, situs inversus, bronchiectasis, and skeletal defects. More than 13 mutated genes have been described that lead to nephronophthisis.

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IX. Renal Tubular Acidosis (RTA)

A.Definition. RTA refers to a group of congenital or acquired disorders that result from the inability of the kidney to maintain normal acid–base balance because of defects in bicarbonate conservation or because of defects in the excretion of hydrogen ions.

B.Etiology (Table 11-2)

1.Congenital forms of RTA are caused by mutations in various transporters in the proximal or distal tubular cells.

2.Acquired forms of RTA may be caused by nephrotoxic drugs (e.g., amphotericin) or systemic diseases (e.g., autoimmune disorders).

C.Clinical features (Table 11-2). Symptoms vary with the type of RTA and with the patient’s age.

1.Infants and young children tend to present with growth failure and vomiting, and, at times with life-threatening metabolic acidosis.

2.Older children and adults may have recurrent calculi, muscle weakness, bone pain, and myalgias.

3.Some forms of RTA result in nephrocalcinosis, which in turn may lead to polyuria from urinary concentrating defects.

4.The classic electrolyte presentation is a hyperchloremic metabolic acidosis with a normal serum anion gap.

D.Types of RTA (Table 11-2)

E.Evaluation. RTA should be considered in patients who present with a non–anion gap hyperchloremic metabolic acidosis. Acidosis should be confirmed by a venous blood gas.

1.Initial laboratory studies should include serum potassium, phosphorus and uric acid, urine pH, and urinalysis to evaluate for proteinuria and glucosuria. Calculation of the urine anion gap (urine Na+ + urine K+ − urine chloride) is important; a positive urine anion gap is seen in Types I and IV RTA and may be seen in Type II RTA.

2.If there are signs of a diffuse tubular disorder (manifested by hypokalemia, hypophosphatemia, and aminoaciduria), the patient should be evaluated for Fanconi syndrome by performing more extensive testing of other tubular functions.

Table 11-2

Types of Renal Tubular Acidosis (RTA)

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*Findings associated with Fanconi syndrome: proximal RTA, hyperphosphaturia, aminoaciduria, glucosuria, and potassium wasting.

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X.Acute Kidney Injury

A.Definition. AKI is defined as an abrupt decrease in the ability to excrete nitrogenous wastes.

B.Etiology (Table 11-3)

C.Clinical features

1.Systemic signs and symptoms depend on the cause and severity of the renal insult but often include lethargy, nausea, vomiting, respiratory distress, hypertension, and sometimes seizures.

2.The clinical presentation may be oliguric (diminished urine output) or nonoliguric (normal urine output). In children, oliguria is defined as a urine output < 1 mL/kg/hour.

D.Evaluation

1.Laboratory tests should include serum electrolytes, BUN, creatinine, urinalysis, and urinary protein and creatinine levels, as well as a more specific investigation for the cause of kidney injury, such as testing for ANCA or drug levels of nephrotoxic medications based on the clinical history.

2.Imaging studies may include a renal or pelvic ultrasound and a nuclear renal scan to evaluate renal function.

E.Management

1.If possible, the specific cause should be addressed (e.g., removal of a nephrotoxic drug).

2.If the patient is intravascularly volume depleted, the intravascular volume should be restored first with appropriate IV fluids, and then total fluid intake should be restricted to the patient’s insensible losses (approximately 300 mL/m2/day) plus output (urine, stool) replacement.

3.Electrolyte intake should be matched to estimated electrolyte losses. Typically, sodium, potassium, and phosphorus intake are restricted.

4.Protein intake should be restricted to the recommended dietary allowance (RDA) of protein for age. Caloric intake should also be at the RDA for age.

5.Patient monitoring should include daily weights, frequent blood pressure measurements, calculation of intake and output, and monitoring of electrolytes.

6.Dialysis therapy (peritoneal dialysis, hemodialysis, or continuous renal replacement therapy) is used when conservative management fails to maintain the patient in safe biochemical, nutritional, and fluid balance.

Table 11-3

Etiologies of Acute Kidney Injury (AKI)

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*

HUS = hemolytic uremic syndrome; PSGN = poststreptococcal glomerulonephritis; FeNa = fractional excretion of sodium; SG = specific gravity; GFR = glomerular filtration rate; Creat = creatinine; BUN = blood urea nitrogen.

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