A 3-year-old boy has had intermittent facial swelling for the past 3 weeks. Symptoms were self-limited and attributed to seasonal allergies. He awoke with significant periorbital and facial edema (Figure 67-1), and pitting edema to his mid-tibia bilaterally. He denies any abdominal pain, headache, rash, or gross hematuria. His evaluation reveals a normal blood pressure, normal renal function, and 4+ protein on a urine dipstick. He was presumptively diagnosed with minimal change disease and started on a course of prednisone. His edema gradually subsided (Figure 67-2) and his proteinuria resolved within the first two weeks of therapy.
Significant facial edema on frontal (A) and lateral (B) views in a 3-year-old boy secondary to minimal change disease. (Used with permission from Cleveland Clinic Children’s Hospital Photo Files.)
Resolution of facial edema in the same child from figure 67-1 following a course of prednisone. (Used with permission from Cleveland Clinic Children’s Hospital Photo Files)
Nephrotic syndrome is a tetrad of signs and symptoms: proteinuria (>50 mg/kg/day), hypoalbuminemia (serum albumin <3 gm/dL), edema, and hyperlipidemia. Prognosis is largely dependent on the glomerular etiology of the proteinuria. Minimal change disease is by far the most common etiology of nephrotic syndrome in childhood and carries an excellent long-term renal prognosis.
Estimated incidence of minimal change disease is 5 per 100,000 children under the age of 16 with a median age of 2.5 years.
Boys are more commonly affected.1
Rare familial cases have been reported.
Etiology and Pathophysiology
Nephrotic syndrome begins with a glomerular lesion, causing significant proteinuria. Protein losses result in hypoalbuminemia. This produces edema, typically facial, lower extremity, and genital. The etiology of the associated hyperlipidemia is not fully elucidated.
Although minimal change disease is the most common cause of nephrotic syndrome, little is known about the disease etiology. The most common hypothesis involves an unidentified circulating factor.2
Children typically present initially with edema (Figures 67-1 and 67-3).
Urinary symptoms are rare. Microscopic hematuria can be seen in up to 10 percent of children with nephrotic syndrome. Gross hematuria has also been rarely described with minimal change disease and is more indicative of glomerulonephritis.5
Young boy with nephrotic syndrome and malnutrition in Africa. Note the prominent periorbital edema from the low albumin due to the combination of renal protein loss and malnutrition. The red hair is a sign of kwashiorkor. (Used with permission from Richard P. Usatine, MD.)