Differential Diagnosis

A. Normal Protein Excretion. Normal daily urinary protein excretion is < 4 mg/m2/h. This may result in 1+ proteinuria (~30 mg/100 mL) in concentrated urine (specific gravity > 1.020 g/mL).

B. Transient Proteinuria. Most cases of incidentally discovered proteinuria resolve within a few weeks. Transient proteinuria can be the result of common febrile illnesses, exercise, and clinically undiagnosed mild, resolving APIGN.

â–  C. Orthostatic (Postural) Proteinuria. Daytime (upright) protein excretion is elevated, but nighttime (supine) urine has little or no protein in it (< 50 mg/8 h). Daily protein excretion rarely exceeds 1 g. Typical patient with this condition is a thin adolescent boy experiencing a growth spurt; younger children and girls may also have this overall benign condition.

D. Fixed (Persistent) Proteinuria

1. Nephrotic-range proteinuria. A value of 3 + to 4 + proteinuria on urine dipstick, random urine protein-to-creatinine ratio > 2 (when concentrations are measured in grams per deciliter), and daily protein excretion > 2 g (some consider > 3 g) is consistent with nephrotic-range proteinuria. In younger children, proteinuria > 40 mg/m2/h is considered nephrotic range. Nephrotic-range proteinuria usually is accompanied by peripheral edema, hypoalbuminemia, and hypercholesterolemia—a clinical condition termed nephrotic syndrome.

a. Minimal change disease (MCD). Most common cause of nephrotic-range proteinuria in children: > 90% in preschool children, ~50% in adolescents. Urine sediment may contain hyaline casts and some RBCs, but cellular casts are absent.

b. Focal segmental glomerulosclerosis (FSGS). This form of nephrotic syndrome is seen with increasing frequency in children; in some studies, as many as 30% of all newly diagnosed cases of nephrotic syndrome were due to FSGS. Incidence of FSGS in African Americans is nearly 50% higher than in Caucasians. Frequently, resistance to steroid treatment is the first warning sign that nephrotic syndrome is due to FSGS rather than to MCD. Other warning signs are hypertension and renal insufficiency.

c. Membranous nephropathy. This form of nephrotic syndrome is uncommon in young children but is seen with increasing frequency in older children, adolescents, and young adults.

d. Glomerulonephritides. Nearly all variants of glomerulonephritis (see discussion of nonnephrotic-range proteinuria that follows) can present with nephrotic-range proteinuria. In such cases, hypertension, decreased renal function, and active urinary sediment (RBCs, WBCs, and cellular casts) can be seen, in addition to typical findings of nephrotic syndrome. Of note, prognosis of any patient with glomerulonephritis involving a high degree of proteinuria is more guarded than that of a patient with the same nephritis but nonnephrotic-range proteinuria.

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