Is Proteinuria a Sign of Kidney Disease?

Protein in the urine is a nonspecific finding and does not necessarily indicate an underlying kidney disorder. Physiologic proteinuria occurs commonly in children and adults from leakage of small amounts of albumin and low-molecular-weight proteins into the urine and may be exaggerated after standing (orthostatic proteinuria). Physiologic urine protein concentration is typically < 4 mg/m²/hr in children and reaches 150 mg/24 hr in adults (Table 53-1). Pathologic proteinuria is usually far in excess of physiologic values. Acute febrile illnesses or vigorous physical activity can cause transient elevations of protein excretion above physiologic levels.

Table 53-1 Quantifying Proteinuria

What Causes Persistent Pathologic Proteinuria?

When pathologic proteinuria is persistent, it is usually a sign of an underlying kidney disease. In addition, when children are known to have kidney disease, the presence and the magnitude of proteinuria are independent factors that predict a poor outcome. A patient with both blood and protein in the urine has a high likelihood of having glomerulonephritis (Chapter 65). Persistent proteinuria without blood occurs in two situations: Glomerular proteinuria occurs in disorders that cause increased permeability of the glomerular basement membrane that allows leakage of large-molecular-weight proteins such as albumin. Examples include nephrotic syndrome, glomerulopathies such as focal segmental glomerulosclerosis, and reflux nephropathy/renal scarring from acute pyelonephritis (Chapter 65). Tubular proteinuria results from defective tubular resorption of low-molecular-weight proteins such as beta₂-microglobulin and occurs in Fanconi’s syndrome, tubulointerstitial nephritis, acute tubular necrosis, reflux nephropathy, and a variety of hereditary diseases.

What Is Orthostatic Proteinuria?

Orthostatic proteinuria accounts for 70% to 80% of all cases of proteinuria in adolescents. Its pathogenesis is not entirely clear but is thought to be mediated by hemodynamic mechanisms during prolonged standing. Children and adolescents with orthostatic proteinuria usually have protein excretion < 1 g/24 hr. They have a benign long-term course and minimal risk of developing renal insufficiency. Establishing the diagnosis is straightforward (see later). Therapy is not needed, but careful explanation and reassurance about the benign nature of this phenomenon are important. Annual follow-up to monitor blood pressure and growth and to perform urinalysis is recommended because orthostatic proteinuria has not been optimally studied.

When Is Proteinuria Likely to Be Detected?

Proteinuria is most commonly identified when a “routine” dipstick urinalysis is performed on an asymptomatic patient at a well-child visit or sports physical examination. Occasionally, findings such as edema, a purpuric rash, hypertension, or gross hematuria will prompt urinalysis that detects proteinuria. The urine dipstick is highly sensitive and specific for albumin. False-positive tests occur when the urine has high specific gravity or is highly alkaline; false-negative tests occur when the urine has low specific gravity or when only non-albumin proteins such as immunoglobulin light chains are present.

What Findings from History Are Important?

Whether a child has symptomatic or asymptomatic persistent proteinuria, you should inquire specifically about fever, recent viral or bacterial illnesses, gross hematuria, swelling of eyes and legs, and abdominal distention. Heavy physical exertion shortly before the office visit may cause proteinuria. Past history of previous urinary tract infections, arthritis, rash, or other underlying disorders may help with diagnosis. A detailed medication history, especially for chronic use of nonsteroidal antiinflammatory drugs, may identify a cause of proteinuria.