Introduction to the Child with Proteinuria

Chapter 517 Introduction to the Child with Proteinuria

The demonstration of proteinuria on a routine screening urinalysis is common; 10% of children aged 8-15 yr test positive for proteinuria by urinary dipstick at some time. The challenge is to differentiate the child with proteinuria related to renal disease from the otherwise healthy child with transient or other benign forms of proteinuria.

The urinary dipstick test offers a qualitative assessment of urinary protein excretion. Dipsticks primarily detect albuminuria and are less sensitive for other forms of proteinuria (low molecular weight proteins, Bence Jones protein, gamma globulins). Visual changes in the color of the dipstick are a semiquantitative measure of increasing urinary protein concentration. The dipstick is reported as negative, trace (10-20 mg/dL), 1+ (30 mg/dL), 2+ (100 mg/dL), 3+ (300 mg/dL), and 4+ (1000-2000 mg/dL).

False-negative test results can occur in patients with dilute urine (specific gravity <1.005) or in disease states in which the predominant urinary protein is not albumin. False-positive test results may be seen in patients with gross hematuria, contamination with antiseptic agents (chlorhexidine, benzalkonium chloride, hydrogen peroxide), urinary pH >7.0, or phenazopyridine therapy. The dipstick may also be falsely positive in patients with highly concentrated urine. A dipstick should be considered positive for protein if it registers >trace (10-29 mg/dL) in a urine sample in which the specific gravity is <1.010. If the specific gravity is >1.015, the dipstick must read ≥1+ to be considered clinically significant.

Because the dipstick reaction offers only a qualitative measurement of urinary protein excretion, children with persistent proteinuria should have proteinuria quantitated with the more precise spot urine protein:creatinine ratio (UPr:UCr). This ratio is calculated by dividing the UPr (mg/dL) concentration by the UCr (mg/dL) concentration and is best performed on a first morning voided urine specimen to eliminate the possibility of orthostatic (postural) proteinuria (Chapter 519). Ratios <0.5 in children <2 yr of age and <0.2 in children ≥2 yr of age suggest normal protein excretion. A ratio >2 suggests nephrotic-range proteinuria. UPr:UCr ratios have been shown to have a high correlation with protein excretion determinations in timed urine collection.

Timed (24-hr) urine collections offer more precise information regarding UPr excretion. A reasonable upper limit of normal protein excretion in healthy children is 150 mg/24 hr (0.15 g/24 hr). More specifically, normal protein excretion in children is defined as ≤4 mg/m²/hr; abnormal is defined as 4-40 mg/m²/hr; and nephrotic range is defined as >40 mg/m²/hr. Timed urine collections are cumbersome to obtain, and accuracy depends on a complete collection. As a result, timed collections have largely been replaced by the spot protein:creatinine ratio.

Microalbuminuria is defined as the presence of albumin in the urine above the normal level but below the detectable range of conventional urine dipstick methods. In adults, microalbuminuria (defined as an albumin excretion of 30-300 mg/g creatinine) is widely accepted as predicting cardiovascular and renal disease. The mean level of albumin excretion has been shown fall between 8 and 10 mg/g creatinine in children >6 yr old. Similar to adults, microalbuminuria in children has been found to be associated with obesity and to predict, with reasonable specificity, the development of diabetic nephropathy in type 1 diabetes mellitus.

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