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Proteinuria

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Objectives

• Be familiar with the causes of intermittent proteinuria

• Be able to accurately assess the results of a dipstick urinalysis

• Know how and when urine samples should be collected when evaluating proteinuria

• Be able to manage a child with pathologic proteinuria

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Definition

• Proteinuria is defined as the abnormal presence of protein in the urine– A small amount of protein is present in the

ultrafiltrate produced by the glomerulus– Much of this protein is absorbed by the

tubules (and some additional proteins are secreted into the urine)

– Ultimately, very little protein is present in the urine that leaves the kidney

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Endocytosis in proximal tubule (>99%)

Albumin relatively impermeable across glomerulus

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Definition

• Proteinuria measured using a dipstick assay– A reagent reacts with albumin producing a color change– Dipstick is reported on a semi-quantitative scale: negative, trace

(10-20 mg/dL), 1+ (30 mg/dL), 2+ (100mg/dL), 3+ (300 mg/dL), 4+ (1000-2000 mg/dL).

• Errors using a dipstick:– False negative tests are often seen in dilute urine (specific

gravity <1.005), and when a protein other than albumin is present in the urine.

– False positives can be seen in a concentrated urine, a basic urine (pH >8), and a urine contaminated by gross hematuria or by antiseptic agents (chlorhexidine or benzalkonium chloride).

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Definitions

• Adults: Proteinuria >150 mg protein/day

• Children: Proteinuria > 4 mg/m2/hr

• Using the dipstick assaya) 1+ protein may be significant in a dilute

sample (Sp Gr 1.005 - 1.015)

b) 2+ protein may be significant in a concentrated sample (Sp Gr >1.015)

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Definitions

• Gold standard for measuring proteinuria:– 24 hr urine

• 24 hour is logistical nightmare for parents– studies have shown that the ratio of protein to

creatinine in a random sample correlates with the value obtained with a 24 hr collection

– ratio often reflects the grams of protein obtained in a 24 hr collection (i.e. Pr:Cr 2.0 on a random sample equals 2 g/24hr)

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Testing

• In average pediatric cohort, up to 10% will test positive on a single sample, but less than 1% will have multiple positive samples.

• AAP Committee on Practice and Ambulatory Medicine recommends a screening U/A at age 5 and during the teenage years.

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Differential

• Non-pathologic causes of proteinuria:– Orthostatic– Febrile– Exercise-induced

• Pathologic proteinuria causes:– tubular (e.g. allergic-interstitial nephritis, ATN)– glomerular (nephrotic syndrome,

glomerulonephritis)

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Differential

• Orthostatic proteinuria - poorly understood phenomenon– The urine from these patients shows proteinuria in an

upright (daytime) sample, but normal urine in a first morning void

– In adults, orthostatic proteinuria is benign, but data in children is unavailable

• Febrile proteinuria - Mild proteinuria (less than or equal to 2+) can be found although the mechanism is unknown

• Exercise induced proteinuria and hematuria– These both typically resolve spontaneously after 48 hr

of rest

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Differential

• Causes of Constant Proteinuria:– Minimal Change Disease– Focal Segmental Glomerulosclerosis– IgA Nephropathy– Membranous Nephropathy– Essential HTN– Diabetes– Lupus

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Mechanisms of Pathology

• Altered Filtration– Glomerular hemodynamics increased

blood flow or pressure– Glomerular pathology reduced filtration

barrier (size and charge)

• Altered reabsorption– Proximal tubule pathology

• Combination

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Management of Pathologic Proteinuria

• If UA positive for protein:– make sure sample not overly concentrated, alkaline,

or contaminated with antiseptic agents– Fever or exercise?– If repeat dipstick is positive, then testing using

random urine protein:creatinine ratios should be performed and orthostatic proteinuria ruled out

• Serum BUN and creatinine should be measured• Renal ultrasound should also be considered, as

well as a referral to a pediatric nephrologist

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