Proteinuria

1. Proteinuria

3. 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

4. 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

5. Endocytosis in proximal tubule (>99%) Albumin relatively impermeable across glomerulus

6. 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).

7. Definitions • Adults: Proteinuria >150 mg protein/day • Children: Proteinuria > 4 mg/m2/hr • Using the dipstick assay a) 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)

8. 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)

9. 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.

10. Differential • Non-pathologic causes of proteinuria: • Orthostatic • Febrile • Exercise-induced • Pathologic proteinuria causes: • tubular (e.g. allergic-interstitial nephritis, ATN) • glomerular (nephrotic syndrome, glomerulonephritis)

11. 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

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

13. 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

14. 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