1. Continuity Clinic Proteinuria

2. Continuity Clinic

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

6. Continuity Clinic 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. Continuity Clinic Definitions Adults: Proteinuria >150 mg protein/day Children: Proteinuria > 4 mg/m 2 /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. Continuity Clinic 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. Continuity Clinic 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. Continuity Clinic 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. Continuity Clinic 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. Continuity Clinic Differential Causes of Constant Proteinuria: –Minimal Change Disease –Focal Segmental Glomerulosclerosis –IgA Nephropathy –Membranous Nephropathy –Essential HTN –Diabetes –Lupus

13. Continuity Clinic 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. Continuity Clinic 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

15. Continuity Clinic