APPROACH TO PROTENURIA Mehryar Mehrkash Pediatric Nephrologist 1 Protein Excretion 2 Normal range protenuria in children is : (4 mg/m 2 /hr ) or (1 gr/m/day ) In neonates, is higher, up to 300 mg/m/day, because of reduced reabsorption of filtered proteins. Abnormal Protein Excretion Urinary protein excretion >100 mg/m/day or 4 mg/m/h is abnormal in children. Nephrotic range proteinuria (heavy proteinuria) is Urinary protein > 40 mg/m/hour or 1 g/m/day > 50 mg/kg/day. 3 low urinary protein excretion 1. Restriction of the filtration of proteins across the glomerular capillary wall. 2. Reabsorption of freely filtered low molecular weight (LMW) proteins (< 25,000 Daltons) by the proximal tubule. 4 Mechanisms of protein excretion 1. Glomerular 2. Tubular 3. Overflow proteinuria 5 7 8 9 Glomerular basal membrane 10 11 tubule Normally, the larger proteins are excluded at the glomerular barrier. Smaller proteins can pass, but are mostly reabsorbed. Glomerular barrier Glomerular Proteinuria Increased filtration of albumin across the glomerular capillary wall. Because of anatomical or functional (loss of anionic charge) lesions. Glomerular disease (MCD) Nonpathologic (fever, intensive exercise.. orthostatic or postural) 12 13 tubule Large proteins are able to pass by the abnormal glomerular barrier. Glomerular proteinuria Primary Minimal change disease Congenital nephrotic syndrome Focal segmental glomerular sclerosis IgA nephropathy (Berger's disease) Membranoproliferative glomerulonephritis Membranous nephropathy Alport syndrome 14 Tubular Proteinuria low molecular weight proteins such as 2- microglobulin, 1-microglobulin, and retinol-binding protein. These molecules filtered across the glomerulus and reabsorbed in the proximal tubule. Associated with other defects in proximal tubular. function( glycosuria,RTA 2, and phosphaturia). 15 16 tubule Malfunctioning tubules unable to reabsorb the smaller proteins filtered at the glomerulus. Tubular proteinuria Fanconi syndrome Heavy metal poisoning Acute tubular necrosis Tubulointerstitial nephritis Secondary to obstructive uropathy 17 Overflow Proteinuria Increased excretion of LMW proteins due to overproduction of a particular protein that exceeds tubular reabsorptive capacity. Primarily observed in adults with a plasma cell dyscrasia (multiple myeloma) Hemolysis,Rhabdomyolysis. 18 19 tubule Filtered load of proteins exceeds the tubular reabsorption rate (similar to glucosuria in hyperglycemia ) 20 21 tubule Filtered load of proteins exceeds the tubular reabsorption rate (similar to glucosuria in hyperglycemia ) Measurement of urinary protein The most common test Urine dipstick detect albumin. Sulfosalicylic acid test detects all proteins. Measure only the urine protein concentration. 22 Urine Dipstick Measures albumin via a colorimetric reaction between albumin and tetrabromophenol blue producing different shades of green. Dipstick testing will not detect LMW proteins. 23 Urinalysis Strips 24 Urinalysis Strips 25 Urinalysis Strips 26 Urinalysis Strips 27 Results Negative Trace : between 15 and 30 mg/dL 1+ : between 30 and 100 mg/dL 2+ : between 100 and 300 mg/dL 3+ : between 300 and 1000 mg/dL 4+ : >1000 mg/dL 28 False-Negative 29 Dilute urine (specific gravity 1025) Gross hematuria Urinary pH >7.0 Contaminated by antiseptic agents (chlorhexidine, benzalkonium chloride, hydrogen peroxide ) Phenazopyridine Iodinated radiocontrast 30 Quantitative Assessment Quantitative Assessment Children with persistent dipstick-positive proteinuria must undergo a quantitative measurement of protein excretion (timed 24-hour urine collection). 31 Quantitative Assessment Protein/cr ratio on a spot urine sample, in the first morning specimen. The normal value is