Proteinuria: Causes Glomerular permeability is affected by molecular weight, size, shape and electrical charge of molecules. It is also influenced by renal hemodynamics. In general, the renal threshold is 68,000 daltons, therefore the glomerular filtrate contains electrolytes (in a similar concentration to plasma) and low molecular weight proteins. These filtered proteins are normally taken up and catabolized by renal tubular epithelial cells, therefore altered renal tubular function can result in these proteins being retained in the urine (tubular proteinuria). Alterations in the glomerular barrier from altered renal blood flow (e.g. passive venous congestion in congestive heart failure) may result in mild proteinuria, whereas glomerular disease will result in a significant and severe proteinuria, consisting mostly of albumin (glomerular proteinuria). Increased filtration of low molecular weight proteins that are in high concentration in blood (hemoglobin, myoglobin, Bence-Jones proteins) will result in a significant proteinuria as the high concentration of these proteins in the filtrate overwhelm the renal tubular resorptive capacity (prerenal proteinuria). Urinary tract inflammation and hemorrhage will also result in proteinuria because of the contribution of plasma proteins. Note that there are also cases in which physiologic proteinuria occurs. These are usually due to alterations in the glomerular barrier and are typically transient in nature. Physiologic proteinuria may occur with exercise and fever. The exact mechanism is unknown, but may be due to alterations in renal hemodynamics. Prerenal proteinuria Glomerular overload: A colostral proteinuria occurs in neonatal animals less than 40 hours old. Tubular overload: Bence-Jones proteins, hemoglobin (intravascular hemolysis), myoglobin (rhabdomyolysis). Hemoglobin and myoglobin will cause a positive result for heme proteins on the dipstick. The protein reaction on the dipstick is less sensitive than SSA-protein to hemoglobin and myoglobin. Renal proteinuria Glomerular proteinuria: In early glomerular disease, proteinuria is selective, with albuminuria only. As renal disease progresses, non-selective proteinuria (albumin and globulins) results. Glomerular disease is responsible for moderate to marked proteinuria, i.e. dipstick readings of > 3+ and urine protein:creatinine ratios of > 3. Causes of glomerular proteinuria include amyloidosis (usually produces the highest urine protein:creatinine ratios, often > 13), glomerulonephritis, diabetic nephropathy and renal neoplasia. Tubular proteinuria: This is due to decreased renal tubule function resulting in decreased absorption of filtered low molecular weight proteins or increased excretion of proteins. This results in a mild to moderate proteinuria, i.e. dipstick readings of 2+ or less and urine protein:creatinine ratios of < 3. Causes of tubular malfunction are many and varied, e.g. Fanconi syndrome, renal ischemia, nephrotoxins (such as aminoglycosides). In cases of tubular proteinuria, there is often other evidence of tubular malfunction in the urine sediment, e.g. inappropriate USG, cylindriuria, glucosuria (without hyperglycemia). Post-renal proteinuria Inflammation: Inflammation and/or infection in the urogenital tract, e.g. cystitis. The urine protein:creatinine ratio is an unreliable indicator of urinary protein loss in the presence of inflammation or infection (i.e. an active urine sediment). Hemorrhage: In severe hemorrhage, the dipstick pad will be unreadable due to the urine color. Hemorrhage results in proteinuria with both dipstick and SSA methods.