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Protein Urine Quantitative

Urine protein is a mixture of plasma proteins, renal tubular proteins, and those from the lower urinary tract.  Very little plasma protein crosses the glomerular capillary membranes in healthy individuals. Traces of albumin and beta globulins may be filtered but are largely reabsorbed by the proximal tubule cells.  Cells of the ascending Loop of Henle may secrete Tamm-Horsfall mucoprotein.

Abnormally increased quantities of protein may appear in the urine because of three major mechanisms.

1.     Glomerular disease 

2.     Spillover of low -molecular weight plasma proteins such as Bence Jones proteins in multiple myeloma, myoglobin in rhabdomyolysis, and hemoglobin in intravascular hemolysis

3.     Impaired renal tubular reabsorption of proteins in tubulointerstitial kidney diseases. 

Quantification of urine protein is useful in categorizing kidney disease and in monitoring treatment. Protein quantitation of a 24-hour urine collection is the gold standard. In healthy adults, urinary protein excretion averages about 40 mg per day and the upper limit of normal is 150 mg per day.  Urine protein concentration may increase to 300 mg/24 hours in healthy adults following vigorous exercise.

A urinary protein excretion rate of more than 3500 mg (3.5 g) per day provides unequivocal evidence of glomerular disease and defines the nephrotic syndrome. This syndrome is defined as proteinuria that is severe enough to cause hypoalbuminemia and edema, often with hypercholesterolemia. Diabetic nephropathy is the commonest cause of nephrotic proteinuria. In nondiabetic patients, a few primary glomerular diseases account for most cases of nephrotic proteinuria.  Minimal change disease is the most frequent glomerulopathy in children (75%) and membranous nephropathy in adults (40%). Focal and segmental glomerulosclerosis accounts for 10–15% of cases of nephrotic syndrome in children and 15–25% in adults.  Intermediate rates of protein excretion, between 150 and 3000 mg per day, may be seen in any type of kidney disease.

Protein concentration in the urine relates to how much protein is filtered and the amount of water in the urine, which varies with hydration status. If a patient filters 200 mg of protein per day, his urine protein concentration could be relatively low if he drinks a lot of water or relatively high if he drinks very little water. This variable explains why the reference method for quantitating protein in the urine is a 24-hour collection. By collecting all the urine over a 24-hour period, then measuring its volume and its protein concentration, the total amount of protein excreted during the day can be calculated.

Creatinine is freely filtered through the glomerulus and is not extensively reabsorbed or secreted. Its concentration in the urine is affected by hydration status, in the same way as protein. The best way to negate the effect of hydration status is to calculate the urine protein to creatinine ratio, which closely correlates with a 24-hour urine protein. The upper limit of normal for the protein to creatinine ratio is 0.2 mg protein/mg creatinine or 200 mg protein/g creatinine. The major advantage of the protein to creatinine ratio is that it can be calculated on a random urine specimen. There is excellent correlation between protein to creatinine ratios in random urine samples and 24-hour collections in healthy individuals, patients with all types of kidney disease, and patients with kidney transplants.

The following discussion illustrates how the protein to creatinine ratio relates to the 24-hour urine. A typical 24-hour creatinine excretion is 15 mg/kg for women and 20 mg/kg for men, corresponding to approximately 1000 mg creatinine per day (1g/day) for women and 1500 mg per day (1.5 g/day) for men. Since the upper limit of normal for 24-hour protein excretion is 150 mg/day, the corresponding ratio is 0.15 mg protein/mg creatinine for women (150mg/g) and 0.1 mg protein/mg creatinine for men (100mg/g).

An important caveat to considering a 24-hour urine as the gold standard is that patients rarely collect 24-hour urines accurately. Simultaneous reporting of urine protein and creatinine is helpful in assessing the completeness of a 24-hour collection and in interpreting low to intermediate protein concentrations in high volume urine samples. Creatinine excretion increases with muscle mass, is lower among women and decreases with age. Men usually excrete 19 to 26 mg of creatinine per kg of body weight daily and women usually excrete 14 to 21 mg/kg body weight. Creatinine values <1g/24 hours for men or <0.9g/24 hours for women nearly always mean that the urine collection was incomplete. Normal urine volume is 0.6 to 2.0 liters per day, but most people produce between 1.0 and 1.5 liters per day. 

Reference range for urine creatinine is 1 –2 g per 24 hours for men and 0.6 – 1.5 g per 24 hours for women.

The reference range for 24-hour urine protein is 0-150 mg/24 hours. The reference range for the protein to creatinine ratio is 0-200 mg/g. 

Specimen requirement is a 24-hour urine collection in a container without preservative. Specimen should be refrigerated during and after the collection. Protein: creatinine ratio can be performed on spot urine samples.

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