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 as a consequence of three major mechanisms.

  1. Glomerular disease is the most common cause of proteinuria.
  2. Less commonly, low -molecular weight plasma proteins may spill over into the urine when they are present in high concentrations. Examples include Bence Jones proteins in multiple myeloma, myoglobin in rhabdomyolysis, and hemoglobin in intravascular hemolysis.
  3. The third mechanism of proteinuria is impaired renal tubular reabsorption of proteins in tubulointerstitial kidney diseases.

Quantification of urine protein is useful in categorizing kidney disease and in monitoring treatment. Urine protein quantitation is usually performed on a 24-hour collection. In healthy adults, urinary protein excretion averages about 40 mg per day and the upper limit of normal is 150 mg per day. A urinary protein excretion rate of more than 3500 mg 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 the majority of 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 is 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, one can calculate the total amount of protein excreted during the day. For any given level of protein excretion, the urine protein concentration will be low in patients who drink a lot of water, but their 24-hour urine volume will be high; in contrast, the urine protein concentration will be high in patients who drink very little fluid, but their 24-hour urine volume will be low. It is important to keep in mind that it is rare that patients collect 24-hour urines accurately, not to mention that it is an exercise most patients would rather not undertake.

Creatinine is freely filtered through the glomerulus and is not extensively reabsorbed or secreted. Thus, its concentration in the urine is affected by hydration status, in the same way described above for proteinuria. If a patient drinks a lot of water, the urine creatinine concentration will be relatively low; if he drinks relatively little water, the urine creatinine concentration will be relatively high. In fact, if one makes a ratio of urine protein concentration divided by urine creatinine concentration in the same sample, one can eliminate the effect of water entirely. And it has been shown repeatedly that the urine protein/creatinine ratio is a good surrogate for a 24-hour urine collection.

The upper limit of normal for the protein/creatinine ratio is roughly 200 (mg protein/g creatinine),a number that can be predicted from other reference range data. The typical 24-hour creatinine excretion is roughly 15 mg/kg for women and 20 mg/kg for men, corresponding to roughly 1000 mg/day (1g/day) for women and 1500 mg/day (1.5 g/day) for men. Since the upper limit of normal for 24-hour protein excretion can be as high as 150 mg/day, the corresponding ratio would be 150 mg/1 g, or 150. The ratio can be calculated from any random urine specimen.

The following Table illustrates how protein concentrations can be misleading. Even though samples 1 and 2 have roughly the same protein concentration, their protein/creatinine ratios (Pr/Cr) are quite different. Sample 2 is very concentrated, as reflected in its high creatinine concentration; once corrected for its concentration, the ratio, 100, indicates that the patient is excreting roughly 100 milligrams of protein per gram of creatinine per day, a value which is normal. In contrast, Sample 1, with about the same protein concentration, comes from a patient with a grossly elevated, pathologic, amount of proteinuria; once corrected for its creatinine concentration, the ratio, 800, suggests that the patient is excreting 800 milligrams of protein per gram of creatinine. In the same way, Samples 3 and 5 represent a comparable amount of proteinuria, roughly 1600 milligrams per gram of creatinine, but the urine protein concentration of Sample 5 is more than four times that of Sample 3. And, finally, Sample 4 has the largest amount of proteinuria, but its protein concentration is not the highest.

Sample Number

Dipstick Protein 

Dipstick Protein 

Quant Protein



Pr/Cr Ratio































In other words, concentration can be misleading, whether one measures the protein concentration by dipstick or by spectrophotometry. One must know the protein/creatinine ratio (or an accurate 24 hour collection) to draw any conclusions about the degree of proteinuria. There is excellent correlation between protein: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.

Simultaneous reporting of urine protein and creatinine is helpful in assessing the completeness of 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 0-225 mg/24 hours (Vitros 950). The reference range for the protein:creatinine ratio 0-150 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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