Protein in the urine

In healthy people, the daily amount of urine contains 50-100 mg of protein.

Detection of protein in the urine( proteinuria) is one of the most important and practically significant signs of kidney and urinary tract damage, which can be either isolated or combined with other changes in urinary sediment in the form of erythrocyturia, leukocyturia, cylinduria, bacteriuria.

The protein content in individual portions of urine collected during the day can vary considerably. For the majority of healthy people, a small proteinuria is observed within 50 mg / day, while in the proteinuria population it reaches more significant values. Proteinuria in the "norm" is non-Gaussian distribution, and the upper limit of proteinuria, equal to 0.020-0.050 g / day or up to 0.033 g / l, occurs in most healthy people, but not in all. At a small part( 10-15%) proteinuria can reach 150 mg / day. In addition, in clinical practice, the specific features of the methods used, which "capture" a different spectrum of urine proteins, are important. Common methods( sample with sulfosalicylic acid for qualitative determination, biuret reaction - for quantitative) in the urine of a healthy person protein, as a rule, do not show. Therefore, if urine traces are found in the urine by usual methods in the urine or its concentration is 0.033 g / l, it is necessary to repeat the analysis, since even a minimal amount should be alarming regarding a possible kidney disease. In doubtful cases it is necessary to determine the daily loss of protein in the urine. To detect changes in the protein spectrum of urine in pathological conditions, it is necessary to have an idea not only about the qualitative, but also the quantitative composition of proteins in the norm. During the day, more protein is released from the urine than at night. Excretion of protein in the urine, exceeding 100-120 mg / day, is often associated with kidney disease, which necessitates further examination of the patient.

More than two hundred proteins have been found in the urine of healthy people of various origins: some are filtered from the blood plasma, others are of kidney origin or secreted by the epithelium of the urinary tract. With the use of modern research methods, more than 30 serum proteins are found in urine. In the urine, it is also possible to identify various tissue proteins that can pass through the glomerulus( they come from the pancreas, heart, liver, blood groups A and B, transplantation Ar, etc.).Part of the protein enters the urine as a result of normal tubular secretion or natural processes of renewal of the renal tissue: soluble Ag glomerular basal membrane, urokallikrein, erythropoietin.

Reference values ​​of of daily proteinuria

The quantitative predominant protein component of normal urine, Tamm-Horsfall mucoprotein( normally in urine 30-50 mg / day), is synthesized by the epithelial cells of the ascending section of the Henle loop and the initial segment of the distal convoluted tubules to proteins of kidney origin.with the exception of macula densa.

The pathogenetic mechanisms of development distinguish between glomerular, tu-bulynaya and mixed proteinuria. Glomerular proteinuria develops as a result of structural damage to the glomerular capillaries. To the violation of the selective permeability of the glomerular filter lead pathological immune( humoral, cellular) reactions, degenerative and sclerosing processes. Tubular proteinuria occurs as a result of impaired tubular absorption( renal tubule disease) of several naturally-filtered proteins( in a healthy person they are subsequently reabsorbed and catabolized by epithelial cells of the proximal tubules).In addition, some proteins secrete tubule cells in the urine. Proteinuria can result from the excessive formation of some proteins( the concentration of the filtered protein in the blood plasma exceeds the ability of the tubules to re-absorb it, which is observed in paraproteinemias - myeloma, lung disease).On the other hand, in some cases, proteinuria in paraproteinemia may also be associated with glomerular lesions( eg, due to the development of amyloidosis).

The tubular type of proteinuria is characterized by a disruption of the reabsorption of proteins in the proximal tubules of the kidneys and the predominant excretion of low-molecular proteins( with a molecular weight of up to 40,000) in the urine. Normally, low-molecular proteins filtered from the blood plasma are almost completely reabsorbed in the proximal tubules. In tubular lesions, the reabsorption of low molecular weight proteins in the proximal tubules of the kidneys decreases, which leads to their increased excretion in the urine. Tubular proteinuria usually does not exceed 2 g / 1.73 m2 / day.

An increase in the excretion of low molecular proteins is also observed with glomerulonephritis( a mixed type of proteinuria), since albumin lowers the tubular reabsorption of low molecular weight proteins when the filtration load is high, competing for common transport mechanisms. As an indicator of tubular proteinuria, the most commonly used expression in urine is P2-microglobulin( molecular weight 11,800), retinol-binding protein( molecular weight 21,000), a1 microglobulin( molecular weight 27,000), cystatin C( molecular weight 13000), as well as investigate the activity of urine enzymes that have a renal origin. An increase in albuminuria with normal excretion of b2-microglobulin is characteristic of glomerular proteinuria, and the predominant excretion of b2-microglobulin is for tubular proteinuria. However, excretion of b2-microglobulin with urine is possible not only in damage to the renal tubules in various kidney diseases, but also in cancer pathology, myeloma, lymphogranulomatosis, Crohn's disease, hepatitis, etc.

In addition, there is a high probability of receiving erroneous results of the study due to the influence of preanalytical factors on the content of this protein.

Pathological proteinuria can be prerenal, renal and postrenal.

Prerenal, or "overload," proteinuria is not associated with kidney damage, but occurs as a result of a number of diseases or pathological conditions accompanied by an increased synthesis of low molecular weight proteins( with a molecular weight of 20,000-40,000) that circulate in the blood and are filtered by normal glomeruli, but not completely reabsorbed( due to their high concentration in the plasma).The most common overload proteinuria is represented by the light chains Ig( Bens-Jones protein), myoglobin, Hb, lysozyme and is observed in myeloma, macroglobulinemia Valdestrome, intravascular hemolysis, rhabdomyolysis, monocytic leukemia and some other diseases.

Renal proteinuria is caused by damage to the glomeruli and / or tubules of the kidneys. Depending on the location of the pathological process in the nephron, the composition and quantity of proteins in the urine naturally changes. With the primary lesion of the glomerulus of the kidneys, the filtration process mainly suffers, which leads to a glomerular type of proteinuria, which can be associated with loss of the polyanionic layer or with violation of the integrity of the glomerular basal membranes. In the first case, low-molecular proteins pass through the uncharged barrier, including albumin( 3.6 nm), transferrin( 4 nm), but not IgG( 5.5 nm);in the second case, large-molecule proteins also enter the urine. The ability of a damaged glomerular barrier to pass into the urine protein molecules of different molecular weight varies depending on the degree and nature of the damage. According to the composition of urine proteins, three types of proteinuria are distinguished: highly selective, selective and nonselective. In a highly selective type, low molecular weight protein fractions( up to 70,000, mainly albumin) are found in the urine. With selective proteinuria in the urine, proteins are detected both in a highly selective type and with a mole.mass up to 150 000, with nonselective proteinuria - with mol.mass 830 000-930 000. To characterize the selectivity of proteinuria, the selectivity index is determined, which is calculated as the ratio of the clearance of high molecular weight proteins( most often IgG) to low molecular weight( albumin or transferrin).A low value of this ratio( & lt; 0.1) indicates a filter defect associated with a violation of its ability to trap charged molecules( selective proteinuria).In contrast, an increase in the index & gt; 0.1 indicates a non-selective nature of proteinuria. Thus, the proteinuria selectivity index reflects the degree of permeability of the glomerular filtration barrier for macromolecules. This is of great diagnostic importance, since selective proteinuria is characteristic of patients with minimal disease and assumes high sensitivity to HA therapy. At the same time, nonselective proteinuria is associated with more severe changes in the basal membrane and occurs with different morphological variants of the primary chronic glomerulonephritis( membranous nephropathy, membrane-proliferative glomerulo- nephritis, focal-segmental glomerulosclerosis), secondary glomerum-lonephritis and, as a rule, indicatesresistance to HA.

?Postural proteinuria is caused by the ingestion of an inflammatory protein-rich exudate into urine in diseases of the urinary tract( cystitis, prostatitis).

Depending on the daily protein loss, the following degrees of proteinuria are distinguished.

Weakly expressed - protein excretion 0.1-0.3 g / day.

Moderate - protein excretion 0.5-1 g / day.

Pronounced protein excretion 1-3 g / day.

Higher degrees of proteinuria are seen as a manifestation of nephrotic syndrome.

Determination of protein content in the daily amount of urine gives a more complete picture of the disease and should be mandatory in the examination of patients with any kidney pathology. Determination of the protein content in daily urine allows the doctor to adequately assess protein losses in the patient( and, accordingly, to correct them), the activity of the pathological process in the kidneys and the effectiveness of the treatment.

To determine the reliable value of proteinuria, it is necessary to collect daily urine correctly. In case of doubt in the reliability of the collection of 24-hour urine, it is easy to control, determining the concentration of creatinine in the urine analyzed. In women with normal muscle mass, the creatinine release is 15-20 mg / kg., In men 20-25 mg / kg. Obtaining as a result of calculations values ​​below these, regardless of the amount of urine delivered to the study, indicates its incorrect collection. In such cases, the results of daily proteinuria will be unreliable( understated).

In healthy people, there is no Bens-Jones protein in the urine. In approximately 20% of cases of multiple myeloma, tumor cells synthesize only Ig light chains. Because of the low molecular weight, they are rapidly removed from the bloodstream and can not be detected in the blood serum. However, they can be detected in the urine. The light Ig chains that precipitate when the urine is heated to a temperature of 45-55 ° C are known as the Bens-Jones protein. Bens-Jones protein is found in the urine with paraproteinemia( myeloma, Waldenström disease, some forms of reticulosis and lymphadenosis).

Paraproteins in the urine are normally absent.

In immunoglobulinopathy, an increase in the concentration of whey proteins, especially macroglobulins, or Ig, combined in immune complexes with clotting factors or other Ar, causes an increase in blood viscosity, which in turn leads to circulatory disturbances in small vessels and damage to their walls by immune complexes. In these cases, the kidneys primarily suffer, which is manifested by proteinuria. Characterization of proteinuria is necessary to clarify the nature of immunoglobulinopathies. One of the causes of proteinuria is the appearance of pathological proteins in the urine of patients with myeloma. An increased content of the total urine protein is noted in almost 90% of such patients. Immunoelectrophoresis of urine proteins allows to reveal pathological PIgA, PIgM, PIgG, H-chains, Bens-Jones protein. Approximately 15-20% of all cases of myeloma are represented by Bence-Jones myeloma, characterized by the formation of exclusively monoclonal light chains. Monoclonal light chains also show up in 50-60% of cases of IgG- and IgA-paraproteinemia and practically in all patients with D-myeloma. With Waldenström macroglobulinemia, the Bens-Jones protein is found in 60-70% of cases, but the total amount of protein in the urine does not exceed 200 mg / day. Identification of Bens-John-sa protein in urine has a special diagnostic and prognostic value. This protein, penetrating the tubules, damages their epithelium and infiltrates the interstitium, resulting in the sclerosis of the kidney stroma, which leads to the development of renal failure - the most common cause of death in myeloma. When a Bens-Jones protein is detected, its typing is necessary: ​​the nephrotoxic effect of a lambda type protein is much higher than that of a protein of the

type. Isolation of the Bens-Jones protein in the urine usually indicates the presence of a tumor process, since it does not form in reactive paraproteinemia. Therefore, early detection of the Bence-Jones protein in the urine, even in trace amounts, is necessary for the early diagnosis of multiple myeloma. It should be remembered that the secretion of the Bence-Jones protein in urine is observed in almost 50% of cases of chronic leukemia.