The causes of the appearance of protein in the urine

In the urine of healthy people, more than two hundred proteins with different origins are found: one is 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. Protein in urine whose causes can be detected by urine analysis can be the result of the ability of various tissue proteins to pass through the glomerulus (they come from the pancreas, heart, liver, antigens of blood groups A and B, transplant antigens, 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 antigen of the glomerular basement membrane, urokallikrein, erythropoietin. 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 with the exception of macula densa.

Pathogenetic mechanisms of development distinguish glomerular, tubular 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 excessive formation of certain proteins (the concentration of the filtered protein in the blood plasma exceeds the ability of tubules to reabsorb it, which is observed in paraproteinemias - myeloma, lung disease). On the other hand, in some cases, proteinuria in paraproteinemia can also be associated with glomerular lesions (eg, due to the development of amyloidosis).

The tubular type of proteinuria is characterized by a disruption in the reabsorption of proteins in the proximal tubules of the kidneys and preferential excretion of low molecular weight proteins in the urine (molecular weight up to 40,000). 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 m ² / 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 proteins when the filtration load is high, competing for common transport mechanisms. As an indicator of tubular proteinuria, the determination in the urine of beta _2- microglobulin (molecular weight 11,800), retinol-binding protein (molecular weight 21,000), _1- microglobulin (molecular weight 27,000), cystatin C ( molecular weight 13,000), as well as the activity of urine enzymes that have a renal origin. An increase in albuminuria in normal excretion of beta _2- microglobulin is characteristic of glomerular proteinuria, and the predominant excretion of beta _2- microglobulin is for tubular proteinuria. However, the excretion of beta _2- microglobulin in the urine is possible not only with 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.

The protein in the urine (pathological proteinuria) can be of several types: 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, hemoglobin, lysozyme and 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 renal tubules. 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 glomeruli of the kidneys, the filtration process mainly suffers, which leads to a glomerular type of proteinuria, which can be associated with a loss of the polyanionic layer or with a 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 non-selective 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 (<0.1) indicates a filter defect associated with a violation of its ability to trap charged molecules (selective proteinuria). On the contrary, an increase in the index> 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 changes and assumes high sensitivity to glucocorticosteroid 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, membranous-proliferative glomerulonephritis, focal-segmental glomerulosclerosis), secondary glomerulonephritis and, as a rule, indicates resistance to glucocorticosteroids.
• Postural proteinuria is caused by the ingestion of an inflammatory protein-rich exudate into urine in diseases of the urinary tract (cystitis, prostatitis).