Causes of protein in urine

More than two hundred proteins of various origins have been found in the urine of healthy people: some are filtered from blood plasma, others are of renal origin or secreted by the epithelium of the urinary tract. Using modern research methods, more than 30 serum proteins are normally found in urine. Protein in the urine, the causes of which can be identified using a urine test, can be the result of the ability of various tissue proteins to pass through the glomerulus (from the pancreas, heart, liver, blood group antigens A and B, transplant antigens, etc.).

Some proteins enter the urine as a result of normal tubular secretion or natural processes of renal tissue renewal: soluble glomerular basement membrane antigen, urokallikrein, erythropoietin. Proteins of renal origin also include the quantitatively predominant protein component of normal urine - Tamm-Horsfall mucoprotein (normally 30-50 mg/day in urine), synthesized by epithelial cells of the ascending limb of the loop of Henle and the initial segment of the distal convoluted tubules with the exception of macula densa.

According to the pathogenetic mechanisms of development, glomerular, tubular and mixed proteinuria are distinguished. Glomerular proteinuria develops as a result of structural damage to the glomerular capillaries. Pathological immune (humoral, cellular) reactions, degenerative and sclerosing processes lead to a violation of the selective permeability of the glomerular filter. Tubular proteinuria occurs as a result of a violation of the tubular absorption (disease of the renal tubules) of several normally filtered proteins (in a healthy person, they are subsequently reabsorbed and catabolized by the epithelial cells of the proximal tubules). In addition, some proteins are secreted into the urine by the tubular cells. Proteinuria can occur due to excessive formation of some proteins (the concentration of the filtered protein in the blood plasma exceeds the ability of the tubules to reabsorb it, which is observed in paraproteinemia - myeloma disease, light chain disease). On the other hand, in some cases proteinuria in paraproteinemia may be associated with damage to the glomeruli (for example, due to the development of amyloidosis).

Tubular proteinuria is characterized by impaired protein reabsorption in the proximal renal tubules and predominant excretion of low-molecular proteins (molecular weight 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 damage, reabsorption of low-molecular proteins in the proximal renal tubules decreases, which leads to their increased excretion in the urine. Tubular proteinuria usually does not exceed 2 g/1.73 m2 ^/ day.

Increased excretion of low-molecular proteins is also observed in glomerulonephritis (mixed type of proteinuria), since with a high filtration load, albumin reduces tubular reabsorption of low-molecular proteins, competing for common transport mechanisms. As an indicator of tubular proteinuria, the most commonly used methods are determination of beta ₂ -microglobulin (mol. mass 11,800), retinol-binding protein (mol. mass 21,000), a ₁ -microglobulin (mol. mass 27,000), cystatin C (mol. mass 13,000) in urine, and also examination of the activity of urinary enzymes of renal origin. Increased albuminuria with normal excretion of beta ₂ -microglobulin is characteristic of glomerular proteinuria, and predominant excretion of beta ₂ -microglobulin is characteristic of tubular proteinuria. However, excretion of beta ₂ -microglobulin with urine is possible not only with damage to the renal tubules in various kidney diseases, but also with oncological pathology, myeloma, lymphogranulomatosis, Crohn's disease, hepatitis, etc.

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

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 increased synthesis of low-molecular proteins (with a molecular weight of 20,000-40,000), which circulate in the blood and are filtered by normal glomeruli, but are not completely reabsorbed (due to their high concentration in the plasma). Most often, overload proteinuria is represented by light chains of Ig (Bence Jones protein), myoglobin, hemoglobin, lysozyme and is observed in myeloma, Waldestrom macroglobulinemia, 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 localization of the pathological process in the nephron, the composition and amount of proteins in the urine naturally change. With predominant damage to the glomeruli of the kidneys, the filtration process is mainly affected, which leads to the glomerular type of proteinuria, which can be associated with the loss of the polyanion layer or with a violation of the integrity of the glomerular basement 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-molecular proteins also enter the urine. The ability of the damaged glomerular barrier to pass protein molecules of different molecular weights into the urine changes 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 non-selective. In the highly selective type, low-molecular protein fractions (up to 70,000, mainly albumin) are detected in the urine. In selective proteinuria, proteins are detected in the urine both in the highly selective type and with a molecular weight of up to 150,000, in non-selective proteinuria - with a molecular weight of 830,000-930,000. To characterize the selectivity of proteinuria, the selectivity index is determined, which is calculated as the ratio of the clearances of high-molecular proteins (most often IgG) to low-molecular (albumin or transferrin). A low value of this ratio (<0.1) indicates a filter defect associated with a violation of its ability to retain 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 change disease and suggests high sensitivity to glucocorticosteroid therapy. At the same time, non-selective proteinuria is associated with more severe changes in the basement membrane and occurs in various morphological variants of primary chronic glomerulonephritis (membranous nephropathy, membranous-proliferative glomerulonephritis, focal segmental glomerulosclerosis), secondary glomerulonephritis and, as a rule, indicates resistance to glucocorticosteroids.
• Postrenal proteinuria is caused by the entry of inflammatory exudate, rich in protein, into the urine during diseases of the urinary tract (cystitis, prostatitis).