Diagnosis of proteinuria (Memo for the doctor)
Dear colleagues! You very often have to order a urine test from your lab to your patients. However, you have probably already come across more than once that the problem of clinical interpretation of the obtained analysis results is not the easiest task. After all, the data presented in numerous reference books and manuals vary significantly and often contradict each other.
Since one of the most diagnostically significant and, accordingly, the most frequently assigned indicators of urinalysis is the determination of protein in the urine, we devoted this publication to him.
In this memo, for your convenience, we have concentrated excerpts from current Russian and international regulatory documents, as well as the latest research studies on the diagnosis of proteinuria, which we hope will help you get answers to daily questions and significantly save your time in searching for the necessary information.
Pathological proteinuria - urinary protein excretion exceeding the physiological norm, is one of the most important and clinically significant symptoms of kidney damage.
Normally, more than two hundred proteins are found in the urine - these are plasma proteins with a low molecular weight (up to 70 kDa), kidney tissue proteins synthesized by the tubular epithelium, the main of which is the Tamm-Horsfall protein, and urinary tract and sex gland epithelium proteins.
Daily urinary protein excretion and its concentration in a single portion of urine for different categories of subjects are presented in Table 1.
Table 1. Normal protein excretion
|Daily protein excretion, g / day
|Protein concentration in a single portion of urine *, g / l
|Children under 10
|no more 0,1
|no more 0,1
|Children over 10 years old and adults
|no more 0,15
|no more 0,1
|no moreе 0,3
|no more 0,15
*Concentrations are indicated for the photometric method for determining protein content in urine using pyrogallol red, which is currently used in the vast majority of laboratories in Russia and the world.
The kidneys are a natural “filter” of blood. Their main function is the maintenance of homeostasis - the selective elimination of substances unnecessary for the body from the blood and the delay necessary.
This function is realized through three mechanisms: glomerular filtration, tubular reabsorption, and tubular secretion.
Thus, the formation of the composition of the final urine can be described by the following formula:
Isolation = (Filtration - Reabsorption) + Secretion.
Glomerular filtration is carried out due to the pressure gradient that arises in the vascular glomerulus between the afferent and efferent arterioles, as well as the structural features of the glomerular (glomerular) filter, which passes water, low molecular weight substances and retains large molecules.
The glomerular filter consists of three layers. The inner layer is the endothelium containing pores closed by a special diaphragm. Outside the endothelium lies a three-layer glomerular basement membrane, the permeability of which is determined by the spatial arrangement of collagen filaments and their electric charge. On the urinary side of the basement membrane is another barrier - the epithelial lining - the podocytic apparatus. The podocyte contains microfilaments that perform an active function during filtration - “ultrafiltration pumps”. Thus, the glomerular filter is a complex multi-stage selective filtering system aimed at ensuring selectivity with respect to the size and charge of the filtered particles. Molecules with a radius of less than 4 nm pass freely through this filter. So, proteins such as myoglobin, prealbumin, lysozyme, α1-microglobulin, ß2-microglobulin, etc. are easily filtered through the basement membranes of the glomeruli. Filtration becomes limited with a molecule radius of more than 4 nm. Particle charge selectivity refers to the property of a glomerular filter to impede the passage of negatively charged macromolecules compared to neutral or positively charged ones due to the presence of anionic sites on the basement membrane, on podocytes, on the endothelium and on the mesangium. Thus, the passage of the main plasma protein - albumin, which has a negative charge, despite its small size (3.6 nm) and small molecular weight (69 kDa), is difficult, mainly due to its charge.
The bulk of the proteins filtered into the tubules (immunoglobulin light chain, transferrin, vitamin D-binding protein, myoglobin) are reabsorbed from primary urine in proximal convoluted tubules. Protein reabsorption is carried out by receptor-mediated endocytosis. The rate of endocytosis increases in proportion to the concentration of protein in the glomerular filtrate until the maximum rate of formation of endocytotic vesicles is reached. Further, during the reabsorption process, the formed endocytotic vacuoles move towards the basal part of the cell and merge with the lysosomes. Proteolysis of proteins occurs in endolysosomal vesicles. The reabsorption mechanism prevents the body from losing protein.
In addition to proteins that are filtered in the glomerulus, urine contains proteins formed in the urinary tract. They make up to 50% of all urine proteins in physiological proteinuria. The main representative of such proteins is the Tamm-Horsfall protein (or uromucoid) - a large glycoprotein secreted by the cells of the ascending loop of Henle.
Proteinuria is divided into physiological (functional) and pathological.
The basis of the mechanism of physiological proteinuria is an increase in hydrostatic pressure in the glomerular capillaries, which leads to the facilitation of the diffusion of proteins through an unaffected glomerular filter. Physiological proteinuria, as a rule, does not exceed 0.250 g / l, is transient and disappears when the factor that caused it disappears. The causes of proteinuria of this type can be physical exertion, prolonged exposure to cold, fever, nervous tension, orthostatic stress.
Pathological proteinuria, depending on the mechanism of occurrence, is divided into prerenal, renal and postrenal proteinuria.
Prerenal proteinuria is not associated with kidney damage, but arises as a result of diseases that are accompanied by increased synthesis of low molecular weight proteins (20–40 kDa) that pass through an intact glomerular filter in excess of the ability of tubules to reabsorb.
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 quantity of uroproteins changes.
When glomeruli are affected (glomerular type of proteinuria), the filtration process mainly suffers. The mechanism of proteinuria of this type may be associated with a violation of the integrity of the glomerular basement membrane or with damage to its polyanion layer, which carries an electric charge. Given the fact that the mechanisms of protein reabsorption in the proximal tubules are normally limited, proteins in excess enter the urine. Depending on the nature and degree of damage to the glomerular filter, selective and non-selective glomerular proteinuria is isolated. As the degree of damage to the glomerular filter increases, the selectivity of proteinuria decreases. With initial damage to the glomerular apparatus with urine, mainly transported blood proteins are released - albumin and transferrin (selective proteinuria). With significant damage to it, high molecular weight proteins (M> 100 kDa) appear in the urine (non-selective proteinuria).
With damage to the tubules of the kidneys (tubular type of proteinuria), 2 pathophysiological mechanisms are possible. At the first, the process of protein reabsorption in the proximal tubules of the kidneys is disrupted, which is accompanied by the appearance of low molecular weight proteins in the urine. In the second case, there is an increase in protein secretion by epithelial cells of the distal nephron, as a result of which an excess of Tamm-Horsfall protein appears in the urine.
Postrenal proteinuria, like prerenal proteinuria, is not associated with kidney damage. It is the result of the entry into the urine of proteins from the cells of the genitourinary tract and, depending on the etiology, is characterized by a different protein spectrum.
The clinical significance of proteinuria
The increase in proteinuria in the dynamics of treatment of a patient with nephrological pathology is always evidence of ineffective treatment, an unfavorable prognostic sign and indicates the activity of the disease.
A decrease in proteinuria during treatment of the patient is an indicator of a slowdown in the progression of the disease.
The role of proteinuria as an independent factor in the progression of kidney damage has been established. In proteinuria, the components of protein proteolysis have a toxic effect on the epithelial cells of the proximal tubules and interstitium, which can lead to the development of tubulointerstitial inflammation and fibrosis and, thus, contribute to the progression of the disease. The basis of this process is the overstrain of reabsorption mechanisms and the depletion of enzyme systems due to excess protein in primary urine (for more details see the section "Morphology of the nephron and the pathogenesis of proteinuria").
Proteinuria is a significant and independent prognostic factor in increasing mortality from diseases of the cardiovascular system (the pathogenesis of cardiovascular diseases in renal pathology is affected by hyperhydration, anemia, impaired calcium-phosphorus metabolism, hypercoagulation).
Thus, reliable diagnosis of proteinuria is an important aspect in clinical practice.
When diagnosing proteinuria, it is very important to standardize preanalytical conditions.
Due to the fact that the qualitative and quantitative composition of urine changes during the day, the most accurate is the determination of protein in daily urine, which allows you to level out the effect of urine output on protein concentration in urine. We give an example: in a patient with a protein excretion of 0.5 g per day, the protein concentration in the urine can vary from 1 g / l (with daily diuresis of 0.5 l) to 0.2 g / l (with daily diuresis of 2, 5 l). However, collecting daily urine is an extremely difficult process even for hospital patients and is practically impossible for young children and elderly patients.
Correctly assessing the renal excretion of protein without determining the amount of daily diuresis allows the calculation of the ratio of protein / creatinine. The physiological rationale for this approach is the following considerations: in the same person under stable conditions, creatinine * excretion in the urine is relatively constant, and its concentration in the urine depends solely on the amount of urine output, which in turn depends on the amount of fluid consumed. Similarly, the amount of diuresis affects the protein concentration in the urine, while the ratio of protein to creatinine remains constant for any amount of diuresis.
Fairly wide variations in the composition of urine are also associated with physical activity. The effect of physical activity on the result of the analysis can be neutralized by the study of the morning portion of urine (which was formed under relatively standardized conditions of night sleep).
Thus, the only alternative to the analysis of daily urine is the simultaneous determination of protein and creatinine in the morning portion of urine, followed by the calculation of their ratio.
*Note: Creatinine is produced in muscles from creatine phosphate. The synthesis of creatinine is relatively constant, as it is almost entirely determined by the total muscle mass of the human body. Creatinine passes freely through the glomerular filter and is not reabsorbed in the renal tubules. The amount of creatinine excreted in patients in a daily urine dose is 18.5–25.0 mg / kg per day for men aged 20 to 50 years, and 16.6–22.4 mg / kg per day for women of the same age . With age, these indicators decrease: in men of 50-70 years old, they are 15.7 - 20.2 mg / kg per day, and in women of the same age - 11.8-16.1 mg / kg per day. When interpreting the results of the analyzes, the limitations of the approach based on the protein / creatinine ratio due to the relationship between the muscle mass of the body and creatinine excretion should be taken into account. Decreased or increased muscle mass can cause underestimation or overestimation of protein excretion in patients.
The following is an example of individual variations in the concentration of protein and creatinine in urine in one of the healthy subjects. The morning urine sample was examined for 7 days. The studies were carried out using the analytical system: URiSCAN-BK protein and creatinine analyzer in urine, Uni-Test-BM reagent kit (for protein in urine) and UTS creatinine reagent kit (for determination of creatinine in urine and serum). The results are presented in Table 2.
Table 2. Individual variations in protein and creatinine concentrations
|The concentration of protein in the urine, g / l
|Urinary creatinine concentration, g / l
|Protein / Creatinine Ratio
As can be seen from the data presented, the spread of protein concentration in the urine is more than 10 times (from 0.013 to 0.166 g / l)! 09/13. the subject drank 3 glasses of water at night, which significantly increased the volume of morning urine output and the protein concentration in the urine was 0.013 g / l, and on September 19 there was the opposite situation - the liquid was not taken before bedtime, which led to a significant concentration of the morning urine and an increase in protein concentration almost 13 times (0.166 g / l). A similar dependence was revealed for creatinine (creatinine concentration changed 6.4 times), which indicates the presence of a common reason for such significant concentration variations of the studied analytes. In this case, this is the volume of urine output. The ratio of protein / creatinine remains relatively constant - it has changed only 1.9 times.
In numerous clinical studies, it was found that the protein-creatinine ratio in the first morning urine dose clearly correlates with the level of daily proteinuria. Thus, a protein / creatinine ratio of more than 3.0-3.5 g of protein / g of creatinine corresponds to a protein excretion above 3.0-3.5 g / day, less than 0.2 g of protein / g of creatinine - a level below 0.2 g /day. therefore, in all current Russian and foreign clinical guidelines for the diagnosis of proteinuria, it is recommended to determine the ratio of total protein / creatinine and albumin / creatinine.
Normally, the ratio of total protein / creatinine according to various sources does not exceed 0.15-0.2 g of protein / creatinine, with tubulointerstitial lesions of the kidneys (reabsorption is impaired), this indicator is in the range from 0.2 g / g to 1.0 g / g, with glomerular diseases (impaired barrier function) exceeds 1.0 g / g, and with severe preeclampsia it can reach 5.0 g protein / g creatinine or more.
In the 2012 National Recommendations “Chronic Kidney Disease: The Basic Principles of Screening, Diagnosis, Prevention and Treatment Approaches”, developed by a working group of members of the Board of the Scientific Society of Nephrologists of Russia, the following postulates for the diagnosis of proteinuria are presented:
Recommendation 2.4: For each patient with CKD, a study of the level of albuminuria / proteinuria should be performed, since this indicator is important for the diagnosis of CKD, the prognosis of its course, the risk of cardiovascular complications, and the choice of treatment tactics.
Recommendation 2.4.1: To assess albuminuria / proteinuria, one should determine its level in daily urine or the albumin / creatinine ratio, or total protein / creatinine in a single morning urine.
Recommendation 2.6: In patients with proteinuria ≥0.5 g / day, to determine the severity of kidney damage instead of albuminuria studies, in terms of budget savings, you can use the determination of total protein in daily urine (daily proteinuria) or the ratio of total protein / creatinine in the morning portions of urine.
In the diagnosis of proteinuria of various origins in children, it is preferable to use the determination of the ratio of protein / creatinine. The latter is due to the fact that the proportion of congenital structural pathologies of the renal system, which are more often diagnosed in children than in adults, is characterized by the excretion of significant amounts of low molecular weight proteins in the urine that are not detected by specific albumin tests.
The proteinuria / albuminuria grade recommended in the latest edition (2013) of KDIGO's Clinical Practice Guidelines (Kidney Disease Improving Global Outcomes) for the diagnosis and treatment of chronic kidney disease is presented in Table. 3.
Table 3. Evaluation of proteinuria and albuminuria (KDIGO 2013)
|Indexing proteinuria and albuminuria by degree
Indicator, evaluation method
|Optimal or slightly increased (А1)
|Very high (А3)
|Albumin in the urine
|Daily Albumin Excretion (g / day)
|Urine Albumin / Creatinine Ratio (g / g)
|Total protein in urine
|Daily excretion of total protein (g / sut)
|Urine Protein / Creatinine Ratio (g / g)
With established pathology of the renal glomeruli, the determination of the protein / creatinine ratio in comparison with the determination of the albumin / creatinine ratio provides additional information on the selectivity of proteinuria. If in the formula albuminuria / proteinuria x 100% the result is> 50%, then this is glomerular proteinuria, <50% is proteinuria of tubular origin. In this case, proteinuria and albuminuria should be presented in the same units of measurement, for example, g / l or mg / l. Example: albuminuria = 100 mg / l, proteinuria = 0.3 g / l. To bring albuminuria in g / l, divide 100 mg / l per 1000, we get 0.1 g / l. Further, according to the above formula, we calculate: 0.1 g / l: 0.3 g / l x 100% = 30%. Proteinuria is tubular.
In this way:
- When examining conditionally healthy individuals, the protein in the urine is determined semi-quantitatively using test strips, which can significantly reduce the cost of the study. Patients with positive test results obtained using test strips need to accurately quantify the protein concentration using the colorimetric method using the PGC method (reaction with pyrogallol red dye).
- When examining people at risk of chronic renal failure (patients with chronic kidney disease, diabetes mellitus, arterial hypertension), as well as pregnant women with suspected preeclampsia, you should immediately begin with the determination of proteinuria by quantitative methods. If they give negative results, a quantitative albuminuria test is prescribed.
- Given the fact that the determination of protein using diagnostic strips due to the chemistry of the reaction is a detector of mainly the albumin fraction of proteins and does not exclude the presence of globulins, hemoglobin, uromucoid, Bens-Jones protein in the urine, proteinuria should be analyzed immediately if appropriate nosologies are suspected conduct quantitative methods.
- Quantitative determination of protein, albumin and creatinine in urine should be carried out in the morning portion of urine with the calculation of the ratio of protein / creatininyl or albumin / creatinine..
- When evaluating proteinuria / albuminuria, extrarenal factors affecting their level (intense physical activity, fever, hypothermia) must be taken into account, it is necessary to ensure compliance with conditions that minimize the variability of the proteinuria / albuminuria index.
- Proteinuria / albuminuria confirmed by repeated examination is a mandatory indication for a nephrologist consultation.
- The combined risk of progression of chronic kidney disease (CKD) and the development of cardiovascular complications depending on the degree of decrease in glomerular filtration rate (GFR) and the severity of albuminuria / proteinuria, as well as the algorithm for monitoring patients with chronic kidney disease are presented in Table 4.
- Differential diagnosis of proteinuria during pregnancy is presented in Table 5.
In conclusion, I would like to note that in order to obtain highly accurate and diagnostically significant results of urine tests in hospitals, it is necessary to equip the laboratory with modern equipment and use modern research methods recommended by professional associations, as well as an ongoing productive dialogue between clinicians and clinical laboratory diagnostics, as at the stage the purpose of the analyzes and their interpretation.
Table 4. Combined risk of CKD progression and the development of cardiovascular complications depending on the degree of GFR reduction and the severity of albuminuria / proteinuria and an algorithm for monitoring patients with chronic kidney disease.
|Albuminuria / proteinuria
|Optimal or slightly increased
|Very high (proteinuria)*
|<0.03 g albumin / g creatinine (<0.03 g albumin / day)
|0.03-0.3 g albumin / g creatinine (0.03-0.3 g albumin / day)
|> 0.3 g albumin / g creatinine (> 0.3 g albumin / day)
(ml / min / 1.73 m2)
|High or optimal
|Nephrologist consultation / observation
|Nephrologist consultation / observation
|Nephrologist consultation / observation
|Nephrologist consultation / observation
- GFR - glomerular filtration rate.
- Albuminuria / proteinuria is defined as the albumin / creatinine ratio or total protein / creatinine in a single (preferably morning) urine sample
- Cell staining: green - low risk (in the absence of signs of kidney damage, GFR categories C1 or C2 do not meet the criteria for CKD), yellow - moderate risk, orange - high risk, red - very high risk.
* In patients with severe protein loss (> 0.5 g / day), it is advisable, from the point of view of budget savings, to study total protein in daily urine or the total protein / creatinine ratio in the morning urine instead of determining albuminuria.
Table 5. Differential diagnosis of proteinuria during pregnancy
|Daily proteinuria level = protein / creatinine ratio
|more 3,0 g
|Physiological proteinuria of pregnant women, nephrosclerosis, nephritis in remission
|Pregnant nephropathy, preeclampsia, chronic glomerulonephritis, rapidly progressive glomerulonephritis, amyloidosis, diabetic nephropathy, paraneoplastic nephropathy, septic nephropathy
|In combination with leukocyturia
|Urinary tract infections
|Kidney damage in systemic connective tissue diseases
|In combination with erythrocyturia (hematuria)
|Alport syndrome, nephrosclerosis, chronic tubulointerstitial nephritis, renal bleeding with an overdose of anticoagulants, DIC, obstetric pathologies (premature placental abruption, threatened abortion)
|Chronic glomerulonephritis, rapidly progressive glomerulonephritis, kidney damage in systemic diseases of the connective tissue paraneoplastic nephropathy, septic nephropathy
|Acute and chronic tubulointerstitial nephritis, hereditary nephritis (Alport syndrome, thin membrane disease)
Nephron morphology and proteinuria pathogenesis
The morphofunctional unit of the kidney is nephron - a specific structure that performs the function of urination. Each kidney has more than 1 million nephrons. Each nephron consists of a glomerulus, a Shumlyansky-Bowman capsule, and a system of consecutive tubules. The nephron filtration barrier form:
- glomerular capillary endothelium, the integrity of which is interrupted by pores with a diameter of 50-100 nm;;
- a three-layer basement membrane in which a network of collagen IV, laminin and nidogen serves as a filter, into which negatively charged glucosaminoglycans (anion barrier) are embedded; and finally,
- “Visceral” leaf of the Bowman capsule epithelium (Fig. 1A).
The visceral leaf in the section is intermittent, since the processes of epithelial cells (podocytes) are intertwined with each other, while free gaps remain between the processes. These slots are covered by a slit-like membrane and have holes with a diameter of 4 nm. The slit membrane contains a protein important for filter permeability, nephrine, which is anchored through another protein, CD2AP, on neighboring processes of podocytes. The nephrin molecules protruding from both sides into the gap are bonded to each other like a zipper and leave free pores between them that barely allow albumin molecules to pass through.
Blood cells are delayed by the first layer of the filter - the endothelium. This is also true for large protein molecules, since in vivo the endothelial pores are coated with a negatively charged layer of proteins. The ability to filter macromolecules (whose molecular mass is about <70 kDa) through the next two layers is determined not only by the pore width of the filter components, but also by the electric charge of the filter surface structures.
The filter is cleaned by mesangium cells and glomerular podocytes, which are able to remove high molecular weight deposits due to phagocytosis and subsequent digestion in lysosomes. With pathology, the mass of deposits increases (for example, antigen-antibody complexes), mesangium cells begin to divide intensely. This leads to the fact that due to the limited space, the capillaries are compressed and the amount of filtrate is reduced.
Ultrafiltrate is formed in the glomerulus, which, along with water, contains only small molecules. Only small molecules with a radius of less than 1.6-1.8 nm are freely filtered. This corresponds to a molecular weight of 6–15 kDa. Inulin, which is used to determine clearance, has a molecular weight of about 5 kDa and belongs to this group. For globulins with a radius of> 4.4 nm (> 80 kDa) the filter is usually impermeable, the same is true for red blood cells, which are even larger. Substances whose molecular radii are within these boundaries are only partially filtered: myoglobin by 75% and albumin by only 0.03%. Low molecular weight substances bound to blood plasma proteins are also poorly filtered. Calcium, for example, is filtered only 60% due to the fact that about 40% of calcium is bound to plasma proteins. Many drugs, in particular the majority of sulfonamides or cardiac glycoside digitoxin, are even more associated with plasma proteins, so they are excreted very slowly by the kidneys.
The permeability of the filter for macromolecules with a radius <4 nm depends on the charge of the molecule (Fig. 1 B). The reason for this is the negative charge on the filter surface structures, for which anionic glyco (sialo) proteins are responsible. They are located on the structures of the basement membrane (both on the capillary side and on the side of the bowman capsule), as well as on the surface of the outer membrane of the processes of podocytes. This fact is important from the point of view of pathophysiology, since a decrease in the charge on the surface structure of the filter dramatically increases the filtration of albumin (Fig. 1B), which leads to the loss of a large amount of this plasma protein in the urine - albuminuria.
Fig. 1. Macro and microstructure of a Bowman capsule filter (A). The dependence of the filter permeability on the charge of the molecule (B, C)
Normally, albumin accounts for about 25-30% of all proteins excreted by the kidneys. This ratio may vary with proteinuria. After passing through the filter, serum-wide proteins such as immunoglobulin light chain, transferrin, vitamin D-binding protein, myoglobin and albumin are reabsorbed, mainly in the proximal renal tubules. The reabsorption process in the nephron prevents the loss of protein by the body. For the reabsorption of proteins from primary urine in the proximal tubules of the nephron, receptor-mediated endocytosis is responsible. The rate of endocytosis increases in proportion to the concentration of protein in the glomerular filtrate until the maximum rate of formation of endocytotic vesicles is reached. Further, during the reabsorption process, the formed endocytotic vacuoles move towards the basal part of the cell and merge with the lysosomes. Proteolysis of proteins occurs in endolysosomal vesicles. In this case, almost all glucose, amino acids, vitamins, a significant amount of ions are returned to the blood. Another mechanism provides the reabsorption of small linear peptides (such as angiotensin II, bradykinin). These peptides are hydrolyzed by the enzymes of the brush border of the proximal tubule epithelium, after which the amino acids are transported into the cell.
Types of pathological proteinuria
Prerenal proteinuria is associated with the appearance of pathological proteins in the plasma, which are normally absent. These proteins have a low molecular weight and pass through the intact renal barrier into the urine. Their appearance in plasma is associated either with increased synthesis, or is the result of the breakdown of tissues or cells. Prerenal proteinuria, in particular, is a consequence of increased production of immunoglobulin light chains in patients with myeloma. With hemolytic anemia, hemoglobin passes through an intact renal filter, with myodystrophy, crash syndrome, myoglobin appears in the urine as a result of damage to muscle tissue.
Glomerular (glomerular) proteinuria is characteristic of all kidney diseases that occur with lesions of the cortical substance in which the glomeruli are located. These are acute and chronic glomerulonephritis, nephropathy in diabetes mellitus, nephropathy of pregnant women, nephrosis, kidney tumors, kidney damage in hypertension, etc. Glomerular proteinuria is caused by damage to the glomerular barrier of the kidneys. Normally, proteins with a low molecular weight (M <70 kDa) - albumin (M = 69 kDa) and microblobulins (M <40 kDa) - α1-microglobulin, ß2-microglobulin, retin-binding protein, etc. are filtered through the glomerular barrier. With initial damage of the glomerular apparatus with urine, mainly transported blood proteins - albumin and transferrin (selective glomerular proteinuria) are secreted. With significant damage to it, high molecular weight proteins (M> 100 kDa) appear in the urine - immunoglobulins (non-selective glomerular proteinuria). As noted above, the glomerular capillary wall has a negative charge, so negatively charged proteins (anions), for example, albumin, are poorly filtered. With nephrotic syndrome, the negative charge of the glomerular filter is lost, and albumin anions are filtered in large quantities. A typical example of this effect is glycation of the surface proteins of the glomerular filter in diabetes mellitus.
Tubular proteinuria. Low molecular weight proteins (M <40 kDa), which are filtered through glomeruli, are mostly (90%) reabsorbed by the proximal tubules of the kidneys. If these tubules are damaged, for example, with tubulointerstitial diseases, the reabsorption process is disturbed and low molecular weight proteinuria appears. The causes of tubular nephropathy can be poisoning with salts of heavy metals (mercury, lead, cadmium), toxic substances (ethylene glycol, carbon tetrachloride), nephrotoxic drugs (aminoglycosides). Tubular nephropathy occurs in acute renal failure, accompanied by tubular necrosis, with interstitial nephritis, Fanconi syndrome, and a congenital defect in the renal tubules.
Another pathophysiological mechanism of tubular proteinuria is the increased production of protein by the cells of the renal epithelium of the distal nephron (Tamm-Horsfall protein - a marker of the early stages of urolithiasis and recurrent stone formation).
Mixed (glomerular-tubular) proteinuria is a sign of combined damage to the glomerular filter and a violation of tubular reabsorption of proteins. Usually this is the manifest stage of all nephropathies, in which both low molecular weight proteins and high molecular weight proteins are found in the urine.
Postrenal proteinuria occurs with bleeding from the urinary tract, local synthesis of immunoglobulins in case of urinary tract infection, as well as polyposis, bladder cancer. The protein composition of urine in postrenal proteinuria may be similar to that in renal proteinuria of the glomerular type.
The types of proteinuria and their main characteristics are summarized in Table 6.
Table 6. The main characteristics of proteinuria in various pathological conditions
|Type of proteinuria
|The mass of proteins, kDa
|Protein excretion, g / day
|Increased synthesis of low molecular weight proteins, tissue breakdown
|up to 50,0
|Increased total protein, normal albumin, depending on the etiology - hemoglobin, myoglobin, Bens-Jones protein
|Increased glomerular permeability for low molecular weight anion proteins
|up to 0,3
|Increased glomerular permeability for high molecular weight proteins
|Albumin, IgА, IgG
|Decreased reabsorption of low molecular weight proteins by the cells of the renal epithelium of the proximal nephron
|α1-microglobulin, ß2-microglobulin, ß-NAG, cystatin С, retin-binding protein
|Increased protein secretion by the cells of the renal epithelium of the distal nephron
|up to 0,2
|Increased glomerular patency of high molecular weight proteins with secondary impairment or saturation of tubular reabsorption
|100–150 and more
|up to 20,0
|Bleeding or inflammation of the urinary tract
|α2-macroglobulin, apolipoprotein А1, IgА
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