High concentration Protein causes foamy urine. In many kidney diseases, proteinuria accompanies other urine abnormalities (eg, hematuria).

Pathogenesis of proteinuria

Although the glomerular basement membrane is a highly selective barrier to large molecules (e.g., most plasma proteins, including albumin), it does not large number The protein passes through the basement membranes of the capillaries into the primary urine. Some of this filtered protein is broken down and reabsorbed by the proximal tubules, but some is excreted into the urine. Upper limit normal level urinary protein excretion is considered to be 150 mg/day, which can be measured by daily urine collection or assessed by the protein/creatinine ratio in a random portion (a value less than 0.3 is considered pathological); for albumin this figure is about 30 mg/day. Albumin excretion of 30-300 mg/day is regarded as microalbuminuria, more high values considered macroalbuminuria. According to the mechanism, proteinuria can be divided into:

• glomerular, I'm tubular,
• reloading,
• functional.

Glomerular proteinuria is caused by glomerular pathology, which is usually accompanied by increased glomerular permeability, this permeability allows increased amounts of plasma proteins (sometimes very large amounts) to pass into the primary urine.

Tubular proteinuria is caused by tubulointerstitial kidney disease, in which protein reabsorption in the proximal tubule is impaired, causing proteinuria (mainly small-molecular proteins such as light-chain immunoglobulins, rather than albumin). The initial disorders are often accompanied by other disorders of tubular function (for example, loss of HC05, glucosuria, aminaciduria) and sometimes glomerular pathology (which also contributes to the development of proteinuria).

Proteinuria overload occurs when excess amounts of small molecular plasma proteins (for example, light chain immunoglobulins secreted in multiple myeloma) exceed the reabsorption capacity of the proximal tubules.

Functional proteinuria occurs when increased blood flow (eg, due to exercise, fever, high-output heart failure) delivers protein to the kidneys. increased amount protein, which leads to an increase in its concentration in the urine. Functional proteinuria disappears when renal blood flow returns to normal.

Orthostatic proteinuria is benign disease(most common among children and adolescents), in which proteinuria is observed mainly when the patient is in an upright position. A greater amount of protein in the urine is observed in daytime(when people spend more time in a horizontal position) than during sleep. Its prognosis is very good and it does not require special treatment.

Consequences. Proteinuria due to kidney disease is usually permanent (ie, persists with repeated testing) and, being in the nephrotic range, can lead to significant protein loss). The presence of protein in urine is toxic to the kidneys and causes kidney damage.

Pathophysiological classification of proteinuria

According to the source of urinary protein and the definition of the existing pathology from this source, according to the pathogenesis, proteinuria is divided into three groups.

Secretory proteinuria occurs due to the filtration through normal glomeruli of abnormally large amounts of low molecular weight proteins, which exceeds the reabsorbing capacity of the tubules. This happens with monoclonal gammaglobulinopathy (multiple myeloma), intravascular hemolysis(hemoglobinuria) and rhabdomyolysis (myoglobinuria). Secretory proteinuria can be detected by urine electrophoresis by the presence of abnormal peaks or “protrusions.” For example, "protrusions" appearing in the y region (or less commonly in the α2 or β region) indicate a monoclonal gammopathy. Further research is carried out using immunoelectrophoresis.

Tubular proteinuria occurs in acute and chronic lesions of the tubulointerstitial region. Protein loss is typically less than 2 g per day and comes from three sources. First, damaged tubules cannot reabsorb completely small molecular weight proteins filtered through the glomerulus, such as β 2 MG and amylase. Second, damaged tubules release brush border components and cellular enzymes such as n-acetiglucosamine and lysozyme into the urine. Finally, with tubulointerstitial damage, the tubular cells of the ascending limb of the loop of Henle and the distal nephron secrete more Tamm-Horsfall protein into the urine. For differential diagnosis For glomerular and tubular proteinuria, electrophoresis and immunoelectrophoresis can be used. A significant predominance of albumin over globulins indicates glomerular proteinuria. In this case, quantitative comparison of urinary ir2MG albumin levels using immunoelectrophoresis or other immunological methods (immunoprecipitation, immunodiffusion and radioimmunoassay) can also be helpful. An albumin to β2MG ratio of 10:1 indicates tubular proteinuria; with glomerular proteinuria, this ratio will exceed 1000:1. Normally, the ratio of albumin and β 2 MG ranges from 50:1 to 200:1.

Glomerular proteinuria occurs when the glomeruli are damaged; the clearance of serum proteins in the ultrafiltrate partially increases. In some forms of glomerulonephritis, this leads to a change in the size of the pores in the walls of the glomerular capillaries, which allows molecules of large molecular weight and even cells to pass through them (as in rapidly progressive glomerulonephritis). In other forms, there is a change in the selective charge of the walls of the glomerular capillaries, which leads to increased filtration of negatively charged albumin (minimal change nephropathy). Some glomerular lesions are characterized by changes in size and charge selectivity ( diabetic nephropathy). Mesangial lesions also lead to proteinuria, possibly due to alteration of normal mesangial clearance functions.

Glomerular proteinuria is represented predominantly by albumin, and when its losses are large (i.e. more than 3.0-3.5 g per day or more than 2 g/m 2 per day) they speak of nephrotic syndrome. Nephrotic syndrome has five components: nephrotic proteinuria, hypoalbuminemia, hyperlipidemia, lipiduria, and edema. With the exception of minimal change glomerulopathy, an increased risk of renal failure is associated with severe proteinuria in glomerular lesions.

Other types of proteinuria. The two forms of proteinuria do not fit into the classification given above. This is benign orthostatic proteinuria in tall adolescents while standing. Protein is found in urine collected after rest and in the morning after waking up, but there is no protein in samples collected immediately after a night's sleep and getting out of bed. In this case, there should be no urine in the sediment pathological changes and proteinuria should not exceed 1 g per day. In half of these patients, proteinuria disappears during the period, but a small number subsequently develop obvious illness kidney Finally, functional transient proteinuria may be associated with other causes: heart failure, fever, or heavy physical work. Proteinuria in runners after completing a marathon distance can be more than 5 g/l.

Classification of proteinuria

The first and most important step for differential diagnosis of proteinuria is to determine which section of the classification it belongs to.

Secretory proteinuria

Secretory proteinuria is suspected when there is a discrepancy between small proteinuria determined by test strips and disproportionate a large number protein in urine collected over 24 hours. This most often occurs with increased excretion of monoclonal light chains, which can be confirmed by immunoelectrophoresis. If monoclonal immunoglobulin is detected in the urine, testing for multiple myeloma, amyloidosis, or lymphoproliferative diseases should be performed. Hemoglobinuria and myoglobinuria can also cause secretory proteinuria. However, these conditions are easy to diagnose because the test for blood in the urine is intensely positive, while microscopic examination of the urine shows no or very few red blood cells. With such research results, you need to look for hemolysis or rhabdomyolysis.

Tubular proteinuria

Tubulointerstitial lesions can cause wide range states. The examination for tubular proteinuria should begin with a thorough history collection from other family members (to exclude polycystic kidney disease), obtaining information about the use of medications as prescribed or without a doctor’s prescription (nephropathy after taking analgesics), the frequency of UTIs (reflux), low back pain, discharge kidney stones, skin rashes, arthralgia, arthritis (hypersensitivity to medicines, collagen-vascular diseases), dry mouth and eyes (Sjögren's syndrome), occupational or accidental exposure to potential poisons and manifestations systemic diseases. Physical manifestations supporting the disease in the differential diagnosis may include marked enlargement of the kidneys (polycystic disease), annular keratopathy (hypercalcemia, hyperparathyroidism), skin rashes(systemic lupus erythematosus, drug hypersensitivity), arthritis (gout, lupus), formation of a lead border on the oral mucosa (lead poisoning). Laboratory examination includes performing a detailed blood test with smear microscopy, determining the level of creatinine, BUN, glucose, calcium, phosphorus uric acid, potassium in blood serum. Bacteriological examination of urine gives additional information to the history, physical examination, general analysis urine and quantitative urine testing (i.e. used for differential diagnosis). Positive or negative results these examinations may indicate the need for further investigations: renal ultrasound (polycystic disease, kidney stones and obstruction), urine, serum or hemoglobin electrophoresis (monoclonal gammopathy, sickle cell anemia), bacteriological examination urine with determination of sensitivity to antibiotics (pyelonephritis, renal tuberculosis), level of angiotensin-converting enzyme in serum (sarcoidosis), excretory urography (sponge kidney), determination of lead level in serum (lead poisoning). Some tubulointerstitial disorders have characteristic histologic features (spongy kidney, amyloidosis, renal myeloma, hypokalemia), but the histologic differences of most tubulointerstitial disorders are difficult to discern. Therefore, biopsy is rarely used to diagnose tubulointerstitial kidney disease. Treatment depends on the cause of the disease.

Glomerular proteinuria

With glomerular proteinuria, a disproportionate amount of albumin appears. Moderate transient proteinuria, especially with acute diseases With full recovery, has virtually no long-term consequences. However, severe and prolonged proteinuria suggests more serious illness. For initial diagnosis and treatment, consultation with a nephrologist is required, since the list of diseases for differential diagnosis is extensive and many of the disorders are rare.

Patients with persistent severe proteinuria require careful diagnostic examination. In this group of individuals, glomerular proteinuria is defined as non-nephrotic (<3,5 г вдень на 1,73 м 2 поверхности тела) или нефротическую (>3.5 g per day per 1.73 m 2 body surface). This somewhat arbitrary division is due to two main observations. First, patients with nonnephrotic proteinuria have a better renal prognosis than patients with more severe proteinuria. Therefore, with aggressive methods There is no need to start treatment. After establishing the main causes when collecting anamnesis, physical examination and serological studies, treatment includes drugs that affect kidney function, such as ACE inhibitors, alone or in combination with BD, followed by determination of renal function and the degree of proteinuria, which may be indicated in selected patients before undergoing renal biopsy and the use of potentially dangerous immunosuppressive therapeutic regimens. Secondly, the course and prognosis of patients with severe proteinuria is determined not only by the results of renal function tests, but also by the pathophysiological consequences of severe proteinuria (nephrotic syndrome).

The diagnosis of nephrotic syndrome is established when protein loss is more than 3.5 g per 1.73 m2 of body surface per day, hypoalbuminemia, hyperlipidemia, lipiduria and edema. Severe proteinuria causes increased tubular reabsorption and metabolism of proteins entering the glomerular ultrafiltrate, which contributes to hypoproteinemia. Sodium and water retention with the occurrence of edema in some patients occurs secondarily as a result of hypoproteinemia, in others primarily as a result of damage to the glomeruli. Hypoproteinemia and a decrease in plasma oncotic pressure can stimulate the synthesis of apolipoprotein in the liver, leading to hyperlipidemia and lipiduria. It has been established that in case of long-term nephrotic disorders (membranous nephropathy), hyperlipidemia can lead to accelerated development of atherosclerosis. Severe proteinuria also predisposes to hypercoagulability, and transient losses of antithrombin III, protein S, and protein C have been described in some patients. nephrotic syndrome loss of proteins in urine can lead to subtle abnormalities such as loss of immunoglobulins and complement (predisposes to infections), thyroid binding globulin (decreased total thyroxine, normal thyroid-stimulating hormone) and vitamin D (hypovitaminosis, hypocalcemia and secondary hyperparathyroidism). Streets with severe proteinuria depending on protein loss, food intake and genetic predisposition arise various complications nephrotic syndrome.

Causes of proteinuria

Causes can be classified by mechanism. Most common reasons Proteinuria is a glomerular pathology, usually clinically manifested by nephrotic syndrome.

The most common causes in adults are:

• Focal segmental glomerulosclerosis.
• Membranous glomerulonephritis.
• Diabetic nephropathy.

The most common causes in children are:

• Minimal change disease (in young children).
• Focal segmental glomerulosclerosis (in older children).

Causes of glomerular proteinuria

• Primary lesion: Minimal changes, mesangial-proliferative (IgA, IgM), focal and segmental glomerulosclerosis, membranous, membranoproliferative, rapidly progressive
• Hereditary: Alport syndrome, Fabry disease, hereditary onychoarthrosis
• Infections: Bacterial, viral, fungal, protozoal and helminthic, including bacterial endocarditis, post-streptococcal glomerulonephritis, visceral abscesses, secondary syphilis, hepatitis B and C, human immunodeficiency virus, malaria
• Metabolic: Diabetes mellitus
• Immunological: Systemic lupus erythematosus, mixed collagenosis, Sjögren's syndrome, Henoch-Schönlein disease, Wegener's granulomatosis, micronodular polyarthritis, Goodpasture's syndrome, cryoglobulinemia
• Medicines: Penicillamine, drugs containing gold or mercury, lithium, NSAIDs, ACE inhibitors, heroin
• Tumors: Multiple myeloma; carcinoma of the lung, colon or breast; lymphoma; leukemia
• Other causes: Sulfur cell anemia, allergies, immunization, cirrhosis, immunoanaphylactic glomerulopathy, amyloidosis, reflux nephropathy, congenital nephrotic syndrome

Causes of tubular proteinuria

• Congenital: Polycystic kidney disease, spongy kidney
• Infections: Pyelonephritis, tuberculosis
• Metabolic: Diabetes mellitus, hyperuricemia, uricosuria, hypercalcemia, hypercalciuria, hypokalemia, oxaluria, cystinosis
• Immunological: Sjögren's syndrome, kidney transplant rejection, drug allergy, sarcoidosis
• Toxic: Overdose of analgesics, radiation nephritis, lithium intoxication, heavy metals(lead, cadmium, mercury), Balkan nephritis, poisoning with cyclosporine, cisplatin, aminoglycosides
• Anatomical: Obstruction, vesicoureteral reflux, spongy kidney
• Mixed: Multiple myeloma, amyloidosis, sickle cell anemia, spongy kidney

Proteinuria testing

Proteinuria itself is usually determined only by urine analysis or the use of rapid dip tests. A history and physical examination sometimes provide valuable information about the possible etiology.

History and physical examination

When examining organs and systems, you need to pay attention to symptoms indicating the cause of proteinuria, incl. red or brown discoloration of the kidney (glomerulonephritis) or bone pain (myeloma).

Patients are asked about existing diseases that can cause proteinuria, including recent serious illnesses(especially accompanied by fever), intense physical activity, known kidney disease, diabetes, pregnancy, sickle cell disease, SLE and malignant tumors(especially myeloma and similar diseases).

Physical examination is of limited value, but vital signs should be assessed to identify arterial hypertension, which indicates glomerulonephritis. During examination, signs of peripheral edema and ascites should be determined, which indicate fluid overload and possibly glomerular pathology.

Laboratory diagnostics

Immersion tests mainly determine the presence of albumin. Precipitation techniques such as heat and sulfosalicylic acid test strips determine the presence of all proteins. Thus, incidentally detected isolated proteinuria is usually albuminuria. Dip tests are relatively insensitive for diagnosing microalbuminuria, so a positive dip test usually indicates overt proteinuria. Also, when using immersion tests, it is unlikely to determine the excretion of small molecular proteins, which is typical for tubular or overload proteinuria.

In patients with positive result dip test (for the presence of protein or other pathological component) should be carried out as usual microscopic examination(analysis) of urine. Pathological results urinalysis (eg, casts and abnormal red blood cells indicating glomerulonephritis; glucose and/or ketone bodies indicating diabetes mellitus) or diseases that may be suspected based on history and physical examination (eg, peripheral edema indicating glomerular pathology) require further evaluation.

If other urinalysis parameters are normal, further tests may be postponed until the presence of protein in the urine is re-determined. If proteinuria is not detected during repeated testing, especially in patients who had intense proteinuria shortly before the study, physical activity, fever or decompensation of heart failure, it is likely to be functional in nature. Persistent proteinuria is a sign of glomerular pathology and requires additional examination and referral of the patient to a nephrologist. Additional examination includes OAK, measurement of serum electrolytes, BUN, creatinine and glucose levels; GFR determinations; estimating the amount of protein excreted (by daily collection or determining the protein/creatinine ratio in a random portion); estimates of kidney size (with ultrasound examination or CT). In most patients with glomerular pathology, the level of proteinuria is in the nephrotic range.

Other tests are usually performed to determine the cause of glomerular lesions, including lipid profile, level of complement components and cryoglobins, serological studies for hepatitis B and C, studies of the level of antinuclear antibodies and electrophoresis of urine and serum proteins. If these noninvasive tests remain diagnostically inconclusive (as is often the case), a kidney biopsy is required. Idiopathic proteinuria and renal failure, especially in older patients, may be due to myelodysplastic disorders (eg, multiple myeloma) or amyloidosis.

In patients under 30 years of age, the possible orthostatic nature of proteinuria should be kept in mind. Diagnosis requires the collection of two urine samples, one from 7 am to 11 pm (day sample) and the other from 11 pm to 7 am (night sample). The diagnosis is confirmed if the level of urinary protein exceeds normal values in the daytime sample (or if the protein/creatinine ratio is greater than 0.3) and remains normal in the nighttime sample.

Biochemical research

Although it is not specific for glomerular lesions, abnormal discharge protein in the urine is a cardinal manifestation of the disease in virtually all patients with glomerulonephritis. Fever, physical work, hyperglycemia and severe hypertension may transiently increase proteinuria.

For more accurate quality and quantitative analysis proteinuria usually requires a 24-hour urine sample. This is done like this: the first morning portion of urine is poured out, then all the urine is carefully collected during the day. The last daily portion is also included in the analysis. If urine is kept refrigerated during collection, no preservatives are required. If this is not possible, then acetic acid must be added to the urine collection vessel.

In urine collected within 24 hours, the daily creatinine content should be determined. In women with stable renal function, daily creatinine excretion should be approximately 15-20 mg per kilogram ideal weight body, in men this figure should be 18-25 mg/kg. Accurate quantitative methods for determining protein in urine by precipitation: precipitation reaction with sulfosalicylic acid, Kjeldahl micromethod, Esbach reagent (a combination of picric and citric acid) and biuret test. The result is expressed in grams per 24 hours or as the ratio of protein content to creatinine excretion.

In patients with severe proteinuria (to assess the effectiveness of treatment), instead of repeating the 24-hour urine collection method, it is better to determine the ratio of protein concentration to creatinine concentration. Normal daily protein excretion in adults ranges from 30 to 130 mg. In children and adolescents, excretion may be 2 times greater. Normally, the protein/creatinine ratio in a random sample is below 0.2. A value above 3 indicates proteinuria of nephrotic origin.

Qualitative assessment of urine protein composition is a valuable adjunct to quantitative research. Using electrophoresis, urine protein is divided by molecular weight into 5 peaks: albumin, α 1, α 2, β and γ-globulins. Normal urine protein consists of protein filtered from blood plasma (50%) and proteins secreted into the urine by cells urinary tract(50%). Of the filtered proteins, the majority is albumin - approximately 15% total protein urine. As well as immunoglobulins (5%), light chains (5%), β 2 -microglobulin ((32MG<0,2%) и другие белки плазмы (25%). Из секретируемых белков - белок Тамма-Хорсфолла попадает в мочу после синтеза его клетками почечных канальцев восходящей части петли Генле. Это единственный белок, находящийся в большом количестве в нормальной моче - 50% общего количества мочевого белка.

Electrophoresis and immunoelectrophoresis are valuable techniques used to determine the origin of urine proteins. The immunofixation method is more sensitive than both of the previous ones. Examination of urine for the content of Ben-Jones protein, which precipitates at 45-55 °C and re-dissolves when heated to a higher temperature, is a less sensitive method than electrophoresis and immunoelectrophoresis for detecting secretory proteinuria.

Differential diagnosis of severe proteinuria

If proteinuria is the result of glomerular damage, the underlying pathology should be looked for. The medical history should reflect the following important details: the presence of diabetes, deafness in other family members (Alport syndrome and other familial nephropathies); ethnicity (IgA nephropathy often occurs in Asians and rarely in African Americans); fever; penchant for traveling; taking medications; blood transfusions; taking drugs; sexual orientation and partners (to identify HIV, hepatitis, syphilis); presence of arthritis; arthralgia; rashes on the cheeks and skin; mouth ulcers; alopecia (systemic lupus erythematosus and other immune and allergic disorders); hemoptysis (Goodpasture's syndrome, Wegener's granulomatosis); sinusitis; sterile otitis (Wegener's granulomatosis); paresthesia; angiokeratomas; dyshidrosis; local neurological deficit (Fabry disease); weight loss; cough; neoplasms in the mammary glands (cancer and secondary membranous nephropathy), allergies, UTIs in children and adolescents (focal sclerosis due to reflux nephropathy), episodes of severe or persistent microhematuria (IgA nephropathy, thin basement membrane disease). The physical examination should be aimed at searching for systemic disease and detecting nephrotic syndrome or its complications. Minimum list of examinations for adults: chest x-ray, complete blood count, electrophoresis of serum and urine proteins, biochemical blood tests, including assessment of kidney and liver function, determination of serum albumin, total protein, total cholesterol and high-density lipoproteins, triglycerides, glucose and calcium. For persons over 40 years of age: guaiac test for the presence of blood in the stool in men and women and mammography in women. People over 50 years of age should have a screening colonoscopy if they have not previously had one. Additional serological tests are carried out depending on the presence or absence of hematuria and the results of the above studies. Possible additional studies include: determination of antinuclear antibodies and antibodies to double-stranded DNA (systemic lupus erythematosus), antineutrophil cytoplasmic antibodies, antiprotein and antimyeloperoxidase antibodies (Wegener's granulomatosis and other vasculitis), S3, C4 (may be reduced in endocarditis, post-streptococcal glomerulonephritis, lupus, membranoproliferative glomerulonephritis - MPGN, cryoglobulinemia), antihyaluronidase and anti-DNase B, O-antistreptolysin (poststreptococcal glomerulonephritis), antibodies to thin basement membranes (Goodpasture syndrome), rheumatoid factor (endocarditis, cryoglobulinemia, rheumatoid arthritis), serum cryoglobulins , APF (sarcoidosis), glycosylated hemoglobin; serological reaction to syphilis; determination of antibodies and antigen to hepatitis B; recombinant immunoblotting and viral load for hepatitis C and immunoadsorbent assay with immobilized enzymes/Western blotting for HIV. These tests should not be mandatory for all patients with glomerular proteinuria, given their cost. The key to selecting the appropriate tests mentioned and not mentioned in this list should be a careful review of the history and physical examination findings.

In the absence of any reason for glomerular proteinuria, after a complete examination, the question of a kidney biopsy is raised. In addition, renal biopsy is indicated in cases of identification of a secondary cause where histological examination will help guide treatment (for example, systemic lupus erythematosus).

Treatment of proteinuria

Treatment is aimed at the cause of proteinuria.

Treatment of severe proteinuria carried out in many directions. Studies have shown that NSAIDs reduce proteinuria in some patients, along with a small decrease in GFR. This treatment helps only a small part of patients; the overall reduction in proteinuria in most patients is extremely insignificant. ACE inhibitors and angiotensin receptor blockers are also prescribed to reduce proteinuria; these drugs have proven effective in treating patients with diabetic nephropathy and idiopathic nephrotic syndrome. The combination of these drugs may further reduce proteinuria. It may take many months after starting ACE inhibitors and/or angiotensin receptor blockers before the maximum reduction in proteinuria occurs when taking a fixed dose; this phenomenon suggests an additional mechanism of action other than hemodynamic changes. Reduction of proteinuria can also be achieved by reducing mean blood pressure below 92 mm Hg, regardless of the group of antihypertensive drugs used. Finally, as further measures to reduce proteinuria, it was proposed to reduce the amount of protein in food to 0.6-0.8 g/kg per day, which reduces the load on the kidneys. In recent years, physicians have been less likely to prescribe a protein-restricted diet due to the effectiveness of bipolar therapy, conflicting data on the effectiveness of low-protein diets, and food safety issues in patients with severe proteinuria (more than 10 g/day). However, patients with severe proteinuria should be advised to follow a diet with a daily protein content close to normal (0.8 g of protein per kilogram of weight).

Caused by the breakdown of cellular elements during prolonged standing of urine; in this situation, proteinuria exceeding 0.3 g/day is considered pathological.

Sedimentary protein tests give false-positive results in the presence of iodine-containing contrast agents, large amounts of antibiotics (penicillins or cephalosporins), and sulfonamide metabolites in the urine.

In the early stages of the development of most nephropathies, predominantly low molecular weight plasma proteins (albumin, ceruloplasmin, transferrin, etc.) penetrate into the urine. However, it is also possible to detect high-molecular proteins (alpha2-macroglobulin, γ-globulin), which are more typical for severe kidney damage with “large” proteinuria.

Selective proteinuria includes proteins with a low molecular weight of no more than 65,000 kDa, mainly albumin. Nonselective proteinuria is characterized by an increase in the clearance of medium- and high-molecular-weight proteins: the composition of urine proteins is dominated by α2-macroglobulin, beta-lipoproteins, and γ-globulin. In addition to plasma proteins, proteins of renal origin are determined in the urine - Tamm-Horsfall uroprotein, secreted by the convoluted tubule epithelium.

Glomerular (glomerular) proteinuria is caused by increased filtration of plasma proteins through the glomerular capillaries. This depends on the structural and functional state of the wall of the glomerular capillaries, the properties of protein molecules, pressure and blood flow velocity, which determine GFR. Glomerular proteinuria is a mandatory feature of most kidney diseases.

The wall of the glomerular capillaries is made up of endothelial cells (with rounded holes between them), a three-layer basement membrane - a hydrated gel, as well as epithelial cells (podocytes) with a plexus of stalked processes. Due to its complex structure, the glomerular capillary wall can “sift” plasma molecules from the capillaries into the space of the glomerular capsule, and this “molecular sieve” function largely depends on the pressure and speed of blood flow in the capillaries.

Under pathological conditions, the size of the “pores” increases, deposits of immune complexes cause local changes in the capillary wall, increasing its permeability to macromolecules. In addition to the size of the glomerular “pores,” electrostatic factors are also important. The glomerular basement membrane is negatively charged; The foot processes of podocytes also carry a negative charge. Under normal conditions, the negative charge of the glomerular filter repels anions - negatively charged molecules (including albumin molecules). The change in charge promotes the filtration of albumin. It is assumed that the fusion of the stalked processes is the morphological equivalent of a change in charge.

Tubular proteinuria is caused by the inability of the proximal tubules to reabsorb plasma low molecular weight proteins filtered in normal glomeruli. Proteinuria rarely exceeds 2 g/day, excreted proteins are represented by albumin, as well as fractions with even lower molecular weight (lysozyme, beta 2-microglobulin, ribonuclease, free light chains of immunoglobulins), which are absent in healthy individuals and in glomerular proteinuria due to 100 % reabsorption by convoluted tubule epithelium. A characteristic sign of tubular proteinuria is the predominance of beta 2-microglobulin over albumin, as well as the absence of high molecular weight proteins. Tubular proteinuria is observed with damage to the renal tubules and interstitium: with tubulointerstitial nephritis, pyelonephritis, kalipenic kidney, acute tubular necrosis, chronic kidney transplant rejection. Tubular proteinuria is also characteristic of many congenital and acquired tubulopathies, in particular Fanconi syndrome.

Proteinuria “overflow” develops with an increase in the concentration of low molecular weight proteins (immunoglobulin light chains, hemoglobin, myoglobin) in the blood plasma. In this case, these proteins are filtered by unchanged glomeruli in quantities exceeding the reabsorption capacity of the tubules. This is the mechanism of proteinuria in multiple myeloma (Bence-Jones proteinuria) and other plasma cell dyscrasias, as well as myoglobinuria.

The so-called functional proteinuria is distinguished. The mechanisms of development and clinical significance of most of its variants are unknown.

• Orthostatic proteinuria occurs with prolonged standing or walking (“proteinuria en marche”) with rapid disappearance in a horizontal position. In this case, the amount of protein excretion in urine does not exceed 1 g/day. Orthostatic proteinuria is glomerular and nonselective and, according to long-term prospective studies, is always benign. If it is isolated, there are no other signs of kidney damage (changes in urinary sediment, increased blood pressure). It is more often observed in adolescence (13-20 years), in half of people it disappears after 5-10 years from the moment of occurrence. Characteristic is the absence of protein in urine tests taken immediately after the patient is in a horizontal position (including in the morning before getting out of bed).
• Proteinuria of tension, found after intense physical activity in at least 20% of healthy individuals, including athletes, is also apparently benign. According to the mechanism of its occurrence, it is considered tubular, caused by the redistribution of intrarenal blood flow and relative ischemia of the proximal tubules.
• With fever with a body temperature of 39-41 ° C, especially in children and the elderly and senile, so-called febrile proteinuria is detected. It is glomerular, the mechanisms of its development are unknown. The occurrence of proteinuria in a patient with fever sometimes indicates the addition of kidney damage; This is supported by simultaneous changes in urinary sediment (leukocyturia, hematuria), large, especially nephrotic levels of protein excretion in the urine, as well as arterial hypertension.

Proteinuria exceeding 3 g/day is a key sign of nephrotic syndrome.

Proteinuria and progression of chronic nephropathies

The significance of proteinuria as a marker of the progression of kidney damage is largely due to the mechanisms of the toxic effect of individual components of the protein ultrafiltrate on the epithelial cells of the proximal tubules and other structures of the renal tubulointerstitium.

Components of protein ultrafiltrate that have a nephrotoxic effect

Protein	Mechanism of action
Albumen	Increased expression of pro-inflammatory chemokines (monocyte chemoattractant protein type 1, RANTES*) Toxic effect on epithelial cells of the proximal tubules (overload and rupture of lysosomes with the release of cytotoxic enzymes) Induction of the synthesis of vasoconstriction molecules, aggravating hypoxia of tubulointerstitial structures Activation of apoptosis of epithelial cells of proximal tubules
Transferrin	Induction of synthesis of complement components by epithelial cells of proximal tubules Increased expression of pro-inflammatory chemokines Formation of reactive oxygen radicals
Complement components	Formation of cytotoxic MAC** (C5b-C9)

• * RANTES (Regulated upon activation, normal T-lymphocyte expressed and secreted) - activated substance expressed and secreted by normal T-lymphocytes.
• ** MAK - membrane attack complex.

Many mesangiocytes and vascular smooth muscle cells undergo similar changes, meaning they acquire the basic properties of a macrophage. Monocytes from the blood actively migrate into the renal tubulointerstitium and also transform into macrophages. Plasma proteins induce processes of tubulointerstitial inflammation and fibrosis called proteinuric tubulointerstitial remodeling.

Today I will talk about nephrotic syndrome which occurs in diabetes mellitus.

Simply put, nephrotic syndrome is a condition caused by a large loss of protein in the urine(more than 3.5 g/day or more than 3 g/l).

Nephron structure

Let me remind you of the structure of the kidneys. The basic structural unit of the kidneys is nephron. Each kidney contains 1.5-2 million nephrons. The nephron consists from renal corpuscle and renal tubule. The renal corpuscle is the initial part of the nephron and consists of glomerulus and covering it Shumlyansky-Bowman capsules. Occurs in the renal glomerulus blood filtration and the formation of primary urine (about 180 liters per day), which resembles blood plasma in composition. Normally, primary urine contains very little protein, since protein molecules, due to their significant volume, are almost unable to penetrate the kidney filter. In the renal tubules, whose length is 3.5-5 cm, reverse absorption (reabsorption) of many substances, water, all glucose and protein occurs. As a result, out of 180 liters of primary urine, a healthy person secretes only 1.5-2 liters of secondary (final) urine.

The kidney consists of a cortex and medulla.
The structure of the nephron is shown.

So, Normally there is practically no protein in secondary urine. Protein appears in the urine if at least one of the following conditions is met:

1. the filter in the renal glomeruli is damaged (pathologically high permeability). As a result, more protein ends up in the urine than it should.
2. the absorption capacity of the epithelium of the renal tubules is impaired (reduced). As a result, the protein cannot be reabsorbed and remains in the urine.

What is proteinuria

The presence of protein in urine is called proteinuria. Normally, only small amounts of protein enter the primary urine through the renal glomeruli, which are reabsorbed (absorbed) in the renal tubules.

Amount of protein in urine

• Selection up to 30-60 mg of protein in urine per day is normal. In laboratory practice, the normal concentration of protein in urine is up to 0.033 g/l.
• From 60-70 to 300 mg per day - microalbuminuria. Albumin is the most abundant in the blood, and the molecular size is relatively small, so it is easier for these proteins to penetrate into the urine. Previously, I wrote in detail about the composition of serum proteins. To determine microalbuminuria, there are a number of test strips that give values ​​per 1 liter.
• Slight (minimal) proteinuria - from 300 mg to 1 g per day.
• Moderate proteinuria - from 1 g to 3-3.5 g per day.
• Massive proteinuria - more than 3.5 g protein per day. With massive proteinuria, nephrotic syndrome develops.

Blood protein fractions(after electrophoresis).

Types of proteinuria

Proteinuria can be physiological or pathological.

Species physiological (functional) proteinuria(usually it is not higher than 1 g/l):

• after cooling(immersion of hands up to the elbows in cold water for 2-5 minutes), mud baths, extensive lubrication of the skin with iodine;
• nutritional: after eating a large protein meal,
• centrogenic: after an attack of convulsions and concussion,
• emotional: under stress, for example, during an exam,
• working (marching, tension proteinuria): after physical activity. Usually does not exceed 1 g/l. Disappears after a few hours. You need to be on your guard, because... may indicate kidney problems.
• orthostatic (postural): in healthy young people under 22 years of age with asthenic physique in an upright body position for more than 30 minutes. Proteinuria goes away in the lying position, so in such people protein is not detected in the morning urine.
• febrile: protein in the urine is detected at elevated body temperature and disappears when it normalizes.

Pathological proteinuria is one of the most important symptoms of kidney damage.

Happens renal origin (renal) And non-renal(rare and does not exceed 1 g/l). Nonrenal proteinuria occurs:

• prerenal(“before the kidneys”): for example, when tissue is destroyed, many protein products accumulate in the blood, which the kidneys cannot cope with.
• postrenal(“after the kidneys”): the release of protein exudate during inflammation of the urinary tract.

From history

More than half a century ago nephrotic syndrome called the word "nephrosis". If you remember from Greek and Latin medical terminology, the suffix " -oz" in the name of the disease emphasizes non-inflammatory, degenerative changes. Indeed, under a conventional (light) microscope, doctors of that time found degeneration and dystrophy of renal tubular cells in the kidneys. And only after the invention of the electron microscope, scientists were able to find out that the main thing in the development of nephrotic syndrome is glomerular damage, and the tubules are affected later - secondarily.

Pathogenesis (development of pathological process)

Now generally accepted immunological concept development of nephrotic syndrome. According to her, the disease is caused by numerous immune complexes, deposited on the basement membranes of the capillaries of the renal glomeruli. Antigen-antibody compounds are called immune complexes. Precipitation of immune complexes circulating in the blood or their formation “in situ” causes inflammation and activation of the immune system, due to which the kidney filter is damaged and begins to leak protein molecules into the primary urine in large quantities. At first, the kidney filter allows only small protein molecules (albumin), such proteinuria is called selective and testifies to initial damage kidney filter. But over time, even large squirrels blood serum, and proteinuria becomes low-selective and even non-selective. Nonselective proteinuria is much more difficult to treat, as it indicates severe damage kidney filter.

There is usually also a relationship between the severity and selectivity of proteinuria: the more protein in the urine, the lower the selectivity(less than 1 g/l - only albumin).

How common is nephrotic syndrome?

75% (!) of cases nephrotic syndrome caused acute and chronic glomerulonephritis. In other cases, the kidneys may be damaged secondarily. To understand what diseases can cause nephrotic syndrome, you need to understand in what cases many antibodies are formed:

• chronic infections: tuberculosis, syphilis, malaria, infective endocarditis, etc.
• autoimmune diseases: systemic lupus erythematosus, scleroderma, rheumatoid arthritis;
• allergic diseases;
• tumors from lymphatic tissue: myeloma (formation of a large number of defective antibodies), lymphogranulomatosis (damage to the lymph nodes).

Nephrotic syndrome can also be caused by:

• diabetes mellitus (due to damage to the capillaries of the renal glomeruli - this is a manifestation of diabetic microangiopathy),
• taking certain medications (mercury, gold, D-penicillamine, etc.),
• Kidney amyloidosis (a disorder of protein metabolism, accompanied by the formation and deposition in tissues of a specific protein-polysaccharide complex - amyloid),
• nephropathy of pregnant women, etc.

The most common cases of nephrotic syndrome are children aged 2-5 years(at this age the child’s immune system is actively becoming familiar with infections) and adults 20-40 years old(and this is the characteristic age of onset of many autoimmune and rheumatic diseases).

Definition of “nephrotic syndrome”

Nephrotic syndrome(according to Wikipedia) - a condition characterized by generalized edema, massive proteinuria (above 3.5 g/day and above 50 mg kg/day), hypoproteinemia and hypoalbuminemia (less than 20 g/l), hyperlipidemia (cholesterol above 6.5 mmol/ l).

The definition looks a little complicated, but there is nothing complicated there. The main feature of nephrotic syndrome is the excretion of large amounts of protein in the urine (i.e. massive proteinuria), at least 3.5 g per day. The protein intake rate is 1-1.5 g/kg per day, i.e. a person weighing 60 kg should consume 60-90 g of protein per day. In nephrotic syndrome, there is a large loss of protein in the urine ( up to 5-15 g per day), due to which the protein content in the blood decreases ( hypoproteinemia). The main part of blood proteins is albumins (normally 35-55 g/l), therefore hypoproteinemia is usually combined with hypoalbuminemia (less than 20 g/l). When the albumin level is less than 30 g/l, water from the blood vessels leaks into the tissues, causing extensive (generalized) edema. I wrote in more detail about blood proteins and the mechanism of similar edema in the topic: Is it possible to swell from hunger? Due to lipid metabolism disorders, patients experience elevated cholesterol levels ( above 6.5 mmol/l, sometimes can reach 20-30 mmol/l with a norm of 4.2-5 mmol/l).

Clinical manifestations of nephrotic syndrome

No matter the reason nephrotic syndrome always looks the same:

• massive proteinuria(up to 80-90% of proteins excreted in urine are albumin),
• hypoproteinemia(normally 60-80 g/l, reduced to 60 g/l, occasionally even to 30-40 g/l),
• dysproteinemia(violation of the correct proportions of serum proteins), most often the level of albumin and β-globulins decreases and the level of? 2, β-globulins, β-lipoproteins, however, these proportions depend on the disease that caused nephrotic syndrome.
• hyperlipidemia and hypercholesterolemia(the content of cholesterol and triglycerides in the blood increases, the blood serum acquires a milky white, “chylous” color).

Left - chylous (milky white) blood serum.
On the right - normal. Below in both figures are settled red blood cells.

Edema are observed in almost everyone, but are expressed differently. Patients have a characteristic appearance: pale, with a puffy face and swollen eyelids. Initially, swelling is noticeable in the eyelids, face, lumbar region, legs and genitals, and then spreads to the entire subcutaneous tissue. Leather pale, cold to the touch, dry, may peel off. It’s easy to determine edema: you need press your finger on the skin and release. In a healthy person, no depressions will remain, but with edema, hole, which will disappear only after a few minutes. The initial stage of swelling of the subcutaneous tissue is called pastiness(from Italian pastoso - pasty), this is an intermediate state between normal and edema.

With massive swelling, cracks may form on the skin of the legs, through which edematous fluid oozes. Cracks are entry points for infection. Edema fluid can accumulate in body cavities and receive its own names: fluid in the abdominal cavity -, in the chest cavity - hydrothorax, in the pericardial cavity - hydropericardium. Extensive swelling of the subcutaneous tissue is called anasarca.

Left - .
On the right is her after treatment.

For nephrotic syndrome decreased metabolism, which is associated with a decrease in thyroid function. The temperature may also be reduced.

Sick inactive and pale. Heart rate and blood pressure are within normal limits or reduced. Since the kidneys produce erythropoietin, which stimulates the formation of red blood cells, anemia with tachycardia may develop. In the lower parts of the lungs, signs of congestion may be detected: weakening of breathing and moist fine rales. Congestion in the lungs can lead to congestive pneumonia.

Ascites- fluid in the abdominal cavity.

The tongue is often coated, the abdomen is enlarged (ascites). Some patients with nephrotic syndrome have what is called nephrotic diarrhea with the loss of large amounts of protein, which is associated with increased permeability of the intestinal mucosa.

Analysis results

URINE: daily diuresis is reduced, Usually urine is less than 1 liter per day, often only 400-600 ml. The relative density of urine is normal (usually 1010-1020) or increased, as it contains a lot of protein and other osmotically active substances. 3.3 g/l of protein in urine increases its relative density by 0.001.

Determined in urine hyaline casts, which are clumps of protein. In the renal tubules they fold and acquire a cylindrical shape, i.e., the shape of the lumen of the tubule. The more protein in the urine, the more hyaline casts there are in the general urinalysis. However, in alkaline urine there are no hyaline casts; they are formed only in an acidic environment. Hematuria (red blood cells in the urine) is not typical for nephrotic syndrome.

You need to know that in the future, as kidney function deteriorates, it will inevitably develop chronic renal failure- . With chronic renal failure, the amount of urine increases and its density decreases, which may be mistakenly perceived as an “improvement.” However, there is little good here: the kidneys stop working and can no longer even concentrate urine.

BLOOD. The most constant sign is increase in ESR(erythrocyte sedimentation rate), reaching 60-85 mm/h with a norm of 1-10 in men and 2-15 mm/h in women. Of the other changes, the most common hypercoagulability(increased coagulability) of blood.

Course of the disease

• 50% of patients have persistent variant: the course of the disease is sluggish and slow, but at the same time persistently progressive. Treatment is ineffective, and after 8-10 years chronic renal failure develops.
• In 20% of patients, nephrotic syndrome occurs in waves, with alternating periods of exacerbations and remissions. Without treatment, remissions are rare.
• Some patients experience rapidly progressing variant the course of nephrotic syndrome, in which chronic renal failure develops in just 1-3 years.

Complications

Complications of nephrotic syndrome are caused both by the characteristics of the disease and by medications (for example, in autoimmune and rheumatic diseases, drugs that suppress the immune system are used, which increases the risk of infections). Complications of nephrotic syndrome include:

1. infections(pneumonia, furunculosis, etc.)
2. thrombosis and thromboembolism(remember about increased blood clotting in such patients?)
3. pneumococcal peritonitis(inflammation of the abdominal cavity caused by pneumococcus). It is rare, but previously such patients died without antibiotics.
4. nephrotic crisis is also extremely rare. Abdominal pain suddenly appears without clear localization, the temperature rises, and redness appears on the skin, similar to erysipelas. Blood pressure drops sharply. Everything together resembles a painting anaphylactic (allergic) shock. Scientists believe that highly active substances accumulate in the blood and edematous fluid, dilating blood vessels and increasing their permeability to blood serum.

About treatment

All patients hospitalized to establish an accurate diagnosis and cause of nephrotic syndrome. Everyone is assigned bed rest, diet with limited salt and liquid(salt promotes swelling). Nutrition for nephrotic syndrome should correspond to the diet 7v(according to Pevzner). Depending on the cause of nephrotic syndrome, immunosuppressants may be prescribed: glucocorticosteroids and cytostatics. Sometimes extracorporeal (extra - above, corpus and corporis - body) methods of blood purification are used - plasmapheresis And hemosorption.

Forecast

Complete and lasting recovery is observed rarely, more often in children with some forms of nephrotic syndrome. Usually, over time, kidney function is impaired, the content of nitrogenous (protein) metabolic products in the blood increases, arterial hypertension occurs, and a complete picture of chronic renal failure (CRF) develops.

When preparing the article, the material used was “ Practical Guide to Nephrology» ed. Professor A. S. Chizh, Mn., 2001.

Normally, in the urine of healthy people, protein is present in minimal quantities - in the form of traces (no more than 0.033 g/l), which cannot be detected using qualitative methods. Higher levels of protein in the urine are classified as proteinuria.

Proteinuria is the appearance of protein in the urine in quantities at which qualitative reactions to protein become positive.

Depending on the protein content in the urine, there are:

• mild proteinuria - up to 1 g/l;
• moderate proteinuria - 2-4 g/l;
• significant proteinuria - more than 4 g/l.

Proteinuria occurs when protein filters from the blood into the kidneys or protein attaches to urine in the urinary tract. Depending on the cause, the following types of proteinuria are distinguished:

1. Renal (renal):

• functional;
• organic.

1. Extrarenal (extrarenal).

Renal (renal) proteinuria occurs as a result of increased permeability of the renal filter due to damage (organic) and without damage (functional) to the kidneys.

Functional proteinuria occurs due to an increase in the permeability of the renal filter in response to strong external irritation or a slowdown in the passage of blood in the glomeruli.

Among them are:

1. Physiological proteinuria in newborns happens quite often in the first 4-10 days after birth and is caused by the presence of a functionally fragile renal filter in the newborn, as well as, probably, by birth trauma;
2. Alimentary proteinuria - occurs after eating protein foods (egg whites);
3. Orthostatic proteinuria - more often observed in adolescents, emaciated people, asthenics with lordosis of the lower thoracic spine. Protein in the urine can appear in significant quantities during prolonged standing, severe curvature of the spine (lordosis), as well as in the event of a sharp change in body position from lying to standing;
4. Feverish proteinuria - occurs at elevated body temperature up to 39-40 ° C in infectious diseases. The causative agent of the infection and the increased temperature irritate the kidney filter, leading to an increase in its permeability;
5. Proteinuria caused by nervous (emotional) and physical (marching) overloads of the body;
6. Proteinuria in pregnant women;
7. Congestive proteinuria - observed in patients with cardiovascular diseases, ascites, abdominal tumors (up to 10 g/l). When blood movement slows down in the vascular glomeruli of the nephron, glomerular hypoxia develops, which leads to an increase in the permeability of the renal filter. Prolonged stagnation of blood can cause organic kidney damage and lead to organic proteinuria.

So, the cause of functional renal proteinuria is an increase in the permeability of the renal filter (in particular the wall of the glomerular vessels); damage to the renal filter does not occur. Therefore, functional proteinuria is usually: mild (up to 1 g/l); are represented by low molecular weight proteins (albumin), short-term (disappear after the end of the stimulus on the renal filter).

Organic proteinuria occurs due to increased permeability of the renal filter as a result of damage to the renal parenchyma. This type of renal proteinuria is observed in acute and chronic nephritis, nephrosis, nephrosclerosis, infectious and toxic kidney damage, as well as in persons with congenital anatomical abnormalities of the kidneys, for example, in the case of polycystic disease, when anatomical changes cause significant organic damage to the renal tissue.

The severity of proteinuria does not always indicate the severity of damage to the renal parenchyma. Sometimes acute glomerulonephritis with high proteinuria can quickly end in recovery, and chronic glomerulonephritis with low protein content in the urine can last a long time and even cause death. A decrease in proteinuria in the case of acute glomerulonephritis is generally a good sign, and in chronic forms such a decrease is very often accompanied by a deterioration in the patient’s condition, as it may be due to functional kidney failure with a decrease in their filtration capacity, due to the death of a large number of renal glomeruli. Moderate proteinuria is recorded in acute and chronic glomerulonephritis, systemic lupus erythematosus, and renal amyloidosis. Significant proteinuria is characteristic of nephrotic syndrome.

Acute and chronic glomerulonephritis. Proteinuria occurs as a result of damage to the renal filter. In glomerulonephritis, antibodies attack the renal filter, resulting in an increase in its filtration capacity, but since tubular reabsorption is not impaired, most of the filtered protein is reabsorbed into the blood as urine passes through the tubular system. Thus, with glomerulonephritis, proteinuria is a constant phenomenon, its level is moderate (up to 5 g/l).

Nephrotic syndrome. Proteinuria occurs due to impaired tubular reabsorption of filtered protein as a result of damage to the renal tubules. Therefore, in nephrotic syndrome, proteinuria is a constant phenomenon, the level of proteinuria is significant (10-30 g/l). It is represented by albumins and globulins.

So, the pathogenesis of organic renal proteinuria is based on an increase in the permeability of the renal filter due to organic damage to the renal parenchyma. Therefore, organic proteinuria is usually moderate or pronounced; long-term; combined with other pathological changes in the urine (hematuria, cylindruria, disfoliation of the epithelium of the renal tubules).

Extrarenal (extrarenal) proteinuria is caused by protein impurities (inflammatory exudate, destroyed cells), which is released through the urinary tract and genitals. Occurs in cystitis, urethritis, prostatitis, vulvovaginitis, urolithiasis and tumors of the urinary tract. The amount of protein in extrarenal proteinuria is insignificant (up to 1 g/l).

Extrarenal proteinuria is usually combined with other pathological changes in the urine (leukocyturia or pyuria and bacteriuria).

Differentiation of different types of proteinuria is carried out by microscopy of urinary sediments and quantitative determination of the formed elements of urinary sediment according to Nechiporenko. Thus, renal organic proteinuria is determined by the presence of renal epithelium, erythrocytes and different types of casts in urine sediments. And extrarenal proteinuria is combined with the presence of a large number of leukocytes and bacteria in the urine.

Recently, the question has been quite often discussed in the domestic literature: what is considered proteinuria? If earlier proteinuria was simply called the detection of protein in urine using conventional qualitative or quantitative methods, the sensitivity and specificity of which were not very high, now, given the increasing introduction into practice of more sensitive and specific methods, proteinuria is said to be when the level of protein in the urine exceeds the norm . The concept of normal protein in urine also varies - which is due to the use of both old and new methods for determining protein in urine, which differ in sensitivity and specificity. Some authors, taking into account the presence of protein in the urine of a healthy person, understand the term proteinuria as generally the excretion of protein in the urine and, for simplicity, divide proteinuria into physiological and pathological, which is now also being debated. Usually under the term proteinuria refers to an increase in protein content in the urine.

In most laboratories, when testing urine “for protein,” they first use qualitative reactions that do not detect protein in the urine of a healthy person. If protein in the urine is detected by qualitative reactions, its quantitative (or semi-quantitative) determination is carried out. In this case, the features of the methods used, covering a different spectrum of uroproteins, are important. Thus, when determining protein using 3% sulfosalicylic acid, the amount of protein up to 0.03 g/l is considered normal, but when using the pyrogallol method, the limit of normal protein values ​​increases to 0.1 g/l. In this regard, the analysis form must indicate the normal protein value for the method used by the laboratory.

When determining the minimum amounts of protein, it is recommended to repeat the analysis; in doubtful cases, the daily loss of protein in urine should be determined. Normally, daily urine contains protein in small quantities. Under physiological conditions, the filtered protein is almost completely reabsorbed by the epithelium of the proximal tubules and its content in the daily amount of urine varies, according to different authors, from traces to 20 - 50, 80 - 100 mg and even up to 150 - 200 mg. Some authors believe that daily protein excretion in the amount of 30–50 mg/day is the physiological norm for an adult. Others believe that urinary protein excretion should not exceed 60 mg/m2 of body surface per day, excluding the first month of life, when the amount of physiological proteinuria can be four times higher than the indicated values.

The general condition for the appearance of proteins in the urine of a healthy person is their sufficiently high concentration in the blood and a molecular weight of no more than 100 - 200 kDa.

In practically healthy people, under the influence of various factors, transient proteinuria. This proteinuria is also called physiological, functional or benign, since it, unlike pathological, does not require treatment.

Physiological proteinuria

March proteinuria

Transient protein excretion in the urine in healthy people may appear after heavy physical activity (long hikes, marathon running, team sports). This is the so-called working (marching) proteinuria or tension proteinuria, observed and described by many researchers. The works of these authors, illustrating the possibility of developing proteinuria under the influence of physical activity, indicate a high degree of its severity, as well as its reversibility. The genesis of such proteinuria is explained by hemolysis with hemoglobinuria and stress secretion of catecholamines with a transient disturbance of glomerular blood flow. In this case, proteinuria is detected in the first portion of urine after physical activity.

The importance of the cooling factor in the genesis of transient proteinuria was noted in healthy people under the influence of cold baths.

Albuminuria solaris

Known albuminuria solaris, which occurs when there is a pronounced reaction of the skin to insolation, as well as when the skin is irritated by certain substances, for example, when it is lubricated with iodine.

Proteinuria with increased levels of adrenaline and norepinephrine in the blood

The possibility of the appearance of proteinuria with an increase in the level of adrenaline and norepinephrine in the blood has been established, which explains the release of protein in the urine during pheochromocytoma and hypertensive crises.

Nutritional proteinuria

Highlight nutritional proteinuria, sometimes appearing after eating a large protein meal.

Centrogenic proteinuria

The possibility of occurrence has been proven centrogenic proteinuria– for epilepsy, concussion.

Emotional proteinuria

Described emotional proteinuria during exams.

Palpable proteinuria

Proteinuria of functional origin also includes the release of protein in the urine, described by some authors, during vigorous and prolonged palpation of the abdomen and kidney area ( palpable proteinuria).

Feverish proteinuria

Feverish proteinuria observed in acute febrile conditions, more often in children and the elderly. Its mechanism is poorly understood. This type of proteinuria persists during the period of increased body temperature and disappears when it decreases and normalizes. If proteinuria persists for many days and weeks after body temperature has returned to normal, then possible organic kidney disease, either new or existing, should be excluded.

Congestive (cardiac) proteinuria

Heart diseases are often diagnosed stagnant, or cardiac proteinuria. As the heart failure resolves, it usually goes away.

Proteinuria of newborns

In newborns, physiological proteinuria is also observed in the first weeks of life.

Orthostatic (postural, lordotic) proteinuria

Orthostatic (postural, lordotic) proteinuria observed in 12–40% of children and adolescents, characterized by the detection of protein in the urine during prolonged standing or walking with rapid disappearance (transient variant of orthostatic proteinuria) or its decrease (persistent variant) in a horizontal position. Its genesis is associated with disturbances of renal hemodynamics, developing due to lordosis, compressing the inferior vena cava in a standing position, or the release of renin (angiotensin II) in response to changes in the volume of circulating plasma during orthostasis.

Physiological proteinuria is usually insignificant - no more than 1.0 g/day.

Modern research methods make it possible to identify a number of changes in the microstructure of the kidneys, the consequence of which is the so-called physiological proteinuria. Based on such considerations, many authors doubt the validity of identifying “functional” proteinuria.

Pathological proteinuria

Pathological proteinuria can be of renal or extrarenal origin.

Renal proteinuria

Renal proteinuria is one of the most important and persistent signs of kidney disease and may be glomerular, or glomerular, And tubular, or canalicular. When these two types are combined, it develops mixed type of proteinuria.

Glomerular proteinuria

Glomerular proteinuria caused by damage to the glomerular filter, occurs with glomerulonephritis and nephropathies associated with metabolic or vascular diseases. At the same time, plasma proteins are filtered from the blood into the urine in large quantities.

Various pathogenetic mechanisms underlie the disruption of the glomerular filter:

1. toxic or inflammatory changes in the glomerular basement membrane (deposition of immune complexes, fibrin, cellular infiltration), causing structural disorganization of the filter;
2. changes in glomerular blood flow (vasoactive agents - renin, angiotensin II, catecholamines), affecting glomerular transcapillary pressure, convection and diffusion processes;
3. lack (deficiency) of specific glomerular glycoproteins and proteoglycans, leading to the loss of a negative charge by the filter.

Glomerular proteinuria is observed in acute and chronic glomerulonephritis, amyloidosis, diabetic glomerulosclerosis, renal vein thrombosis, congestive kidney, hypertension, nephrosclerosis.

Glomerular proteinuria can be selective or non-selective depending on the severity of damage to the glomerular filter.

Selective proteinuria

Selective proteinuria occurs with minimal (often reversible) damage to the glomerular filter (nephrotic syndrome with minimal changes), is represented by proteins with a molecular weight of no higher than 68,000 - albumin and transferrin.

Non-selective proteinuria

Non-selective proteinuria more common with more severe damage to the filter, characterized by increased clearance of medium- and high-molecular plasma proteins (urine proteins also contain alpha2-globulins and gamma globulins). Nonselective proteinuria is observed in nephrotic and mixed forms of glomerulonephritis, secondary glomerulonephritis.

Tubular proteinuria (tubular proteinuria)

Tubular proteinuria is associated either with the inability of the tubules to reabsorb proteins that have passed through the unchanged glomerular filter, or due to the release of protein by the epithelium of the tubules themselves.

Tubular proteinuria is observed in acute and chronic pyelonephritis, heavy metal poisoning, acute tubular necrosis, interstitial nephritis, chronic kidney transplant rejection, kalipenic nephropathy, and genetic tubulopathies.

Extrarenal proteinuria

Extrarenal proteinuria occurs in the absence of a pathological process in the kidneys themselves and is divided into prerenal and postrenal.

Prerenal proteinuria

Prerenal proteinuria develops in the presence of an unusually high plasma concentration of low molecular weight protein, which is filtered by normal glomeruli in an amount exceeding the physiological capacity of the tubules for reabsorption. A similar type of proteinuria is observed in myeloma (low molecular weight Bence Jones protein and other paraproteins appear in the blood), with severe hemolysis (due to hemoglobin), rhabdomyolysis, myopathy (due to myoglobin), monocytic leukemia (due to lysozyme).

Postrenal proteinuria

Postrenal proteinuria caused by the release of mucus and protein exudate in the urine due to inflammation of the urinary tract or bleeding. Diseases that may be accompanied by extrarenal proteinuria are urolithiasis, kidney tuberculosis, kidney or urinary tract tumors, cystitis, pyelitis, prostatitis, urethritis, vulvovaginitis. Postrenal proteinuria is often very minor and practically less important.

Proteinuria severity

Depending on the severity, mild, moderate and severe proteinuria are distinguished.

Mild proteinuria

Mild proteinuria(from 300 mg to 1 g / day) can be observed in acute urinary tract infections, obstructive uropathy and vesicoureteral reflux, tubulopathies, urolithiasis, chronic interstitial nephritis, kidney tumors, polycystic disease.

Moderate proteinuria

Moderate proteinuria(from 1 to 3 g/day) is observed in acute tubular necrosis, hepatorenal syndrome, primary and secondary glomerulonephritis (without nephrotic syndrome), proteinuric stage of amyloidosis.

Severe (pronounced) proteinuria

Under severe, or severe proteinuria define a loss of protein in the urine that exceeds 3.0 g per day or 0.1 g or more per kilogram of body weight in 24 hours. Such proteinuria is almost always associated with dysfunction of the glomerular filtration barrier in terms of protein size or charge and is observed in nephrotic syndrome.

Detection and quantitative assessment of proteinuria are important both for diagnosis and for assessing the course of the pathological process and the effectiveness of treatment. In conclusion, it should be noted that the diagnostic significance of proteinuria is assessed in conjunction with other changes in the urine.

Literature:

• L. V. Kozlovskaya, A. Yu. Nikolaev. A textbook on clinical laboratory research methods. Moscow, Medicine, 1985
• A. V. Papayan, N. D. Savenkova "Clinical nephrology of childhood", St. Petersburg, SOTIS, 1997
• Kurilyak O.A. "Protein in urine - methods of determination and normal limits (current state of the problem)"
• A. V. Kozlov, “Proteinuria: methods for its detection,” lecture, St. Petersburg, SPbMAPO, 2000.
• V. L. Emanuel, “Laboratory diagnosis of kidney diseases. Urinary syndrome,” - Directory of the head of the clinical laboratory, No. 12, December 2006.
• O. V. Novoselova, M. B. Pyatigorskaya, Yu. E. Mikhailov, “Clinical aspects of identifying and assessing proteinuria”, Handbook of the head of the clinical laboratory, No. 1, January 2007.