Massive proteinuria is characteristic of. Selective proteinuria and its clinical significance

A high concentration of protein causes the appearance of foamy urine. In many kidney disorders, proteinuria accompanies other urinary disorders (eg, hematuria).

The pathogenesis of proteinuria

Although the glomerular basement membrane is a highly selective barrier to large molecules (eg, most plasma proteins, including albumin), a small amount of the protein passes through capillary basement membranes 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. The upper limit of the normal level of protein excretion in the urine is 150 mg/day, which can be measured by daily urine collection or estimated by the protein / creatinine ratio in a random serving (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 considered microalbuminuria, higher values ​​are considered macroalbuminuria. According to the mechanism, proteinuria can be divided into:

• glomerular, I am tubular,
• reloading,
• functional.

Glomerular proteinuria is caused by glomerular pathology, which is usually accompanied by increased glomerular permeability, this permeability allows an increased amount of plasma proteins (sometimes very large amounts) to enter 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 weight proteins such as light chain immunoglobulins rather than albumins). The underlying disorders are often accompanied by other tubular dysfunction (eg, loss of HCO5, glucosuria, aminaciduria) and sometimes glomerular pathology (which also contributes to proteinuria).

Overload proteinuria occurs when an excess of small molecule plasma proteins (eg, light chain immunoglobulins secreted in multiple myeloma) exceeds the reabsorption capacity of the proximal tubules.

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

Orthostatic proteinuria is a benign disease (most common in children and adolescents) in which proteinuria occurs mainly when the patient is in an upright position. More protein in the urine is observed during the daytime (when people spend more time in a horizontal position) than during sleep. The prognosis for her is very good and she does not require special treatment.

Effects. Proteinuria due to kidney disease is usually persistent (i.e. persists on repeat testing) and, if in the nephrotic range, can result in significant protein loss). The presence of protein in the urine is toxic to the kidneys and causes damage to them.

Pathophysiological classification of proteinuria

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

Secretory proteinuria occurs due to the filtration through normal glomeruli of an abnormally large amount 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 urinary electrophoresis by the presence of abnormal peaks or "protrusions". For example, "protrusions" appearing in the y region (or less commonly in the α 2 or β region) indicate 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, the damaged tubules cannot fully reabsorb the 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-acetylglucosamine and lysozyme into the urine. Finally, in tubulointerstitial lesions, the cells of the tubules of the ascending loop of Henle and the distal nephron secrete more Tamm-Horsfall protein into the urine. For differential diagnosis of 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 the level of albumin u2MG in the urine using immunoelectrophoresis or other immunological methods (immunoprecipitation, immunodiffusion and radioimmunoassay) can also help. An albumin to β2MG ratio of 10:1 indicates tubular proteinuria, with glomerular proteinuria this ratio would be greater than 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 partially increases in the ultrafiltrate. In some forms of glomerulonephritis, this leads to a change in the pore size of 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 (nephropathy with minimal changes). Some glomerular lesions are characterized by changes in size and charge selectivity (diabetic nephropathy). Mesangial lesions also lead to proteinuria, possibly due to a change in normal mesangial clearance functions.

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

Other types of proteinuria. Two forms of proteinuria do not fit into the classification given above. This is benign orthostatic proteinuria in tall adolescents in a standing position. 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. At the same time, there should be no pathological changes in the urine sediment and proteinuria should not exceed 1 g per day. In half of these patients, proteinuria disappears within Schlett, but a small number develop overt kidney disease later on. Finally, functional transient proteinuria is associated with other causes: heart failure, fever, or heavy physical work. Proteinuria in runners after overcoming the marathon distance can be more than 5 g / l.

Classification of proteinuria

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

Secretory proteinuria

Secretory proteinuria is suggested when there is a discrepancy between mild proteinuria as measured by test strips and a disproportionate amount of protein in urine collected over a 24-hour period. This most often occurs with increased excretion of monoclonal light chains, which can be confirmed by immunoelectrophoresis. If monoclonal immunoglobulin is detected in urine, screening for multiple myeloma, amyloidosis, or lymphoproliferative disorders 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 reveals no or very few red blood cells. With such test results, one should look for hemolysis or rhabdomyolysis.

tubular proteinuria

Tubulointerstitial lesion can cause a wide range of conditions. Evaluation for tubular proteinuria should begin with a thorough history of other family members (to rule out polycystic kidney disease), prescription or non-prescribed medication (nephropathy after analgesics), frequency of UTIs (reflux), lower back pain, kidney stones, skin rashes, arthralgias, arthritis (hypersensitivity to drugs, collagen-vascular diseases), dry mouth and eyes (Sjögren's syndrome), occupational or accidental exposure to potential poisons and manifestations of systemic diseases. Physical manifestations confirming the disease in the differential diagnosis may include pronounced enlargement of the kidneys (polycystic), annular keratopathy (hypercalcemia, hyperparathyroidism), skin rashes (systemic lupus erythematosus, drug hypersensitivity), arthritis (gout, lupus), the formation of a lead border on the mucous lining of the oral cavity (lead poisoning). Laboratory examination includes performing a detailed blood test with smear microscopy, determining the level of creatinine, BUN, glucose, calcium, uric acid phosphorus, potassium in the blood serum. A bacteriological examination of urine provides additional information to the data of anamnesis, physical examination, general urinalysis and quantitative analysis of urine (i.e., it is used for differential diagnosis). Positive or negative results of these examinations may indicate the need for further investigations: ultrasonography of the kidneys (polycystic, kidney stones and obstruction), electrophoresis of urine, serum or hemoglobin (monoclonal gammopathy, sickle cell anemia), bacteriological examination of urine with determination of sensitivity to antibiotics ( pyelonephritis, renal tuberculosis), serum angiotensin-converting enzyme (sarcoidosis), excretory urography (spongy kidney), serum lead determination (lead poisoning). Some tubulointerstitial disorders have characteristic histological features (spongy kidney, amyloidosis, renal myeloma, hypokalemia), but the histological distinctions of most tubulointerstitial disorders are difficult to distinguish. 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 in acute diseases with complete recovery, has practically no long-term consequences. However, severe and prolonged proteinuria suggests a more serious disease. For initial diagnosis and treatment, a 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 a thorough diagnostic evaluation. 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 of body surface). This somewhat arbitrary division stems from two main observations. First, patients with non-nephrotic proteinuria have a better prognosis for renal function than patients with more severe proteinuria. Therefore, it is not worth starting with aggressive methods of treatment. Once the underlying cause has been established through history, physical examination, and serology, treatment includes drugs that affect kidney function, such as ACE inhibitors, alone or in combination with a BAR, followed by assessment of kidney function and the degree of proteinuria, which may be indicated in selected patients before kidney 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 the determination of kidney function, but also by the pathophysiological consequences of severe proteinuria (nephrotic syndrome).

The diagnosis of nephrotic syndrome is established with a protein loss of more than 3.5 g per 1.73 m2 of body surface per day, hypoalbuminemia, hyperlipidemia, lipiduria and edema. Severe proteinuria causes an increase in tubular reabsorption and metabolism of proteins entering the glomerular ultrafiltrate, which contributes to hypoproteinemia. Retention of sodium and water with the occurrence of edema in some patients occurs secondarily as a result of hypoproteinemia, in others primarily due to 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 with long-term nephrotic disorders (membranous nephropathy), hyperlipidemia can lead to accelerated development of atherosclerosis. Severe proteinuria also predisposes to hypercoagulability, transient losses of antithrombin III, protein S and protein C have been described in some patients. thyroid-binding globulin (decrease in total thyroxin, normal thyroid-stimulating hormone) and vitamin D (hypovitaminosis, hypocalcemia and secondary hyperparathyroidism). Streets with severe proteinuria, depending on the loss of protein, food intake and genetic predisposition, there are various complications of nephrotic syndrome.

Causes of proteinuria

Causes can be classified by mechanism. The most common cause of proteinuria is 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 onychoarthritis
• Infections: Bacterial, viral, fungal, protozoal and helminthic, including bacterial endocarditis, poststreptococcal 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, Schoenlein-Henoch disease, Wegener's granulomatosis, micronodular polyarthritis, Goodpasture's syndrome, cryoglobulinemia
• Drugs: Penicillamine, drugs containing gold or mercury, lithium, NSAIDs, ACE inhibitors, heroin
• Tumors: Multiple myeloma; lung, colon or breast carcinoma; lymphoma; leukemia
• Other Causes: Serum 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, renal transplant rejection, drug allergy, sarcoidosis
• Toxic: Overdose of analgesics, radiation nephritis, intoxication with lithium, 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 examination

Proteinuria itself is usually determined only by urinalysis or rapid submersible tests. History taking and physical examination sometimes provide valuable information about a possible etiology.

History and physical examination

When examining organs and systems, it is necessary to pay attention to symptoms that indicate the cause of proteinuria, incl. red or brown color of the kidney (glomerulonephritis) or bone pain (myeloma).

Patients are asked about existing medical conditions that may cause proteinuria, including recent severe illness (especially those accompanied by fever), intense physical activity, known kidney disease, diabetes, pregnancy, sickle cell anemia, SLE, and malignancies (especially myeloma and related diseases) .

Physical examination is of limited value, but vital signs should be assessed to detect hypertension, which is indicative of glomerulonephritis. On examination, signs of peripheral edema and ascites should be identified that are indicative of fluid overload and possibly glomerular pathology.

Laboratory diagnostics

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

In patients with a positive dip test result (for the presence of a protein or other pathological component), a routine microscopic examination (analysis) of the urine should be performed. Abnormal urinalysis findings (eg, casts and abnormal RBCs suggestive of glomerulonephritis; glucose and/or ketone bodies suggesting diabetes mellitus) or disorders that may be suspected based on history and physical exam findings (eg, peripheral edema suggestive of glomerular pathology) require further investigation.

If other urinalysis values ​​are normal, further testing may be deferred until the presence of protein in the urine is re-determined. If proteinuria is not detected during re-examination, especially in patients who have experienced intense physical activity, fever, or decompensated heart failure shortly before the study, its functional nature is likely. Persistent proteinuria is a sign of glomerular pathology and requires additional examination and referral of the patient to a nephrologist. Additional testing includes OAK, measurement of serum electrolytes, urea nitrogen, creatinine, and glucose levels; definitions of GFR; estimates of the amount of protein released (by daily collection or determination of the ratio of protein / creatinine in a random portion); assessment of kidney size (by ultrasound 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 disease, including lipid profile, complement and cryoglubolin levels, hepatitis B and C serology, antinuclear antibody tests, and urine and serum protein electrophoresis. If these non-invasive tests remain diagnostically inconclusive (as they often are), a kidney biopsy is required. Idiopathic proteinuria and renal failure, especially in elderly patients, may be due to myelodysplastic disorders (eg, multiple myeloma) or amyloidosis.

In patients younger than 30 years, the possible orthostatic nature of proteinuria should be borne 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 urinary protein level 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 not specific to glomerular involvement, abnormal urinary protein excretion is a cardinal manifestation of the disease in virtually all patients with glomerulonephritis. Fever, exercise, hyperglycemia, and severe hypertension may increase proteinuria in a short time.

For a more accurate qualitative and quantitative analysis of proteinuria, it is usually necessary to conduct a study of daily urine. This is done as follows: the first morning portion of urine is poured out, then all urine is carefully collected during the day. The last daily portion is also included in the analysis. If the urine is kept refrigerated at the time of collection, no preservatives need to be added. If this is not possible, then acetic acid should be added to the urine collection vessel.

In urine collected within 24 hours, the daily content of creatinine should be determined. In women with stable kidney function, the daily creatinine excretion should be approximately 15-20 mg per kilogram of ideal body weight, in men this figure should be 18-25 mg/kg. Accurate quantitative methods for determining protein in urine by the precipitation method: precipitation reaction with sulfosalicylic acid, Kjeldahl micromethod, Esbach's reagent (combination of picric and citric acids) and biuret test. The result is expressed in grams per 24 hours or as the ratio of protein 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. Normally, in adults, daily protein excretion ranges from 30 to 130 mg. In children and adolescents, excretion can be 2 times greater. Normally, the protein/creatinine ratio in a random sample is below 0.2. A value above 3 indicates nephrotic proteinuria.

Qualitative assessment of urine protein composition is a valuable addition to quantitative research. Using electrophoresis, urine protein is separated by molecular weight into 5 peaks: albumin, α 1 , α 2 , β and γ-globulins. Normally, urine protein consists of protein filtered from blood plasma (50%) and proteins secreted into the urine by cells of the urinary tract (50%). Most of the filtered proteins are albumin - approximately 15% of the total urine protein. 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 methods used to determine the origin of urine proteins. The method of immunofixation is more sensitive than both of the previous ones. The study 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 sought. The anamnesis should reflect the following important details: the presence of diabetes, deafness in other family members (Alport syndrome and other family nephropathies); ethnicity (IgA nephropathy is common in Asians and rarely in African Americans); fever; propensity to travel; taking medications; blood transfusions; taking drugs; sexual orientation and partners (to detect HIV, hepatitis, syphilis); the presence of arthritis; arthralgia; rashes on the cheeks and skin; sores in the mouth; alopecia (systemic lupus erythematosus and other immune and allergic disorders); hemoptysis (Goodpasture's syndrome, Wegener's granulomatosis); sinusitis; sterile otitis media (Wegener's granulomatosis); paresthesia; angiokeratoma; 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 look for systemic disease and detect nephrotic syndrome or its complications. Minimum examination list for adults: chest x-ray, complete blood count, serum and urine protein electrophoresis, biochemical blood tests, including assessment of kidney and liver function, 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 age 50 should have a screening colonoscopy if this has not been done before. Additional serological studies 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), C3, C4 (may be reduced in endocarditis, poststreptococcal glomerulonephritis, lupus, membranoproliferative glomerulonephritis - MPGN, cryoglobulinemia), antihyaluronidase and anti-DNase B, O-antistreptolysin (poststreptococcal glomerulonephritis), antibodies to thin basement membranes (Goodpasture's syndrome), rheumatoid factor (endocarditis, cryoglobulinemia, rheumatoid arthritis), serum cryoglobulins, ACE (sarcoidosis), glycosylated hemoglobin; serological reaction to syphilis; determination of antibodies and antigen to hepatitis B; recombinant immunoblotting and viral load for hepatitis C and enzyme-immobilized immunoadsorbent/western blotting for HIV. These studies should not be mandatory for all patients with glomerular proteinuria, given their cost. The key to selecting appropriate studies, mentioned and not mentioned in this list, should be a careful analysis of the results of the history and physical examination data.

In the absence of any cause for glomerular proteinuria, after a complete examination, a kidney biopsy is considered. In addition, renal biopsy is indicated when a secondary cause is identified, when histologic examination may help guide treatment (eg, in systemic lupus erythematosus).

Treatment of proteinuria

Treatment is directed at the cause of the proteinuria.

Treatment of severe proteinuria carried out in many directions. Studies have shown that NSAIDs reduce proteinuria in some patients, along with a slight decrease in GFR. Such 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 the treatment of patients with diabetic nephropathy and idiopathic nephrotic syndrome. The combination of these drugs may further reduce proteinuria. From the beginning of taking ACE inhibitors and / or angiotensin receptor blockers, it can take many months before there is a maximum decrease in proteinuria when taking a fixed dose; this phenomenon suggests an additional mechanism of action other than hemodynamic changes. Reducing proteinuria can also be achieved by lowering the mean blood pressure below 92 mm Hg, regardless of the group of antihypertensive drugs used. Finally, as a further measure 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, which is associated with the effectiveness of BAR, conflicting data on the effectiveness of a low-protein diet, and nutritional 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 body weight).

Proteinuria is the excretion of protein in the urine in excess of normal values. This is the most common sign of kidney damage. Normally, no more than 50 mg of protein is excreted into the urine per day, consisting of filtered plasma low molecular weight proteins.

• The defeat of the renal tubules (interstitial nephritis, tubulopathies) leads to a violation of the reabsorption of the filtered protein and its appearance in the urine.
• Hemodynamic factors - the speed and volume of capillary blood flow, the balance of hydrostatic and oncotic pressure are also important for the appearance of proteinuria. The permeability of the capillary wall increases, contributing to proteinuria, both with a decrease in the rate of blood flow in the capillaries, and with glomerular hyperperfusion and intraglomerular hypertension. The possible role of hemodynamic changes should be taken into account when evaluating proteinuria, especially transient, and in patients with circulatory failure.

Symptoms and diagnosis of proteinuria

Associated with diseases proteinuria is divided into functional and pathological.

Functional proteinuria observed in patients with healthy kidneys. Functional proteinuria is low (up to 1 g / day), usually transient, isolated (there are no other signs of kidney damage), rarely combined with erythrocyturia, leukocyturia, cylindruria. There are several types of functional proteinuria:

• Orthostatic. It occurs in young people 13-20 years old, does not exceed 1 g / day, disappears in the supine position. This type of proteinuria is diagnosed using an orthostatic test - the patient collects the first morning portion of urine without getting out of bed, then performs a small physical activity (walking up the stairs), after which he collects the second portion of urine for analysis. The absence of protein in the first and the presence in the second portion of urine indicate orthostatic proteinuria.
• Feverish (up to 1-2 g / day). It is observed in febrile conditions, more often in children and the elderly, disappears with normalization of body temperature, it is based on an increase in glomerular filtration.
• Tension proteinuria (marching). Occurs after severe physical exertion, is detected in the first portion of urine, disappears during normal physical exertion. It is based on the redistribution of blood flow with relative ischemia of the proximal tubules.
• Proteinuria in obesity. Associated with the development of intraglomerular hypertension and hyperfiltration against the background of increased concentrations of renin and angiotensin. With weight loss and treatment with ACE inhibitors, it may decrease and even disappear.
• physiological proteinuria. Pregnancy can lead to its appearance, since it is accompanied by an increase in glomerular filtration without an increase in tubular reabsorption. The level should not exceed 0.3 g/day.
• Idiopathic transient. It is detected in healthy individuals during a medical examination and is absent in subsequent urine tests.

Pathological proteinuria is detected in diseases of the kidneys, urinary tract, as well as when exposed to extrarenal factors.

By source Proteinuria can be prerenal, renal or postrenal.

prerenal, or proteinuria "overflow", observed in multiple myeloma (Bence-Jones proteinuria), rhabdomyolysis, Waldenstrom's macroglobulinemia, massive intravascular hemolysis. Congestion proteinuria can range from 0.1 to 20 g/day. High proteinuria (more than 3.5 g / day.) in this case is not a sign of nephrotic syndrome, since it is not accompanied by hypoalbuminemia and its other signs. To identify myeloma nephropathy, the patient needs to examine the urine for Bence-Jones protein.

Renal proteinuria according to the mechanism of occurrence, it can be glomerular and tubular.

Glomerular proteinuria is observed in most kidney diseases - glomerulonephritis (primary and systemic diseases), kidney amyloidosis, diabetic glomerulosclerosis, as well as in hypertension, "congestive" kidney.

Tubular proteinuria is observed in interstitial nephritis, pyelonephritis, congenital tubulopathies (Fanconi syndrome) and other kidney diseases with a predominant lesion of the tubules.

Glomerular and tubular proteinuria are differentiated by the presence of α1-microglobulin and quantitative comparison of albumin and β2-microglobulin in urine, which normally ranges from 50:1 to 200:1. The ratio of albumin and β2-microglobulin is 10:1, and α1-microglobulin is indicative of tubular proteinuria. With glomerular proteinuria, this ratio will exceed 1000:1.

Postrenal proteinuria has an extrarenal origin, develops in the presence of a bacterial inflammatory process in the urinary system (pyelonephritis) due to an increase in the exudation of plasma proteins into the urine.

Composition allocate selective and non-selective proteinuria.

Selective proteinuria characterized by the release of a low molecular weight protein, mainly albumin. Prognostically, it is considered more favorable than non-selective.

At non-selective proteinuria protein is released with medium and high molecular weight (α2-macroglobulins, β-lipoproteins, γ-globulins). A wide protein spectrum of non-selective proteinuria indicates severe kidney damage, characteristic of postrenal proteinuria.

By severity (value) allocate microalbuminuria, low, moderate, high (nephrotic) proteinuria.

microalbuminuria- urinary excretion of minimal, only slightly exceeding the physiological norm, albumin (from 30 to 300-500 mg / day). Microalbuminuria is the first early symptom of diabetic nephropathy, kidney damage in arterial hypertension, renal transplant rejection. Therefore, for categories of patients with such indicators, it is necessary to prescribe a study of daily urine for microalbuminuria in the absence of changes in the general analysis of urine.

Low(up to 1 g/day) and moderate(from 1 to 3 g / day) are observed in various diseases of the kidneys and urinary tract (glomerulonephritis, pyelonephritis, nephrolithiasis, kidney tumors, tuberculosis, etc.). The amount of proteinuria depends on the degree of kidney damage and on the severity of the inflammatory process in the urinary tract.

At high (nephrotic) proteinuria protein loss is more than 3.5 g/day. The presence of high proteinuria in combination with hypoalbuminemia is a sign of nephrotic syndrome.

It should be remembered that the concentration of protein in single portions of urine during the day varies. For a more accurate idea of ​​the severity of proteinuria, daily urine (daily proteinuria) is examined.

It is 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 in the urine, a large amount of antibiotics (penicillins or cephalosporins), sulfonamide metabolites.

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 weight proteins (alpha2-macroglobulin, y-globulin), more typical for severe kidney damage with "large" proteinuria.

Selective include proteinuria, represented by proteins with a low molecular weight of not more than 65,000 kDa, mainly albumin. Non-selective proteinuria is characterized by an increase in the clearance of medium and high molecular weight proteins: a 2 -macroglobulin, beta-lipoproteins, and y-globulin predominate in the composition of urine proteins. In addition to plasma proteins in the urine, proteins of renal origin are determined - the Tamm-Horsfall uroprotein secreted by the epithelium of the convoluted tubules.

Glomerular (glomerular) proteinuria is due to increased filtration of plasma proteins through the glomerular capillaries. It depends on the structural and functional state of the glomerular capillary wall, properties of protein molecules, pressure and blood flow velocity, which determine GFR. Glomerular proteinuria is an obligatory symptom 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 pedunculated processes. Due to its complex structure, the glomerular capillary wall can "sieve" plasma molecules from the capillaries into the space of the glomerular capsule, and this function of the "molecular sieve" largely depends on the pressure and blood flow velocity in the capillaries.

Under pathological conditions, the sizes of "pores" increase, deposits of immune complexes cause local changes in the capillary wall, increase its permeability for macromolecules. In addition to the size of the glomerular "pores", electrostatic factors are also important. The glomerular basement membrane is negatively charged; the peduncle 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 contributes to the filtration of albumin. It is believed that the fusion of the pedicle processes is the morphological equivalent of a change in charge.

Tubular (tubular) proteinuria is due to 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 an 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 the epithelium of the convoluted tubules. A characteristic feature 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, potassium penic kidney, acute tubular necrosis, chronic rejection of the kidney transplant. Tubular proteinuria is also characteristic of many congenital and acquired tubulopathies, in particular Fanconi's syndrome.

Proteinuria "overflow" develops with an increase in the concentration of low molecular weight proteins (light chains of immunoglobulins, hemoglobin, myoglobin) in the blood plasma. At the same time, these proteins are filtered by unchanged glomeruli in an amount exceeding the ability of the tubules to reabsorb. 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 the clinical significance of most of its variants are not known.

• Orthostatic proteinuria occurs with prolonged standing or walking ("proteinuria en marche") with a rapid disappearance in a horizontal position. At the same time, the amount of excretion of proteins in the urine does not exceed 1 g / day. Orthostatic proteinuria is glomerular and non-selective and, according to long-term prospective studies, is always benign. With its isolated nature, there are no other signs of kidney damage (changes in the urinary sediment, increased blood pressure). It is more often observed in adolescence (13-20 years), in half of the people it disappears after 5-10 years from the moment of occurrence. Characteristic is the absence of protein in urine samples taken immediately after the patient is in a horizontal position (including in the morning before getting out of bed).
• Strain proteinuria, found after intense physical exertion in at least 20% of healthy individuals, including athletes, also appears to be benign. According to the mechanism of occurrence, it is considered tubular, due to the redistribution of intrarenal blood flow and relative ischemia of the proximal tubules.
• With a fever with a body temperature of 39-41 ° C, especially in children and the elderly and senile, so-called febrile proteinuria is found. It is glomerular, the mechanisms of its development are not known. The occurrence of proteinuria in a patient with fever sometimes indicates the addition of kidney damage; This is supported by simultaneously occurring changes in the urinary sediment (leukocyturia, hematuria), large, especially nephrotic values ​​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 value 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 the protein ultrafiltrate that have a nephrotoxic effect

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

Many mesangiocytes and vascular smooth muscle cells undergo similar changes, signifying the acquisition of the basic properties of a macrophage. In the renal tubulointerstitium, monocytes from the blood actively migrate, also turning into macrophages. Plasma proteins induce tubulointerstitial inflammation and fibrosis processes called proteinuric remodeling of the tubulointerstitium.

Selective proteinuria refers to the ability of a damaged glomerular filter to pass protein molecules, depending on the size, i.e., molecular weight. Based on this definition, selectivity should be an indicator of the degree of damage to the renal glomerular filter and may be of diagnostic and prognostic value. This issue has been the subject of serious study in recent years, although Longsworth and McInnes (1940) by free electrophoresis of serum and urine in two cases of lipoid nephrosis found that the composition of urine and serum proteins is a mirror image of each other (high levels of albumin in urine and low - in serum; an increase in the content of α2-globulins in serum and their absence in urine). High-molecular proteins - α2- and γ-globulins - were absent in the urine. This type of uroproteinogram has been called nephrotic and is considered typical of selective proteinuria. At the same time, in glomerulonephritis, selectivity was significantly reduced, γ-globulins also entered the urine, and the urine proteinogram began to resemble the serum proteinogram. This type of proteinogram is called nephritic, or serum.

Moeller and Steger (1955) showed that in all cases of degenerative inflammatory diseases of the kidneys, the proportion of α1-globulin in serum is always less than the proportion of α2-globulin. In urine, there are usually inverse proportions.

It is very important to develop the question of how to determine the selectivity of proteinuria and the permeability of the kidney for protein. Bing suggested using [% Urine Albumin]/[% Plasma Albumin] as a preliminary guideline. In the event that this index (called the renal permeability index) exceeds 2, then it is characteristic of nephrosis, while an index less than 2 is typical of nephritis. However, this figure proved to be clearly insufficient during the test. So, in one of the cases of amyloidosis of the kidneys with severe nephrotic syndrome observed by D. B. Tsykin in our clinic, the Bing index did not exceed 1. Luetscher (1940) found that the albumin-globulin coefficient in the urine with pathological proteinuria is greater than normal, but with nephrotic syndrome, it is always higher than with "terminal nephritis", with its characteristic significant release of all globulins. However, Wolvius and Verschure (1957), having measured the total clearance of globulins and the clearance of albumins, could not note findings pathognomonic for individual diseases, although there was some difference.

So, the ratio of globulin / albumin, which was former in nephrotic syndrome
equal to 0.1-0.2, as uremia developed, it increased to 0.3-0.4. A more accurate test for renal proteinuria selectivity is described by Blainey et al. (1960). Their method consists in the fact that on the vertical axis the results of determining the clearance of proteins are plotted as the molecular weight increases, expressed as a percentage of the clearance of siderophilin (the logarithmic values ​​of the indicators are plotted). The logarithms of the molecular weights of the same proteins (α1-acid clycoprotein, albumin, siderophilin, ү2-immunoglobulin, үA, α2-macroglobulin) are plotted along the horizontal axis. The slope of the curve to the horizontal determines the selectivity of proteinuria. Joachim (1964, cited by Schultze, Haremans, 1966) in this respect divided all patients into groups: high selectivity - an angle of 67°; medium - angles 63-67 °, low - less than 62 °. In cases with an angle of 54°, the selectivity was the lowest (Fig. 1).

Rice. 1. Selectivity of protein excretion (Fα2 and Sα2) with urine by determining the ratio of their clearances (Cl) to siderophilin clearance (βc).
Horizontally - logarithms of molecular weights of proteins; vertically - the logarithm of the ratio of protein clearance to siderophilin clearance.

Comparison of proteinograms of serum and urine should be done with some caution due to the fact that the protein mirror of the blood reflects not only the leaching of serum proteins through the renal filter, but also those changes that are characteristic of the disease itself. Seromucoid and glycoproteins (of both α-fractions) appear in the serum in the acute phase of the disease, and the content of γ-globulins also increases in the subacute and subchronic course (Heremans et al., 1960). In addition, when comparing serum and urine proteins, it should be remembered that, although with nephrotic syndrome (Cleve et al., 1957) there are no proteins in the blood that are different from those observed in healthy individuals, the basement membrane can still have a particularly active enzymatic effect on passing proteins through it (with amyloid nephrosis, this is described by Vaux, Gyr and Hermann, 1962).

Of known value is the dynamic study of the clearance of specific proteins, of which siderophilin (transferrin), haptoglobin, and hemoglobin have been specially studied. It has already been noted above that the clearance of siderophilin is widely used as a standard against which comparison is made with the isolation of other proteins. With regard to haptoglobinuria, it must be borne in mind that haptoglobin is not only a specific protein, but also the protein, the content of which in the serum increases in the acute phase of diseases and can serve as a test of exacerbation (activity) of the latter.

These methods, with all the reservations, make it possible to characterize the state of the renal filter and serum proteinograms with a certain accuracy. We currently have data obtained in our clinic by D. B. Tsykin and M. M. Shcherba, who modified the method of protein electrophoresis in starch gel proposed in 1955 by Smithies.

Soluble starch of industrial production was used, from which an 18% gel was prepared on a borate buffer with a pH of 8.6, an ionic strength of 0.3. Electrophoresis was carried out at a voltage of 13 V/cm of the gel length for 3.5 hours. Proteinograms were stained with bromphenol blue, and the results were processed using a photodensitometer.

On fig. Table 1 shows the data for determining the clearance of various proteins in relation to the clearance of siderophilin in three patients with nephrotic syndrome with varying degrees of selectivity.

Rice. 2. Proteinograms of urine and serum of patient B.
Diagnosis: nephrotic syndrome. Amyloidosis. PrA - prealbumin; A - albumin; PsA - postalbumins; Fα2 - fast α2-globulins; βc - siderophilin; Hp - haptoglobins; sα2 - slow α2-globulin; βlp - β - lipoprotein; ү - ү-globulins.

Patient B., 30 years old. Diagnosis: renal amyloidosis, nephrotic syndrome. Admitted to the clinic 7/11 1967 with complaints of weakness, swelling of the face, thirst. In May 1955, after a catarrh of the upper respiratory tract, she noticed swelling of the legs; urinalysis revealed proteinuria up to 6.6‰. After a long hospitalization, edema decreased, but proteinuria remained within 3.3‰. Then the edema reappeared and remained moderate until admission to the clinic. BP did not rise. Since 1958, the patient has been suffering from hypochromic iron deficiency anemia of unknown origin. At admission, the patient was found to have an enlarged liver (a dense edge was palpable, protruding by 6 cm) and spleen (protruding by 3 cm). There were no changes in the chest organs. Blood test:
er. - 2,990,000; Hb. - 52 units; l. - 7500; e. - 7.5; b. - 1.5; p. - 1; with. - 56.5; limf. - 23.5; my. - 6; reticulum - 2; ROE - 73 mm/h. Sample from Congorot (twice) - sharply positive. Bone marrow examination 10/II - inhibition of erythroblastic germ with delayed maturation. Urine changes: daily protein loss 15.0-24.0-12.0-18.7 g (with diuresis from 1000 to 1800 ml). In one serving - protein 23.1‰, l. - 12-30 p / sight .; erythrocytes are changed, single in the preparation; fatty single cylinders in p / sp .; granular - 0-2 in p / sp .; waxy - single in p / sp. Residual nitrogen - 36 mg%. The iron content is 6.5ү%. Specific gravity fluctuations according to Zimnitsky - 1015-1020. Serum sodium - 141 meq / l, potassium - 5 meq! l. Examination of the gastrointestinal tract did not reveal any changes. X-ray (including tomography) of the chest organs - without deviations from the norm. Mantoux reactions in dilution 10-6, 10-5 and 10-4 are negative (10-4 is weakly positive).

Thus, it was not possible to establish the cause of the development of amyloidosis of the liver, kidneys and spleen in the patient.

The produced proteinogram of serum and urine established (Fig. 2) that not only small-, but also large-molecular protein fractions are released. On fig. 1 shows the decrease in the clearance of the secreted protein as its molecular weight increases. However, the low selectivity of proteinuria is determined by the passage and sufficiently high clearance of high molecular weight proteins (< = 57°).

Another example of non-selective proteinuria is the case history of patient M.

Patient M., 23 years old. Entered the clinic on 10/II 1967. Sick since June 1966, when there was a sudden edema on the shins. Then, on June 21, the temperature rose and the swelling increased. The temperature after the start of treatment (penicillin, prednisolone, diuretics) fell after 2 days. The edema decreased, but there was 3.3‰ protein in the urine. In September, the temperature again rises and edema increases. Body weight increased from 78 to 96 kg, protein in urine up to 66‰. There was a sharp weakness, shortness of breath. In the past - malaria at the age of 8. There are no chronic intoxications. He was admitted to the clinic with pastosity of the whole body, especially on the shins and abdomen. BP 130-120/70-85 mmHg Art. Urinalysis: protein - 6.6 - 33‰, leukocytes - up to 80 in p / sp., erythrocytes - from 18 in p / sp. to densely covering all p / sp., hyaline cylinders - up to 4, granular - up to 7, waxy - single in p / sp.

Blood tests: Hb. - 67-43 units; er. - 3,500,000-2,060,000; l. - 9200; b. - one; e. - 2; p. - 5; with. - 63; limf. - 23; mon. - 3; reticulum - 2; ROE - 78-60 mm in 1 hour.

Daily protein loss: 16.25-16.8 g. Diuresis - 500 ml. Residual nitrogen - 43.9-24.5 mg%. Blood creatinine - 4.5-2.5 mg%. Cholesterol - 487-120 mg%. ECG signs of diffuse changes in the myocardium. The fundus is normal. Zimnitsky's test: day diuresis - 960 ml, night - 690 ml. Oud. weight - 1015-1018. With infusion pyelography and tomograms, the left kidney is contoured 7X14.5 cm, the right one is indistinct. 40 minutes after the end of the injection of contrast, both pelvises of normal size were filled. LE cells were not found. Transaminase (glutopyrogrape) - 12.5 units. Serum sodium - 148 meq/l; potassium in blood serum - 7.15 meq / l. Bilirubin - 0.2 mg%. Treatment: hypothiazide, aldactone, vikasol, hemostimulin, vitamins, penicillin, chloramphenicol, pregpin, calcium chloride, polyvinol, 2-aminocaproic acid, erythrocyte mass. The treatment turned out to be ineffective, and with the growing picture of renal failure, the patient died. The diagnosis of progressive diffuse glomerulonephritis was confirmed at autopsy.

The non-selectivity of proteinuria and severe dysproteinemia are well proven in Fig. 1 and 3, where it is seen that the slope of the curve is small, amounting to 55°, and large-molecular serum proteins appear in the urine.

Rice. 3. Proteinograms of urine and serum of patient M.
Diagnosis: chronic glomerulonephritis with a progressive course. nephrotic syndrome. The designations are the same as in Fig. 2.

The diagnostic and therapeutic value of selective proteinuria in relation to a number of individual diseases is still not entirely clear, although it is promising. So, in 1958, in the clinic of M. S. Vovsi, studying the protein fractions of blood and urine using the method of electrophoresis on paper, Ya. . In 1965, M. A. Ado conducted a comparative study of the content of proteins and glycoproteins in blood serum and urine in nephrotic syndrome of various etiologies (chronic nephritis, systemic lupus erythematosus, amyloidosis) using the method of electrophoresis on paper. In amyloidosis and lupus nephritis, the highest content of γ-globulins was observed in the urine. In addition, with systemic lupus erythematosus, a large amount of a2-globulin was observed in the urine. The content of α1- and β-globulins was the same in all patients. The study of glycoproteins made it possible to characterize the properties of urine fractions in more detail.

The conclusion about the diagnostic value of selective proteinuria is based mainly on a comparison of the obtained data with the histological picture of the disease, characterized by the results of a biopsy, and with the effectiveness of steroid therapy. So, Blainey et al. (1960), comparing the selectivity of proteinuria with the histological picture, indicate that in the most severe form of the lesion (membranous glomerulonephritis), the lowest selectivity is noted, while with "minimal changes" in the glomeruli, the selectivity is greatest. Joachim and co-authors (1964) examined 21 patients and found that the effectiveness of steroid therapy depends on the selectivity of proteinuria; the latter decreases as residual nitrogen increases. Based on a comparison of selective proteinuria with the state of partial kidney functions, the authors suggest that if in an adult with nephrotic syndrome an increase in the content of residual nitrogen and a decrease in inulin clearance do not give reason to expect the effectiveness of steroid therapy, then even with unchanged indicators, this prediction should be made with great care.

Cameron and Wihite (1965), examining 28 children and adults with nephrotic syndrome, found that: 1) in all patients aged 2 to 73 years, there is a clear relationship revealed during mathematical processing between the logarithm of protein clearance and the logarithm of protein molecular weight, found in urine 2) "blind" comparison of selective proteinuria with histological data showed that selectivity decreases with increasing severity of glomerular damage; 3) selective proteinuria does not change for many months either spontaneously or under the influence of steroids and does not depend on the age of the patients and the duration of the disease.

Recent studies largely support this view. Thus, Cameron (1966) examined 126 patients who excreted more than 2.6 g of protein per day; in 87 of them, biopsy data and results of steroid therapy were compared with the degree of proteinuria selectivity. The author found that selective proteinuria does not correlate with daily protein loss. The highest selectivity was observed with normal or almost normal histological structure of the glomerulus, while it was minimal with the greatest changes. None of the patients with non-selective proteinuria had good results after a course of steroid treatment. On this basis, the author began to use selective proteinuria as a criterion for selecting patients for treatment with immunosuppressants. Considering that in patients with proteinuria greater than 2 g/day, selective proteinuria correlates with different histological types of nephritis, clinical outcome, and treatment effect, Cameron concludes that it provides the same information about the severity of the process as a biopsy. In an attempt to simplify the clinical application of the method, Cameron and Blaudford (1966) took advantage of Soothill's proposal to determine the clearance of only two proteins with a small (transferin) and a large (ү7Sү-globulin) molecular weight. After examining 134 patients with nephrotic syndrome due to glomerulonephritis (proven by biopsy), they emphasize that proteinuria remains selective for a long time, regardless of remission, steroid and immunosuppressant therapy, and selectivity is the lowest with damage to the basement membrane.

The high selectivity of proteinuria with minimal histological changes is indicated by both Vere and Waldruck (1966), who examined 6 adult patients with nephrotic syndrome, where steroid therapy had a good clinical effect without affecting the selectivity of protein release. Not without interest is the observation of Mac-Lean and Robson (1966) that non-selective proteinuria can also occur in ischemic renal failure with tubular necrosis.

However, along with this, there are works whose authors do not attach great importance to selective proteinuria. So, in 1966, Barcelo and Pollak, examining 15 patients, did not find any relationship between histological changes and the nature of proteinuria. Noting the rarity of the appearance of high molecular weight proteins in the urine even in cases of significant thickening of the basement membrane, the authors at the same time point to a large variability in the clearance of low molecular weight proteins. However, the conclusion about the lack of any value of selective proteinuria for diagnosis and prognosis may be due to the fact that the authors observed patients in whom proteinuria was not so pronounced, and the methods of urine concentration were insufficiently perfect. However, Meriel et al. (1962) came to the conclusion that all the morphological changes found in the biopsy are not an expression of the increased permeability for proteins that is taking place; therefore, the center of the problem of proteinuria in nephrotic syndrome lies not in the anatomical, but in the pathophysiological causes of increased permeability of the renal filter, i.e., the basement membrane.

A well-known correlation between morphological changes and selectivity was noted by M. S. Ignatova et al. (1969). D. V. Tsykin and I. K. Klemina in our clinic, examining 39 patients with glomerulonephritis, established a correspondence between the degree of damage to the basement membrane and the selectivity angle calculated from the clearances of two proteins - albumin and haptoglobin.

It is recommended that all people take a general urine test once a year for preventive purposes. This simple and cheap study can tell a lot about the state of the urinary system and the body as a whole. Sometimes abnormalities are found in the analyzes, one of which may be proteinuria.

Proteinuria: what is a violation

In the human body, urine is synthesized in the kidneys, or rather, in their glomeruli and tubular system. Subsequently, it enters the bladder through the ureters, where it accumulates and then is excreted from the body through the urethra.

In a healthy person, urine has a clear ratio of salts, proteins and other organic compounds. But as a result of a number of pathological processes, the quality of blood filtration can be impaired, and substances in large quantities or elements that are not typical for it begin to penetrate into the urine.

Urine formation is a complex but very fast process during which the blood is cleared of most harmful substances.

Proteinuria is a special condition of the body, accompanied by the excretion of protein with urine in quantities that exceed the norm to a greater or lesser extent. This is most often a sign of kidney damage.

With the normal functioning of the organs of the urinary system, no more than 0.036 g / l of protein is excreted per day with urine, regardless of the age of the patient. Only in pregnant women in the second and third trimesters, this figure can reach 0.04 and 0.05 g / l, respectively.

Types and features of proteinuria

To correctly determine the cause of the development of proteinuria, its nature should be determined by several parameters. Depending on what led to the onset of pathology, there are:

• functional proteinuria, manifested in absolutely healthy people. In this case, there is an increase in the concentration of protein in the urine by 50 mg, but there is no cylindruria, erythrocyturia, leukocyturia, that is, the release of cylindrical cells, erythrocytes and leukocytes. Thus, proteinuria is isolated and usually asymptomatic, in other words, there are no other pathological changes. It can develop due to various circumstances, therefore, they distinguish:
  • orthostatic proteinuria, which is a consequence of prolonged standing. The disorder is often diagnosed in patients aged 13–20 years, and a characteristic feature is the disappearance of an increased concentration of protein in urine when the analysis is taken in the supine position;
  • febrile, developing against the background of heat, mainly in children and the elderly. When the temperature normalizes, proteinuria also disappears;
  • transient (marching, stress), which is the result of intense physical exertion and disappears after their elimination. This form of impairment is rare in children;
  • physiological, diagnosed in pregnant women, after hypothermia, eating certain foods, seizures, prolonged standing in an upright position, etc .;
  • provoked by obesity;
  • idiopathic, that is, formed for unknown reasons;
• pathological, which is a consequence of the occurrence of diseases of the urinary system, cardiovascular or some others.

Functional proteinuria does not require treatment and resolves on its own after the elimination of the factors that provoked its appearance.

According to the source of the appearance of the protein, pathological proteinuria is divided into:

• renal, developing as a result of damage to the organs of the urinary system. In turn, it is divided into:
  • tubular (tubular), due to a decrease in the ability of the kidney tubules to re-absorb plasma proteins with low molecular weight filtered by the glomeruli. It is typical for pyelonephritis, rejection of a transplanted kidney, congenital and acquired tubulopathies;
  • glomerular (glomerular), arising from increased filtration of plasma proteins through the capillaries of the glomeruli. It is this type of proteinuria that is a sign of most kidney pathologies;
• extrarenal (false), diagnosed due to the fact that leukocytes, bacteria and other organic substances become the source of proteins. It is divided into:
  • prerenal, resulting from exposure to systemic pathologies. For example, diabetic proteinuria, which occurs against the background of diabetes mellitus 10-15 years after the onset of the first symptoms;
  • postrenal, developing with diseases of the ureters, bladder, prostate or urethra.

Depending on the composition of the protein contained in urine, there are:

• selective - characterized by the release of proteins with a small molecular weight, i.e., mainly albumins;
• non-selective - manifested by an increase in clearance (purification) of high- and medium-molecular proteins, as a result of which α2-macroglobulin, β-lipoproteins, γ-globulins are present in urine in increased quantities.

According to the amount of protein released per day, proteinuria is divided into:

• microalbuminuria - 60–300 mg;
• light - 300–1000 mg;
• moderate - 1–3.5 g;
• massive - more than 3.5 g.

Causes of high protein in urine

The main cause of proteinuria in people of any age is the pathology of the urinary system, especially the kidneys. Her appearance can be one of the signs:

• amyloidosis of the kidneys;
• glomerulonephritis;
• nephrolithiasis;
• tuberculosis of the kidneys;
• urethritis;
• myeloma nephropathy;
• thrombosis of renal vessels;
• acute tubular necrosis;
• diabetic glomerulosclerosis, etc.

Also, proteinuria can develop against the background of:

• hypertension, especially hypertensive crisis;
• diabetes;
• oncological diseases of the heart, lungs and other organs.

As for the physiological form of the disorder, it can be a consequence of:

• a sharp increase in the intensity of physical activity;
• forced long standing;
• pregnancy;
• excessive exposure to the sun;
• severe stress;
• protein abuse.

False-positive urinalysis results for protein content can be obtained after taking high doses of antibiotics of the penicillin or cephalosporin series, sulfa drugs and iodine-containing contrast agents.

Features of proteinuria in children - video

Symptoms

Since proteinuria itself is a sign of many diseases, usually, in addition to it, other disorders of the condition are also observed. To determine the increase in the amount of protein in the urine, it is necessary to take tests or at least purchase special test strips for home diagnostics at the pharmacy. You can understand that they are necessary by the appearance of "foam" on the surface of the urine, as well as sediment or flakes of white or gray color.

Diagnostic methods

To detect proteinuria, patients are assigned a standard clinical urinalysis. It allows you to quickly determine the concentration of protein in urine, but this is not enough to determine the cause of the development of a violation. Therefore, after identifying proteinuria, to diagnose its nature, the following is carried out:

• determination of the daily amount of protein in the urine. Analysis is required to rule out tension proteinuria. Its essence is to collect each portion of urine during the day and calculate the volume of proteins in it;
• analysis for Bence-Jones protein, which is normally absent in urine, since it is produced by cells during the formation of malignant tumors. Thanks to this laboratory study, it is possible to confirm or exclude the possibility of developing myeloma, plasmacytoma, primary amyloidosis, osteosarcoma and other similar diseases;
• Ultrasound of the kidneys, bladder and prostate. This study is necessary to exclude the possibility of violations in the structure of organs.

If the pathological origin of proteinuria is confirmed, patients are prescribed:

• a general blood test to detect signs of infection: an increase in the number of leukocytes, an acceleration of ESR, etc.;
• Reberg's test (a study that is based on determining the content of creatinine in blood serum and urine). The analysis is necessary to assess the excretory ability of the kidneys, which makes it possible to differentiate functional and organic lesions;
• urinalysis according to Nechiporenko is required for a more accurate determination of the content of various compounds in the urine;
• bacteriological examination of urine is indispensable in the presence of suspicions of the development of an infectious disease to determine its causative agent and select the most effective drug.

In the differential diagnosis of diseases that caused the development of proteinuria, first of all, the nature of the secreted proteins is taken into account, that is, their qualitative analysis is carried out. If research reveals:

• proteins formed as a result of the destruction of leukocytes, erythrocytes or bacterial cells indicate the presence of nephrolithiasis, tuberculosis or tumors of the kidneys and urinary tract;
• albumins and globulins of different molecular weights indicate the renal origin of the disorder, i.e. the development of glomrulonephritis, amyloidosis, nephropathy, etc.

Express diagnosis of proteinuria - video

What treatments are available

It is important to understand that proteinuria is only a sign of a developing disease. Therefore, therapy is not aimed at eliminating the violation, but at eliminating the causes that caused the increased excretion of protein in the urine.

Treatment of proteinuria begins only after the exact identification of existing pathologies, and its nature directly depends on the type of disease.

Patients are prescribed:

• medicines indicated in a particular case;
• diet
• physiotherapy procedures.

Treatment of children and adolescents is carried out in accordance with the diagnosis and does not have significant differences from the therapy carried out by adults.

Medical therapy

The composition of drug therapy for patients may include:

• anticoagulants (Aspirin Cardio, Heparin, Warfarin, Fenilin) ​​- drugs that reduce platelet production, thereby reducing the tendency to form blood clots;
• antibiotics (Amoxicillin, Ampicillin, Zinnat, Ciprolet, Cefazolin, Cefalexin, Cifran, Ofloxacin, Amikacin, Sumamed, Vilprafen) - drugs that destroy infectious agents and are prescribed mainly for pyelonephritis, glomerulonephritis, cystitis, etc .;
• antihypertensive drugs of the ACE inhibitor group (Captopril, Enap, Hartil, Tritace, Ramipril) - drugs that lower blood pressure are necessary for hypertension;
• corticosteroids (Prednisolone, Dexamethasone, Kenakort, Medrol, Polcortolone) - agents that help eliminate the inflammatory process;
• homeopathic preparations (Canephron, Arsenicum album, Renel, Solidago compositum, Berberis-homaccord, JOB-nephrolith) - drugs that help to quickly eliminate inflammation, achieve recovery, increase the overall resistance of the body;
• anticancer drugs (Methotrexate, Vincristine, Cisplatin) - drugs prescribed when tumors are detected.

Drugs prescribed for proteinuria - photo gallery

Medrol - a strong anti-inflammatory agent Sumamed - an effective antibiotic of the macrolide group Canephron - a popular homeopathic remedy that gently restores kidney cells
Methotrexate is an antitumor drug prescribed for the treatment of cancer Warfarin is one of the most popular anticoagulants

Folk methods

Traditional medicine is used exclusively as a supplement to the main treatment. This is:

Diet food

An important role in the fight against diseases of the urinary system is given to proper nutrition. Patients are advised to exclude foods containing large amounts of protein and some others from the diet until complete recovery:

• legumes;
• cottage cheese;
• smoked meats;
• spices;
• semolina, oatmeal, wheat and pearl barley;
• mushrooms;
• fish, meat broths;
• pasta;
• nuts.

You should also limit your salt intake significantly. On the contrary, it is recommended to include in the daily menu:

• fresh and steamed vegetables;
• low-fat varieties of veal and beef, poultry meat;
• fruits;
• rosehip infusion;
• milk products.

Useful and harmful products - photo gallery

Mushrooms contain a lot of protein Cottage cheese should be excluded from the diet If you are sick, you need to limit salt intake to 2 g per day Vegetables will saturate the body with vitamins and minerals Rosehip infusion is useful for proteinuria

Physiotherapy

Sometimes, as part of treatment, patients are prescribed:

• plasmapheresis - the procedure for separating part of the blood into plasma and formed elements, followed by purification of the liquid component on a special apparatus and return to the bloodstream;
• hemosorption - a method in which toxic products are removed from the blood due to its interaction with a sorbent outside the patient's body.

Prognosis of treatment and complications: is the pathology life-threatening

The very presence in urine of proteins atypical for it or in concentrations that differ from the norm is a sign of a violation of the state of the body. Nevertheless, not only various diseases can harm health and provoke the development of a number of dangerous complications, but also proteins that penetrate the tubular and pyelocaliceal system have a destructive effect on them.

As a result of the release of excess amounts of albumin:

• increased inflammation;
• epithelial cells are destroyed;
• there is a spasm of the proximal renal tubules.

Penetration into the urine of transferrin provokes:

• the formation of free radicals that can lead to the development of oncological pathologies;
• increased inflammation, etc.

Other proteins also adversely affect the anatomical structures of the kidneys. Moreover, the higher the proteinuria, the more harmful it is for the organs. Therefore, this condition requires the prompt identification of the causes of its occurrence and the adoption of appropriate therapeutic measures.

Left untreated, proteinuria can lead to:

• renal failure;
• complications from the cardiovascular system;
• complications caused by existing diseases.

With timely seeking medical help and competent full-fledged treatment, the excretion of protein in the urine is normalized.

The effect of protein on the kidneys - video

Prevention measures

To minimize the risk of proteinuria, it is recommended to normalize the daily routine, give up bad habits and switch to a rational balanced diet. Nevertheless, the main method of prevention is the timely treatment of all emerging disorders and diseases.

Thus, proteinuria may indicate the development of the disease or be the result of the patient's activity. But in any case, it is necessary to accurately find out the causes of its occurrence in order to reduce the risk of complications and negative effects on the kidneys.