What you need to know about protein levels in urine? Elevated levels of protein in urine: what does it mean? Presence of protein in urine 0 2

30.04.2024 -

Passing through the kidneys, the blood is filtered - as a result, only those substances that the body needs remain in it, and the rest is excreted in the urine.

Protein molecules are large, and the filtering system of the renal corpuscles does not allow them to pass through. However, due to inflammation or other pathological reasons, the integrity of the tissues in the nephrons is disrupted, and the protein passes freely through their filters.

Proteinuria is the appearance of protein in the urine, and I will discuss the causes and treatment of this condition in this publication.

Quick page navigation

Two types of proteins are found in the urine of women and men - immunoglobulin and albumin, and most often the latter, which is why you can come across the concept of albuminuria. This is nothing more than widespread proteinuria.

The presence of protein in urine occurs:

Transient, associated with fever, chronic diseases outside the urinary system (tonsillitis, laryngitis) and functional causes - dietary habits (a lot of protein in the diet), physical fatigue, swimming in cold water.
Constant, which is caused by pathological changes in the kidneys.

Proteinuria is also divided into types depending on the amount of protein (units - g/l/day):

trace - up to 0.033;
mild - 0.1-0.3;
moderate - up to 1;
pronounced - up to 3 or more.

There are many reasons for protein in the urine, and the first place is occupied by kidney pathologies:

pyelonephritis;
lipoid nephrosis;
amyloidosis;
glomerulonephritis;
polycystic kidney disease;
nephropathy in diabetes mellitus;
kidney carcinoma;
obstructive uropathy.

Among blood diseases, the causes of increased protein in the urine can be myeloma, leukemia, plasmacytoma, myelodysplastic syndrome. These pathologies do not damage the kidney tissue, but increase the load on them - the level of proteins in the blood increases, and the nephrons do not have time to completely filter them. Protein inclusions in urine also appear with urethritis and prostatitis.

Marked increase in protein in urine may cause the following violations:

inflammation of the genitourinary organs;
tumors in the lungs or gastrointestinal tract;
kidney injuries;
central nervous system diseases;
intestinal obstruction;
tuberculosis;
hyperthyroidism;
subacute endocarditis caused by infections;
arterial hypertension;
chronic hypertension;
intoxication of the body due to poisoning and infectious diseases;
extensive burns;
sickle cell anemia;
diabetes;
congestion in heart failure;
lupus nephritis.

Physiological increase in protein in urine temporary and is not a symptom of any disease, occurs in the following cases:

high physical activity;
prolonged fasting;
dehydration.

The amount of protein excreted in the urine also increases in stressful situations, when norepinephrine is administered, and when taking certain other medications.

In inflammatory diseases may be found elevated protein and leukocytes in urine. A common cause is pyelonephritis, diabetes mellitus, blood diseases, genitourinary tract infections, and appendicitis.

Leukocytes, along with protein, are present in urine analysis and as a result of taking aminoglycosides, antibiotics, thiazide diuretics, and ACE inhibitors.

There should be no red blood cells in the urine. Protein, red blood cells and white blood cells appear in the urine due to injuries, inflammation of the kidneys, tumors in the urinary tract, tuberculosis, hemorrhagic cystitis, stones in the kidneys and bladder.

This is a serious signal - if you do not find out the exact cause and do not start treatment on time, the disease can develop into kidney failure.

The norm of protein in urine in women and men

The urine of a healthy person contains protein no more than 0.003 g/l- in a single portion of urine this amount is not even detected.

For the volume of daily urine, the normal value is up to 0.1 g. For protein in urine, the norm is the same for women and men.

In a child up to 1 month. normal values are up to 0.24 g/m², and in children older than a month it decreases to 0.06 g/m² of body surface.

Foods that increase protein in urine

Excess protein food increases the load on the kidneys. The body does not have the ability to accumulate excess proteins - reserves of substances and energy are always stored as fat or burned during physical activity.

If you follow a protein diet or your diet is dominated by such foods, then excess protein will inevitably increase. The body needs to either convert it (into fat when sedentary, into muscle mass and energy when moving). But the rate of metabolic processes is limited, so there will come a time when the protein begins to be excreted in the urine.

If you eat a lot of protein foods, it is important to consume at least 2.5 liters of clean water every day and be active. Otherwise, the kidneys will not be able to filter urine normally, which can lead to metabolic disorders and the development of urolithiasis.

Other products also reduce the filtering capacity of the kidneys:

Alcoholic drinks irritate the organ parenchyma, thicken the blood, increasing the load on the urinary system;
Salty and sweet foods retain water in the body, slowing down its free movement - congestion and swelling develop, which
Increases blood toxicity - this negatively affects the functioning of the kidney filters.

Symptoms of a pathological increase in protein in the urine

Mild proteinuria and trace amounts of protein in the urine do not manifest themselves in any way. In this case, symptoms of diseases that led to a slight increase in this indicator may be observed, for example, an increase in temperature due to inflammation.

With a significant presence of protein in the urine, swelling appears. This occurs because due to the loss of proteins, the colloid osmotic pressure of blood plasma decreases, and it partially exits the vessels into the tissues.

If protein in the urine is elevated for a long time, the following symptoms develop:

Painful sensations in the bones;
Dizziness, drowsiness;
Fast fatiguability;
Fever due to inflammation (chills and fever);
Lack of appetite;
Nausea and vomiting;
Turbidity or whitishness of urine due to the presence of albumin in it, or redness if the kidneys pass red blood cells along with protein.

Signs of dysmetabolic nephropathy are often observed - high blood pressure, swelling under the eyes, on the legs and fingers, headaches, constipation, sweating.

Is high protein in urine during pregnancy normal?

The volume of circulating blood in a woman’s body during this period is increased, so the kidneys begin to work harder. The normal level of protein in urine during pregnancy is considered to be up to 30 mg/l.

When analysis values are from 30 to 300 mg, they speak of microalbuminuria. It can be caused by an abundance of protein foods in the diet, frequent stress, hypothermia, and cystitis.

An increase in protein to 300 mg or more is observed with pyelonephritis and glomeluronephritis.

The most serious condition in which protein in the urine increases during pregnancy is gestosis. This complication is accompanied by an increase in blood pressure, edema, and in extreme cases, convulsions, cerebral edema, coma, bleeding and death. Therefore, it is important for pregnant women to pay attention to any symptoms and regularly take urine tests.

It happens that even with proper nutrition and the absence of symptoms, the presence of protein in the urine of women is detected. What does it mean? Trace amounts of protein can be detected if hygiene is not observed during urine collection.

In this case, vaginal discharge, which contains up to 3% free proteins and mucin (a glycoprotein consisting of carbohydrate and protein), enters the urine.

If there are no obvious reasons, and the protein in the urine is more than normal, undergo a thorough examination - perhaps some disease is occurring in a latent form.

Treatment tactics, drugs

To prescribe the correct treatment, the doctor needs to find out the cause of proteinuria. If protein release is associated with the physiological state of the body, then therapy is not carried out.

In this case, it is recommended to review your diet, reduce stress, and be less nervous (the doctor may recommend mild sedatives).

Inflammatory diseases

The causes of increased protein in the urine in women and men, associated with inflammatory processes in the genitourinary system, are treated with antibiotics and restoratives.

Antimicrobial drugs are selected taking into account the sensitivity of the pathogen, the form of the disease and the individual characteristics of the patient.

When treating pyelonephritis, the following are indicated:

antibiotics (Ciprofloxacin, Cefepime);
NSAIDs to reduce inflammation and pain (Diclofenac);
bed rest during exacerbation;
supportive herbal medicine (diuretic herbs, rose hips, chamomile, Monurel);
drinking plenty of water;
diuretics (Furosemide);
Fluconazole or Amphotericin are indicated for fungal etiology of the disease.

In case of sepsis (symptoms of suppuration - severe pain, increased temperature, decreased pressure), removal of the kidney is indicated - nephrectomy.

For glomerulonephritis, antimicrobial drugs are prescribed with restriction of proteins and salt. Cytostatics, glucocorticoids, hospitalization and bed rest are indicated in case of exacerbation.

Nephropathy

The level of protein in the urine increases with nephropathy. The treatment regimen depends on the underlying cause (diabetes, metabolic disorders, intoxication, gestosis in pregnant women) and is determined individually.

For diabetic nephropathy, careful monitoring of blood glucose levels is necessary, and a low-protein, salt-free diet is indicated. Among the drugs prescribed are ACE inhibitors, agents for normalizing the lipid spectrum (nicotinic acid, Simvastin, Probucol).

In severe cases, Erythropoietin is also used to normalize hemoglobin, a hemodialysis procedure, or a decision is made about a kidney transplant.

Preeclampsia in pregnant women

Gestosis during pregnancy can occur in four forms, or stages:

dropsy - edematous syndrome develops;
nephropathy - failure of the kidneys;
preeclampsia - cerebrovascular accident;
eclampsia is an extreme stage, a precomatous state, a threat to life.

Any of the forms requires immediate hospitalization and hospital treatment. The woman is advised to rest completely and eat a salt-restricted diet.

Drug therapy includes:

sedatives;
relieving vascular spasms (drip administration of magnesium sulfate is often used);
replenishment of blood volume using isotonic solutions and blood products;
means for normalizing blood pressure;
diuretics to prevent brain swelling;
administration of vitamins.

Why is high protein in urine dangerous?

Proteinuria requires timely identification and elimination of its cause. Increased protein in the urine without treatment is dangerous for the development of the following conditions:

Reduced sensitivity to infections and toxins;
Blood clotting disorders, which can lead to prolonged bleeding;
If thyroxine-binding globulin leaves the body in the urine, then there is a high risk of developing hypothyroidism;
Damage to both kidneys, death due to nephropathy;
With gestosis in pregnant women - pulmonary edema, acute renal failure, coma, hemorrhages in internal organs, threat of fetal death, severe
Uterine bleeding.

An increase in protein in the urine does not allow self-medication - by contacting a specialist in time, you can avoid the development of severe complications.

Basophils are the causes of increased blood levels in adults, o...

From the article you will learn about protein in the urine, what it means in women, is it normal, and how to treat it. Proteins (proteins) are a necessary component of all living structures. They provide structural function, metabolic processes, are catalysts for many biochemical reactions, and also carry out the transport of other molecules.

Determining the level of protein in urine is the first step in diagnosing kidney pathologies. In addition, analysis is necessary to determine the effectiveness of the chosen treatment tactics.

Total protein in urine is a laboratory analysis that allows one to identify kidney pathologies at an early stage with a high degree of reliability, as well as diagnose secondary damage to the glomerular apparatus in chronic diseases.

In a healthy person, a small amount of protein molecules is excreted in the urine due to the presence of a filtration mechanism in the glomeruli of the kidneys. The filter is capable of preventing the reverse diffusion of large charged molecules into the primary filtrate. It is known that small molecules of peptides (molecular weight up to 20 kDa) are able to freely penetrate through the filtration mechanism, and high molecular weight albumin (65 kDa) is retained by them.

The presence of protein in the urine is a signal to prescribe an additional extended examination of the patient. This fact is due to the fact that normally the overwhelming concentration of peptide molecules is reabsorbed into the bloodstream in the convoluted tubules of the kidneys. In this case, only a small amount is excreted along with urine. About 20% of the total number of released peptides are low molecular weight antibodies (immunoglobulins), while 40% are albumins and mucoproteins.

Why is the analysis prescribed?

A referral for analysis to determine total protein in the urine can be prescribed by a general practitioner, nephrologist, endocrinologist or cardiologist. It is used for the following purposes:

early diagnosis of pathological conditions of the kidneys (focal sclerosing glomerulonephritis, membranous glomerulonephritis or degenerative kidney disease);
diagnosis of cardiovascular pathologies;
differential diagnosis of the causes of edema;
identifying disturbances in the normal functioning of the kidneys due to diabetes mellitus, Libman-Sachs disease, as well as amyloid dystrophy;
determining the likelihood of developing chronic kidney failure;
assessing the effectiveness of the selected drug treatment tactics and preventing the development of recurrent pathologies.

Who can get the test?

The study is prescribed for patients with diabetes mellitus, as well as for symptoms of kidney failure:

excessive swelling of the lower extremities or face;
accumulation of free fluid in the peritoneal cavity;
unexplained weight gain;
persistently high blood pressure for a long time;
blood when urinating;
a sharp decrease in the amount of urine excreted per day;
increased drowsiness and decreased performance.

In addition, the normal level of protein in urine in men and women should be determined during a routine annual examination. The analysis is of particular importance for patients at risk: age over 50 years, smoking and alcohol abuse, as well as the presence of aggravating factors in the family history.

Table of norms for protein in urine in women by age

Important: the data presented is for informational purposes only and is not sufficient to make a final diagnosis.

Only the attending physician has the right to decipher the results of the study, who determines the diagnosis and prescribes appropriate treatment based on the patient’s general medical history, as well as data from other laboratory tests and instrumental studies.

The standard units of measurement are mg/day; however, some laboratories use g/day. Units of measurement are converted using the formula: g/day*1000= mg/day.

It should be noted that when selecting reference (normal) values, the gender and age of the patient should be taken into account.

The table shows acceptable protein concentrations in urine in healthy women, selected according to age.

It has been established that after intense strength training, an increased protein content in the urine is recorded, the value of which reaches 250 mg/day. However, the concentration of the parameter under consideration should return to the reference values within 1 day.

Normal level of protein in urine in men

Normally, protein in the urine of men, as well as women, should be either completely absent or present in trace amounts. The maximum permissible values are 150 mg/day.

Proteinuria – pathology or normal?

Proteinuria is a condition in which a patient has increased protein in the urine. In the vast majority of cases, this condition does not relate to pathologies, but is a variant of the norm or the result of improper preparation of the patient for the donation of biomaterial (physical or emotional fatigue, acute stage of an infectious process, or dehydration).

Elevated protein is diagnosed in approximately 20% of the healthy population. In this case, proteinuria is considered normal. In only 2% this condition is the cause of serious pathology. With benign proteinuria, protein in the urine in men and women is recorded at a concentration of 200 mg per day or less.

Orthostatic proteinuria

Separately, there is orthostatic proteinuria - a condition characterized by an increased concentration of total protein only after prolonged walking or being in a horizontal static position. This fact explains the discrepancy in results in the presence of orthostatic proteinuria: positive when examining daily urine and negative when diagnosing a single portion. According to statistics, this condition occurs in 5% of the population under 30 years of age.

Increased protein in the urine can also be found as a result of its active synthesis in the human body, which leads to the need to enhance filtration processes by the kidneys. In this case, there is an excess of the possibility of reabsorption of protein molecules in the renal tubules and their diffusion into the urine. This condition is also a variant of the norm.

The exception is situations when not low-molecular-weight organic peptides are detected, but specific molecules, for example, Bence-Jones protein. It is known that the sensitivity of the method is not enough to determine the concentration of this protein. If there is a suspicion of a malignant lesion of epithelial tissue (myeloma), it is necessary to undergo a urine screening test for Bence Jones protein.

When is proteinuria a pathology?

A condition characterized by an increase in protein in the urine over a long period of time accompanies various pathologies of the urinary organs. Depending on the mechanism of occurrence, it is customary to divide proteinuria into:

glomerular, which occurs against the background of a violation of the integrity of the basement membrane of the renal glomeruli. It is known that the basement membrane acts as a natural barrier that prevents the diffusion of large molecules with a charge, and when it is damaged, there is a free flow of proteins into the urine. This condition can be an independent pathology or occur as a consequence of an underlying disease, for example, diabetes mellitus (from 30 to 500 mg of protein per day). Another cause of glomerular proteinuria is the use of medications;
tubular - the result of a disorder in the process of reabsorption of substances in the renal tubules. In this case, a lower protein level is recorded in urine analysis (no more than 200 mg per day) compared to the glomerular type. The most common cause of this condition is a complication of hypertension.

Other reasons for exceeding the norm

The reasons for increased protein in the urine in men and women are also:

infection of the urinary system with pathogenic microorganisms, for example, cystitis or urethritis;
bladder oncology;
vulvitis, vaginitis, etc.
chronic heart failure;
inflammation of the inner lining of the heart;
extensive injuries;
intestinal obstruction.

Preparing for analysis

The reliability of the results obtained by the patient primarily depends on his preparation for the test. The material for the study is a single portion of morning urine. Or all the urine collected by the patient himself during the day.

Before collecting biomaterial, you should avoid drinking alcohol 24 hours before. As well as fatty and smoked dishes. You must stop using diuretics within 48 hours. And for women, collect biomaterial - 2 days after menstruation or before it.

How to reduce protein in urine?

In order for increased protein in the urine in men, women and children to return to normal values, it is necessary to first establish the reason for its deviation from the norm. False-positive results indicating proteinuria are often detected in the morning portion of biomaterial in the analysis for the criterion in question. That is why, if an abnormality in protein in the urine is detected, a repeat test is prescribed.

Depending on the initial cause, appropriate treatment for protein in the urine is prescribed. In the case of an infectious disease, it is necessary to determine the type of pathogenic microorganism that provoked it. After this, a test is carried out to determine the sensitivity of the isolated species of bacteria to various groups of antibiotics. The most effective antibacterial drugs are prescribed to the patient.

In the case of arterial hypertension, medications that lower blood pressure are selected, and in the case of cancer pathologies, a course of chemotherapy is determined.

Diet for high protein in urine

One of the key points in treatment is quitting smoking and alcohol. As well as diet. Patients are recommended:

limit the amount of salt consumed to 2 g per day;
exclude meat and fish in order to reduce protein intake;
drink no more than 1 liter of liquid per day (including juices, soups, tea);
consume rice dishes and fermented milk products with a low percentage of fat, as well as raw and steamed vegetables;
give preference to rosehip tea and currant fruit drinks.

Protein in urine - treatment with folk remedies

Important: traditional medicine methods cannot act as the main treatment for high levels of proteins in the urine.

The priority treatment should remain the one prescribed by the attending physician from the methods of official medicine. This fact is argued by the fact that herbal decoctions and infusions are not effective enough to completely cure the underlying disease. They can only have an auxiliary effect and enhance the effect of certain medications.

Bee products have a positive effect on the immune system due to their pronounced antimicrobial and anti-inflammatory properties. In addition, they are able to strengthen the wall of blood vessels and serve as a source of vitamins. In consultation with a doctor, it is permissible to use alcohol and water decoctions based on propolis. The limitation for use is individual intolerance to bee waste products. You should also consume a large amount of fresh berries and fruit drinks based on them.

It is important to understand that when treated with folk remedies, the level of protein in the urine of men and women is not immediately restored. The minimum duration of the course should be 3-4 weeks.

conclusions

Thus, to summarize, it is necessary to highlight the important points:

Normally, protein in the urine of men, women and children is completely absent. Or its concentration does not exceed 150 mg per day;
the presence of proteins in the analysis is not always a signal of pathology. However, it is necessary to undergo a comprehensive examination in order to determine the cause;
if protein and leukocytes are detected in the urine, then additional laboratory and instrumental diagnostic methods are prescribed. The cause may be an infectious disease or cancer;
The sensitivity of the method is not enough to diagnose Bence Jones protein, which is a marker of oncology of the urinary organs.

A healthy person excretes 1.0–1.5 liters of urine per day. The content of 8–10 mg/dl of protein in it is a physiological phenomenon. The daily norm of protein in urine is 100–150 mg and should not raise suspicions. Globulin, mucoprotein and albumin are what make up the total protein in the urine. A large outflow of albumin indicates a violation of the filtration process in the kidneys and is called proteinuria or albuminuria.

Each substance in the urine is assigned a “healthy” norm, and if the protein level fluctuates, this may indicate kidney pathology.

Methods for determining protein in urine

A general urine test involves using either the first (morning) portion or taking a daily sample. The latter is preferable for assessing the level of proteinuria, since the protein content has pronounced daily fluctuations. Urine is collected into one container during the day, and the total volume is measured. For a laboratory that tests urine for protein, a standard sample (50 to 100 ml) from this container is sufficient; the rest is not required. To obtain additional information, a Zimnitsky test is additionally performed, which shows whether urine levels per day are normal.

Methods for determining protein in urine
View	Subspecies			Peculiarities
Quality	Heller's test			Examination of urine for the presence of protein
	Sulfosalicylic acid test
	Boiling analysis
Quantitative		Turbidimetric	Protein from urine interacts with the reagent, resulting in reduced solubility. Sulfosalicylic and trichloroacetic acids and benzethonium chloride are used as reagents.
		Colorimetric	With some substances, the protein in the urine changes color. This is the basis of the biuret reaction and the Lowry method. Other reagents are also used - brilliant blue, pyrogallol red.
Semi-quantitative			They give a relative idea of the amount of protein, the result is interpreted by the change in color of the sample. Semi-quantitative methods include test strips and the Brandberg-Roberts-Stolnikov method.

Protein norms for women, men and children

Protein in urine normally in an adult should not exceed 0.033 g/l. In this case, the daily norm is not higher than 0.05 g/l. For pregnant women, the norm of protein in daily urine is higher - 0.3 g/l, and in morning urine the same - 0.033 g/l. Protein norms differ in a general urine test and in children: 0.036 g/l for the morning portion and 0.06 g/l per day. Most often in laboratories, analysis is carried out using two methods, which show how much protein fraction is contained in urine. The above normal values are valid for analysis performed with sulfosalicylic acid. If you used pyrogallol red dye, the values will differ by three times.

Causes of albuminuria

filtration in the renal glomeruli occurs in the wrong way;
protein absorption in the tubules is impaired;
Some diseases put a heavy burden on the kidneys - when protein in the blood is elevated, the kidneys simply “do not have time” to filter it.

Other causes are considered non-renal. This is how functional albuminuria develops. Protein in urine analysis appears in allergic reactions, epilepsy, heart failure, leukemia, poisoning, myeloma, chemotherapy, and systemic diseases. Most often, this indicator in the patient’s tests will be the first sign of hypertension.

An increase in protein in urine may be due to non-pathological factors, so additional tests will be required.

Promotion Levels

Quantitative methods for determining protein in urine give errors, so it is recommended to conduct several tests and then use a formula to calculate the correct value. The protein content in urine is measured in g/l or mg/l. These protein indicators make it possible to determine the level of proteinuria, suggest the cause, assess the prognosis and decide on a strategy.

External manifestations

For the body to function properly, constant exchange between blood and tissues is necessary. It is possible only if there is a certain osmotic pressure in the blood vessels. Blood plasma proteins maintain such a level of pressure when low-molecular substances easily move from an environment with a high concentration to an environment with a lower one. The loss of protein molecules leads to the release of blood from its channel into the tissue, which is fraught with severe swelling. This is how moderate and severe proteinuria manifests itself.

The initial stages of albuminuria are asymptomatic. The patient pays attention only to the manifestations of the underlying disease, which is the cause of the appearance of protein in the urine.

Trace proteinuria is an increase in protein levels in urine due to the consumption of certain foods.

The term “proteinuria” refers to the appearance of any type of protein in the urine in quantities exceeding physiological (normal) values.

Detection of an increased level of protein in the urine is the most studied and significant pathological symptom in the practice of a doctor, indicating a malfunction of the urinary system.

The severity of proteinuria can vary significantly between patients, depending on the underlying disease. In addition, the detection of protein in the urine can be observed in isolation or in combination with other changes in the TAM (hematuria, leukocyturia, bacteriuria).

History of the discovery of the syndrome

The first information about changes in the chemical composition of urine in certain diseases was obtained back in the 17th century. Thus, in 1694, the outstanding Leiden physician F. Dekker first discovered protein in the urine of patients with proven kidney pathology.

In his research, he was able to demonstrate that urine contains a substance that coagulates and coagulates when heated, which in turn leads to the formation of "turbidity."

Based on the experiments carried out, F. Dekker proposed specific methods for detecting this impurity using acetic acid.

As a pathological syndrome, proteinuria was described by D. Cotugno in 1764, identifying it in a patient with acute pyelonephritis. Proteinuria and renal pathology are finally associated with R. Bright.

To identify the protein, he used a fairly simple and specific technique - heating a small amount of urine in a spoon over a flame (the protein precipitated after denaturation). In a number of experiments, nitric acid was used to detect proteins.

R. Bright reliably established the connection between proteinuria and chronic nephritis, which for some time received the name “Bright’s disease.”

2. Boundaries of normality and pathology

Often, when asked about the presence of protein in the urine of healthy individuals, an ambiguous answer can be obtained. What is considered the normal range for diagnosing pathological proteinuria? There are quite contradictory data in the medical literature.

With the protein concentration in a single portion of urine, everything is quite simple; normally it should not exceed 0.03 g/l (in children under one year old up to 0.002 g/l, in children over one year old - 0.036 g/l).
The level of daily protein loss in urine should normally not exceed 0.15 g/day (up to 100 mg/day Pushkarev I.A. 1985; 150 mg/day Bergstein J., 1999; 200 mg/day B.M. Brenner, 2007) .

At the same time, the calculated concentrations of the level of daily proteinuria based on the given norms in a healthy person (taking into account diuresis of up to 1.5 l/day) show the possibility of excreting up to 0.1 grams of protein.

Such discrepancies are explained by individual and racial characteristics of protein excretion in the urine.

The vast majority of people have mild proteinuria (about 40-50 mg per day). In 10-15% of the population, daily urinary protein excretion reaches 0.150 g/day without confirmation of urinary system pathology.

The chosen diagnostic method is of great importance in assessing the degree of daily protein loss in urine.

By generally accepted methods, such as the sulfosalicylic acid test or the biuret reaction, protein is not detected in the urine of a healthy population. Patients who detect a one-time increase in protein levels in the urine are often prescribed.

3. Protein composition of urine

To assess proteinuria correctly, you need to have an idea of the qualitative and quantitative composition of normal urine.

In a portion of the urine of a healthy person, up to 200 different proteins can be identified, filtered from the blood or secreted by epithelial cells of the urinary system.

Approximately 50-70% of urine protein is uroromucoid (uromodulin) - a product of renal tissue synthesis. In the lumen of the renal tubules, uromodulin forms a specific gel-like structure, impermeable to water, but permeable to ions.

Uromodulin is detected in kidney tissue from the 16th day of embryogenesis. In daily urine it is detected in the amount of 20 - 100 mg, and its synthesis increases with high salt intake and taking loop diuretics (furasemide, torsemide).

The appearance of tissue proteins may be the result of normal renal excretion and constant renewal of kidney tissue.

Plasma proteins are the second in terms of specific gravity.. When using high-quality diagnostic systems, about 30 plasma proteins can be detected in urine, the leading position among which is albumin.

Proteins from tissues of the heart, pancreas, liver, and transplant antigens can be detected in urine. Damage to heart tissue in patients is accompanied by myoglobinuria, and some tumors lead to increased excretion of low molecular weight proteins.

Almost all known human hormones are excreted in the urine. In pregnant women, proteins secreted by placental tissue can be detected in the urine.

4. The mechanism of appearance of protein in urine

Urine formation occurs in the main structural element of the kidney - the renal glomerulus (a network of arterial capillaries enclosed in a capsule).

Blood entering the glomerular capillaries is filtered through a special glomerular membrane to form primary urine. The glomerular filtration membrane has a rather complex structure and includes:

1 The inner layer is represented by endothelium, most of which is covered with pores with a diameter of 40 nm. The pores are covered by a diaphragm, so protein filtration at this stage is determined by both the size of the pores and the condition of this diaphragm;
2 A three-layer membrane (basal), located outside the inner layer. Its permeability to protein molecules is determined by its electrical charge and the arrangement of collagen filaments;
3 Epithelial lining (podocytic apparatus), located on the urinary side of the basement membrane. This layer is responsible for the active filtration process using microfilaments.

In a healthy person, the glomerular filter can pass proteins of a certain size (no more than 4 nm, weighing no more than 70 kDa). Proteins such as serum albumin, myoglobin, prealbumins, lysozyme, microglobulins, etc. are freely filtered.

In addition to size, the charge of the protein molecule plays an important role in the filtration process. The basement membrane is normally negatively charged and does not allow active filtration of plasma proteins that have the same charge.

Figure 1 - Structure of the nephron

If small plasma proteins manage to pass the renal filter, they are almost completely absorbed in the renal tubules.

Summarizing the above, physiological protein excretion is the result of the interaction of the glomerular and tubular mechanisms, and damage to either part of the nephron can lead to proteinuria.

Detection of transient or permanent proteinuria in a person requires a thorough examination. Next, let's move on to studying the main reasons for the increase in protein levels in the urine.

5. Functional proteinuria

Functional proteinuria is not associated with damage to renal tissue. It is based on a transient disturbance of protein filtration. This condition can occur when:

1 Severe psycho-emotional stress;
2 Eating large amounts of protein;
3 Dehydration, electrolyte disturbances;
4 Chronic heart failure, hypertension;
5 Fever;
6 Against the background of exhausting physical exercise (marching proteinuria);
7 Against the background of hypothermia.

In infants, dehydration proteinuria often occurs, which is based on feeding disturbances, toxicosis, diarrhea, and vomiting. After removal of the provoking factor, such proteinuria stops.

In adolescents, so-called orthostatic proteinuria can be detected - increased protein excretion in the urine when moving to a standing position. Children predisposed to orthostatic proteinuria are diagnosed with active growth, low muscle mass, kyphosis, lumbar lordosis, low blood pressure and absolutely normal kidney function.

Proteinuria occurs when a teenager stands. Lordosis of the spine leads to the fact that the anterior surface of the liver moves down and somewhat presses the inferior vena cava. Stagnation of blood in the renal veins provokes the release of protein in the urine.

In physiological proteinuria, the largest proportion is made up of low-molecular-mass proteins (up to 20 kDa), for example, Ig, 40% are high-mass proteins (65 kDa), 40% are uromodulin.

6. Pathological proteinuria

Pathological proteinuria develops when the renal glomeruli, where filtration occurs, or the renal tubules, where reabsorption of protein molecules occurs, is damaged.

Depending on the level of damage, three types of pathological proteinuria can be distinguished:

1 Prerenal, or overload, associated with increased protein breakdown and the appearance of increased concentrations of low molecular weight proteins in the blood plasma.
2 Renal, associated with damage to the filtration apparatus of the renal glomerulus and/or renal tubules, where reabsorption of protein molecules occurs.
3 Postrenal, caused by pathology of the underlying urinary tract. Most often caused by inflammatory exudation.

6.1. Prerenal

The basis of prerenal proteinuria is the appearance in the patient's blood plasma of proteins with a small molecule size, which can pass through a healthy kidney filter and enter the urine in large quantities.

The appearance of such proteins in the plasma is associated either with their increased synthesis or with the breakdown of tissue structures and cells. This condition can occur when:

1 Plasmablastic leukemia;
2 Multiple myeloma;
3 Connective tissue diseases;
4 Rhabdomyolysis;
5 Lymphoma with paraproteinemia;
6 Hemolytic anemia;
7 Macroglobulinemia.

Most often, this type of proteinuria is caused by an increase in the blood of Ig light chains (Bence Jones protein), myoglobin, hemoglobin, and lysozyme.

Congestive forms of prerenal proteinuria are possible, which occur with decompensated heart disease, metastases, and abdominal tumors.

Neurogenic prerenal proteinuria can be classified as a separate category, which can be provoked by an epileptic seizure, traumatic brain injury, hemorrhage, or vegetative crisis.

6.2. Renal

In this case, an increase in protein levels in the urine is associated with damage to the renal parenchyma or renal interstitium. This is typical for the following conditions:

1 Glomerulonephritis (acute or chronic);
2 Nephropathy in diabetes;
3 Nephropathy of pregnancy;
4 Amyloidosis;
5 Kidney tumors;
6 Hypertensive nephrosclerosis;
7 Gout.

Depending on the location of the damage, the composition and volume of proteins excreted in the urine changes, which makes it possible to distinguish:

1 Renal glomerular (glomerular) proteinuria, which develops when the renal cortex, in which the nephrons are located, is damaged.
2 Renal tubular proteinuria, which develops against the background of problems with the reabsorption of proteins in the proximal tubules.

6.2.1. Damage to the renal glomeruli

When the renal glomeruli are damaged, changes of the glomerular type are recorded in the urine:

1 With the loss of the negative charge of the basement membrane, low molecular weight protein molecules (albumin and transferrin) begin to predominate in the urine.
2 If the integrity of the pores in the membranes is damaged, large-molecular compounds (immunoglobulin G) are detected in the urine.

Thus, the nature of damage to the renal filter affects the ability to pass protein molecules of different sizes and masses.

That is why, according to the composition of uroproteins, proteinuria is distinguished:

1 Highly selective - excretion of low molecular weight proteins with a mass of up to 70 kDa (mainly albumin);
2 Selective - excretion of both low molecular weight and proteins with a mass of up to 150 kDa;
3 Non-selective - isolation of a protein with a mass from 830 to 930 kDa.

To determine the degree of selectivity, a special index is used, which is the ratio of the isolation of proteins with high mass to low molecular weight (usually the IgG/albumin ratio).

A ratio of up to 0.1 (selective) indicates a filtration defect associated with a violation of the ability to retain negatively charged molecules. An increase in the index of more than 0.1 indicates non-selectivity and permeability of the filter pores for macromolecules.

Determining the degree of selectivity of glomerular proteinuria is important for developing patient management tactics.

The selective nature of protein loss in the urine indicates minimal damage, so the effectiveness of glucocorticosteroids is high in such patients.

Non-selectivity is associated with more severe changes in the renal filter (membranous nephropathy, glomerulosclerosis, proliferative glomerulonephritis); in treatment, as a rule, resistance to steroids is observed.

Increased hydrostatic pressure in the glomeruli can also lead to increased protein filtration, which is a variant of glomerular proteinuria.

6.2.2. Tubular protein loss

It develops against the background of impaired reabsorption of proteins in the renal tubules and is manifested by the release of low molecular weight proteins (weight below 40 kDa), which are normally completely reabsorbed.

Tubular proteinuria, as a rule, does not exceed 2 g/1.73 mx2/day.

Pathologies accompanied by tubular protein loss include:

1 Interstitial nephritis;
2 Urinary infections;
3 Urolithiasis;
4 Toxic effects;
5 Wilson's disease;
6 Fanconi syndrome.

Indicators of tubular proteinuria are B2-microglobulin, retinol-binding protein and/or alpha1-microglobulin.

The level of excretion of B2-microglobulin has the greatest diagnostic value. An increase in the level of albumin in the urine with a normal content of B2-microglobulin indicates damage to the glomeruli, while the predominance of B2-microglobulin indicates tubular pathology. At the same time, we should not forget about the possibility of erroneous analysis results.

6.3. Postrenal

Postrenal proteinuria is caused by the release of inflammatory exudate rich in protein into the urine and is associated with damage to the underlying parts of the urinary tract. This condition can occur when:

1 Inflammatory pathology of the urinary tract (cystitis, urethritis, prostatitis);
2 Bleeding from the urinary tract;
3 Bladder polyps;
4 Tumors of the urinary tract.

Fig 1 - Differential diagnosis of proteinuria. Source -V.L. Emanuel. Problems of pathology of the urogenital system // Journal of laboratory medicine. No. 7, 2015.

7. Gradations of proteinuria

Based on the amount of protein excretion, it is advisable to distinguish between the variability of proteinuria, which ranges from microproteinuria to a high, nephrotic degree (above 3 g/day).

The term MAU (microalbuminuria) refers to the excretion of albumin in the urine in an amount above the physiological norm, but below the sensitivity of standard test systems.

It is customary to talk about UIA when the daily loss is from 10 mg to 300 mg of albumin. MAU may be the only early sign of glomerular damage, for example, in diabetic nephropathy.

MAU appears long before the decline in GFR (glomerular filtration rate) begins. Microalbuminuria also occurs in hypertension and kidney transplant rejection.

Low grade proteinuria (300 mg -1 g/day) can be detected in acute urinary tract infections, urinary tract obstruction, urolithiasis, and nonspecific nephritis.

Moderate loss of proteins (1 g - 3 g/s) develops with acute tubular necrosis, glomerulonephritis, hepatorenal syndrome, amyloidosis.

A large loss of protein in the urine (more than 3 g/s) is almost always associated with a disruption of the glomerular filter and a change in the “size-charge ratio” of proteins and membranes.

8. Clinical manifestations

Proteinuria, which occurs in a mild form, usually does not have any clinical manifestations or is masked by the symptoms of the underlying pathology.

With a significant increase in the concentration of protein in the urine, foaming occurs during urination. This “foam” lasts quite a long time.

Constant and significant loss of proteins in the urine can lead to the development of edema of the face, limbs, and abdomen.

9. Kidney failure

Proteinuria is one of the most significant risk factors for the formation and progression of CKD (chronic kidney disease). A relationship has been proven between the increase in protein loss in the urine and the rate of decline in kidney function.

In one of the latest meta-analyses (Stoycheff, 2011), the role of proteinuria as an independent risk factor for CKD progression was once again proven.

Proteinuria (including MAU) are risk factors for the development of complications from the cardiovascular system.

International expert recommendations use a normogram to determine the risk of an unfavorable prognosis for the development of CKD and renal failure (Figure 2). The higher the level of proteinuria, the higher the risk of fatal outcomes.

Fig 2. - Risk nomogram for unfavorable prognosis KDIGO-2012, 2013: green – low risk (if there are no other markers of renal pathology or the pathology itself), yellow – moderate risk, orange – high risk, red – very high risk

10. Treatment tactics

The tactics for managing a patient with proteinuria directly depend on the cause, the risk of an unfavorable outcome, and the prognosis, which determines the need for dynamic monitoring by a therapist or nephrologist.

General information about the study

Total protein in urine is an early and sensitive sign of primary kidney diseases and secondary nephropathies in systemic diseases. Normally, only a small amount of protein is lost in the urine due to the filtration mechanism of the renal glomerulus - a filter that prevents the penetration of large charged proteins into the primary filtrate. While low molecular weight proteins (less than 20,000 daltons) freely pass through the glomerular filter, the supply of high molecular weight albumin (65,000 daltons) is limited. Most of the protein is reabsorbed into the bloodstream in the proximal tubules of the kidney, with the result that only a small amount is ultimately excreted in the urine. About 20% of the protein secreted normally is low molecular weight immunoglobulins, and 40% each is albumin and mucoproteins secreted in the distal renal tubules. Normal protein loss is 40-80 mg per day, the release of more than 150 mg per day is called proteinuria. In this case, the main amount of protein is albumin.

It should be noted that in most cases, proteinuria is not a pathological sign. Protein in the urine is detected in 17% of the population and only 2% of them cause serious illness. In other cases, proteinuria is considered functional (or benign); it is observed in many conditions, such as fever, increased physical activity, stress, acute infectious disease, and dehydration. Such proteinuria is not associated with kidney disease, and protein loss is insignificant (less than 2 g/day). One of the types of functional proteinuria is orthostatic (postural) proteinuria, when protein in the urine is detected only after prolonged standing or walking and is absent in a horizontal position. Therefore, with orthostatic proteinuria, an analysis of total protein in the morning urine will be negative, and an analysis of 24-hour urine will reveal the presence of protein. Orthostatic proteinuria occurs in 3-5% of people under 30 years of age.

Protein in the urine also appears as a result of its excess production in the body and increased filtration in the kidneys. In this case, the amount of protein entering the filtrate exceeds the possibilities of reabsorption in the renal tubules and is ultimately excreted in the urine. This “overflow” proteinuria is also not associated with kidney disease. It can accompany hemoglobinuria with intravascular hemolysis, myoglobinuria with muscle tissue damage, multiple myeloma and other plasma cell diseases. With this type of proteinuria, it is not albumin that is present in the urine, but some specific protein (hemoglobin in hemolysis, Bence Jones protein in myeloma). In order to identify specific proteins in urine, a 24-hour urine test is used.

For many kidney diseases, proteinuria is a characteristic and constant symptom. According to the mechanism of occurrence, renal proteinuria is divided into glomerular and tubular. Proteinuria, in which protein in the urine appears as a result of damage to the basement membrane, is called glomerular. The glomerular basement membrane is the main anatomical and functional barrier to large and charged molecules; therefore, when it is damaged, proteins freely enter the primary filtrate and are excreted in the urine. Damage to the basement membrane can occur primarily (in idiopathic membranous glomerulonephritis) or secondary, as a complication of a disease (in diabetic nephropathy due to diabetes mellitus). The most common is glomerular proteinuria. Diseases accompanied by damage to the basement membrane and glomerular proteinuria include lipoid nephrosis, idiopathic membranous glomerulonephritis, focal segmental glomerular sclerosis and other primary glomerulopathies, as well as diabetes mellitus, connective tissue diseases, post-streptococcal glomerulonephritis and other secondary glomerulopathies. Glomerular proteinuria is also characteristic of kidney damage associated with certain medications (non-steroidal anti-inflammatory drugs, penicillamine, lithium, opiates). The most common cause of glomerular proteinuria is diabetes mellitus and its complication – diabetic nephropathy. The early stage of diabetic nephropathy is characterized by the secretion of a small amount of protein (30-300 mg/day), the so-called microalbuminuria. As diabetic nephropathy progresses, protein loss increases (macroalbuminemia). The degree of glomerular proteinuria varies, often exceeding 2 g per day and can reach more than 5 g of protein per day.

When protein reabsorption function in the renal tubules is impaired, tubular proteinuria occurs. As a rule, protein loss with this option does not reach such high values as with glomerular proteinuria, and amounts to up to 2 g per day. Impaired protein reabsorption and tubular proteinuria are accompanied by hypertensive nephroangiosclerosis, urate nephropathy, intoxication with lead and mercury salts, Fanconi syndrome, as well as drug-induced nephropathy when using non-steroidal anti-inflammatory drugs and some antibiotics. The most common cause of tubular proteinuria is hypertension and its complication – hypertensive nephroangiosclerosis.

An increase in protein in the urine is observed in infectious diseases of the urinary system (cystitis, urethritis), as well as in renal cell carcinoma and bladder cancer.

The loss of a significant amount of protein in the urine (more than 3-3.5 g/l) leads to hypoalbuminemia, a decrease in blood oncotic pressure and both external and internal edema (edema of the lower extremities, ascites). Significant proteinuria provides an unfavorable prognosis for chronic renal failure. Persistent loss of small amounts of albumin does not cause any symptoms. The danger of microalbuminuria is the increased risk of coronary heart disease (especially myocardial infarction).

Quite often, as a result of a variety of reasons, the analysis of morning urine for total protein is false positive. Therefore, proteinuria is diagnosed only after repeated analysis. If two or more tests of the morning urine sample are positive for total protein, proteinuria is considered persistent, and the examination is supplemented by an analysis of 24-hour urine for total protein.

Testing morning urine for total protein is a screening method for detecting proteinuria. It does not allow assessment of the degree of proteinuria. In addition, the method is sensitive to albumin, but does not detect low-molecular-weight proteins (for example, Bence-Jones protein in myeloma). In order to determine the degree of proteinuria in a patient with a positive morning urine sample for total protein, 24-hour urine is also tested for total protein. If multiple myeloma is suspected, 24-hour urine is also analyzed, and it is necessary to conduct additional research for specific proteins - electrophoresis. It should be noted that analysis of 24-hour urine for total protein does not differentiate the variants of proteinuria and does not reveal the exact cause of the disease, so it must be supplemented with some other laboratory and instrumental methods.

What is the research used for?

For the diagnosis of lipoid nephrosis, idiopathic membranous glomerulonephritis, focal segmental glomerular sclerosis and other primary glomerulopathies.
For the diagnosis of kidney damage in diabetes mellitus, systemic connective tissue diseases (systemic lupus erythematosus), amyloidosis and other multiorgan diseases with possible kidney involvement.
For the diagnosis of kidney damage in patients at increased risk of chronic renal failure.
To assess the risk of developing chronic renal failure and coronary heart disease in patients with kidney disease.
To assess renal function during treatment with nephrotoxic drugs: aminoglycosides (gentamicin), amphotericin B, cisplatin, cyclosporine, non-steroidal anti-inflammatory drugs (aspirin, diclofenac), ACE inhibitors (enalapril, ramipril), sulfonamides, penicillin, thiazide, furosemide and some others.

When is the study scheduled?

For symptoms of nephropathy: edema of the lower extremities and periorbital region, ascites, weight gain, arterial hypertension, micro- and gross hematuria, oliguria, increased fatigue.
For diabetes mellitus, systemic connective tissue diseases, amyloidosis and other multi-organ diseases with possible kidney involvement.
With existing risk factors for chronic renal failure: arterial hypertension, smoking, heredity, age over 50 years, obesity.
When assessing the risk of developing chronic renal failure and coronary heart disease in patients with kidney disease.
When prescribing nephrotoxic drugs: aminoglycosides, amphotericin B, cisplatin, cyclosporine, non-steroidal anti-inflammatory drugs, ACE inhibitors, sulfonamides, penicillins, thiazide diuretics, furosemide and some others.