Proteinuria is an increase in the concentration of protein in the urine of more than 150 mg per day. The range of etiological factors of this condition is extremely wide - from emotional stress and the common cold, accompanied by high fever, to severe kidney disease, systemic autoimmune processes and oncohematological diseases. Severe proteinuria within the framework of nephrotic syndrome is clinically manifested by peripheral edema on the face and lower extremities. There are many methods for determining protein in urine. Traditionally, a clinical urinalysis is used as the primary examination. Correction of proteinuria is carried out by treating the underlying disease.
Classification
Normally, a small amount of protein can be found in healthy people - this is physiological proteinuria. It is often observed in newborns, which is associated with the immaturity of the renal filter. Also, in children of preschool and school age, orthostatic proteinuria occurs, which appears when the child is in an upright position (clamping of the renal veins and blood stasis occurs) and disappears when he assumes a horizontal position.
In some situations, short-term (transient) proteinuria is possible:
- When hypothermia or overheating of the body.
- With nervous tension.
- With high fever.
- After prolonged physical exertion, with prolonged walking (marching proteinuria).
- After taking a large amount of protein food (alimentary proteinuria).
- After gross palpation of the kidneys by a doctor, especially in children.
- With severe fluid loss (dehydration proteinuria) with diarrhea, vomiting, sweating.
- After intense sun exposure (proteinuria solaris).
- After an epileptic seizure or concussion (centrogenic proteinuria).
According to the severity, proteinuria is divided into:
- Minor - from 15 to 50 mg per day.
- Moderate - from 50 to 300 mg per day.
- Massive - more than 3g per day.
By origin, pathological proteinuria are:
1. Prerenal ("overload"). Associated with high blood levels of low molecular weight proteins (paraproteins, monoclonal immunoglobulins) in malignant hematological pathologies or with stagnation of blood in the renal vessels in heart failure.
2. Renal. The most common option. Increased protein excretion is caused by kidney pathology. Depending on the lesion of one or another part of the nephron, renal proteinuria is divided into:
- glomerular (glomerular) - typical for diseases with damage to the glomerular apparatus of the kidneys (glomerulonephritis, diabetic nephropathy, nephropathy during pregnancy or with arterial hypertension);
- tubular - characterized by a violation of the reabsorption of proteins in the renal tubules. It occurs with tubulointerstitial nephritis, taking nephrotoxic drugs, heavy metal poisoning, etc .;
- mixed - a combination of impaired filtration and reabsorption of proteins. It can be observed in the advanced stage of almost any organic pathology of the kidneys.
3. Postrenal. The cause may be inflammatory or degenerative changes in the urinary tract - pyelonephritis, cystitis, bladder polyposis, bleeding from the urinary system.
Proteinuria in pregnancy
Causes of prerenal proteinuria
This type of proteinuria is also called "overload". It occurs when the concentration of low molecular weight proteins in the blood is so high that passing through the renal filter, they do not have time to be reabsorbed in the tubules of the nephron. The degree of protein excretion can be both insignificant and pronounced. Prerenal proteinuria develops in the following diseases:
- monoclonal gammopathy. Pathological proteins (paraproteins) are synthesized by plasma cells in large quantities in multiple myeloma, Waldenström's macroglobulinemia, heavy chain disease, etc.
- hemolytic anemia. In diseases accompanied by intravascular hemolysis (autoimmune hemolytic anemia, hereditary microspherocytosis, hemoglobinopathies), hemoglobin released from erythrocytes binds to the haptoglobin protein and enters the urine
- Breakdown of muscle tissue. A similar situation occurs with the destruction of muscles (rhabdomyolysis). Rhabdomyolysis occurs with prolonged compression syndrome (crush syndrome), myodystrophy, and taking medications (statins).
With hemolysis and rhabdomyolysis, proteinuria occurs quite quickly and in the vast majority of cases disappears just as quickly. With paraproteinemia, it increases slowly, over several years, and begins to decrease only after courses of chemotherapy. Also, very rarely, prerenal proteinuria can be caused by increased hydrostatic pressure in the glomeruli due to severe venous congestion. This is possible with severe chronic heart failure.
Causes of renal proteinuria
Glomerular proteinuria
This is the most common type of pathological proteinuria. An increase in protein excretion is associated with damage to the glomerular apparatus (renal glomeruli). Due to a defect in the renal filter, a large amount of blood plasma proteins, primarily albumin, enters the urine. The degree of proteinuria can be very pronounced (more than 3 g/l).
Often occurs in conjunction with other pathological urinary syndromes - hematuria, leukocyturia. Increased urinary protein excretion usually occurs gradually. Proteinuria regresses under the influence of specific anti-inflammatory therapy, but can persist for a long time, depending on the severity of the disease. Diseases in which glomerular proteinuria is observed:
- Primary glomerular pathology: minimal change disease (common in children), membranous glomerulonephritis, focal glomerulosclerosis.
- Secondary glomerular pathology: diabetic nephropathy, kidney damage in hypertension, nephropathy in diffuse collagenoses (systemic lupus erythematosus, systemic scleroderma), systemic vasculitis (polyarteritis nodosa, granulomatosis with polyangiitis, hemorrhagic purpura Shenlein-Genoch).
More rare etiological factors of glomerular proteinuria include:
- Kidney cancer.
- Amyloidosis.
- Familial Mediterranean fever (periodic illness).
- Goodpasture syndrome.
- Alport syndrome.
- Fabry disease.
- Membranous nephropathy in malignant neoplasms (breast cancer, lung cancer, oncohematological diseases).
- Imerslung-Gresbeck syndrome.
tubular proteinuria
In this type of proteinuria, blood proteins that normally pass through the glomeruli are not reabsorbed by the renal tubules due to damage to them. Therefore, protein losses are most often insignificant - no more than 1 gram per day. The rate of development of proteinuria depends on the cause, it can occur both acutely and gradually. Some diseases are difficult enough to treat, which is why proteinuria persists. Protein losses occur in congenital and acquired tubulopathies:
- Interstitial nephritis (due to nephrotoxic drugs such as aminoglycoside antibiotics, NSAIDs, anticancer drugs).
- Poisoning with salts of heavy metals (mercury, lead).
- Acute tubular necrosis.
- Polycystic kidney disease.
- Renal tubular acidosis (Fanconi syndrome).
- Vitamin D overdose.
- Rejection of a kidney transplant.
- obstructive uropathy.
- Sarcoidosis.
- Hepatolenticular degeneration (Wilson-Konovalov's disease).
Causes of postrenal proteinuria
This type of proteinuria is caused by the ingestion of an inflammatory protein-rich exudate into the urine. This is more common in urinary tract infections (pyelonephritis, cystitis). Less commonly, the cause may be bleeding from the urinary tract caused by urolithiasis, bladder cancer. In general, protein losses are insignificant and rarely reach high values. Often associated with leukocyturia, bacteriuria, or hematuria. With infections of the urinary tract, already at the beginning of antibiotic therapy, proteinuria begins to disappear.
Other reasons
There are also so-called "extrarenal proteinuria", which occur in the following pathological conditions and diseases:
- Severe somatic conditions (sepsis, trauma, extensive burns).
- Endocrine disorders (thyrotoxicosis).
- Poisoning with organic compounds (phenol).
- Sickle cell anemia.
Diagnostics
Detection of proteins in the urine requires immediate contact with a general practitioner or nephrologist to determine the cause. To differentiate physiological and pathological proteinuria, when questioning the patient, it is clarified what preceded its appearance, for example, high fever, intense physical activity, intake of high-protein foods. Anamnestic data are extremely important, such as the presence of a diagnosed chronic disease in a patient, the use of drugs.
A physical examination is also carried out - measuring blood pressure, checking the skin for peripheral edema, Pasternatsky's symptom. In case of suspected autoimmune rheumatological pathology, the joints are carefully examined for swelling, redness, restriction or pain in movement.
Traditionally, during the initial examination, the determination of proteins in the urine is performed as part of a general urinalysis. It should be borne in mind that the test strips used in OAM have some features:
- With a high pH of urine or taking iodine preparations, antimalarials, a false positive result is possible.
- The reagent zone of test strips is more sensitive to albumin and extremely low sensitive to other proteins - beta-2 microglobulin, immunoglobulin G. The Bence-Jones protein characteristic of multiple myeloma is not detected by this method at all.
To establish the correct diagnosis, studies can be prescribed to more accurately determine the type of proteins excreted in the urine and the severity of proteinuria:
- Daily urine protein . This analysis provides more reliable information about the level of protein loss.
- Protein/creatinine ratio. Due to the complexity of collecting urine during the day, this method can serve as a full-fledged analogue, since the concentration of creatinine in the urine is a fairly stable indicator.
- Albumin/creatininone ratio. It is used to diagnose microalbuminuria. It is often prescribed to patients with diabetes mellitus to track the onset of the development of diabetic nephropathy.
- Serum and urine protein electrophoresis. In this analysis, proteins are separated into fractions, which allows you to evaluate the predominant type of protein. An increase in the content of beta-2 microglobulin indicates tubular pathology, and alpha-2 macroglobulin indicates a postrenal type of proteinuria. Myeloma is characterized by an increase in monoclonal immunoglobulins (high M-gradient).
- Determination of Bence-Jones protein. This protein is the light chain of immunoglobulins secreted by tumor plasma cells. Its detection indicates multiple myeloma or Waldenström's macroglobulinemia.
- Immunofixation of urine proteins. It is prescribed for suspected paraproteinemia. The study reveals a high concentration of varieties of light chains of immunoglobulins (gamma, lambda, kappa).
- Calculation of the selectivity index. To assess the severity of glomerular proteinuria, the content of proteins with low (albumin, transferrin) and high molecular weight (immunoglobulin G) is determined. The predominance of high molecular weight proteins indicates a pronounced lesion of the glomerular apparatus, which requires more aggressive anti-inflammatory therapy.
Also, to clarify the diagnosis, the following studies are carried out:
- Blood tests. In the general blood test, nonspecific signs of chronic inflammation may be noted - a decrease in hemoglobin, leukocytosis, an increase in ESR. In a biochemical blood test, an increase in the concentration of urea, creatinine, C-reactive protein is detected. For nephrotic syndrome is characterized by a decrease in total protein, albumin, hyperlipidemia.
- General urine analysis. Other indicators of OAM, such as hematuria, bacteriuria, leukocyturia often help in the differential diagnosis. On microscopic examination of urine sediment, the presence of renal epithelial cells indicates the renal type of proteinuria, the altered erythrocyte morphology is characteristic of glomerular pathology.
- Immunological research. In autoimmune rheumatological diseases, an increased content of rheumatoid factor and other autoantibodies (anticytoplasmic, antibodies to DNA, topoisomerase) are found in the blood.
- Ultrasound/CT of the kidneys. On ultrasound or CT of the kidneys, changes in the renal parenchyma, expansion of the pyelocaliceal system, the presence of cysts or calculi can be detected.
- X-ray. In patients with rheumatic diseases, radiography of the affected joints often shows narrowing of the joint space, periarticular osteoporosis. In multiple myeloma, x-rays of flat bones (especially skull bones) show typical areas of osteolysis and osteodestruction.
- Bone marrow research. If the patient has clinical and laboratory signs of paraproteinemia (Waldenström's macroglobulinemia or multiple myeloma), bone marrow biopsy should be performed to confirm, which reveals plasma cell infiltration, stromal fibrosis, as well as immunophenotyping to assess the expression of tumor markers (CD19, CD20, CD38).
Diagnosis of proteinuria
Correction
Conservative therapy
There are no independent methods for correcting urinary protein loss. It is necessary to treat the underlying disease. Short-term proteinuria resolves on its own and does not require any therapy. Orthostatic proteinuria in the vast majority of children disappears at the onset of puberty, sometimes persisting up to 18-2 years.
Patients with diabetes are prescribed a strict diet with a restriction of foods high in easily digestible carbohydrates and animal fats. With interstitial nephritis, provoked by the intake of nephrotoxic drugs, their urgent cancellation is necessary. Also, for various pathologies that cause proteinuria, the following drugs are used:
- Insulin and hypoglycemic drugs. In type 1 diabetes, daily injections of short-acting and long-acting insulin are required. In type 2 diabetes, hypoglycemic agents are prescribed - biguanides (metformin), sulfonylurea derivatives (glibenclamide), DPP-4 inhibitors (vildagliptin).
- Antibacterial drugs. In pyelonephritis, the drugs of choice are penicillin antibiotics (amoxicillin), cephalosporins (ceftriaxone). For cystitis, fosfomycin trometamol is effective.
- ACE inhibitors. This group of drugs (lisinopril, perindopril) has a nephroprotective effect and is prescribed to all patients with nephrotic syndrome, especially patients with diabetic nephropathy.
- Glucocorticosteroids. Hormonal agents (prednisolone, methylprednisolone) have anti-inflammatory and immunosuppressive effects. They are used in the treatment of glomerulonephritis and almost any rheumatological pathology.
- Cytostatics. Cytostatic drugs (azathioprine, cyclosporine) are used in severe forms of glomerulonephritis, necrotizing vasculitis, when steroid monotherapy is ineffective.
- Chemotherapy. Patients with confirmed paraproteinemia are shown courses of chemotherapeutic agents. Combinations of alkylating agents (chlorambucil), nucleoside analogues (fludarabine) and monoclonal antibodies (rituximab) are prescribed. With the ineffectiveness of these funds, thalidomide, bortezomib are used.
Surgery
In case of kidney cancer or polycystic disease, the main type of treatment is surgery (laparoscopic or open) - kidney resection or total nephrectomy. Some patients with Waldenström's macroglobulinemia or multiple myeloma are considered for hematopoietic stem cell transplantation.
Forecast
Persistent proteinuria, i.e. detected in more than 2 urine tests indicates the presence of a serious disease. Therefore, if it is detected, you should immediately seek medical advice. The prognosis is determined by the underlying pathology - it is favorable with a mild form of urinary tract infection, minimal change disease. An unfavorable outcome is most typical for rapidly progressive forms of glomerulonephritis, oncological diseases, and monoclonal gammopathy.