Uremic toxins in the blood of patients with end-stage renal failure with intestinal dysbiosis

Other diseases starting with the letter “U”: Acne, Thyroid nodules and cysts, Ureaplasmosis, Uremia, Urethritis

A condition in which excess metabolic products accumulate in the blood is called uremia. The syndrome occurs when the kidneys are damaged, when the body loses the ability to remove toxic substances formed as a result of vital activity from the body. Under the influence of these substances, damage to healthy cells occurs, disruption of biochemical processes, and a shift in the acid-base balance of the body.

General information

Anyone who has encountered problems with kidney function knows what uremia The causes are progressive renal failure , which entails various metabolic disorders and the functioning of most organs.
Severe renal failure causes acute or chronic autointoxication , which leads to secondary metabolic and hormonal disorders, general tissue degeneration and a dysfunctional state of the whole organism. The causes of the pathological condition lie in the delay in the bloodstream of nitrogenous metabolic products ( azotemia ) and other toxic compounds, and are also initiated by a disorder of water-salt, acid-base balance, and, in general, osmotic homeostasis .

The terminology comes from the ancient Greek words “ouron” - urine, “hemma” - blood (literally urine-blood) and was proposed by the French scientists Pierri and Leritier.

Story

Urea was crystallized and identified between 1797 and 1808.[11] Urea was suspected to be the source of ammonia in urine at the time, and this was confirmed in 1817. It has been suggested that excess urea may lead to certain diseases. It was later confirmed in 1821 that the body did indeed produce urea and was excreted through the kidneys.[11] In 1827, urea was first synthesized in the laboratory, confirming its composition and making it the first synthesized biological substance. In 1856, urea was produced. in vitro

through protein oxidation.
It was in 1850 that Thomas Datrocher seeded the idea of ​​dialysis with the discovery of the separation of smaller molecules from larger ones through a semi-permeable membrane.[11] It was in 1829 and 1831 that there was strong evidence that some patients had elevated blood urea levels. They also suggested that harm could be caused. Later studies showed that serious neurological disorders such as coma and seizures did not correlate with physical findings including generalized cerebral edema. This suggested that uremia was a form of blood poisoning.[11] In 1851, E. Frerich described the clinical uremic syndrome and suggested that the mechanism of its cause was toxicity. In 1856, J. Pickard developed a sensitive method for reproducibly measuring urea in blood. He was able to detect a 40% decrease in urea concentration between the renal artery and the renal vein. This work confirmed the fact that renal failure coincided with an increase in blood urea levels. It was J. Pickard with E. Frerich's work that popularized the term uremia
.[11]

Pathogenesis

Most often, uremia is based on acute or chronic renal failure, with the first causing uremic syndrome in the second and third stages, and the second, chronic, in the terminal stage.

Normally, metabolic products should be excreted in the urine, but kidney disorders and a decrease in the number of normally functioning nephrons lead to the accumulation of a significant amount of organic substances, most of which are toxic. The largest role is played by urea , sodium cyanate , ammonia , creatinine , guanidine , uric acid , β2-microglobulins, β2-glucoprotein pyridine derivatives , various peptides, amino acids , aliphatic, aromatic amines, polyamines, indoles, phenols, myoinositol , acetone y , lipochromes, cyclic adenosine monophosphates, glucuronic and oxalic acid, enzymes and hormones as:

• parathyroid hormone , together with hypocalcemia and hyperphosphatemia, causes cardiac dysfunction and osteodystrophy , polyneuropathy , anemia , hypertriacylglycerolemia ;
• growth hormone , glucagon , insulin , prolactin - initiates a disorder of carbohydrate and fat metabolism, amenorrhea and impotence .

General information about urine

Also, other substances of exogenous origin, which normally should have been excreted by the kidneys, can also have a negative complex toxic effect. All of these metabolic shifts lead to hyperkalemia , hyperphosphatemia , hypermagnesemia , hypo- or hypernatremia , hypocalcemia , overhydration and acidosis .

The pathogenesis of acute uremia is most often based on a violation of the systemic blood circulation inside the kidneys, that is, shock , which is aggravated by the pathological initiation of hemostasis and fibrinolysis . As a result, massive hemolysis , immune cytolysis and melting of necrotic areas of muscle fibers occur.

Hematological dialysis

Uremia can be eliminated not only with the help of medications. Symptoms and treatment may vary. In cases where the disease is no longer amenable to drugs, it is treated using hematological dialysis. It is considered the highest priority method today. Hematological dialysis is carried out using a special device, popularly known as an “artificial kidney”. Human blood is passed through the device, removing pathological metabolic products from it. The fear of patients to undergo hematological dialysis is explained by the widespread belief that they are addicted to the “artificial kidney”. This has not been practically confirmed and has no scientific basis for existence. Moreover, in some cases, a person’s life can only be saved by using the device. Hematological dialysis is aimed at restoring the normal state of uremia, and then etiological treatment is carried out to eliminate the primary cause of the pathology.

Causes

Acute uremic syndrome provoked by shock (including severe trauma, burns and frostbite) usually develops:

• as a result of poisoning, infections or disturbances of water-electrolyte, as well as acid-base balance, that is, factors acting largely on the prerenal tier;
• in case of acute interstitial nephritis, pyelonephritis or glomerulonephritis against the background of anuria , poisoning with nephrotropic poisons, as well as obstruction of the main vessels of the kidneys, they speak of a pathology of renal origin;
• due to sudden disturbances in the patency of both or a single upper urinary passage (in patients with one functioning kidney), called postrenal uremia;
• in connection with the renoprivative state.

Whereas chronic uremia usually occurs against the background of glomerulonephritis, pyelonephritis, hereditary nephritis, polycystic kidney disease, diabetes mellitus , prostate adenoma and kidney stones .

Provoking factors for uremia are also:

• tuberculosis;
• poisoning;
• prostate problems;
• gynecological female diseases;
• increased level of sexual activity;
• very sedentary lifestyle;
• congenital forms of nephritis.

Recommendations

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Symptoms of uremia

Symptoms change at different stages of uremia development:

• the first stage begins with a decrease in appetite , asthenia , apathy , there may be complaints of a feeling of thirst or nausea, persistent constant headaches , sleep disturbances (usually in the form of insomnia ) and memory, while the body temperature does not rise above 35.0°C;
• at the next stage, one can observe general lethargy, drowsiness , delirium , hallucinations , convulsions and muscle twitching, developing as a result of poisoning of the structures of the nervous system;
• in the later stages, released toxins (mainly nitrogenous products) reach the gastrointestinal tract and cause continuous vomiting and/or diarrhea , while the tendency to frequent bleeding , hemorrhages and scratching appear on the skin due to skin itching , vision and hearing deteriorate, it is possible notice the smell of ammonia from the patient’s mouth, cough, shortness of breath, his noisy, deep breathing, the so-called Kussmaul , which has uneven pauses, since toxins have reached the respiratory center; sometimes pathological Cheyne-Stokes breathing can occur.

The terminal condition includes symptoms such as:

• decreased blood pressure ;
• the appearance of “uremic frost” on the nose, chin and neck - urea crystals in the form of a whitish precipitate;
• “The death knell of kidney patients” is a kind of noise - friction of the pericardium, which can be detected by listening.

Ultimately, death is preceded by unconsciousness and uremic coma , which depresses the functions of the central nervous system, which is important to distinguish from diabetic and hepatic coma.

The pathological influence of chronic uremia can last for years, occur in latent, azotemic and terminal phases and cause irreversible changes in the kidneys, but at the same time be asymptomatic, practically without provoking serious illness or other symptoms. Patients can feel relatively satisfactory for quite a long time. This occurs due to the compensatory forces of the body and disorders can only be identified through laboratory data.

Tests and diagnostics

To make a diagnosis of uremia, medical history and clinical manifestations are studied, and various laboratory tests are performed:

• general blood and urine tests;
• Rehberg test - to determine the level of creatinine in the urine and bloodstream;
• Zimnitsky test - to assess the ability of the kidneys to dilute urine;
• biochemical blood tests for the level of urea, uric acid, creatinine, detection of elevated electrolyte levels;
• Ultrasound of the kidneys to assess the condition of the cortex and medulla, identify tumors, stones, sclerotic or other pathological changes in the kidneys;
• carrying out excretory (excretory) urography and computed tomography.

Treatment

Treatment is prescribed depending on the disease being diagnosed, as well as symptomatic care. An animal in serious condition must be hospitalized under round-the-clock supervision to ensure rest, intensive therapy, urinary monitoring, and cardiac and respiratory monitoring.

Treatment regimens for various diseases are generally similar. Below are some examples.

Acute renal failure:

1. Restore diuresis. In the absence of this, placing a urethral catheter, or pumping urine out of the bladder with a syringe.
2. Infusion therapy to restore water-salt balance.
3. The use of drugs that restore microcirculation and blood flow in the kidneys, as well as diuretics.
4. Symptomatic treatment.
5. In severe cases of hemodialysis.
6. The prognosis is most often unfavorable.

Chronic renal failure:

1. Infusion therapy.
2. To prevent the occurrence of edema, use diuretics. The use of drugs that improve renal perfusion, when blood pressure increases, calcium channel blockers, ACE inhibitors, antibiotics may be used to prevent the development of infection.
3. Provide food for the animal.
4. At a severe stage, hemodialysis.
5. The prognosis ranges from cautious to unfavorable.

Urolithiasis disease:

1. Depending on the nature of stone formation: conservative or surgical treatment.
2. Conservative treatment: use of antispasmodics, antibiotics, novocaine blockades, pH stabilization, use of specialized feeds, restoration of urine outflow (including through bladder catheterization and lavage).
3. Surgery: removal of stones if conservative treatment is not effective.
4. In the future, proper nutrition and increasing the amount of fluid consumed to prevent the formation of new stones.

Pyelonephritis:

1. Antibiotic therapy, including the use of sulfonamide drugs.
2. Antimicrobial drugs.
3. Infusion therapy and the use of diuretics.
4. If necessary, symptomatic treatment: antispasmodics, antipyretics, painkillers, novocaine blockade.
5. 5. In case of purulent pyelonephritis, corticosteroids are used.

Prevention

The main modern preventive methods to prevent the development of uremia are:

• timely examination of the urinary system and treatment of identified diseases;
• avoiding hypothermia;
• daily adherence to a normal drinking regime (at least 2 liters of clean water, preferably non-carbonated mineral water);
• eliminating factors that damage the kidneys, for example, consumption of alcohol, pesticides, heavy metals, non-narcotic analgesics, etc.;
• elimination of teratogenic factors during pregnancy.

Drug therapy

Treatment of uremia is based on syndromic therapy, not symptomatic, because this disease is a syndrome that includes different symptoms. Treatment can be carried out using hardware or drug therapy.

The drug treatment for uremia involves detoxification and rehydration therapy. Based on the severity of the patient’s condition, a certain amount of drugs is prescribed. In some situations, medication treatment is the patient's only hope. This method is mainly used in the initial stages, when more serious methods cannot be used.

Diet for uremia

Low protein diet

• Efficacy: therapeutic effect after 2 weeks
• Timing: constantly
• Cost of products: 1300-1400 rubles. in Week

Patients suffering from uremia should follow a special diet. Their nutrition should be complete, fully providing the body with all vital nutrients, but with the lowest possible content of protein products. At the same time, it is important to avoid fatty, fried, too peppery and spicy foods, as well as canned foods.

To ensure that the body does not become depleted, but receives the necessary plastic resources, the menu should include:

• wheat bran, soybeans, lentils, peas, beans and other legumes;
• drinking plenty of fluids, especially alkaline ones, to neutralize acidosis;
• reduced amount of salt to reduce the risk of swelling;
• foods rich in vitamin B6 : various nuts and whole grain baked goods;
• It is also important to consume lecithin daily; it is found in buckwheat, lettuce, cabbage, peas and carrots.

Consequences and complications

Acute intoxication and the release of nitrogenous metabolites leads to irritation of the skin, mucous and serous membranes and, as a result, to uremic pneumonia , swelling of the brain and other tissues, gastritis , enterocolitis , laryngotracheitis , stomatitis , tracheitis , pleurisy , pericarditis , heart failure , arrhythmia , anorexia , osteoporosis , osteomalacia , dysfunction of the liver, functional abilities of the bone marrow, which is manifested by immunodeficiency states. thrombocytopenia and anemia develop .

In the chronic course of uremia, glomerular filtration can decrease to 10 ml per minute and lead to complete exhaustion of the body’s ability to adapt to functional disorders of the kidneys. The condition is usually complicated by infections, impaired urodynamics, severe arterial hypertension , circulatory failure and pericarditis .

Death with anuria occurs after 5-7 days from acidosis , hyperkalemia and overhydration . Other causes may be pericarditis , tamponade and cardiac arrest , sepsis , etc.