Amyloidosis of the kidneys - Causes, symptoms and treatment. MF.

Amyloidosis of the kidney is a disease in which the deposition in the kidney tissue of a special insoluble protein - amyloid.

Causes of amyloidosis

Several types of amyloidosis are distinguished depending on the mechanism of the disease development and the structural characteristics of amyloid.

AA-amyloidosis is one of the most common types of kidney amyloidosis. This group includes secondary amyloidosis, the cause of which, as a rule, is rheumatoid arthritis;chronic purulent-destructive diseases, for example, osteomyelitis, tuberculosis;inflammatory bowel disease, such as ulcerative colitis, Crohn's disease;as well as tumors, especially malignant ones. AA-amyloid is formed from a protein that is secreted by the cells of the liver and some cells of the blood during inflammation. In the presence of hereditary failure in the structure of this protein, instead of a normal soluble protein, an insoluble amyloid is produced. In conditions of pronounced or long-term inflammation, the concentration of amyloid in the blood increases, it begins to settle and accumulate in the kidney tissue, causing the disease.

AL-amyloidosis is another type of kidney disease. It is based on primary amyloidosis and / or myeloma. In this case, due to genetic abnormalities of the protein structure under normal conditions( the absence of predisposing factors such as inflammation), a defective insoluble protein is produced which also accumulates in various organs.

ATTR-amyloidosis .A rare group of diseases, which include such pathologies as familial amyloid polyneuropathy and systemic senile amyloidosis. Family amyloid polyneuropathy is a hereditary disease that occurs when amyloid accumulates in the neural tissue and is characterized by severe damage to the nervous system. Systemic senile amyloidosis develops in people older than 70 years due to age-related changes in normal proteins, which become insoluble.

Symptoms of amyloidosis of the kidneys

In amyloidosis, an insoluble protein, usually formed in large amounts, settles in the kidney tissue, causing disruption of its basic functions.

The main clinical sign of both primary and secondary amyloidosis is renal involvement. Very often, kidney disease is asymptomatic and is found in stage III-IV renal failure.

In primary amyloidosis, the disease develops early, at the age of about 40 years, characterized by a progressive course and high lethality. Secondary amyloidosis is diagnosed at the age of about 60 years, during the course of the disease the symptoms of the disease that caused amyloidosis predominate.

There are several consecutive stages of the development of the disease. This division is more typical for secondary amyloidosis.

1. Preclinical .In this stage, the amount of amyloid in the kidneys is not enough to significantly impair their function. Therefore, the signs of the disease - the causes of amyloidosis - are predominant. These can be bone pain and fever in osteomyelitis, changes in the function of the respiratory system in pulmonary tuberculosis, joint damage in rheumatoid arthritis. General urine analysis and instrumental methods of research, such as ultrasound, do not reveal kidney pathology. This stage, depending on the background disease, lasts 3-5 years on average.

2. Proteinuric .Amyloid accumulates in the kidney cells in sufficient quantity, which helps increase their permeability for high molecular substances. As a result, the blood protein appears in the urine, which is determined by its study. The amount of protein in the urine constantly increases with time, since the process of damage to kidney cells is irreversible. At this stage, there are no external manifestations of kidney disease. The protein in the urine is detected accidentally during routine medical examinations or during the diagnosis of other diseases. Proteinuric stage lasts an average of 10-15 years.

3. The nephrotic stage is characterized by pronounced external manifestations, which, in most cases, are due to a low level of protein in the blood due to its massive excretion in the urine. Typical are complaints of significant general weakness, nausea, loss of appetite, thirst, dry mouth. Patients lose weight sharply. With a sharp transition from the prone position to the vertical position, the blood pressure drops sharply, down to the fainting condition. Characteristic persistent diarrhea due to the accumulation of amyloid in the wall of the intestine and the defeat of nerve endings. Appear and develop swelling rapidly. In the beginning, they appear in the lower extremities, on the face, dyspnoea may appear during normal physical activity( associated with the accumulation of fluid in the lung tissue).Then edema takes on a widespread character, up to accumulation of large volumes of fluid in the pleural cavity( hydrothorax), in the abdominal cavity( ascites), in the cavity of the outer shell of the heart( hydropericardium).

Appearance of a patient with nephrotic syndrome.

A sharp decrease in the amount of urine until it is absent. Along with edema, enlarged lymph nodes, a liver, a spleen are revealed, which indicates the deposition of amyloid in them. At the same time these organs are dense, painless, often, especially the liver, reach huge sizes.

4. The uremic stage of is the final of the disease. The kidney wrinkles, loses its normal structure and ability to perform all its functions. At this stage, renal insufficiency of the fourth degree or chronic renal disease of stage V is diagnosed. Against the background of pronounced edema, there are symptoms of uremic( due to metabolic products, which are normally excreted in the urine) intoxication. Nausea, vomiting, not bringing relief, general weakness, abdominal pain, possibly a fever of 37-37.5 degrees. Urine, as a rule, is absent. Often reduced pressure and a rare pulse of weak filling. At this stage, to remove toxic products of metabolism, substitution renal therapy( peritoneal dialysis, hemodialysis and its variants) is shown.

Hemodialysis session.

But, unfortunately, at the present stage there are no methods that allow to completely remove amyloid from the body. Therefore, even in conditions of dialysis sessions, mortality in such patients remains high due to the defeat of other organs( heart, vessels, liver, pancreas and others).

In the description of amyloidosis, we can not fail to mention the defeat of the heart, which begins at the same time, and sometimes even earlier than kidney disease. Amyloid accumulates in the heart tissue, cause the development of heart failure. At the same time, the heart grows in size, its wall becomes rigid, the valves are affected. As a result, the heart can not cope with the usual load, the blood stagnates in the lungs or on the periphery, which aggravates swelling and respiratory failure. In addition, arrhythmias often develop in the enlarged heart due to disturbance of nervous regulation, many of which are potentially fatal. Also, due to heart and vascular lesions, the pressure at the beginning of the disease is elevated, and with the lack of effect from drugs, in the final stage, steadily lowered.

Diagnosis of amyloidosis

In laboratory tests, the following changes are identified:

• General blood analysis .A persistent and significant increase in ESR( erythrocyte sedimentation rate) is already in the early stages of the disease. With the development of renal failure, a decrease in hemoglobin and the number of erythrocytes is observed. An increase in the number of platelets indicates the involvement of the spleen in the pathological process.
• Biochemical blood test .In the nephrotic stage of the disease, attention is drawn to the decrease in the amount of protein, including albumin, an increased content of cholesterol and low-density lipoproteins. Using the method of electrophoresis, it is possible to extract a defective insoluble protein from the blood.
• Urinalysis .Beginning with the proteinuric stage, a large amount of protein is characteristic. The method of immunoelectrophoresis can detect the Bans-Jones protein, which is typical for AL-amyloidosis in myeloma.

To confirm the diagnosis, a biopsy( sampling of the site of the altered tissue for the purpose of microscopic examination) is necessary. If suspected of AL-amyloidosis, a bone marrow biopsy is performed from the sternum( sternal puncture) or iliac bone( trepanobiopsy).In all cases, a biopsy of the rectal mucosa, a portion of the intestinal wall or kidney tissue, or a liver is indicated. In the study, amyloid typing is possible, which determines further therapeutic tactics.

Treatment of amyloidosis

The goal of amyloidosis therapy is to reduce the formation of pathological protein and protect the organs from its effects.

In AA-amyloidosis, the main role belongs to anti-inflammatory measures, including surgical methods. So, with osteomyelitis, it is necessary to remove the areas of purulent melting of the bone, with an abscess( a cavity filled with pus) of the lung - drainage of the abscess. Especially important is the timely treatment of rheumatoid arthritis as one of the main causes of the disease.

In the presence of amyloidosis of the kidneys, treatment with cytostatics( methotrexate, cyclophosphamide) is indicated, which allows delaying the onset and slowing the progression of renal failure. The greatest effect in all forms of amyloidosis was observed in some plant cytostatics( colchicine).

With AL-amyloidosis combined therapy with cytostatics and hormonal drugs( prednisolone) is used.

In secondary amyloidosis, the treatment of the underlying disease is carried out first, after which the symptoms of amyloidosis often disappear. There is also symptomatic therapy: multivitamins( parenteral), diuretic drugs( with pronounced swelling), plasma transfusion. With diarrhea, astringents are prescribed( bismuth nitrate, adsorbents).

In the final of the disease, it is vital to conduct dialysis sessions. But nevertheless, the main method of treating the nephrotic and uremic stage of the disease is a kidney transplant.

In renal amyloidosis, the general regimen is the same as for chronic glomerulonephritis.

Prevention of amyloidosis

Prophylaxis should be aimed at treating diseases accompanied by chronic inflammation, as well as timely diagnosis and competent treatment of amyloidosis, taking into account its type.

Doctor therapist, nephrologist Sirotkina EV