Amyloidosis and kidney damage

Amyloidosis is a group concept that unites diseases that are characterized by extracellular deposition of a specific insoluble fibrillar protein, amyloid.

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Epidemiology

The prevalence of renal amyloidosis has not been adequately studied to date. In the USA, the incidence of amyloidosis varies from 5.1 to 12.8 cases per 100,000 population per year. These data concern mainly the prevalence of AL amyloidosis, primary or in the context of myeloma disease and other B-hemoblastoses. In the Third World countries, according to PN Hawkins (1995), the mortality rate from AL amyloidosis is 1 per 2000 population (0.05%). The incidence of reactive AA amyloidosis has been better studied in Europe. Thus, according to PN Hawkins et al. (1995), in Europe AA amyloidosis develops in 5% of patients with chronic inflammatory diseases; according to other sources, AA amyloidosis complicates the course of rheumatoid arthritis in 6-10% of cases.

On average, the share of AA-amyloid nephropathy in the structure of kidney diseases in Europe is 2.5-2.8%, and in the structure of diseases that lead to chronic renal failure - 1% (according to the European Dialysis and Transplantation Association). Apparently, the data on the prevalence of various types of amyloidosis obtained in different regions can generally be extrapolated to other areas of the globe, while the impression is formed about the most widespread occurrence of reactive AA-amyloidosis, if we take into account the high frequency of rheumatoid arthritis (0.4-1%).

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Causes amyloidosis and kidney damage.

The term "amyloid" was proposed in 1853 by the German pathologist R. Virchow to designate a substance deposited in the organs of patients with "fatty disease" in tuberculosis, syphilis, leprosy, which he mistakenly considered similar to starch due to the characteristic reaction with iodine. Research in the 20th century showed that the basis of the amyloid substance is protein, and polysaccharides account for no more than 4% of the total mass, but the terms "amyloid" and "amyloidosis" were established, including under the influence of the scientific authority of R. Virchow.

The basis of tissue deposits of amyloid are amyloid fibrils - special protein structures with a diameter of 5-10 nm and a length of up to 800 nm, consisting of 2 or more parallel filaments. Protein subunits of amyloid fibrils are characterized by a specific spatial orientation of the molecule - cross-P-folded conformation. It is this that determines the tinctorial and optical properties inherent in amyloid. The most specific of them is the property of double refraction of the beam during microscopy of preparations stained with Congo red in polarized light, giving an apple-green glow. The detection of this property is the basis for the diagnosis of amyloidosis.

The β-folded configuration of the fibril is associated with the resistance of amyloid to proteolytic enzymes of the intercellular matrix, which causes its significant accumulation with progressive destruction of the affected organ and loss of its function.

Despite the heterogeneity of amyloid fibrils (glycoproteins), among amyloidogenic factors, the leading role is given to the conformational lability of amyloid precursor proteins, specific for each type of amyloidosis, the content of which in the fibril reaches 80%.

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Symptoms amyloidosis and kidney damage.

In clinical practice, the most significant are the AA and AL types of systemic amyloidosis, which involve many organs in the pathological process, but more often manifest with symptoms of single-organ damage. AA and AL types of amyloidosis are observed in men 1.8 times more often than in women. Secondary amyloidosis is characterized by an earlier onset than primary amyloidosis (the average age of patients is about 40 and 65 years, respectively). Symptoms of AL renal amyloidosis are more diverse: in addition to numerous clinical manifestations common to the AA type, there are symptoms characteristic only of the AL type (periorbital purpura, macroglossia and other muscular pseudohypertrophies). On the other hand, individual symptoms of primary renal amyloidosis are also possible with ATTR (polyneuropathy, carpal tunnel syndrome) and Abeta ₂ M amyloidosis (carpal tunnel syndrome).

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Diagnostics amyloidosis and kidney damage.

Diagnosis of renal amyloidosis is very difficult, since examination data vary significantly in patients with different types of amyloidosis.

In secondary AA amyloidosis, 80% of patients seek medical attention during the onset of nephrotic syndrome of varying severity. The main complaint of such patients is edema of varying severity and symptoms of a disease predisposing to amyloidosis - rheumatoid arthritis, osteomyelitis, periodic disease, etc.

A less severe and varied clinical picture is characteristic of AL amyloidosis. The main complaints are dyspnea of varying degrees, orthostatic phenomena, syncopal states caused by a combination of cardiac amyloidosis and orthostatic hypotension; patients usually have edema caused by nephroitic syndrome and, to a lesser extent, circulatory failure. Significant weight loss (9-18 kg) is characteristic due to impaired muscle trophism in patients with peripheral amyloid polyneuropathy.

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Treatment amyloidosis and kidney damage.

According to modern concepts, treatment of renal amyloidosis is a reduction in the amount of precursor proteins (or, if possible, their removal) in order to slow down or stop the progression of the disease. The unfavorable prognosis in the natural course of amyloidosis justifies the use of some aggressive drug regimens or other radical measures (high-dose chemotherapy followed by autologous stem cell transplantation in patients with AL amyloidosis).

The clinical improvement that can be achieved with these types of renal amyloidosis treatment is to stabilize or restore the function of vital organs, as well as to prevent further generalization of the process, which increases the life expectancy of patients. The morphological criterion for the effectiveness of renal amyloidosis treatment is considered to be a decrease in amyloid deposits in tissues, which can currently be assessed using radioisotope scintigraphy with a serum beta component. In addition to the main therapeutic regimens, the treatment of renal amyloidosis should include symptomatic methods aimed at reducing the severity of congestive circulatory failure, arrhythmias, edema syndrome, and correction of arterial hypotension or hypertension.

Forecast

Renal amyloidosis is characterized by a steadily progressive course. The prognosis of renal amyloidosis depends on the type of amyloid, the degree of involvement of various organs, mainly the heart and kidneys, the presence and nature of the predisposing disease.

The prognosis for AL amyloidosis is the most serious. According to the Mayo Clinic, the average life expectancy of patients with this type of amyloidosis is only 13.2 months, 5-year survival is 7%, 10-year survival is only 1%. At the same time, the lowest life expectancy is noted in patients with congestive circulatory failure (6 months) and orthostatic arterial hypotension (8 months). The life expectancy of patients with nephrotic syndrome is on average 16 months.

In the presence of myeloma disease, the prognosis of AL-type amyloidosis worsens, the life expectancy of patients is shortened (5 months). The most common causes of death in patients with AL-type amyloidosis are heart failure and cardiac arrhythmia (48%), uremia (15%), sepsis and infections (8%). Despite the fact that death from uremia is noted much less frequently than from cardiac causes, chronic renal failure of varying severity is recorded in more than 60% of the deceased.

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