Amyloidosis and kidney damage

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

[1], [2], [3], [4], [5]

Epidemiology

The prevalence of renal amyloidosis has not been sufficiently 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 relate mainly to the prevalence of AL-amyloidosis, primary or in the context of myeloma and other B-hemoblastoses. In the "third world" countries, according to PN Hawkins (1995), mortality from AL-amyloidosis is 1 per 2000 population (0.05%). The frequency of reactive AA-amyloidosis is better studied in Europe. So, 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 proportion of AA-amyloid nephropathy in the structure of kidney diseases in Europe is 2.5-2.8%, and in the structure of diseases that led to chronic kidney failure, 1% (according to the European Association of Dialysis and Transplantation). Apparently, the data on the prevalence of various variants of amyloidosis obtained in different regions can be extrapolated to other parts of the globe in general, with the impression that the reactive AA-amyloidosis is the most common, given the high incidence of rheumatoid arthritis (0.4 -1%).

[6], [7], [8], [9], [10], [11], [12], [13]

Causes of the amyloidosis and kidney damage

The term "amyloid" was proposed in 1853 by the German pathologist R. Virchow to refer to the substance deposited in the organs of patients with "sebaceous disease" in tuberculosis, syphilis, lepros, which he mistakenly considered similar to starch due to a characteristic reaction with iodine. Studies of the XX 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" are fixed, including under the influence of the scientific authority of R. Virchow.

The basis of tissue deposits of amyloid is 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. The protein subunits of amyloid fibrils are characterized by a peculiar spatial orientation of the molecule-a cross-P-fold conformation. It determines the inherent amyloid tinctorial and optical properties. The most specific of these is the property of double refraction of the beam with microscopy of stained Congo red preparations in polarized light, giving an apple-green glow. The identification of this property is the basis for the diagnosis of amyloidosis.

With the P-fold configuration of the fibril, the stability of amyloid is related 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), the conformational lability of amyloid precursor proteins, specific for each type of amyloidosis, whose content in the fibril reaches 80%, is the leading role among amyloidogenic factors.

[14], [15], [16]

Symptoms of the amyloidosis and kidney damage

In clinical practice, the most important are AA- and AL-types of systemic amyloidosis that occur with the involvement of many organs in the pathological process, but more often manifest symptoms of mono-organ damage. AA and AL types of amyloidosis in men are 1.8 times more frequent than in women. The secondary amyloidosis is characterized by an earlier onset than with the primary (the average age of the diseased is about 40 and 65 years, respectively). Symptoms of amyloidosis of AL kidneys are more diverse: in addition to numerous clinical manifestations common to the AA type, symptoms typical for AL-type (periorbital purpura, macroglossia and other muscle pseudohypertrophies) exist. On the other hand, some symptoms of primary amyloidosis are possible with ATTR (polyneuropathy, carpal tunnel syndrome) and Abeta ₂ M-amyloidosis (carpal tunnel syndrome).

[17], [18], [19]

Diagnostics of the amyloidosis and kidney damage

Diagnosis of kidney amyloidosis is very difficult, as the examination data vary significantly in patients with different types of amyloidosis.

In secondary AA-amyloidosis, 80% of patients consult a doctor during the onset of nephrotic syndrome of varying severity. The main complaint of such patients is swelling of different severity and symptoms of predisposing to amyloidosis disease -  rheumatoid arthritis,  osteomyelitis, periodic illness, etc.

A more severe and diverse clinical picture is characteristic of AL-amyloidosis. The main complaints - dyspnea of varying degrees, the phenomenon of orthostatism, syncopal conditions caused by a combination of amyloidosis of the heart and orthostatic hypotension; usually in patients observed  swelling due to nephrotic syndrome and to a lesser extent - circulatory insufficiency. Characterized by a significant loss of body weight (9-18 kg) due to muscle trophism in patients with peripheral amyloid polyneuropathy.

[20], [21], [22], [23], [24]

Treatment of the amyloidosis and kidney damage

According to modern ideas, the treatment of renal amyloidosis is a reduction in the number of progenitor proteins (or, if possible, their removal) in order to slow or stop the progression of the disease. An unfavorable prognosis for the natural course of amyloidosis justifies the use of some aggressive medicinal 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 of the effectiveness of treatment of amyloidosis of the kidneys is the reduction of amyloid deposits in tissues, which can now be estimated using radioisotope scintigraphy with a serum beta-component. In addition to the main therapeutic regimens, treatment of renal amyloidosis should include symptomatic methods aimed at reducing the severity of congestive circulatory insufficiency, arrhythmias, edematous syndrome, correction of arterial hypotension or hypertension.

Forecast

Amyloidosis of the kidneys is characterized by a steadily progressing course. The prognosis of kidney 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.

With AL-type amyloidosis, the prognosis is most serious. According to the Mayo Clinic, the average life expectancy of patients with this type of amyloidosis is only 13.2 months, a 5-year survival rate of 7%, a 10-year survival rate of only 1%. The lowest life-span was observed in patients with congestive circulatory failure (6 months) and orthostatic arterial hypotension (8 months). The life expectancy of patients with nephrotic syndrome is an average of 16 months.

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

[25], [26], [27], [28]