Amyloidosis and kidney damage - Diagnosis

Physical examination and findings

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.

The most severe and varied clinical picture is characteristic of AL amyloidosis. The main symptoms of renal amyloidosis 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 nephrotic syndrome and, to a lesser extent, by circulatory failure. Significant weight loss (9-18 kg) is characteristic due to impaired muscle trophism in patients with peripheral amyloid polyneuropathy. Another reason for weight loss is motor diarrhea, observed in 25% of patients due to amyloid damage to the intestinal nerve plexuses, less often (4-5%) due to true malabsorption syndrome. When examining patients, an enlarged liver and/or spleen is usually detected. The liver is dense, painless, with a smooth edge, often gigantic.

A specific feature that distinguishes AL amyloidosis from other types is macroglossia and pseudohypertrophy of the peripheral muscles. Amyloid infiltration of the tongue and sublingual region causes its sharp increase. It may not fit in the oral cavity; chewing and speech functions are impaired, patients often choke; speech becomes inarticulate. Unlike amyloid macroglossia, tongue enlargement in hypothyroidism and anemia is caused by edema of the interstitial tissue and, therefore, is not accompanied by significant compaction of the tongue tissue and does not impair its function. Amyloid infiltration of muscles is accompanied by their pseudohypertrophy - increased muscle relief with a significant decrease in muscle strength.

Another symptom specific to the AL type of amyloidosis is periorbital hemorrhage, usually provoked by coughing, straining, which is compared to "raccoon eyes" or hemorrhagic "glasses". Hemorrhages further progress, occur with friction of the skin, shaving, palpation of the abdomen, cover significant areas of the body and provoke the formation of trophic disorders on the skin, up to bedsores.

The clinical manifestations of other types of amyloidosis depend on the primary localization of amyloid deposits and their prevalence, sometimes significant, while the clinical picture may resemble the manifestations of AL amyloidosis.

Laboratory diagnostics of renal amyloidosis

Clinical blood tests reveal a persistent and significant increase in ESR, often in the early stages of the disease. Anemia is a rare symptom of amyloidosis, developing primarily in patients with chronic renal failure. Almost half of patients with AA and AL types of amyloidosis have thrombocytosis, which, along with the appearance of erythrocytes with Jolly bodies in circulation, is considered a manifestation of functional hyposplenism as a result of amyloid damage to the spleen.

Almost 90% of patients with AL-type amyloidosis have monoclonal immunoglobulin (M-gradient) detected in the blood using conventional electrophoresis; immunoelectrophoresis with immunofixation is more informative. The concentration of M-gradient in patients with primary AL-amyloidosis does not reach values typical of myeloma disease (>30 g/l in the blood and 2.5 g/day in the urine). AL-type amyloidosis is characterized by the presence of Bene-Jones protein in the urine, the most accurate method for determining which is immunoelectrophoresis using immunofixation. A method has also been developed for determining free light chains of immunoglobulins in the blood, which is most suitable not only for highly sensitive diagnostics of the M-gradient, but also for monitoring the course of the disease and the effectiveness of treatment.

In addition to immunophoretic detection of monoclonal gammopathy, all patients with AL-type amyloidosis undergo a myelogram study in order to detect plasma cell dyscrasia, the cause of this type of amyloidosis: in primary amyloidosis, the number of plasma cells is on average 5%, but in 20% of patients it exceeds 10%; in amyloidosis associated with myeloma disease, the average number of plasma cells exceeds 15%.

Instrumental diagnostics of renal amyloidosis

Amyloidosis, suspected on the basis of clinical and laboratory data, must be confirmed morphologically by detecting amyloid in tissue biopsies.

If AL amyloidosis is suspected, a puncture and/or trephine biopsy of the bone marrow is performed. Plasma cell count and amyloid staining help differentiate primary and myeloma-associated variants of AL amyloidosis and, in addition, diagnose amyloidosis itself. A positive bone marrow amyloid test result is observed in 60% of patients with AL amyloidosis.

A simple and safe diagnostic procedure is considered to be aspiration biopsy of subcutaneous fat, which reveals amyloid in 80% of cases of AL-type amyloidosis. The advantages of this procedure, in addition to its informativeness, also include the rarity of bleeding, which allows this method to be used in patients with blood clotting disorders (patients with primary amyloidosis often have a deficiency of the X-coagulation factor, which can lead to hemorrhages).

Diagnosis of renal amyloidosis requires biopsy of the rectal mucosa, kidney, and liver. Biopsy of the rectal mucosa and submucosal layer allows detecting amyloid in 70% of patients, and kidney biopsy - in almost 100% of cases. In patients with carpal tunnel syndrome, tissue removed during its decompression is tested for amyloid.

Biopsy material for detection of amyloid should be stained with Congo red. With light microscopy, amyloid appears as an amorphous eosinophilic mass of pink or orange color, and with polarized light microscopy, apple-green glow of these areas is detected, which is caused by the phenomenon of double refraction. Staining with thioflavin T, which determines light green fluorescence, is more sensitive, but less specific, and therefore, for more accurate diagnosis of amyloidosis, it is recommended to use both staining methods.

Modern morphological diagnostics of amyloidosis includes not only detection but also typing of amyloid, since its type determines the therapeutic tactics. For typing, a test with potassium permanganate is most often used. When treating Congo red-stained preparations with a 5% solution of potassium permanganate, the AA-type of amyloid loses its color and loses its property of double refraction, while the AL-type of amyloid retains them. The use of alkaline guanidine allows differentiating the AA- and AL-types of amyloidosis by the time of disappearance of the color of Congo red-positive preparations after their treatment with alkaline guanidine - within 30 minutes (AA-type) or 1-2 hours (not AA-type). However, staining methods are not reliable enough in establishing the type of amyloid.

The most effective method for typing amyloid is considered to be immunohistochemical research using antisera to the main types of amyloid protein (specific AT against AA protein, immunoglobulin light chains, transthyretin and beta _2- microglobulin).

A valuable method for assessing amyloid deposits in vivo is radioisotope scintigraphy with ¹³¹ 1-labeled serum beta component. The method allows monitoring the distribution and volume of amyloid in organs and tissues at all stages of disease development, including during treatment. The principle of the method is based on the fact that the labeled serum component P specifically and reversibly binds to all types of amyloid fibrils and is included in the composition of amyloid deposits in an amount proportional to their volume, which is visualized on a series of scintigrams. In patients with dialysis amyloidosis, an alternative scintigraphic method is considered to be the use of radioisotope-labeled beta ₂ -microglobulin.