Amyloidosis and Kidney Damage: Diagnosis

Inspection and physical examination data

The examination data differ 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.

The most severe and diverse clinical picture is characteristic of AL-amyloidosis. The main symptoms of amyloidosis of the kidneys are dyspnea of various degrees, the phenomena 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. Another reason for weight loss is motor diarrhea, which is observed in 25% of patients due to amyloid damage of the intestinal nerve plexuses, less often (4-5%) because of the true syndrome of impaired absorption. When examining patients usually show an increase in the liver and / or spleen. The liver is dense, painless, with a flat edge, often gigantic.

A specific feature that distinguishes AL-amyloidosis from other types is macroglossia and pseudohypertrophy of peripheral muscles. Infiltration of amyloid in the tongue and the sublingual region causes a sharp increase in it. It may not fit in the mouth; the chewing and speech functions are broken, the patients are often ruffled; speech becomes inarticulate. Unlike amyloid macroglossia, an increase in the tongue with hypothyroidism and anemia is due to the swelling of the interstitial tissue and, therefore, is not accompanied by a significant compaction of the tissue of the tongue and does not interfere with its function. Infiltration of amyloid muscle is accompanied by their pseudohypertrophy - enhanced muscular relief with a significant decrease in muscle strength.

Another specific symptom for AL-type amyloidosis is periorbital haemorrhage, usually caused by a cough, straining, which is compared with "raccoon eyes" or hemorrhagic "glasses." Hemorrhages continue to progress, arise with skin friction, 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 main localization of amyloid deposits and their prevalence, sometimes significant, while the clinical picture may resemble the manifestation of AL-amyloidosis.

Laboratory Diagnosis of Kidney Amyloidosis

In a clinical study of blood, a persistent and significant increase in ESR is noted, often already in the early stages of the disease. Anemia is a rare symptom of amyloidosis, which develops mainly in patients with chronic renal insufficiency. Almost half of patients with AA and AL types of amyloidosis have thrombocytosis, which, along with the appearance of erythrocytes with Jolly bodies in the circulation, is considered as a manifestation of functional hypersplenism as a result of amyloid damage to the spleen.

Almost 90% of patients with AL-type of amyloidosis in the blood detect monoclonal immunoglobulin (M-gradient) with conventional electrophoresis; more informative is the use of immunoelectrophoresis with immunofixation. The concentration of M-gradient in patients with primary AL-amyloidosis does not reach the values characteristic of myeloma (> 30 g / l in the blood and 2.5 g / day in the urine). The AL-type amyloidosis is characterized by the presence of the Bene-Jones protein in the urine, the most accurate method of determining which is immunoelectrophoresis with the use of immunofixation. A method has also been developed for the determination of free light chains of immunoglobulins in the blood, which is most suitable not only for highly sensitive diagnosis 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 in order to detect plasma-cell dyscrasia, the causes of this type of amyloidosis, conduct a myelogram study: in primary amyloidosis, the number of plasma cells averages 5%, but in 20% of patients it exceeds 10%; in amyloidosis associated with myeloma, the average number of plasma cells exceeds 15%.

Instrumental diagnosis of amyloidosis of the kidneys

Assumed on the basis of clinical and laboratory data, amyloidosis must be confirmed morphologically by the detection of amyloid in tissue biopsies.

If the AL type of amyloidosis is suspected, a bone marrow puncture and / or trepanobiopsy is performed. Plasma cell counting and amyloid coloring contribute to the differentiation of the primary and myeloma-associated variants of AL-type amyloidosis and, in addition, to the diagnosis of amyloidosis itself. A positive result of bone marrow research on amyloid is noted in 60% of patients with AL-type of amyloidosis.

A simple and safe diagnostic procedure is considered aspiration biopsy of subcutaneous fat, in which amyloid is detected in 80% of cases of AL-type amyloidosis. The advantages of this procedure are, besides informativeness, also the rarity of bleeding development, which allows using this method in patients with disorders of blood clotting (patients with primary amyloidosis often have deficiency of X-factor coagulation, which can develop hemorrhages).

Diagnosis of kidney amyloidosis requires a biopsy of the rectal mucosa, kidney, liver. A biopsy of the mucosa and submucosal layer of the rectum allows detection of amyloid in 70% of patients, and kidney biopsy - in almost 100% of cases. In patients with carpal tunnel syndrome, amyloid is subjected to a tissue removed during decompression.

Biopsy material for the detection of amyloid must be stained Congo red. In light microscopy, the amyloid looks like an amorphous eosinophilic mass of pink or orange, and microscopy in polarized light reveals the apple-green glow of these areas, which is due to the birefringence phenomenon. The coloration of thioflavin T, at which the light green fluorescence is determined, is more sensitive but less specific, and therefore it is recommended to apply both color methods for a more accurate diagnosis of amyloidosis.

Modern morphological diagnosis of amyloidosis involves not only the detection, but also the typing of amyloid, since its type determines therapeutic tactics. For typing, the most commonly used sample is potassium permanganate. When treating stained Congo red preparations with a 5% solution of potassium permanganate, the AA-type amyloid loses color and loses the birefringence property, whereas the AL-type amyloid retains them. The use of alkaline guanidine allows us to differentiate the AA and AL types of amyloidosis by the time of the disappearance of the color of Congo-positive preparations after treatment with alkaline guanidine - for 30 min (AA-type) or 1-2 h (not AA-type). However, the color methods are not sufficiently reliable in establishing the type of amyloid.

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

A valuable method for assessing amyloid deposits in vivo is radioisotope scintigraphy with a labeled ¹³¹ 1 serum beta-component. The method allows to monitor the distribution and volume of amyloid in organs and tissues at all stages of the disease development, including during the treatment. The principle of the method is based on the fact that the labeled serum component of 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 that is visualized on a series of scintigrams. In patients with dialysis amyloidosis, an alternative scintigraphic method is the use of beta ₂ -microglobulin labeled with radioisotopes .