What Is Renal Amyloidosis?

Amyloidosis is a rare systemic disease. It was discovered in the early years that this amyloid responds to iodine and is named after starch. In fact, it is mainly insoluble fibrin, but the old name is still used to this day. The ground is used. The etiology of this disease is not completely clear. The renal amyloidosis affected by the whole body is divided into primary, secondary, familial, and hemodialysis-related amyloidosis based on different fibrinogenesis credits. The clinical manifestations of this disease are caused by the precipitation of amyloid in the whole body, and the renal disease caused by the precipitation in the kidney is called renal amyloidosis. The incidence is mainly middle-aged and elderly, with more men than women.

Basic Information

English name

renal amyloidosis

Visiting department

Internal medicine

Multiple groups

Middle-aged and elderly men

Common locations

kidney

Common symptoms

Proteinuria, orthostatic hypotension, edema, weight loss, weakness, fatigue, etc.

Causes of renal amyloidosis

Studies have found that 85% to 95% of all amyloid deposits are fiber components, which are water-soluble and low ionic strength buffers with molecular weights ranging from 4000 to 25,000 Da. So far, more than 20 kinds of precursor proteins of amyloid have been identified. The primary structures of these proteins are different, and they can exist in either dissolved or fiber form. In the form of fibers, X-ray diffraction can see that these amyloid fibers have a common core structure, that is, an anti-parallel sheet-like structure perpendicular to the long axis of amyloid fibers. Amyloid fiber albumin is amorphous and glassy Transparent material, hematoxylin (HE) stained light pink, Congo red stained brick red. Apple-green birefringence was revealed under a polarizing microscope, and many tightly intertwined, unbranched fine fibers were seen under an electron microscope. The fiber has a diameter of 5 to 10 nm and a length of 30 to 100 nm.

Therefore, some scholars believe that amyloidosis is a protein secondary structure disease. The study also found that it is clear that these proteins not only have etiological significance, but also have a direct relationship with clinical manifestations, related diseases, treatment and prognosis. Therefore, it is recommended that clinicians further analyze the chemistry of amyloid deposits after establishing the diagnosis of amyloidosis. composition.

Clinical manifestations of renal amyloidosis

It is a systemic disorder, in addition to kidney involvement, there are other organs involved; due to the different organs involved, the severity and location of the lesion, the clinical manifestations are also different; secondary patients due to different underlying diseases, their Clinical manifestations vary. There are also those whose whole body involvement is not obvious and whose renal involvement is the first manifestation.

Performance of the kidneys

More than three-quarters of patients with amyloidosis have manifestations of kidney disease. Only early glomerular amyloid deposits were seen in the light microscope. Amyloid deposits were widely deposited in the glomerular capillary basement membrane in the late stage. It can be occluded, and the glomerular wastement causes the glomeruli to form unstructured amyloid clumps. Amyloid deposits can also be seen in the tubule basement membrane, renal interstitial and arterioles. HE staining shows light pink masses and Congo red staining shows brick Red clumps. Electron microscopy showed that the bundled amyloid fiber filaments with a diameter of 5-10 nm, no branches, and stiff were arranged randomly. Immunofluorescence was positive for immunoglobulin IgG, IgM, and complement C3. Serum immunofluorescence and immunohistochemical examination showed positive anti-streptide k, anti-light chain protein X or anti-AA antibodies, which has diagnostic and differential diagnostic value. The clinical manifestations of renal involvement are divided into 4 stages.

(1) In the preclinical stage, there are no conscious symptoms and signs, and the test is normal. Only a renal biopsy can make a diagnosis. This period can be as long as 5 to 6 years.

(2) Proteinuria phase Seen in 76% of patients. Proteinuria is the earliest manifestation, and more than half of them are mainly large molecular weight, low-selective proteinuria, with varying degrees. The degree of proteinuria is related to the location and extent of amyloid deposition in the glomerulus, which can manifest as asymptomatic proteinuria, which lasts for several years. Microscopic hematuria and casts are rare. Patients with hypertension account for 20% to 50%. Orthostatic hypotension is a characteristic manifestation of autonomic neuropathy.

(3) Nephrotic Syndrome A large amount of proteinuria, hypoalbuminemia and edema, hyperlipidemia are rare, and a few have only a small amount of long-term proteinuria. Renal venous thrombosis is the most common complication of nephrotic syndrome. Most of them are hidden and manifest as refractory nephrotic syndrome. A few cases are acute onset with abdominal pain, increased hematuria, increased proteinuria, and worsened renal function. B-ultrasound revealed that the kidneys were significantly larger than before. Nephrotic syndrome is caused by 30% to 40% of patients with AA protein, and 35% caused by AL protein. Once the nephrotic syndrome appears, the disease progresses rapidly, and the prognosis is poor. The survival rate of 3 years is less than 10%.

(4) Period of uremia Following nephrotic syndrome, progressive renal dysfunction occurs, and up to half of them have azotemia, and severely die of uremia. Renal tubules and renal interstitial lesions can be involved, the latter manifested as polyuria, and even showed diabetes insipidus. In a few cases, there were electrolyte disorders such as renal diabetes, renal tubular acidosis, and hypokalemia. It can take from 1 to 3 years to progress from nephrotic syndrome to uremia. The degree of glomerular amyloidosis is poorly correlated with renal function.

2. Performance of extra-renal organs

(1) Primary amyloidosis (AL type) is common in weight loss, weakness, and fatigue, and multiple organ involvement is common. The kidney is the most common, with the stomach accounting for 50%; the heart (40%) is invaded, causing myocardial disease, enlarged heart, arrhythmia, and conduction block. In severe cases, sudden death can occur, and 50% die from congestive heart failure and arrhythmia The most common cause of death in patients with idiopathic AL protein type; gastrointestinal mucosa involvement can cause symptoms such as constipation, diarrhea, malabsorption, and intestinal obstruction. Submucosal blood vessel involvement can be accompanied by gastrointestinal bleeding, or even fatal bleeding. Tongue involvement involves giant tongues, the patient's speech is unclear, difficulty swallowing, and the giant tongues hang down when lying on his back, making a loud snoring sound. Symptoms such as gastric cancer during gastric involvement, repeated vomiting and difficulty in eating; autonomic or peripheral nerve involvement (19%) manifested as multiple peripheral neuritis, paresthesia (numbness in gloves or socks-like distribution, numbness), and hypotonia and tendons Hyporeflexia; ulnar nerve damage and peripheral tendon manifested as carpal tunnel syndrome due to amyloid deposits; can cause autonomic dysfunction, manifested as orthostatic hypotension, gastrointestinal dysfunction, bladder dysfunction or impotence. Central nervous system involvement in elderly patients is manifested as dementia; bone marrow involvement can cause compensatory erythrocytosis. Smooth muscle and skeletal muscle involvement is manifested as muscle weakness; joint involvement is manifested as multiple joint swelling and pain, or bone cystic change due to bone involvement; liver damage is 16%, and skin purpura is 5% to 15%.

(2) The symptoms of secondary renal amyloidosis (type AA) kidney disease are often masked by the primary symptoms, and the liver and spleen are also the main affected organs. The liver and spleen are enlarged, and the liver area is severe. Hepatic hypofunction, elevated portal pressure, ascites may occur, and jaundice is rare, and is more common in the late stages of the disease. In addition, the adrenal glands are often involved. The lesions are most severe in the cortex close to the medulla, and the adrenal cortex is enlarged. Tissue necrosis is often caused by adrenal venous thrombosis, and hypofunction is manifested as Addison's disease.

(3) Renal amyloidosis associated with multiple myeloma The main symptom is unbearable bone pain. X-ray films showed bone destruction or fracture. Bone destruction often causes elevated blood calcium, secondary hyperuricemia, abnormally increased serum globulin, and coagulin in urine.

(4) Senile amyloidosis often occurs in the brain, heart, pancreas, aorta, seminal vesicles, and bone and joint tissues. Cellular dysfunction and death of the deposited organs due to amyloid deposition. Vasculitis caused by Congo red stained amyloid fibrous deposition can be seen on the vessel wall of the lesion. Vascular wall involvement is characteristic of senile amyloidosis, so this amyloid protein is thought to originate from the circulatory system. Due to different underlying diseases, the chemical structure of amyloid protein is also different.

(5) Hemodialysis-related amyloidosis The abnormal increase of amyloid (A2-M) in 2 microglobulin multimers in patients with long-term hemodialysis is closely related to the bone and joint complications of patients. The clinical manifestations are as follows: Carpal tunnel syndrome (CTS): Patient has pain, numbness and dyskinesia in one or both hands. The incidence of dialysis less than 5 years was low. The incidence of 9 years of dialysis was 13 times that of 5 years. The incidence of dialysis over 17 years was 100%. A2-M deposits in carpal tunnel tissue, ulnar nerve, and surrounding tendon sheaths; amyloid arthritis: shoulder, hip, knee, wrist, sternocleisure, interphalangeal, ankle, elbow, cervical and lumbar spine joints Can be affected, the former four are most affected. Joint swelling and pain, limited function, and rigidity. X-ray films showed that the joint cavity was narrowed, bone was damaged, and bone damage in the cystic light-transmitting area was seen near the joint. When finger joints are involved, tendon sheath inflammation can cause "trigger fingers" and tendon rupture. Pathological fractures: Cystic bone damage occurs in the femoral head, femoral neck, or acetabulum. Pathological fractures can occur. A2-M extra-bone deposition: rare. A2-M can be deposited in the gastrointestinal tract, heart, liver, spleen, lung, adrenal gland, prostate, testis and other extra-bone tissues. A2-M amyloid deposits can be seen on the wall of the affected site, and the symptoms caused by different deposition sites are also different.

Renal amyloidosis diagnosis

Clinical characteristics

When an unexplained nephrotic syndrome occurs in a man over 50 years of age, renal damage due to primary amyloidosis should be suspected. If there are chronic infections, rheumatoid arthritis, multiple myeloma or other tumors at the same time, it should be highly suspected as secondary amyloidosis and renal damage. If the patient with chronic hemodialysis has osteoarthritis, it should be suspected Amyloidosis due to globulin accumulation.

2. Pathological examination

Renal pathology is the most reliable way to establish a diagnosis. Pathological examinations of other parts (such as rectal, gums, tongue, oral mucosa, skin and tendon biopsy, and abdominal fat aspiration) show amyloid deposits and confirm the diagnosis. Congo red-stained tissue samples are treated with 5% potassium permanganate, and then Congo red staining can be used to identify AL protein and AA protein, that is, to identify primary or secondary amyloidosis. AA protein is sensitive to potassium permanganate and has a small affinity for Congo Red. The coloring test is negative, while AL protein has a high affinity for Congo Red and is positive for the coloring test.

3. After diagnosis of amyloidosis

The clinical cause and laboratory examination should be combined to finally determine the cause, and the difference should be systemic amyloidosis or localized amyloidosis according to the location of amyloid deposition.

4. Differential diagnosis

According to the diameter and arrangement of fibrofilin seen under the electron microscope, it needs to be distinguished from fibroid glomerulopathy, tentacle-like immune glomerulonephropathy, light chain deposition disease and cryoglobulinemia.

Renal amyloidosis treatment

The prognosis of amyloidosis is poor. According to statistics, the average survival time is less than 2 years. There is currently no effective treatment for primary amyloidosis. Commonly used drugs are melphalan, prednisone, chlorambucil, cyclophosphamide, and colchicine. But generally the results are not satisfactory. Recently, it has been reported that bone marrow or stem cell transplantation after treatment with high-dose melphalan has better therapeutic prospects. The treatment of secondary amyloidosis is mainly for the treatment of underlying diseases, and actively controls chronic inflammation and infectious diseases and tumors.

Renal amyloidosis prognosis

End-stage renal failure caused by amyloidosis usually has a shorter survival time than one year. The main cause of death is amyloid heart damage. Heart failure, heart rhythm disorders, and sudden death are the main causes of death. The use of dialysis instead of treatment cannot extend the life of patients.