Pediatric renal amyloidosis

　　I. Etiology

　　The etiology of this condition is not yet clear. Some reports suggest that it is related to immune mechanisms, that is, secondary cases may be related to allergic reactions, and primary cases have a family history of the disease, which is an autosomal dominant or recessive genetic disease. This condition is divided into several categories according to the presence or absence of primary disease or the site of amyloid deposition:

　　1. Primary amyloidosis mainly affects the following organs in order: heart, digestive tract, tongue, spleen, liver, kidney, lung.

　　2. Secondary amyloidosis often occurs secondary to various chronic infectious diseases, connective tissue diseases, and metabolic diseases (diabetes), mainly affecting the following organs in order: kidney, spleen, adrenal glands, liver, lymph nodes, pancreas, etc.

　　3. Amyloidosis due to familial genetic reasons occurs due to amyloidosis, the most common being familial Mediterranean fever (familial Mediterranean fever).

　　4. Localized amyloidosis Amyloid substances are locally deposited in the nasopharynx, lower respiratory tract, skin, and other parts. This section mainly discusses renal amyloidosis.

　　Secondly, pathogenesis

　　1. Amyloid fibrin protein Amyloid fibrin is an amorphous glassy transparent substance, stained light pink by hematoxylin, and red brick by Congo red. Under polarized microscopy, it exhibits apple green birefringence. Under an electron microscope, it can be seen that it is composed of non-branching small fibers, the most common feature of which is β-pleated-sheet formation (β-pleated-sheet formation) as shown by X-ray diffraction. Amyloid fibrin protein includes the following 8 components, with AL protein and AA protein as the main components.

　　(1) AL protein (amyloid protein, light chain derived): Derived from immunoglobulin light chain fragments, found in more than 50% of primary amyloidosis and 75% of multiple myeloma patients. Serum protein electrophoresis shows a monospecific globulin peak, mainly γ-type, with a few κ-type. AL protein has a molecular weight of 5,000 to 23,000 D and can be excreted in urine. Bence-Jones protein belongs to this type.

　　(2) AA protein (amyloid protein A): Unrelated to immunoglobulins, its precursor is serum amyloid protein A (serum amyloid protein A, SAA), found in secondary amyloidosis and familial Mediterranean fever. AA protein has the same N-terminal amino acid residues as SAA protein but a different molecular weight, with a molecular weight of 4,500 to 9,200 D for the former and 12,500 D for the latter. SAA protein is synthesized in the liver and has a low content in the blood. During an inflammatory episode, the concentration of SAA protein and C-reactive protein produced by the liver simultaneously increases. The production of SAA protein may be related to interleukin-1 produced by activated monocytes and macrophages.

　　(3) AF protein (amyloid familial protein): Genetic familial amyloidosis associated with neuropathy, the amyloid protein contains proalbumin components, and this proalbumin has a high affinity for peripheral nerves.

　　(4) ASC protein (amyloid senile cardiac protein): Contains proalbumin components and is found in patients with familial senile amyloidosis associated with cardiac lesions.

　　(5) AE protein (endocrine-related amyloid protein): This protein component is found in endocrine diseases, such as medullary thyroid cancer.

　　(6) Aβ2-微球蛋白 (amyloid-β2-microglobulin, Aβ2-M): Commonly found in patients undergoing long-term hemodialysis, it tends to deposit in the tendons near the ulnar nerve and wrist joint, causing carpal tunnel syndrome. This amyloid protein has a molecular weight of about 12,000 D and has a similar structure to β2-microglobulin. It is rarely deposited in the liver, heart, or spleen.

　　(7) SAP protein (serum amyloid P component): The sequence of amino acid residues in SAP protein is similar to that of C-reactive protein. The concentration of SAP in the blood does not increase during inflammation, which is different from SAA protein.

　　(8) Mixed-type amyloid protein: In the blood of some patients with amyloidosis, several types of the aforementioned different types of amyloid proteins coexist.

　　2. Pathogenesis

　　(1) Excessive production of protein: Amyloidosis may be related to abnormal immune function of the body, abnormal protein metabolism, and denaturation and decomposition of connective tissue, but it is now believed to be caused by the deposition of a group of proteins. This group of proteins has common characteristics, and the excessive production of these proteins helps their deposition, especially in patients with AL-type amyloidosis complicated with multiple myeloma.

　　(2) Secondary amyloidosis: In secondary amyloidosis and familial Mediterranean fever, some serum AA apolipoprotein synthesized during the acute phase can serve as AA amyloid substance deposition; in amyloidosis caused by β2-M, the serum level of β2-M increases due to overproduction or secretion or reduced degradation, but the deposition is not related to serum levels. However, some articles believe that the increased serum level of β2-M is sufficient to accumulate in tissues and cause amyloidosis. The possible pathogenesis of Aβ2-M deposition in long-term hemodialysis patients is as follows:

　　① Patients with uremic hemodialysis: Patients with uremic hemodialysis have lost renal function, and the filtration of β2-M by the glomerulus decreases, leading to an increase in blood β2-M accumulation. Long-term use of general dialyzers for hemodialysis, due to the minimal clearance of β2-M by copper phthalocyanine membrane and cellulose membrane, if PAN membrane, polysulfone membrane, or methylcellulose membrane dialyzers are used, due to the increased convective clearance of Aβ2-M, and increased adsorption of β2-M on the membrane surface, it can increase the clearance of Aβ2-M, and reduce the level of β2-M in the blood.

　　② Endotoxin contamination in dialysis fluid and the effect of dialysis membrane: It can activate mononuclear macrophages and lymphocytes, leading to an increase in cytokines such as interleukin-1 (IL-1), tumor necrosis factor (TNF), and transforming growth factor (TGF), which are released into bone matrix and cartilage, promoting the deposition of Aβ2-M in bone and causing disease. Their bone resorption-promoting effect is greater than that of parathyroid hormone.

　　(3) Changes in molecular biochemical characteristics: In some amyloid proteins, especially ASC protein or AE protein, due to the substitution of a single amino acid, the deposited protein is different from the normal similar protein, and it is believed that the deposition may be directly related to changes in molecular biochemical characteristics caused by changes in peptide sequence. In AL-type amyloidosis, the deposited light chain is often a hydrolysis fragment of the original light chain, and occasionally the original light chain.

　　(4) Mutation and degradation of amyloid deposition media: Due to partial mutation and degradation of possible media for amyloid deposition, the proteins involved in β2-M deposition are more acidic and have more advanced glycosylation characteristics than normal β2-M. Glycosylated β2-M can cause a transient increase in TNF-α, IL-1, and monocyte chemotaxis.

　　(5) Deposited together with amino polysaccharides and SAP protein: Indeed, all amyloid proteins often deposit together with amino polysaccharides and amyloid P substance (i.e., SAP protein), and the molecular mechanism of amyloid protein deposition is still under study.

　　Can complicate hypertension, orthostatic hypotension, hypoalbuminemia, polyuria, renal glycosuria, metabolic acidosis, hypokalemia, infection, etc. In the late stage, uremia may occur, and damage to various systems may occur, leading to heart failure, secondary vascular thrombotic complications, hemorrhage and thrombosis, etc.

　　First, the manifestation of the kidney

　　1. Preclinical stage:There are no自觉 symptoms or signs, and the test results are also normal. Only renal biopsy can make the diagnosis. This stage can last for 5 to 6 years.

　　2. Proteinuria stage:Seen in 76% of patients, proteinuria is the earliest manifestation. Before the appearance of proteinuria, amyloid substances can be detected in tissues. More than half of the patients mainly have high molecular weight, low selective proteinuria, of varying degrees. Urinary protein is almost all albumin, serum globulin increases, urinary globulin increases, and often Benign protein. The 24-hour urinary protein excretion can reach 20 to 30g, and the degree of glomerular damage is not related to the amount of proteinuria. Even a small amount of amyloid deposition in the glomeruli can lead to proteinuria when renal function is highly impaired. Therefore, the incidence of nephrotic syndrome is also high, which can manifest as asymptomatic proteinuria lasting for several years, microscopic hematuria and cellular casts are rare. The latest statistics show that 20% to 50% are accompanied by hypertension, and orthostatic hypotension is a characteristic manifestation of autonomic neuropathy.

　　3. Nephrotic syndrome stage:Large amounts of proteinuria, hypoalbuminemia, and edema, hyperlipidemia is less common, a few cases have only long-term small amounts of proteinuria, renal vein thrombosis is the most common complication of nephrotic syndrome, most of which have an insidious onset, presenting with refractory nephrotic syndrome, a few cases have an acute onset, with abdominal pain, worsening hematuria, increased proteinuria, and deterioration of renal function. Abdominal X-ray or B-ultrasound examination shows that the kidneys are significantly larger than before. Nephrotic syndrome caused by AA protein accounts for 30% to 40%, and AL protein accounts for 35%. Once nephrotic syndrome appears, the condition progresses rapidly, the prognosis is poor, and the survival rate of 3 years is not more than 10%. Patients often die early due to weakness and chronic infection.

　　4. Uremic stage:After nephrotic syndrome, progressive renal function decline occurs, up to half of the patients have azotemia, severe cases die of uremia, the renal tubules and interstitium may be involved occasionally, the latter is manifested as polyuria, even presenting with diabetes insipidus, a few cases have renal glycosuria, tubular acidosis and hypokalemia and other electrolyte disorders. The development from nephrotic syndrome to uremia requires 1 to 3 years, and the degree of amyloid deposition in the glomeruli is poorly correlated with renal function.

　　II. The manifestations of each type are as follows.

　　1. Primary amyloidosis disease:The male-to-female ratio is 5:2, the median age of onset in males is 63 years, and in females is 59 years. It is rare before the age of 40, and common symptoms include weight loss, weakness, and fatigue. Multiple organ involvement is common.

　　(1) Kidney involvement: It is the most common, accounting for 50%.

　　(2) Heart involvement: It commonly invades the heart (40%), causing myocardial lesions, cardiac enlargement, arrhythmias, and conduction block, which can lead to sudden death. 50% die from congestive heart failure and arrhythmias, which is the most common cause of death in primary AL protein type patients.

　　(3) Gastrointestinal involvement: It is common, and involvement of the gastrointestinal mucosa can cause constipation, diarrhea, malabsorption, and intestinal obstruction. Involvement of submucosal blood vessels may be accompanied by gastrointestinal bleeding, even massive bleeding leading to death. Involvement of the tongue may cause macroglossia, with the patient speaking unclearly and having difficulty swallowing. When lying on the back, the macroglossia may hang down and produce a loud snoring sound. Involvement of the stomach may present symptoms similar to gastric cancer, with repeated vomiting making it difficult to eat.

　　(4) Autonomic or peripheral nerve involvement (19%): It presents as multiple peripheral neuritis, paresthesia of the extremities, hypotonia, and decreased tendon reflexes; damage to the ulnar nerve and surrounding tendons due to amyloid deposition may present as carpal tunnel syndrome. It can lead to autonomic dysfunction, manifesting as orthostatic hypotension, gastrointestinal dysfunction, bladder dysfunction, or impotence, and in elderly patients, central nervous system involvement may present as dementia.

　　(5) Bone marrow involvement: It can cause compensatory erythrocytosis.

　　(6) Joint involvement: It presents as multiple joint swelling and pain, or as bone cystic changes due to bone involvement.

　　(7) Others: Liver damage is 16%, purpura of the skin is 5% to 15%, and smooth muscle and skeletal muscle involvement may present as muscle weakness.

　　2. Secondary renal amyloidosis disease:The symptoms of kidney disease are often masked by primary disease symptoms, and the liver and spleen are also major organs affected. The liver and spleen are often enlarged, with liver pain, and in severe cases, liver function may decrease, portal hypertension may increase, ascites may occur, jaundice is rare and often seen in the late stage of the disease. In addition, the adrenal glands are often affected, with the lesion being most severe in the cortical layer close to the medulla. The adrenal cortex may become enlarged, often leading to tissue necrosis and decreased function due to adrenal vein thrombosis, manifesting as Addison's disease.

　　3. Hereditary familial amyloidosis disease:Hereditary familial amyloidosis syndrome is rare, including various diseases, common ones are Familial Mediterranean Fever (FMF), which is an autosomal recessive genetic disease. Glomerular amyloidosis is commonly characterized by proteinuria (often nephrotic syndrome) and progressive renal insufficiency. It often presents with recurrent urticaria and deafness symptoms. Others include Finnish Amyloidosis, etc. Hereditary familial amyloidosis can be divided into nephrotic, neuropathic, and mixed types.

　　4. Localized amyloidosis disease:Localized amyloidosis is a disease in which amyloid lesions are only seen in individual organs or tissues, such as the brain, cardiovascular system, skin, and urinary tract. The first two are more common in elderly patients.

　　3. Amyloid substances

　　Deposition of amyloid substances in sympathetic ganglia and adrenal glands can cause orthostatic hypotension, deposition in the proximal renal tubules can cause Fanconi syndrome, deposition in the distal renal tubules can cause hyperkalemic tubular acidosis, and deposition in the medulla can cause nephrogenic diabetes insipidus. A complete diagnosis includes: the定性 of amyloidosis, the primary disease, the type of amyloid substance, the extent of involvement of important organs, and complications.

　　There are currently no effective preventive measures, as secondary cases are often seen in chronic infectious diseases, rheumatism, and other conditions. Effective prevention of these diseases can undoubtedly reduce the incidence of this condition. Unger et al. have suggested that androgen antagonists may become a stimulating factor for spermatocutaneous cells, triggering local occurrence of AL-type amyloidosis, which deserves clinical attention.

　　1. Blood examination:Blood biochemical examination shows increased fibrinogen, which can cause renal venous thrombosis. Increased urinary protein can also lead to renal insufficiency. Approximately 30% of renal venous thrombosis is caused by this condition. The presence of Howell-Jolly bodies in peripheral blood suggests involvement of the spleen.

　　2. Protein electrophoresis examination:In 2/3 of patients, monomeric abnormal proteins can be found in serum electrophoresis or immunoelectrophoresis, while the positive rate of urine tests can be increased to 86%. Immunoelectrophoresis and immunofixation are sometimes used to measure trace proteins in blood or urine. In serum protein electrophoresis, the gamma globulin is normal, while the M protein (monoclonal immunoglobulin) in primary amyloidosis is elevated. The measurement of immunoglobulin concentration is helpful in the classification and diagnosis of multiple myeloma. Patients with urine containing Bence-Jones protein can react with antiserum against κ and γ chains but not with any type of immunoglobulin heavy chain.

　　3. Elevated levels of SAA protein in the blood:The determination of the level of SAA protein in the blood, where AA protein evolves from its precursor SAA protein, indicates secondary amyloidosis caused by AA protein when the concentration of SAA in the blood increases. In rheumatoid arthritis, ulcerative colitis, tuberculosis, tumors, and during the acute phase of chronic infections, SAA levels are elevated and accompanied by increased C-reactive protein levels. Therefore, the level of SAA can be used to distinguish whether an infection is in the active phase, with SAA levels greater than 0.2 μg/ml seen in active inflammation. After infection control, the level of SAA decreases. In long-term dialysis patients with bone disease, abnormally elevated levels of β2M in the blood can help diagnose bone disease associated with amyloidosis.

　　4. Congo red test:As an auxiliary diagnostic test, amyloid protein has an affinity for Congo red. After injecting a certain amount of Congo red, the absorption rate of normal people is 10% in 1 hour, the absorption rate of glomerulonephritis is 20% in 1 hour, and the absorption rate in nephropathy is 40%. In renal amyloidosis, the absorption rate is 30% in 20 minutes. If the absorption rate is greater than 60% in 1 hour, it is considered positive. This method has little significance for the diagnosis of early primary amyloidosis, as the amyloid substance deposition in the early affected organs is less, and the absorption of Congo red is less, so it is often negative. In addition, when the serum albumin level is low in liver disease, it affects the absorption rate; for those with large amounts of proteinuria, the amount of Congo red absorbed in the urine should be excluded when calculating the absorption rate. This method is less reliable and is now rarely used.

　　5. Amyloid protein amino acid sequence analysis:The amino acid composition and residue sequence of amyloid protein help to distinguish between AL protein and AA protein.

　　6. Pathological examination:Pathological examination is the most reliable method for diagnosis, and visceral puncture biopsy greatly improves the diagnostic rate before death. In cases with marked proteinuria, the positive rate of kidney biopsy is close to 100%, and kidney biopsy is prone to bleeding, but less severe than liver biopsy. Therefore, it is currently considered more advisable to perform kidney biopsy than liver biopsy, and it has become the main method for diagnosing renal amyloidosis. The positive rate of liver biopsy is low, only 50%, and there is a risk of massive hemorrhage, so it should be done with caution. The positive rate of bone marrow biopsy is about 50%, and the collection of rectal mucosal biopsy should be deep, including the固有层 of the mucosa, with a positive rate of 73%. In AL or AA-type amyloidosis, the aspirated abdominal wall fat may also show amyloid protein deposition, with a diagnostic positive rate of 70% to 80%. Other possible tissue examination sites include the gums, skin (low sensitivity), gastric mucosa, and small intestine. Endoscopic brushing cytology and biopsy can improve the positive rate of gastric examination. The synovial tissue excised after the carpal tunnel is relaxed is definitely positive, but these tissues are usually not used for diagnostic evaluation. After the biopsy specimens are treated with 5% potassium permanganate, Congo red staining is performed. AA protein is sensitive to potassium permanganate and has a small affinity for Congo red, resulting in a negative staining test, while AL protein has a large affinity for Congo red, resulting in a positive staining test. Therefore, this method can be used to distinguish whether the lesion is caused by AA protein or AL protein, which is helpful in distinguishing primary from secondary amyloidosis. Bone biopsy is the best method for early diagnosis of Aβ2-M deposition in bone. Potassium permanganate-Congo red staining is positive, while staining is negative in AA or AF amyloid proteins, which is helpful for differential diagnosis. If amyloid fibers with irregularly curved arrangements and a diameter of 8-10 nm are seen under an electron microscope, a definitive diagnosis can be made.

　　The etiology of pediatric renal amyloidosis is unknown, and there are no special dietary requirements in general. It is recommended that children pay attention to eating more nutritious food and supplementing the nutrients lacking in their bodies.

　　First, treatment

　　1. Treatment of AL-type renal amyloidosis: The original treatment principle was mainly symptomatic, but current research focuses on inhibiting or removing abnormal immunoglobulins to achieve the purpose of inhibiting amyloid fibril formation. Since AL protein is produced by plasma cells, immunosuppressants are currently mainly used. It is generally believed that cyclophosphamide, benzyl mustard, and melphalan are effective in alleviating myeloma and can prolong life. Monotherapy with adrenal cortical hormones not only has no significant effect but can also worsen kidney damage. Some advocate the use of penicillamine, colchicine, dimethyl sulfoxide, and melphalan (levophenylalanine mustard), and the exact efficacy awaits further study. In recent years, there has been more research on hormones, melphalan, and colchicine.

　　(1) Methylprednisolone pulse therapy combined with alpha-interferon treatment: Dhodapkar et al. treated 9 patients with primary amyloidosis using methylprednisolone pulse therapy combined with alpha-interferon treatment. The method is to take one course every 35 days, during which from the 1st to the 4th day, 9th to 12th day, and 17th to 20th day, methylprednisolone 40mg/d is administered, and alpha-interferon (3-6) × 10^6 U/d is given after 3-6 courses, with medication given 3 times a week. Among them, 3 patients still received methylprednisolone 40mg/d every 4-8 weeks in the first year of maintaining treatment with alpha-interferon. The results showed that in 9 patients, 8 patients had significant improvement in organ function; in 7 patients with nephrotic syndrome, 6 patients had a reduction of more than 50% in urinary protein excretion within 3-9 months (average 4 months); 2 patients with heart failure showed no significant improvement. They believe that the characteristic of this therapy is that it has no bone marrow suppression while achieving good efficacy.

　　Skinner et al. conducted a controlled study on 100 patients with idiopathic amyloidosis. The patients were divided into a melphalan + prednisone + colchicine combination therapy group and a colchicine monotherapy group according to stratified sampling principles. The results showed that the total average survival time of 100 patients was 8.4 months, with 12.2 months for the combination therapy group and 6.7 months for the monotherapy group (P=0.087). The combination therapy was more effective for patients without heart and kidney damage as the main manifestation. Kvle et al. divided 220 patients with amyloidosis (including AL-type and AA-type) into colchicine group (Group I, 72 cases), melphalan + prednisone group (Group II, 77 cases), and melphalan + prednisone + colchicine group (Group III, 71 cases). The average survival period was 8.5 months for Group I, 18 months for Group II, and 17 months for Group III, with significant differences between the latter two groups and Group I (P<0.001). For those whose serum and urine monoclonal proteins decreased at the 12th month, the average survival period reached 50 months, while for those without decrease, it was only 36 months (P=0.03). This study suggests that the combination of melphalan + colchicine and melphalan + prednisone + colchicine can significantly improve efficacy.

　　Comenzo et al. conducted a clinical study on 5 patients with AL-type amyloidosis, combining high-dose melphalan intravenous therapy (a single dose of 70-120mg/m2) with stem cell support therapy (infusion of autologous growth factor-activated bone marrow stem cells). After 12-17 months of follow-up, all 5 patients were in good general condition, with clinical manifestations of involved organs缓解. One patient with nephrotic syndrome showed a 50% reduction in urine protein, with no significant change in serum creatinine concentration; one patient with myocardial lesions experienced improvement in heart symptoms, with a decrease in the thickness of the inferior wall and interventricular septum; patients with multiple neurological lesions, gastric dilation, and liver enlargement all showed objective improvement after treatment. After 12 months of treatment, 3 patients had negative blood tests for malignant plasma cells. They believe that intravenous high-dose melphalan therapy combined with stem cell support therapy is safe and effective, which can lead to complete remission in some patients, and can simultaneously improve the function of involved organs and organic lesions. Their series of research results also suggest that intensive chemotherapy and bone marrow transplantation for AL-type amyloidosis can lead to complete remission in many patients, significantly extending survival time. The use of bone marrow growth factors (myeloid growth factors) or mobilized blood stem cells can reduce the mortality rate of patients.

　　The treatment of non-AL type renal amyloidosis. Treatment of primary diseases such as tuberculosis and chronic infection for renal amyloidosis caused by amyloid proteins other than AL type can often improve clinical symptoms. In recent years, there have been scattered reports on the treatment of renal amyloidosis in patients with inflammatory bowel disease. Kullmann et al. reported a case of a 54-year-old Crohn's disease patient with nephrotic syndrome as the initial symptom. Immunosuppressive therapy with azathioprine not only worsened renal function but also did not reduce urinary protein. Then, renal hypertension occurred. Menges et al. reported a 20-year-old ulcerative colitis patient who developed secondary renal amyloidosis, manifested as nephrotic syndrome and general edema. On the basis of routine ulcerative colitis treatment, the use of low-dose colchicine reduced urinary protein from 10g/d to about 3g/d, and general edema was completely eliminated.

　　The treatment of rapidly progressive glomerulonephritis caused by renal amyloidosis is similar to that of primary glomerular diseases, such as rapidly progressive glomerulonephritis. Early diagnosis and timely treatment are crucial. The main treatment measures include hormone shock therapy, immunosuppressive agent shock therapy, and plasma exchange. Watanabe et al. reported a case of a 47-year-old female patient with rheumatoid arthritis for 20 years who developed renal amyloidosis, manifested as nephrotic syndrome and rapidly progressive glomerulonephritis. The serum amyloid A protein concentration was 83.9 mg/ml, with positive anti-nuclear antibodies, but negative for anti-leukocyte cytoplasmic antibodies, circulating immune complexes, and anti-glomerular basement membrane antibodies. Renal tissue examination showed severe necrotic crescentic glomerulonephritis with AA-type amyloid fiber deposition. During dialysis treatment, corticosteroid shock therapy was administered, and plasma exchange was performed frequently, resulting in a rapid improvement in clinical symptoms. The reporter believes that plasma exchange therapy for this patient not only helps to clear autoantibodies but also helps to clear cytokines involved in vasculitis and glomerular inflammation. Corticosteroids can inhibit the infiltration of cells to produce inflammatory cytokines. Moroni et al. reported 3 cases of amyloidosis patients who developed rapidly progressive glomerulonephritis during the course of the disease. Pathological examination found a large number of crescent formation in the kidneys overlapping with renal amyloidosis. On the basis of methylprednisolone shock therapy, immunosuppressants and oral corticosteroid preparations were given, and partial renal function recovery was achieved in 2 patients; another patient stopped hormone treatment within a few days after the onset of purulent infection in bones and joints, and renal function continued to deteriorate, finally undergoing hemodialysis treatment. They believe that on the basis of renal amyloidosis, it is possible to overlap with extracapillary glomerulonephritis. Early diagnosis and timely treatment for such patients can still achieve a certain degree of clinical remission.

　　4. Treatment of hemorrhage and thrombosis associated with amyloidosis and thrombosis In some AL-type amyloidosis patients, hemorrhagic tendency may occur, which is related to the deposition and destruction of amyloid substances in the vascular wall, decreased coagulation function [secondary reduction in coagulation factor X, increased circulating heparin-like anticoagulants (circulating heparin-like anticoagulants)], and hyperfibrinolysis. The secondary reduction in coagulation factor X may be due to the nonspecific adsorption of the factor by the deposited amyloid fibers in the tissue. Plasma transfusion can temporarily relieve the coagulation function of patients with idiopathic amyloidosis, but the maintenance time is short. Recently, studies by Beardell et al. suggest that plasma exchange can effectively and persistently improve the coagulation function of patients with secondary coagulation factor X reduction due to amyloidosis. Anticoagulant treatment is effective when secondary vascular thrombotic complications occur due to amyloidosis.

　　5. Symptomatic treatment

　　(1) Nephrotic syndrome: When presenting with nephrotic syndrome, diuretics and high-protein diet can be administered.

　　(2) Renal vein thrombosis: When complicated with renal vein thrombosis, it is necessary to avoid a decrease in blood volume and dehydration. The efficacy of adrenal cortical hormones needs to be proven, and their side effects and complications also need to be considered. However, as the treatment for the primary disease of this condition, treatment before renal transplantation and in the presence of adrenal cortical insufficiency should still be given. When renal insufficiency occurs, treatment should be carried out according to the general treatment for renal insufficiency.

　　(3) Renal failure: Hemodialysis and renal transplantation can be performed in cases of renal failure, and this method can be considered for patients with renal insufficiency, which can improve the survival rate of patients. The primary disease or amyloidogenic factors are not removed, and the transplanted kidney can also develop amyloidosis. For patients with chronic renal failure undergoing maintenance hemodialysis, the clearance rate of blood β2-microglobulin is low, and long-term hyperβ2-microglobulinemia can lead to complications such as amyloidosis associated with hemodialysis. The use of high-hemocompatibility high-flux dialysis has a higher clearance and adsorption rate of β2-microglobulin than conventional hemodialysis.

　　6. Special therapy: Colchicine can be used for long-term (2-3 years) prophylactic treatment for familial Mediterranean fever, which can reduce the frequency of attacks. The dose is 1.2-1.8mg/(kg·d), administered intravenously slowly in 2-3 divided doses. It can be diluted with 40ml of normal saline using 25% glucose. After the frequency of attacks decreases, the medication should continue, with a daily maintenance dose of 0.6mg. Due to the fact that this drug can cause transient diarrhea and may lead to chromosomal abnormalities, oligospermia, bone marrow suppression, and depression, it should be used with caution. This therapy is only used for children with significantly limited activity. In addition, there have been reports of clinical symptoms and renal function improvement with the use of dimethyl sulfoxide (Dimethylsulfoxide).

　　II. Prognosis

　　The prognosis of this condition is poor, and new therapies are needed to improve the prognosis. The survival period is related to the extent of involvement of the primary disease and important organs (heart, gastrointestinal tract, nervous system, and kidneys). The research results of Rajkumar et al. suggest that progressive amyloidosis is the most common cause of death in patients with primary amyloidosis and nervous system damage. Patients with a higher serum albumin concentration (〉30g/L) have a longer survival time. The existing treatment measures cannot improve their prognosis. It is generally believed that patients with AL-type amyloidosis accompanied by heart or renal failure have the worst prognosis. However, Goldsmith et al. reported a case of a 46-year-old male patient with renal AL-type amyloidosis, who presented with severe nephrotic syndrome and survived for more than 21 years. The patient first received intensive chemotherapy after diagnosis, entered end-stage renal failure 10 years later, and then successfully received cadaveric kidney transplantation, with renal survival of more than 10 years, and still without significant renal and systemic amyloidosis. Jadoul et al. reported a case of a patient who, 10 years after successful kidney transplantation, still had no significant improvement in the pathological changes of wrist amyloidosis, suggesting that dialysis-related amyloidosis is not easily reversible even after successful kidney transplantation, and the pre-existing amyloid lesions are not easily resolved.