Primary macroglobulinemia renal damage

　　Renal damage caused by primary macroglobulinemia (WM) is due to renal lymphoid cell infiltration, hypercoagulability, amyloidosis, and immune-mediated glomerulonephritis, mainly due to the deposition of IgM in renal tissue.

　　The etiology of Waldenstrom macroglobulinemia (WM) is unknown, but studies have found that patients with the disease have abnormal proliferation of B cells with surface molecule mutations and chromosomal abnormalities. No obvious precipitating factors have been found, such as social demographic differences, past medical history, drug history, alcoholism history, special occupational history, radiation exposure history, or family tumor history. Nevertheless, reports of WM occurring in families have been documented. A family of four brothers had serum antigens with different IgM, and their manifestations were not uniform, such as WM, unclassified monoclonal gammopathy of undetermined significance (MGUS), MGUS with peripheral neuropathy, and primary amyloidosis; in addition, among 12 relatives, 5 had elevated serum immunoglobulin levels including IgA, IgG, and IgM, suggesting abnormal immunoglobulin synthesis.

　　1, Variations in cell surface markers

　　Studying cell surface markers suggests that WM patients show abnormalities in the early stage of B cell differentiation, which is different from the plasma cell abnormalities in multiple myeloma patients. WM cells express all surface antigens of normal B cells (CD19, CD20, and CD24), but about 75% of WM patients only express one light chain (κ chain). Unlike normal B cells, WM B cells often express CD9, CD10 (CALLA), and CD11b, and may express CD5. Lymphocytes, plasma cells, and plasma cell-like lymphocytes in WM all originate from the same clone, but their maturity levels are different, and it is found that the expression of CD45 isomers by B cells at different differentiation stages is uneven.

　　2, Chromosomal abnormalities

　　WM commonly has chromosomal abnormalities, but specific abnormalities have not yet been scanned.

　　The main complications of renal damage in primary macroglobulinemia are disease progression, leading to anemia, bleeding, and infection. Some patients may die due to the development of diffuse large B-cell lymphoma (Richter syndrome) or acute myelocytic leukemia. The production of complications is mainly related to lymphadenopathy, hepatosplenomegaly, lymphocytic and plasma cell-like lymphocyte hyperplasia in the bone marrow and lymph nodes, metabolic abnormalities caused by increased monoclonal IgM in the blood, and erythroid and granulocytic progenitor cell metabolic abnormalities. Severe anemia can lead to anemia heart disease, renal insufficiency, nephrotic syndrome, neurological lesions, and hepatosplenomegaly.

　　The clinical manifestations of renal damage in primary macroglobulinemia include high viscosity blood syndrome, which can cause a series of neurological symptoms such as headache, dizziness, vertigo, diplopia, hearing loss, sensory abnormalities, transient hemiparesis, and ataxia, known as the Bing-Neel syndrome. Ocular lesions include retinal hemorrhage, venous segmental dilatation, papilledema, cardiac enlargement, arrhythmia, and heart failure. There may also be bleeding tendencies such as gingival bleeding, nosebleeds, middle ear bleeding, purpura of the skin and mucous membranes, and cyanosis of the extremities. The main clinical manifestation of renal damage is proteinuria, which is usually mild or moderate and occasionally can develop into massive proteinuria, leading to nephrotic syndrome. Proteinuria is non-selective, often accompanied by hematuria, a decrease in glomerular filtration rate, azotemia, renal tubular concentration dysfunction, and a tendency to lead to acute renal failure during dehydration. Physical examination often shows lymphadenopathy, hepatomegaly, and splenomegaly, accompanied by symptoms of anemia.

　　Patients with renal damage in primary macroglobulinemia should pay attention to rest, combine work and rest, live in an orderly manner, maintain an optimistic, positive, and upward attitude towards life, follow a regular diet and sleep, avoid overexertion, keep a cheerful mood, and develop good living habits.

　　The treatment for renal damage in primary macroglobulinemia is based on the severity, nature, and different stages of the patient's condition, with different treatments given. If the patient is asymptomatic, it can often maintain stable for many years without treatment, only requiring close follow-up. Early and active symptomatic treatment for patients with the disease, such as targeted prevention of infection, increasing the ratio of normal white blood cells and red blood cells, reducing proteinuria, preventing renal failure, and other symptomatic treatments are necessary means to reduce mortality and prolong survival.

　　The main clinical examination methods for renal damage in primary macroglobulinemia include blood examination, bone marrow examination, chromosome karyotype examination, urine examination, pathological examination, and imaging examination, as follows:

　　1. Blood examination

　　There is normochromic normocytic anemia, with reduced red blood cell deformability index, red blood cell strands in a necklace-like shape, and there may be a decrease in all blood cells. A small amount may appear in peripheral blood (

　　2. Bone marrow examination

　　Abnormal plasma cell-like lymphocyte proliferation can be observed, and these lymphocytes have the characteristics of secretory cells, such as abundant rough endoplasmic reticulum for the synthesis and secretion of immunoglobulins and developed Golgi apparatus.

　　3. Chromosome karyotype examination

　　Primary macroglobulinemia may be a variant of B cell lymphoma.

　　4. Urine examination

　　When renal damage is present, proteinuria and hematuria can be observed, with proteinuria mostly mild to moderate, occasionally progressing to proteinuria in the range of nephrotic syndrome. Glomerular filtration rate decreases, leading to azotemia, renal tubular concentrating dysfunction. When there is a large amount of lymphoid cell infiltration, IgM and plasma cell-like cells can often be found in the urine under immunofluorescence microscopy. The positive rate of urine immunoelectrophoresis can reach up to 90%, and the positive rate of urine light chain protein is 30% to 50%.

　　5. Pathological examination

　　Thrombosis occurs in the glomerular capillaries, and the thrombus contains a large amount of IgM with less fibrin, hence also known as 'pseudo-thrombus'. There are IgM deposits on the inner side of the glomerular basement membrane, which appear highly eosinophilic under light microscopy, deep purple under PAS staining, and red or green under Trichrome staining. In addition, there are also PAS-positive deposits in the glomerular mesangial area, the mesangium appears nodular, and it is difficult to differentiate from diabetic glomerulosclerosis under light microscopy.

　　6. Imaging Examination

　　If secondary amyloidosis occurs, the two kidneys can be significantly enlarged, and skeletal imaging examination generally has no osteolytic lesions.

　　The diet of patients with primary macroglobulinemia renal damage should be light and nutritious, with more vegetables, fruits, milk, turtle, and other foods rich in various amino acids, vitamins, proteins, and easily digestible tonics. Spicy and greasy foods should be avoided.

　　In the early stage of renal damage in primary macroglobulinemia, if the condition is stable, symptoms are mild, or the development is slow, treatment may not be required; if symptoms are obvious, with bleeding, anemia, liver, spleen, lymph node enlargement, and symptoms of hypercoagulability, treatment should be given. The main purpose of the treatment of this disease is to reduce the concentration of plasma macroglobulin and hypercoagulability. The specific treatment methods of Western medicine are as follows:

　　1. Alkylating Agent

　　Especially busulfan, fludarabine analogs, cladribine, and rituximab. Busulfan is taken orally with an efficacy rate of more than 50% and a median survival period of 5 years. Continuous oral administration of low-dose busulfan for 2 to 4 weeks, followed by maintenance dosage. The maintenance period lasts for several years until remission. Cyclophosphamide can be taken orally to inhibit the synthesis of macroglobulin. Nitrogen mustard and glucocorticoids can also be used. The oral treatment plan of penicillamine can also be used to separate the disulfide bonds of macroglobulin, destroy the IgM molecule, and reduce blood viscosity.

　　2. Plasma Exchange Therapy

　　For patients with明显 hypercoagulability, this therapy can quickly relieve symptoms, and low molecular weight dextran can be administered intravenously to reduce blood viscosity. Since blood viscosity is parallel to IgM concentration, if the concentration of serum macroglobulin decreases by 15% to 20%, it can usually promote a significant decrease in blood viscosity, therefore, in the first plasma exchange therapy, it is necessary to replace more than half of the total plasma volume in the body to achieve a significant therapeutic effect, and to maintain the effect, it is necessary to repeat the exchange every 1 to 2 months, each time replacing 400 to 800 ml of plasma.

　　3. Immunotherapy

　　Treated with anti-CD20 monoclonal antibody, 30% of patients are effective; bone marrow transplantation or peripheral blood stem cell transplantation can be used for treatment.