primary macroglobulinemia renal impairment
Introduction
Introduction to primary macroglobulinemia and renal damage Primary macroglobulinemia was first reported by Waldenstrom in 1944, so it is also known as Waldenstrom macroglobulinemia (WM). The disease is a syndrome of increased monoclonal IgM with lymphoid cell hyperplasia and sometimes glomerular damage. Its clinical features are lymphadenopathy, hepatosplenomegaly, lymphocytes and plasmacytoids in bone marrow and lymph nodes. Lymphocyte proliferation, increased monoclonal IgM in the blood. basic knowledge The proportion of illness: 0.005% Susceptible people: no special people Mode of infection: non-infectious Complications: acute renal failure
Cause
Cause of renal damage in primary macroglobulinemia
(1) Causes of the disease
Renal damage caused by macroglobulinemia is mainly due to the following reasons: renal lymphoid cell infiltration; hyperviscosity; amyloidosis; immune-mediated glomerulonephritis, mainly deposition of IgM in renal tissue .
The cause of WM is unknown, but studies have found that there are cell surface molecular variations and chromosomal abnormalities in abnormal proliferating B cells of patients with this disease. No obvious predisposing factors have been found, such as social demographic differences, past disease history, drug history, alcoholism. History, special occupational history, history of radiation exposure or family history of cancer, although there is a report of family history of WM, a 4 brother, each body serum has different antigenic IgM, and the performance of each body is not the same, Such as WM, undetermined monoclonal immunoglobulin disease (MGUS), MGUS with primary neuropathy and primary amyloidosis; in addition, 5 of 12 relatives showed serum immunoglobulin levels including IgA, IgG Increased IgM, suggesting abnormalities in immunoglobulin synthesis.
1. Cell surface marker variant cell surface marker studies suggest that WM patients have abnormalities in the early stage of B cell differentiation, which is different from plasma cell abnormalities in patients with multiple myeloma. WM cells express all surface antigens of normal B cells (CD19, CD20 and CD24), but about 75% of WM patients express only one light chain (kappa chain). Unlike normal B cells, B cells in WM often express CD9, CD10 (CALLA) and CD11b, and may express CD5, WM. The lymphocytes, plasma cells and plasmacytoid lymphocytes were all derived from the same clone, but their maturity was different, and it was found that the expression of CD45 isomers by B cells in different differentiation stages was not uniform.
2. Chromosomal abnormalities WM common cell chromosomal abnormalities, but specific abnormalities have not yet been scanned.
(two) pathogenesis
Most of the WM patients have more than 30% of the total monoclonal protein IgM. The macroglobulin of 1/3 of patients has the characteristics of cold agglutinin. Because of the large amount of IgM in the blood, red blood cells, white blood cells and platelets can adhere to form a high viscosity. Hysteresis, although IgG and IgA multiple myeloma, IgG in plasma and IgA covalently linked into a multimer, can also occur high viscosity blood syndrome, but far more than the primary macroglobulin Hemorrhage is rare. It is generally believed that abnormal immunoglobulin concentration in plasma exceeds 50g/L, and he is prone to high blood viscosity syndrome. WM patients often have severe high-viscosity syndrome, which is an important cause of systemic symptoms. The main cause of kidney damage, the main mechanism of kidney damage caused by macroglobulinemia is as follows:
Renal lymphoid cell infiltration
WM intrarenal lymphoid cell infiltration is 50% to 60%, but tubular tubular formation and "myeloma kidney" are rarely seen, and the incidence of tumor cell infiltration in the kidney is higher than in patients with IgG multiple myeloma. High, generally greater than 30%.
Hyperviscosity
Almost all patients in WM may develop symptoms and signs of hyperviscosity and hypercapnia at some stage of the disease, compared with only 4.2% of patients with IgG multiple myeloma. Symptoms, the apparent difference between the two may be related to IgM mainly in intravascular deposition, only 40% of IgG is deposited in blood vessels; secondly, it is also related to the shape and structure of IgM.
Amyloidosis
There is little amyloidosis in WM patients. In terms of organ infiltration, there is no significant difference between primary amyloidosis and myeloma-related amyloidosis. It is generally believed that patients with both myeloma and amyloidosis have poor prognosis. The average survival time is less than 12 months. When chemotherapy relieves the disease, the patient's survival period can be prolonged, and the amyloidosis can gradually subside.
Immune-mediated glomerulonephritis
Patients with WM often have glomerular lesions. In some patients, cryoglobulin associated with immune complex nephritis can be detected. More than 40% of patients with macroglobulinemia can be found to deposit a large amount of IgM under the endothelium.
Prevention
Prevention of renal damage in primary macroglobulinemia
The treatment of this disease is based on the severity of the patient's condition, different treatments for good and bad, and different periods. If the patient is asymptomatic, it can be kept stable for many years without treatment. Only strict follow-up is needed to reduce the early symptomatic treatment of patients with own disease. Mortality is a necessary means of prolonging survival.
Complication
Primary macroglobulinemia, renal damage complications Complications acute renal failure
The main complications are disease progression, anemia, hemorrhage, infection, and some patients die from the development of diffuse large cell lymphoma (Richter syndrome) and acute myeloid leukemia. Complications are mainly caused by lymphadenopathy, hepatosplenomegaly, lymphocyte and plasmacytoid lymphocytes in bone marrow and lymph nodes, and metabolic abnormalities caused by increased monoclonal IgM in the blood. Causes abnormal metabolism of erythroid and granulocyte progenitor cells.
Symptom
Primary macroglobulinemia, renal damage symptoms, common symptoms, vertigo bleeding, hematuria, proteinuria, nephrotic syndrome, renal failure, arrhythmia, heart failure
The main clinical manifestation of macroglobulinemia is hyperviscosity syndrome. Hyperviscosity can cause a series of symptoms of the nervous system, such as headache, dizziness, dizziness, diplopia, deafness, paresthesia, transient hemiplegia and Abortion, known as Bing-Neel syndrome, ocular lesions have retinal hemorrhage, venous segmental filling and thickening and optic disc edema, heart enlargement, arrhythmia and heart failure, but also bleeding tendency, such as gum bleeding, nose Bleeding, middle ear bleeding, skin mucous purpura, cyanosis of the extremities, etc., the main clinical manifestations of renal damage caused by this disease are proteinuria, usually mild or moderate, occasionally can develop a large amount of proteinuria, nephrotic syndrome, Proteinuria is non-selective, often accompanied by hematuria, decreased glomerular filtration rate, azotemia, tubular dysfunction, and acute renal failure during dehydration.
Physical examination showed more lymphadenopathy (15%), liver enlargement (20%) and splenomegaly (15%) with anemia.
Examine
Examination of renal damage in primary macroglobulinemia
1. Blood test: normal pigmented cell anemia, red blood cell deformability index decreased, red blood cell concatenation showed a sputum-like shape, there may be a decrease in whole blood cells, and a small amount (<5%) of atypical immature plasma cells may appear in peripheral blood. Small lymphoid cells or plasmacytoid lymphocytes; ESR increased; serum protein electrophoresis showed M protein. As the patient's age increased, the incidence of M protein increased. The rate of M protein increased in patients older than 50 years. It was 3.5%, compared with 11% for those aged 80-90. Immunoelectrophoresis showed a significant increase in monoclonal IgM. All patients had elevated IgM and were considered to be a circulating tumor marker. The Sia test is a rapid screening test for macroglobulinemia. The patient's serum is dropped into a test tube of distilled water, and precipitation occurs immediately. In addition, more than 10% of the macroglobulin has a cold-precipitating property, and is jelly-like in the case of cold.
2. Bone marrow examination: abnormal plasmacytoid lymphocyte hyperplasia can be seen. These lymphocytes are characterized by abundant secretory cells that synthesize and secrete immunoglobulins and secreted cells such as developed Golgi.
3. Karyotype examination: Hirase et al reported 2 cases of patients with primary macroglobulinemia whose karyotypes were t(11;18)(q21;q21),t(2;11;18)(q21 -23; q21; q21), and the karyotype of B cell lymphoma is t(11; 18) (q21; q21), thus suggesting that primary macroglobulinemia may be a variant of B cell lymphoma.
4. Urine examination: proteinuria and hematuria can be seen in renal damage, proteinuria is mostly mild to moderate, occasionally it can progress to proteinuria in the range of nephrotic syndrome, glomerular filtration rate is reduced, and azotemia occurs. , renal tubular dysfunction, when lymphoid cells in large infiltration, IgM and plasma cell-like cells often appear in urine by immunofluorescence microscopy, urine immunoelectrophoresis positive rate can be as high as 90%, urinary light chain protein positive rate is 30 %~50%.
5. Pathological examination: glomerular capillary thrombosis, thrombus contains a lot of IgM, less fibrin, it is also known as "pseudo-thrombus", there is IgM deposit inside the glomerular basement membrane, highly optotic under light microscope Acidic, PAS staining is dark purple, Trichrome staining is red or green, in addition, the glomerular mesangial area also has PAS staining positive deposits, the mesentery is nodular, and it is not easy to be associated with diabetic glomerulosclerosis under light microscope. Identification.
6. Imaging examination: If secondary amyloidosis occurs, it can be seen that the two kidneys are significantly enlarged, and bone imaging examinations generally have no osteolytic lesions.
Diagnosis
Diagnosis and diagnosis of renal damage caused by primary macroglobulinemia
diagnosis
The diagnosis of renal damage, first of all to determine the presence of macroglobulinemia; further to identify primary or secondary, benign or malignant macroglobulinemia, if secondary macroglobulinemia, it should be A differential diagnosis is made between common secondary causes.
The diagnosis of WM is as follows:
1. Typical symptoms and signs: such as elderly patients with unexplained anemia and bleeding tendency, central and / or peripheral nervous system symptoms, visual impairment, Raynaud's phenomenon, hepatosplenomegaly.
2. Serum IgM monoclonal globulin concentration> 30g / L, whole blood cells decreased, a small amount (<5%) of atypical naive plasma cells in the peripheral blood, blood viscosity increased.
3. Bone marrow, liver, spleen, and lymph nodes have lymphoid plasma cell infiltration.
The diagnosis of WM must be differentiated from multiple myeloma, chronic lymphocytic leukemia, lymphoma, undifferentiated lymphoproliferative disease, and IgM type MGUS.
Diagnosis of renal damage: On the basis of the diagnosis of primary macroglobulinemia, the renal damage performance of the patient should be further examined. If there is proteinuria, hematuria and pathological examination indicators are met, the diagnosis can be established.
Differential diagnosis
1.IgM type MGUS: The main feature is serum IgM concentration <20g / L, and will not increase with the progression of the disease; no anemia, hepatosplenomegaly, lymph node lesions and systemic symptoms, generally no obvious proteinuria, no or only A very small amount of urine per week protein and bone marrow micro-lymphocyte infiltration.
2. Lymphatic proliferative diseases with increased IgM levels: except for IgM concentrations <30g/L and high-viscosity rates are lower than WM, there are also anemia or other systemic symptoms, and their survival time or other characteristics are There is no significant difference in WM. There is no consensus and WM identification for lymphoproliferative diseases (called lymphoplasmacytic lymphoma) with high concentration of IgM (>30g/L).
3. Occult WM: refers to some WM patients without systemic symptoms, but IgM levels > 30g / L, mild anemia and bone marrow with moderate lymphoid cell infiltration, these patients have the characteristics of occult macroglobulinemia, Similar to smoldering multiple myeloma, they can remain stable for long periods of time without treatment before symptoms appear.
4. Hyperviscosity: The diagnosis of this disease is mainly based on typical clinical manifestations and "relative" serum viscosity, but the relative serum viscosity and serum abnormal immunoglobulin concentration are not linearly related, this difference and immune ball Protein aggregation ability, degree of polycondensation, cold precipitation ability and formation of euglobulin in vitro are related to factors such as mild increase in serum viscosity, and clinical symptoms and signs are very typical, and should be distinguished from the disease.
5. Secondary macroglobulinemia.
6. Primary macroglobulinemia Kidney damage should also be differentiated from kidney diseases caused by other causes.
