primary monoclonal globulin disease kidney damage
Introduction
Introduction to primary malignant globulin disease Monoclonal globulin disease can be divided into primary monoclonal globulin disease and secondary monoclonal globulin disease. Primary monoclonal globulin disease is a group of diseases characterized by the proliferation of monoclonal plasma cells. Refers to the M protein component in serum, but its importance is that MGUS sometimes progresses to monoclonal globulin disorders such as multiple myeloma (MM), primary amyloidosis and primary macroglobulinemia, etc. Primary monoclonal globulin disease can cause kidney damage. basic knowledge The proportion of the disease: adult incidence rate of 0.005% - 0.01% Susceptible people: no special people Mode of infection: non-infectious Complications: anemia
Cause
Cause of renal damage in primary monoclonal globulin disease
Causes:
The etiology of this disease is unknown, secondary monoclonal globulinemia is seen in chronic lymphocytic leukemia, lymphoma, colon cancer and other cancers; non-neoplastic diseases such as mucous edema-like moss, Gaucher disease, chronic activity Hepatitis, connective tissue disease and myasthenia gravis.
Pathogenesis:
The pathogenesis of renal damage caused by this disease is not completely clear, and may be similar to the pathogenesis of primary amyloidosis. The main reason for the deposition of glomeruli by M component is: 1. Passive adsorption of glomeruli. 2. Circulating immune complexes and/or cryoglobulin deposits cause glomerular damage.
In glomerular nephritis, glomerular lesions are mainly caused by deposition of immune complexes. It is confirmed that the immunoglobulin in the renal eluate of this disease is homologous to serum monoclonal immunoglobulin.
Prevention
Primary monoclonal globulin disease prevention of kidney damage
Some patients with this disease can develop MM, WM, AL and malignant lymphoproliferative diseases. Once the disease develops into a malignant disease, it is often difficult to change. The purpose of prevention is to delay the development of the disease and prolong the survival of the patient. The main measures are to strengthen the primary. Disease and symptomatic treatment, for those with severe renal impairment, should be actively chemotherapy and dialysis.
Complication
Primary monoclonal globulin disease, renal damage complications Complications anemia
Primary monoclonal globulin disease is a group of diseases characterized by proliferation of monoclonal plasma cells, which refers to M protein components in serum, but its importance is that MGUS sometimes progresses to monoclonal globulin diseases such as multiple bone marrow. Tumor (MM), primary amyloidosis and primary macroglobulinemia. Primary monoclonal globulin disease can cause kidney damage. Secondary monoclonal globulinemia is seen in chronic lymphocytic leukemia, lymphoma, colon cancer and other cancers; non-tumor-like diseases such as mucous edema-like moss, that is, patients with diffuse skin and visceral vascular wall acid viscosity Protein deposition, serum M protein components significantly increased, Gaucher (ie, high snow, Gaucher) disease, chronic active hepatitis, connective tissue disease and myasthenia gravis.
Symptom
Primary monoclonal globulin disease symptoms of kidney damage Common symptoms Urinary protein hypertension, weight loss, proteinuria, fatigue, loss of appetite, kidney damage, nephrotic syndrome, edema
Kidney damage is not common in this disease, the main manifestation of kidney damage is glomerulonephritis, patients often feel tired and weak, loss of appetite, weight loss, anemia, edema, hypertension and proteinuria, a large number of proteinuria can occur nephrotic syndrome Most of them have different degrees of renal dysfunction, clinically can be acute glomerulonephritis, and 1 case reported clinically acute glomerulonephritis patients, plasma globulin increased significantly (45g / L), protein electrophoresis The globulin is 35%, which is a monoclonal peak, and the IgG is 27.6-35g/L. The immunoelectrophoresis shows the IgG2 subtype light chain monoclonal peak, the urine protein is 6.8g/d, and the peri-protein is negative. The following features:
1. The patient's whole blood and plasma viscosity, aggregation index increased, skin microcirculation dysfunction.
2. The undetermined monoclonal globulin disease is characterized by a plasma M protein of less than 30 g/L, a plasma cell of less than 10% in the bone marrow, a small amount of M protein in the urine, no hemolytic anemia, hypercalcemia, and kidney. Incomplete function, more importantly, M protein is stable and will not develop abnormally. If the plasma cell marker index is elevated and circulating plasma cells are present in peripheral blood, it indicates that the disease is in active phase.
3. There is no definite significance of monoclonal globulin disease, its condition can change with time. When the disease course is about 10 years, 16% of patients are aggravated. If it is about 25 years, 40% of patients will get worse. 25 % of patients can develop MM, wM, AL and malignant lymphoproliferative disorders, with a median of 10 years (2 to 29 years) from the discovery of M protein to the development of MM.
Examine
Examination of renal damage in primary monoclonal globulin disease
1. Blood examination: Most of them have different degrees of anemia, mostly positive cells are pigmentary; when malnutrition can be large cell; when there is iron deficiency and other iron deficiency factors, it can be small cells with low pigmentation, white blood cells and platelets can be normal in early stage. , the proportion of lymphocytes is slightly increased, the whole blood cell can be reduced in the late stage, the blood smear shows that the red blood cells are arranged in a striate line, the red blood cells are different in size, sometimes there are nucleated cells, and the eosinophils are increased, about 70% of the patients can be surrounded by blood. Looking for plasma cells or myeloma cells, a small number of patients can see a small number of myeloma cells and naive cells. If the myeloma cells are >20%, or the absolute value is >2.0×109/L, they can be diagnosed as plasma cell leukemia, and the erythrocyte sedimentation rate is increased. .
2. Bone marrow examination: Bone marrow examination is decisive for the diagnosis of this disease. The bone marrow is often proliferative. The myeloma cells are generally more than 5%, and many of them can reach 95%. The tumor cells are sometimes unevenly distributed. Secondary bone perforation can be diagnosed. The diagnosis of solitary myeloma is high after the X-ray is determined, and the plasma cell system is significantly increased. It is mainly composed of multiple myeloma cells. Its characteristics are:
(1) Cell size varies, sometimes giant, multiple myeloma cells.
(2) The nuclear chromatin is meticulous, with 1 or 2 nucleoli.
(3) abnormal cytoplasmic staining, some of which are basophilic, some are eosinophilic, sometimes red or crystalline inclusions in the cytoplasm are Roche's bodies, and the light-stained areas around the nucleus are often not obvious or disappear, and may be small Aniline blue particles or vacuoles, sometimes visible in blue globular cytoplasmic inclusion bodies, according to morphological differences, myeloma cells are divided into mature, immature, intermediate and protoplasmic cell type 4, under electron microscope It can be seen that the rough endoplasmic reticulum of bone marrow cancer cells is rich and the morphology is different; the ribosome is reduced, the Golgi apparatus is developed; the mitochondria are larger, the number has increased, and the sputum is high and swells.
3. abnormal globulin in blood: high globulin is one of the important characteristics of this disease, plasma globulin is significantly increased (45g / L), protein electrophoresis on the globulin is 35%, serum protein electrophoresis in the region, region Or a narrow-bottom peak appeared in the 2 region, which was a monoclonal peak with an IgG of 27.6-35 g/L. Immunoelectrophoresis showed a monoclonal peak of IgG2 subtype light chain, which was confirmed by immunoelectrophoresis and chemical analysis to be a monoclonal plasma cell. The secreted structure of immunoglobulin or polypeptide chain subunit (light chain), ie, monoclonal immunoglobulin, or M protein, can be classified into IgG type, IgA type, IgD type, IgE according to immunoelectrophoresis analysis. Type and light chain type, in addition, very few patients without M protein is called non-secretory type.
4. Urine-peripherin: also known as coagulating protein, formed by excess light chain through the glomerulus to the urine, serum protein electrophoresis or immunofixation electrophoresis can detect M protein, general plasma M protein concentration <30g / L About 50% of the patients can be positive, the initial local-week protein often appears intermittently, and often appears in the late stage, so this-week protein is negative, and can not rule out the disease, but this-week protein positive reaction is not the disease Specificity indicators.
5. Urine test found no or mild proteinuria, a small number of proteinuria appeared, individual nephrotic syndrome proteinuria, urine protein up to 6.8g / d, severe renal damage can occur hematuria and tubular urine, serum urea Nitrogen and creatinine increased.
6. Others If the bone is extensively damaged, there may be an increase in serum calcium or hyperuricemia. The patient may have a viscosity of whole blood and plasma, an increase in aggregation index, and dysfunction of skin microcirculation.
The undetermined monoclonal globulin disease is characterized by a small amount of M protein in the urine, no hemolytic anemia, hypercalcemia, renal insufficiency, and more importantly, the M protein is stable and does not develop abnormally. An increase in the plasma cell marker index and the presence of circulating plasma cells in the peripheral blood suggest that the disease is in an active phase.
1. X-ray examination is of great significance in the diagnosis of this disease, but it is not very sensitive. Only when bone decalcification is >30%, X-ray can show abnormal signs. X-ray changes have the following four manifestations:
(1) osteolytic lesions: X-ray findings have multiple round shapes with clear edges such as drill-like bone defect shadows, commonly found in skulls, pelvis, spine, femur, ribs and humeral heads.
(2) Diffuse osteoporosis: common in early patients, mostly in the vertebrae, ribs, pelvis and skull, can also be seen in the limbs.
(3) pathological fractures: common in the ribs and spine, the spine can be a compression fracture.
(4) Osteoporosis: only seen in a small number of patients, mostly localized sclerosis, and occurs around osteolytic lesions.
2. Renal biopsy light microscopy showed that the main pathological manifestations of the kidney were diffuse proliferative glomerulonephritis in endothelial cells and mesangial cells. Immunofluorescence showed that monoclonal immunoglobulin was deposited in glomeruli, and specific antiserum tests showed The glomerular deposit is a circulating M component. Although this type of lesion is similar to immune complex nephritis, the elution test cannot confirm the specific antigen. Electron microscopy shows the deposition of electron dense substance in the basement membrane, endothelial cells and epithelial cells.
Diagnosis
Diagnosis and diagnosis of primary malignant globulin disease with renal damage
diagnosis
The diagnosis of this disease mainly relies on plasma protein electrophoresis. At the same time, it should be noted whether the disease is active, primary or secondary, and attention should be paid to whether there is a definite clinical significance.
It can be diagnosed if:
1. Serum M protein concentration <30g / L.
2. Bone marrow smear plasma cells <10%.
3. No or only a small amount of this-week protein.
4. No osteolytic lesions, anemia, hypercalcemia and renal insufficiency.
5. Serum M protein concentration was stable for a long time, and there was no malignant change during follow-up.
Renal biopsy has pathological manifestations of renal damage and excludes secondary monoclonal globulinemia to diagnose primary monoclonal globulin disease with renal damage.
Differential diagnosis
The disease should be differentiated from multiple myeloma (MM), but it may be difficult, according to serum M protein concentration, hemoglobin concentration, polyclonal immunoglobulin level, urinary light chain excretion, the proportion of bone marrow plasma cells, whether there is Changes in osteolytic lesions, hypercalcemia, or renal insufficiency often contribute to identification.
1. High serum M protein levels are often associated with malignant lesions. Serum M protein >30 g/L usually indicates significant MM, but some of these patients remain stable and unchanged for a long time.
2. The decrease in serum normal polyclonal immunoglobulin concentration is common in malignant tumors, but it can also be seen in some patients with MGUS and can remain malignant.
3. The presence of this-week proteinuria suggests a neoplastic lesion. However, many patients with MGUS have a stable follow-up for many years despite a small amount of pre-week proteinuria <50 mg/d.
4. The bone marrow plasma cells >10% are characteristic of MM, but some patients can keep the disease stable.
5. Osteopathic lesions, hypercalcemia or unexplained renal insufficiency, strongly suggest MM, but metastatic cancer must be excluded.
6. MM patients often have elevated IL-6 levels, while MGUS is normal.
7. Thoracic and lumbar spine MRI can help identify the MM and MGUS.
8. Using the plasma cell marker index (determining its DNA synthesis) is helpful for the identification of both. The marked increase of plasma cell marker index is a strong indication of active MM, but the normal plasma cell marker index can also exist in 1/3. Above MM patients.
9. Increased peripheral blood plasma cells are also a good marker of active MM.
In short, there is currently no good indicator to distinguish MGUS from MM. The most reliable identification method is to dynamically monitor serum M protein concentration through follow-up and regularly evaluate the dynamic changes of the condition and laboratory test results. Recent advances in phenotypic, cytogenetics, and molecular biology may be expected to provide new evidence for their identification.
