multiple myeloma nephropathy
Introduction
Introduction to multiple myeloma nephropathy Multiple myeloma nephropathy refers to the infiltration of myeloma cells and the massive renal abnormalities caused by the discharge of abnormal immunoglobulins from the urine. Multiple myeloma nephropathy is the most common cause of renal failure due to tubular tubular formation. Therefore, it is also called myelomacastnephropathy (MCN). The clinical manifestations are mainly spilled proteinuria, which may cause chronic or acute renal insufficiency, nephrotic syndrome and Fanconi syndrome. basic knowledge The proportion of illness: 0.002% Susceptible people: no specific people Mode of infection: non-infectious Complications: pneumonia sepsis
Cause
Causes of multiple myeloma nephropathy
Large amounts of light chain proteins cause tubular damage (20%):
Myeloma cells produce a large number of abnormal monoclonal immunoglobulins, in which the immunoglobulin light chain can be filtered from the glomerulus due to its high molecular weight, and enters the renal tubules in a large amount, far exceeding the maximum reabsorption rate of the renal tubules. The chain protein is excreted from the urine, called overflow proteinuria. The biggest feature of MMN is the presence of a large number of light chain immunoglobulins in the renal tubules, which form a special cast type, causing tubular obstruction in the renal tubules, and can also cause renal tubules. Damage.
High calcium nephropathy (20%):
In addition to secreting monoclonal immunoglobulin, osteoblast cells secrete a large number of osteoclast activating factors, which stimulate osteoclasts, produce localized osteolysis, and increase calcium into the blood. In addition, osteomyelopathy lesions have osteogenesis. Cell activation is inhibited, all of the above factors can lead to hypercalcemia, high urinary calcium, causing damage to kidney tissue and kidney function, high blood calcium and high urinary calcium promote calcium salts in the renal tubules, interstitial deposition, causing renal calcium deposition disease Extensive calcareous deposition leads to a decrease in renal concentrating function. High concentrations of calcium salts aggregate into BJP into tubular or formed stones in the renal tubules, further impairing renal tubular function. Therefore, hypercalcemia and light chain protein are considered to be The main risk factors of MMN.
Uric acid nephropathy (15%):
MM patients due to destruction of tumor cells, or chemotherapy, nucleic acid catabolism enhanced, excessive production of blood uric acid secondary hyperuricemia, long-term hyperuricemia, renal medulla in hypoxic, low pH state Uric acid deposition causes damage to the tubulointerstitial. In addition, urate crystals not only damage the renal tubular epithelial cells, but also block the renal tubules, form renal obstruction, and develop obstructive nephropathy.
Tumor cell infiltration of bone marrow is the main organ that produces plasma cells. Therefore, the primary lesion of MM is mainly in the bone marrow. In addition to bone marrow, lymph nodes, spleen, digestive tract, and submucosal lymphoid tissue of the upper respiratory tract can also produce plasma cells, which become primary lesions. In addition to the primary lesions, tumor cells can also infiltrate other tissues and organs, kidney, lung, digestive tract, heart, thyroid, testis, ovary, uterus, adrenal gland, subcutaneous tissue can also be involved, tumor cells infiltrate the renal parenchyma, can make The renal tissue is damaged. It is generally considered that the tumor cells directly infiltrate the renal tissue, and the volume of the affected kidney is significantly increased.
In the amyloidosis of MM, the complex of monoclonal immunoglobulin light chain and polysaccharide is deposited in tissues and organs, causing amyloidosis, causing corresponding clinical manifestations, such as tongue hypertrophy, hepatosplenomegaly, heart enlargement, peripheral neuropathy, renal function Damage, etc., can cause renal amyloidosis, amyloid fibers mainly deposited in the glomerular basement membrane, mesangium, renal tubule basement membrane and interstitial, and finally lead to renal failure.
Hyperviscosity Myeloma cells secrete large amounts of monoclonal immunoglobulin, which increases blood viscosity and causes renal hemodynamics and microcirculatory disorders.
The cryoglobulinemia abnormal immunoglobulin has the characteristics of cold precipitation and is easy to accumulate in the glomerular capillaries, leading to kidney damage.
Urinary tract infection MM patients with low systemic resistance, easy to accompany urinary tract infection, resulting in reduced systemic resistance, first, immunodeficiency, myeloma cells secrete certain substances, inhibit macrophage function, make it mediated normal The immunoglobulin synthesis is inhibited; the second is that the abnormal light chain protein secreted by myeloma cells impairs the phagocytosis and modulating effects of granulocytes on bacteria, and in addition, the local factors leading to urinary tract infection are urinary tract and uric acid. Salt crystals block renal tubules, urinary calculi cause obstruction, and local resistance to urinary tract mucosa decreases.
The etiology of MM has not been fully elucidated. Animal experiments and clinical observations may indicate factors related to genetic factors, viral infection, ionizing radiation, and chronic antigen stimulation. In recent years, studies have found that C-myc gene recombines, and some have high levels of H-ras gene protein. The abnormal regulation of lymphocyte factor, especially interleukin-6 secretion, is associated with the pathogenesis of MM.
Pathogenesis
The etiology of MM abnormal protein in glomerular deposition remains unclear. The pathogenesis of nephropathy and nephrotoxicity of free light chain protein in MM patients, hypercalcemia, hyperuricemia, hyperviscosity syndrome and renal amyloidosis Related, other plasma cell infiltration such as renal tubular acidosis and renal parenchyma are also involved in the pathogenesis of MM nephropathy. According to the site of the lesion, MM nephropathy can be divided into renal tubular damage and glomerular damage.
1. Nephrotoxicity of immunoglobulin light chain B lymphocyte or plasma cell abnormal proliferation, production and secretion of abnormal monoclonal immunoglobulin, due to unbalanced synthesis of heavy and light chains, resulting in excessive free light chain, flow It is easily filtered through the glomerulus. When the filtration excess exceeds the maximum reabsorption capacity of the renal tubule, it is excreted from the urine and is called Bence-Jones proteinuria.
(1) tubular obstruction theory: This theory believes that the light chain protein filtered by glomerulus exceeds the maximum reabsorption capacity of the proximal tubule, the light chain protein that is not reabsorbed reaches the distal renal tubule, and the concentrated acidity The tubule fluid forms a tubular shape with Tamm-Horsfall (TH) protein, which blocks the distal renal tubules. These tubular components are composed of light chain protein and TH protein, and there are fibrinogen and albumin, which are eosinophilic. There are inflammatory cells and syncytium, which form a huge cast, which completely obstructs the distal tubules and/or collecting ducts. This is a characteristic of myeloma kidneys, many of which are specific, such as microspheres. Needle-shaped, pentagonal or hexagonal crystals, which have been stained with TH protein and light chain protein, have not been found in about 30% of patients. Therefore, many scholars have suggested that certain light chain proteins can directly damage tubular cells.
(2) renal tubular toxicity theory: the light chain protein in the glomerular filtrate is reabsorbed by the proximal renal tubule, degraded in the lysosome and produced toxicity, causing renal tubular damage, light chain protein in 10-4 ~ 10- At 6 M concentration, the activity of Na-K-ATPase in the renal tubular epithelial membrane was inhibited, indicating that light chain protein has a direct toxic effect on renal tubular epithelial cells. The toxic effect of light chain on renal tissue is higher than that of light chain. The strong, light chain protein has different degrees of nephrotoxicity and is thought to be related to the amino acid composition of the light chain protein variable region, which is related to the difference in physical and chemical properties such as net charge and solubility. Direct renal tubular damage is positively charged. The filtration protein is most prominent, and the change of urine pH plays an important role in light chain nephrotoxicity. Acidic urine can increase the filtration of light chain excretion, while alkaline urine reduces its excretion. If acidification can aggravate light chain protein In the case of nephrotoxicity, the tubular obstruction theory is more important than the direct toxicity theory of the renal tubules.
(3) Light chain deposition disease: glomerular mesangial hyperplasia or nodular sclerosis can be seen in MM patients, similar to Kimmelstiel-Wilson lesions of diabetic nephropathy, in the glomerulus On the outer side of the subcutaneous and renal tubule basement membrane, amorphous particulate matter deposition is observed, which reacts with the kappa- or lambda-type light chain (mainly -type) monoclonal antiserum, in addition, in the renal interstitial, renal tubular wall Monoclonal light chains or fragments thereof can also be seen in the vascular wall of the liver sinus and many organs. Patients often have more proteinuria, which can reach the standard of nephrotic syndrome with progressive renal failure.
2. Hypercalcemia MM has hypercalcemia of 30%, blood calcium is usually 2.75 ~ 3.25mmol / L, a few can be greater than 3.25mmol / L, which and myeloma cells secrete a large number of osteoclast activating factor (osteoclastic Activating factor), which leads to a close relationship between bone resorption. Osteoblast activation is inhibited at the lesion site. Due to these factors, localized bone resorption occurs, calcium enters the bloodstream, hypercalcemia occurs, and serum calcium can be obtained. It is divided into two parts: protein-bound calcium and non-protein-bound calcium. In MM, immunoglobulin and light chain protein are significantly increased, which can lead to mild to moderate hypercalcemia. At this time, calcium ions can be normal, due to MM when the parathyroid gland Hormone secretion does not increase, and hypercalciuria can occur.
When blood calcium is greater than 3mmol/L, it can cause kidney damage. Hypercalcemia caused by hypercalcemic nephropathy is one of the main factors of renal failure in MM patients. The renal damage caused by hypercalcemia is mainly in the renal tubules and collecting ducts. The mitochondria of renal tubular cells are swollen, and there is calcium deposition in the mitochondria, cytoplasm and tubule basement membrane. Calcium deposition gradually develops to the interstitial around the tubules, forming kidney. Calcium deposition disease (nephrocalcinosis), lesions are most prominent in the medullary ascending branch and medullary collecting duct, fibrosis around the glomerulus, clinical urinary concentrating dysfunction, renal tubular acidosis and urinary tract stones, and finally progress to kidney Functional failure.
The main pathogenic factors of MM nephropathy are light chain protein and hypercalcemia. The main reason for this is that the TH protein is aggregated. In the distal tubules and collecting ducts, obstructive casts are formed, so in myeloma. In myelonla cast nephropathy, the two synergistically.
3. Uric acid nephropathy due to increased catabolism of MM patients with nucleic acid, often hyperuricemia, especially in concurrent plasma cell leukemia or chemotherapy, blood uric acid increased more obvious, but acute uric acid nephropathy is rare, long-term high uric acid In patients with hypotension, the renal medulla tends to cause uric acid deposition to crystallize under hypoxic and low pH conditions, forming a tubular shape in the renal tubules, causing obstruction of the kidney and causing damage to the renal tubule-interstitial.
4. AMI patients with amyloidosis 6% with amyloidosis, amyloid fibril is derived from the amino terminal fragment of the immunoglobulin light chain variable region in an acidic environment, so it is called AL protein (amyloid light chain protein), this protein has a smaller molecular weight than the light chain, and is between 2 and in serum electrophoresis. It is mainly deposited in the glomerular basement membrane, mesangium, renal tubule basement membrane and interstitial in the kidney. Quality, leading to renal dysfunction, MM complicated with renal amyloidosis, the prognosis is dangerous, the survival period is often no more than 1 year.
5. Hyperviscosemia (Hyperviscosemia) Myeloma cells secrete a large number of monoclonal immunoglobulins, which promote the accumulation of red blood cells in the blood to form a scorpion-like shape. The plasma moves outwards to concentrate the blood, resulting in increased blood viscosity and kidney. Small ball capillaries, renal blood flow is significantly reduced, renal insufficiency occurs, in addition, high red blood cell aggregation and hyperviscosity can cause renal vein thrombosis, further impairing renal function, although high viscosity syndrome (hyperviscosity syndrome) It is not as common as patients with macroglobulinemia, but when the molecules of IgG or IgM proteins are polymerized and high concentrations are present, high-viscosity syndrome can occur. These abnormal proteins can also pass the immune response and coagulation factors I, II. V, VII, and VIII combine to cause bleeding.
6. Patients with pyelonephritis MM have extremely reduced immune and antibacterial ability, so infection and sepsis are the most common causes of death in patients. The kidneys are caused by light chain protein and hypercalcemia, and extensive tubular obstruction of renal tubules and renal parenchymal calcium deposits. The local disease resistance is significantly reduced, so it is easy to secondary pyelonephritis, which can accelerate the deterioration of renal function, and even acute renal failure. On the other hand, bacteria enter the bloodstream to cause sepsis, especially Gram-negative bacilli sepsis, and the mortality rate is very high.
7. Dehydration and contrast agents can induce acute renal failure. Even in patients with MM, even if the kidney function is normal, due to light chain proteinuria, hyperviscosity and hyperuricemia, patients with dehydration can easily induce acute renal failure. Contrast agents should be used with caution, especially large doses of contrast agents, which can temporarily reduce renal blood flow and glomerular filtration rate, increase blood viscosity, and promote the precipitation of TH mucin in the renal tubules. Contrast agents can also be increased. Renal tubules secrete uric acid, causing obstruction of the small lumen, and the incidence of acute renal failure caused by contrast agent in MM is 7%.
8. Renal tissue lymphoid plasma cell infiltration Myeloma cells are less common in infiltration of renal tissue, even in advanced cases, no more than 30%, at this time the kidney volume increased significantly.
Prevention
Multiple myeloma nephropathy prevention
MM is a malignant tumor. When myeloma cells infiltrate and cause kidney disease, the condition is often irreversible. The purpose of prevention is to delay the development of the disease and prolong the survival of the patient. The main measures are active anti-infective treatment, strengthening the primary disease and symptomatic. For patients with acute renal failure, in addition to active chemotherapy and dialysis, plasmapheresis should be performed simultaneously.
Complication
Multiple myeloma nephropathy complications Complications pneumonia
Common complications include pneumonia, sepsis, urinary tract infection, renal amyloidosis, renal failure and renal tubular acidosis, and pathological fractures. Patients with renal impairment have chronic renal failure and high phosphoric acid. Uremic stones can form in hyperemia, hypercalcemia, and hyperuricemia.
Symptom
Multiple myeloma nephropathy symptoms common symptoms nosebleed skin purpura whole blood cell reduction bleeding tendency gum bleeding red blood cells in a string
MM can invade all tissues of the body, and its clinical manifestations are multi-system and diversified, but mainly due to anemia, bone damage and kidney disease. From the perspective of nephrology, its clinical manifestations can be classified into extra-renal and renal manifestations. class.
Extrarenal performance
(1) Blood system: The early stage is mainly anemia. Many patients have anemia as the first symptom. Most of them are positive cells, positive pigment type, and anemia gradually becomes obvious as the condition worsens. This is due to the infiltration of myeloma cells and the destruction of red bone marrow. Can be accompanied by mild hemolysis or shortened red blood cell life, red blood cells on the blood smear showed a string of money, bone marrow examination, abnormal proliferation of plasma cells more than 10% (original, young plasma cells are common), often have a complete blood cell reduction in the later stage, a few The patient has a large number of myeloma cells in the blood, and if it exceeds 2×109/L, it is called plasma cell leukemia.
Clinically, in addition to the symptoms of anemia, there is a tendency to hemorrhage. Nasal bleeding and gum bleeding are common, and there may also be skin purpura. This is due to thrombocytopenia, M protein encapsulates platelet surface, M protein passes immune function and blood coagulation factor I. , II, V, VII and VIII are combined to cause loss of blood coagulation activity and the like.
Some patients have a large increase in plasma M protein, especially IgA is easily aggregated into a multimer, resulting in hyperviscosity, resulting in slow blood flow in the blood vessels, causing tissue congestion, hypoxia, dizziness, dizziness, vertigo, tinnitus, Numbness of the fingers can cause disturbance of consciousness and heart failure. A small number of patients are accompanied by cryoglobulinemia, and there may be Raynaud phenomenon and dry necrosis of the fingertips.
(2) skeletal system: bone pain is one of the main symptoms of MM early, and it increases with the progress of the disease. The pain is more common in the ankle and chest. Occasionally, spontaneous fracture, chest and lumbar destruction, compression of the spinal cord Causes paraplegia or nerve root damage, plasma cells invading bones can also cause lumps of varying sizes, common in ribs, clavicle, sternum and skull, forming beaded nodules at the junction of the chest, ribs and clavicle, and only a few cases damage individual bones It is called solitary myeloma.
Skeletal destruction is mainly caused by abnormal plasma cells secreting osteoclast activating factor, causing osteolytic destruction, inhibiting osteoblast function and causing osteoporosis and focal bone destruction, and increasing serum calcium concentration, while alkaline phosphatase is generally normal.
The X-ray characteristics of bone changes are:
1 Typical osteolytic lesions are perforated, worm-like or small cystic destructive lesions, commonly found in pelvis, ribs, skulls and thoracolumbar vertebrae.
2 Osteoporosis is more common in the spine and pelvis.
3 pathological fractures often occur in the ribs, spine and sternum, X-ray conventional radiographs, CT, ECT, etc. can often find lesions.
(3) Others: extramedullary infiltration of plasma cells can cause liver, spleen and lymph node enlargement, and can also infiltrate other soft tissues. Due to the obvious reduction of normal immunoglobulin, T lymphocyte subsets imbalance and neutropenia, it is easy to be secondary. Infection, respiratory and urinary tract infections, and even sepsis often occur. Perri and Iggo believe that secondary infection is the leading cause of death in MM patients, especially in the second to third months after the initial chemotherapy.
2. Kidney manifestation MM patients will have clinical manifestations of renal damage sooner or later in the course of the disease, about half of them with proteinuria or renal insufficiency as the first complaint, and then bone marrow damage and anemia and other symptoms, clinically misdiagnosed or missed diagnosis Such patients are often misdiagnosed as chronic glomerulonephritis, and Sakhuja et al. retrospectively analyzed 204 patients with MM. After 10 years of follow-up, renal damage was found in 55 patients (27%), and the vast majority of patients (94.5%) showed kidney. Decline, 7.3% of patients with nephrotic syndrome, 53% of MM patients with renal failure can clearly identify predisposing factors including dehydration (33%), hypercalcemia (24%), nephrotoxic drugs (16%) , sepsis (9%), recent surgery (5%) and use of contrast agents (2%), and found in patients with MM involving more severe anemia, hypercalcemia, local-week proteinuria and bone destruction, review The main clinical manifestations of domestic and foreign literatures are summarized as follows:
(1) Simple proteinuria: Proteinuria is an early manifestation of myeloma nephropathy. Some patients only show proteinuria. After several years, other symptoms of myeloma or renal insufficiency appear, so it is easy to be misdiagnosed as glomerulonephritis. Asymptomatic proteinuria or occult nephritis, some people think that myeloma often has an asymptomatic period of about 20 years, called pre-myeloma, only persistent proteinuria, these cases are likely to be immunized by primary benign monoclonal The globulin disease evolved, the main component of urinary protein is light chain protein, ie, the peri-protein, and a clear low molecular protein band was observed on the urinary protein disc electrophoresis [at molecular weight (2.2-4.4) × 104D] When the light chain protein damages the proximal convoluted tubules, in addition to the light chain protein in the urine, 2 microglobulin, lysozyme and albumin are also present, and more middle molecular proteins and high molecular proteins are present, indicating that the lesion has affected the kidney. Small balls, the amount of urine protein can be more or less, 24h urine protein ranging from a few grams to more than 10 grams, even up to 20g, the largest foreign report can reach 70g.
(2) nephrotic syndrome type: this type of clinical is rare, such as the typical manifestations of nephrotic syndrome, most with renal amyloidosis, immune-mediated glomerular disease or light chain-induced nodular glomeruli Sclerosis, it should be noted that the patient's urine discharges a large amount of monoclonal light chain protein, more than 3.5g / d, poor nutrition makes serum albumin reduced, misdiagnosed as primary nephrotic syndrome, but the urine of these patients The dipstick test using the urine protein test paper is often negative, while the acetic acid heating method or the Coomassie Brilliant Blue method is qualitatively 3+~4+, and the albumin is less on the urine protein electrophoresis and the globulin is significantly increased.
(3) renal tubular insufficiency type: renal damage in MM patients is the earliest and most common renal tubules, light chain protein tube type obstructs renal damage caused by distal renal tubules, called myeloma cast nephropathy, Light chain protein decomposes in the epithelial cells of the proximal convoluted tubules, causing toxic damage, also known as light chain nephropathy. The light chain protein in urine is mainly kappa type. In the course of MM, secondary hyperuricemia Hypercalcemia and amyloidosis can lead to renal tubular insufficiency, clinically often expressed as Fanconi syndrome, which can occur several years before the onset of myeloma symptoms. Its clinical features are amino aciduria, glucoseuria, phosphate. Urine, bicarbonate urine and proteinuria below 50kD molecular weight, accompanied by renal tubular acidosis and antidiuretic hormone resistant polyuria, in addition, renal rickets, osteoporosis and hypokalemia can also occur, also Type I renal tubular acidosis occurs.
(4) Acute renal failure: About half of the patients in the MM course suddenly develop acute renal failure, and the pathogenesis is comprehensive, mostly due to a single factor. Chronic tubular damage is the basis, light chain protein Important role, but half of acute renal failure is reversible, the main predisposing factors are:
1 Dehydration caused by various reasons and insufficient blood volume, such as vomiting, diarrhea or diuresis.
2 original hyperuricemia, increased blood uric acid after chemotherapy, leading to acute uric acid nephropathy.
3 serious infection.
4 use nephrotoxic drugs, such as aminoglycoside antibiotics, antipyretic analgesics and contrast agents.
(5) Chronic renal failure: chronic renal failure occurs in patients with myeloma nephropathy, myeloma cells directly infiltrate the renal parenchyma, renal tubular and glomerular damage caused by light chain proteins, renal amyloidosis, hyperuricemia Long-term damage to kidney tissue such as hypercalcemia and hyperviscosity can eventually lead to renal tubular and glomerular failure, severe anemia, nausea, vomiting, loss of appetite, polyuria, nocturia, etc. Chronic uremia syndrome, the renal damage of this disease is mainly tubulointerstitial, so there is often no high blood pressure in chronic renal failure, even if it is often not very serious.
Examine
Examination of multiple myeloma nephropathy
Blood test
(1) Peripheral blood: The degree of anemia is different, the severe anemia is common in the late stage, the white blood cell count can be normal, increase or decrease, the platelet count is mostly reduced, and the red blood cells in the blood sample can form a string shape, which occurs in patients with high plasma globulin. Approximately 20% of patients may have a small number of myeloma cells, and the erythrocyte sedimentation rate is mostly high.
(2) Determination of abnormal globulin:
1 About 95% of patients have hyperglobulinemia and M protein, serum total protein exceeds normal, globulin increases, albumin is normal or decreased, white globulin ratio is inverted, and immunoelectrophoresis is applied. According to the difference of M component, it can be divided into the following Each type: IgG type accounts for 50% to 60%; IgA type accounts for 20% to 25%; condensed protein or light chain type accounts for 20%; IgD type accounts for 1.5%, often accompanied by light chain; IgE type and IgM type It is very rare, accounting for only 0.5% and less than 0.1% respectively. In addition, 1% of patients with multiple myeloma can not isolate M protein in serum, which is called "non-secretory" myeloma, and a few patients still exist in serum. Cryoglobulin, which self-precipitates at a low temperature of 4 ° C, but redissolves at 37 ° C.
2 Ben-week protein: This-week protein is composed of excess light chain, which has a small molecular weight and can be excreted from the urine through the mesangial membrane. 50% to 80% of myeloma patients can be positive. In the early stage of the disease, this - Weekly protein often appears in the gap, often appear in the late stage, so this-week protein is negative, can not rule out the disease, should check urine repeatedly, it is best to check 24h urine or 300 times the urine concentration, in order to improve the positive detection of this protein rate.
(3) Others: Hypercalcemia can occur due to extensive destruction of bone. Blood phosphorus is mainly excreted by the kidneys, so blood phosphorus is normal when kidney function is normal, but blood phosphorus can be significantly increased in patients with advanced renal insufficiency, especially in patients with renal insufficiency. Because myeloma is mainly bone destruction, and no new bone formation, serum alkaline phosphatase is mostly normal or slightly increased, which is significantly different from bone metastasis cancer. Due to the decomposition of tumor cells, glycoprotein destruction, high uric acid may occur. Hyperemia, causing uric acid stones when severe.
2. Abnormal renal function, BUN>10.71mmol/L (30mg/dl), serum Cr>176.8mol/L (2mg/dl).
3. Urine examination is markedly hyperuricemia, which can be seen in amino aciduria, glucoseuria, phosphate urine, bicarbonate urine and proteinuria below 50kD molecular weight. The patient excreted a large amount of monoclonal light chain protein in the urine, exceeding 3.5g/d. Poor nutrition makes serum albumin decrease, misdiagnosed as primary nephrotic syndrome, urine is often negative by dipstick test using urine protein test paper, and acetic acid heating method or Coomassie brilliant blue urine protein qualitative 3+~ 4+, urinary protein electrophoresis has less albumin and a significant increase in globulin.
4. Bone marrow examination has the significance of specific diagnosis. In the early stage of the disease, the bone marrow lesions may be focal and nodular. The negative one examination can not rule out the disease. It is suitable for multi-site puncture. The bone marrow nucleated cells are mostly proliferating active or Significantly active, when the plasma cells are more than 10%, accompanied by morphological abnormalities, the possibility of myeloma should be considered.
5. X-ray examination often has the following signs:
(1) Diffuse osteoporosis.
(2) Osteolytic destruction.
(3) pathological fractures.
Diagnosis
Diagnosis and diagnosis of multiple myeloma nephropathy
Diagnostic criteria
Anyone with one or more manifestations of low back pain, lower extremity pain or dyskinesia, anemia, proteinuria or renal failure with low blood pressure, repeated infection, bleeding and pathological fractures must be considered Possible.
1. American Southwest Cancer Group Diagnostic MM Standard
(1) Main criteria: 1 tissue biopsy is plasmacytoma, 2 bone marrow plasma cells increase, more than 30%, 3M protein IgG>35g/L (3.5g/dl) or IgA>20g/L (2.0g/dl), The light chain is discharged more than 1g per day.
(2) Secondary criteria: 1 increased myeloma cells by 10% to 30%, 2M protein IgG <35g/L (<3.5g/dl) or IgA<20g/L (2.0g/dl), 3 osteolytic lesions , 4 normal immunoglobulin decreased, such as IgM <500mg / L (50mg / dl), IgA <1g / L (100mg / dl), IgG <6g / L (600mg / dl).
(3) For a symptomatic patient, one of the following conditions can be diagnosed: primary diagnostic criteria 1 or 2+ secondary criteria 1, 2 or 3; primary diagnostic criteria 3; secondary diagnostic criteria 1 + 2 + 3 Or 1+2+4.
2. The clinical stage of multiple myeloma is still based on Durie (1982) staging:
(1) Stage I: The following conditions must be met: the number of myeloma cells is <0.6×1012/m2, hemoglobin>100g/L, serum calcium3mmol/L, normal bone X-ray (grade 0) or isolated osteolytic disease only. M protein component IgG <50g, /L, IgA <30g / L; urinary light chain protein <4g / 24h.
(2) Stage II: The number of myeloma cells is between (0.6 ~ 1.2) × 1012 / m2, and other indicators are between stage I and stage III.
(3) Stage III: It must meet one or more of the following: 1 the number of myeloma cells>1.2×1012/m2, 2 hemoglobin<8.5g/L, 3 serum calcium>3mmol/L, 4X line see obvious multiple Osteolytic damage, high productivity of 5M component, IgG>70g/L, IgA>50g/L, urinary light chain protein>12g/24h.
According to the normal renal function or not, the disease can be divided into A, B group: Group A: normal renal function, BUN10.71mmol/L (30mg/dl), serum Cr176.8mol/L (2mg/dl) B. Renal dysfunction, BUN>10.71mmol/L (30mg/dl), serum Cr>176.8mol/L (2mg/dl).
According to the above criteria, abbreviated as IA, IB, IIA, IIB, IIIA and IIIB.
In the diagnosis of MM, it is worth noting that the characteristic symptoms of MM include bone pain, weakness and fatigue. When the patient is diagnosed, M protein can be detected in serum or urine in 98% of cases, and nearly 80% of bone X-ray abnormalities are present. There are renal insufficiency in 1/4 case (serum Cr176.8mol/L). The main cause of renal failure is myeloma kidney and hypercalcemia. The main reason for MM diagnosis is that the number of bone marrow smear plasma cells exceeds 10 %, and see the original, the number of young plasma cells or plasma cells more than 30%; or according to the plasma cell tumor and serum (urine) in the M protein or X-ray has obvious osteolytic lesions, nephrotic syndrome, Renal insufficiency, congestive heart failure, orthostatic hypotension, sensorimotor peripheral neuropathy, and M protein in serum or urine suggestive of primary amyloidosis, and diagnosis depends on biopsy in the presence of amyloid tissue.
When diagnosing MM, special attention should be paid to the identification of monoclonal globulin disease, occult multiple myeloma, plasma cell leukemia, osteosclerosing myeloma, plasmacytoma and heavy chain disease.
1. Reactive plasmacytosis Myeloma has limited plasma cell growth, all of which are normal mature plasma cells. The immunoglobulin is normal polyclonal, and the level is limited (such as IgG<30g/L). The clinical manifestation depends on the original. Onset, no clinical manifestations related to MM.
2. Unknown monoclonal immunoglobulinemia (MGUS).
3. Kidney disease In the elderly patients with kidney damage and bone pain or anemia that is not parallel with renal insufficiency (renal anemia and renal insufficiency degree parallel), the relevant MM examination.
4. Primary macroglobulinemia
(1) Lymphocyte-like plasma cell proliferation in the bone marrow.
(2) Generally no osteolytic lesions.
(3) Hypercalcemia, renal dysfunction is rare.
5. The clinical manifestation of primary systemic amyloidosis is caused by the precipitation of amyloid (ie, the light chain of immunoglobulin) in tissues and organs. Laboratory tests may (but not necessarily) find serum and/or There are monoclonal immunoglobulin light chains in the urine, urinary-peripherin-positive, hypoalbuminemia, renal insufficiency (blood urea nitrogen, elevated creatinine), no myeloma cell infiltration in the bone marrow, and bone-free osteolysis Lesion, no hypercalcemia, high viscosity syndrome.
6. Heavy chain disease is characterized by the synthesis and secretion of incomplete monoclonal immunoglobulin by diseased clonal plasma cells, that is, only the heavy chain and the light chain are absent, and the identification of MM mainly relies on immunoelectrophoresis to find only monoclonal immunity in blood. The presence of a globulin heavy chain, but no monoclonal immunoglobulin light chain, quantitative determination of blood and urine immunoglobulin light chain can help identify heavy chain disease and MM, the former without blood and urine and the latter with blood and urine A monoclonal immunoglobulin light chain is present.
7. Monoclonal immunoglobulin associated with non-plasma disease increases the increase of monoclonal immunoglobulin can also be seen in the following non-plasma cell diseases may be associated with increased monoclonal immunoglobulin: chronic infection, autoimmune disease, malignant Hematological diseases, non-malignant hematological diseases, non-hematological malignancies, nervous system diseases, skin diseases, organ transplants, etc., the identification points are as follows:
(1) The level of increase of monoclonal immunoglobulin is limited, usually IgG<35g/L, IgA>20g/L, and IgM<10g/L.
(2) It does not cause any clinical symptoms by itself, and its clinical manifestation depends entirely on the primary disease.
(3) There were no myeloma cells in bone marrow aspiration, and there was no osteolytic lesion on X-ray examination.
8. Low back pain when the elderly patients with low back pain mainly complained, especially the low back pain was persistent and increased after the activity, local tenderness, accompanied by anemia or erythrocyte sedimentation rate increased significantly, although X-ray examination showed no osteolytic lesions Or compression fractures should also be examined (bone marrow puncture, protein electrophoresis, immunoelectrophoresis, etc.) to rule out or affirm the diagnosis of multiple myeloma.
9. Bone metastases
(1) There is no M component in the general blood, and the level of occasional monoclonal immunoglobulin is limited.
(2) Bone marrow puncture or biopsy can be seen in a pile of metastatic cancer cells, and the morphology and distribution of the cells are significantly different from those of myeloma cells.
(3) The immunophenotype is AE1/AE3 positive.
(4) The clinical manifestations of the primary tumor.
10. Other diseases that violate bones and need to be differentiated from MM. Hyperparathyroidism: Osteoporosis is characterized by extensive decalcification, fibrocystic osteitis and bone cyst formation; no monoclonal immunoglobulin or light in blood and urine Chain, no myeloma cells in the bone marrow.
Differential diagnosis
Lymphoma can invade bones to form bone mass: no myeloma cells in the bone marrow; no extensive osteoporosis and multiple osteolytic lesions.
Other tumors invade bones and form bone tumors: fibrosarcoma, Ein sarcoma, neuroectodermal tumor, angiosarcoma, etc.
