Cryoglobulinemia kidney damage
Introduction
Introduction to cryoglobulinemia and renal damage Cryoglobulin refers to a type of globulin that precipitates or freezes when the plasma temperature drops to 4-20 ° C. When the temperature rises to 37 ° C, the normal serum contains only traces of cryoglobulin. When its concentration exceeds 100 mg/L, it is called cryoglobulinemia. Patients with elevated serum cryoglobulin are often accompanied by glomerular lesions, called renal malaglobulinemia (renaldamageduetocryoglobulinemia). basic knowledge The proportion of illness: 0.002% Susceptible people: no special people Mode of infection: non-infectious Complications: uremia acute renal failure
Cause
Causes of renal damage in cryoglobulinemia
Systemic vasculitis (30%):
Systemic vasculitis is a group of diseases caused by vascular inflammatory lesions that can affect arteries, veins, capillaries, and even lymphatic vessels. Because of the different parts, size, type and pathology of the affected blood vessels, its clinical manifestations are diversified.
Leukemia (20%):
Leukemia is a type of malignant clonal disease of hematopoietic stem cells. Clonal leukemia cells proliferate and accumulate in bone marrow and other hematopoietic tissues due to uncontrolled proliferation, differentiation disorders, and blocked apoptosis, and infiltrate other tissues and organs, while normal hematopoiesis is inhibited. Clinically, varying degrees of anemia, hemorrhage, infection, fever, and swelling of the liver, spleen, lymph nodes, and bone pain can be seen.
Hepatitis C (20%):
Hepatitis C virus, referred to as hepatitis C and hepatitis C, is a viral hepatitis caused by hepatitis C virus (HCV) infection, which is mainly transmitted by blood transfusion, acupuncture, and drug use.
The main cause of cryoglobulinemia is due to abnormal immunoglobulins in the circulation of patients with various diseases in cold conditions, including SLE, glomerulonephritis after acute streptococcal infection, systemic vasculitis, leukemia, C Hepatitis and other acute and chronic infections, Sjogren's syndrome, Wald enstrom macroglobulinemia and multiple myeloma, the factors that cause the development of glomerulonephritis depend on the activity of cryoglobulin, and cutaneous vasculitis needs The activity of cryoglobulin and rheumatoid factor suggests that skin and kidney vasculitis have different pathogenesis, but the common feature is that immunoglobulin coagulates under cold conditions and deposits in small blood vessels in the whole body to cause vascular inflammatory diseases.
Pathogenesis
Cryoglobulinemia is mainly caused by vasculitis caused by the deposition of circulating immune complexes and complement in the small and medium blood vessels of the whole body. The incidence of nephropathy of type II and III in primary cryoglobulinemia is high, especially II. More common, these cold globulins are mostly antigen-antibody complexes, which reach the kidney with blood flow, deposit on the glomerular capillary wall, and activate complement to cause a series of inflammatory reactions. The pathogenesis is similar to the immune complex glomerulonephritis. In addition to the above mechanisms, some patients are also involved in the onset of disease, such as thrombosis in the glomerular capillary lumen, containing cryoglobulin, no complement components, cold balls in the skin and renal vasculitis. In patients with proteinemia, IgG and IgM are deposited on the capillary wall, and complement components are rarely seen. These lesions may be caused directly by cryoglobulin, and the development of cold immunoglobulin-associated glomerulonephritis may be related to A defect in the function of the Fc receptor in the reticuloendothelial system is associated with kidney disease, which is very common if the circulating cryoglobulin concentration exceeds 1 g/dl.
Prevention
Cold blood globulinemia prevention of kidney damage
1. Do not underestimate the cold. Most chronic kidney diseases are immune diseases. Colds or infections can induce immunity and accelerate disease development.
2. Work and rest combine to rest, the body's metabolites increase after the work, increase the workload of the kidneys, can make the condition worse, so avoiding the tired rest is beneficial to the recovery of kidney function.
Complication
Cold globulinemia renal damage complications Complications uremia acute renal failure
Often complicated by vasculitis syndrome of the whole body skin and chronic uremia of the kidney, severe cases can be complicated by acute renal failure.
Symptom
Cryoglobulinemia, renal damage symptoms, common symptoms, skin purpura, chronic kidney damage, cold globulin, sinking... Nephrotic syndrome, renal failure, hepatosplenomegaly, polymorphic cryoglobulinemia, lymphadenopathy, hematuria
1. The basic types of cryoglobulinemia are divided into three types:
(1) Monoclonal cryoglobulinemia (type I): IgM is the most common immunoglobulin, followed by IgG, IgA and light chain proteins, common in multiple myeloma and primary macroglobulin blood. Symptoms (50%), other lymphoproliferative disorders and a few autoimmune diseases (25%), primary cryoglobulinemia accounts for about 25%, this type of malignant disease most common in the hematopoietic system, patients The white blood cell count in the blood increases erroneously because of the formation of large polymers, the erythrocyte sedimentation rate is faster at 37 ° C than at room temperature, and the concentration of C 4 is significantly lower than C 3 .
(2) Monoclonal-polyclonal cryoglobulinemia (type II): serum contains a monoclonal immunoglobulin with anti-polyclonal immunoglobulin activity. This monoclonal immunoglobulin is mostly IgM. Secondly, it is IgG and IgA, so it constitutes IgM-IgG type, IgG-IgG and IgA-IgG type immune complexes, more common in multiple myeloma, primary macroglobulinemia and other lymphoproliferative diseases (60 % to 70%), autoimmune disease (30%) and primary cryoglobulinemia accounted for 10%, this type is often associated with glomerular disease, infectious disease (virus or bacteria, especially hepatitis C) Related to viruses, anti-hepatitis C virus antibodies, hepatitis C virus core antigen and hepatitis C virus RNA are found in cold globulin and kidney sediments of patients with hepatitis C virus infection. Interferon alpha treatment can be temporarily To improve its clinical symptoms, it is estimated that 50% to 75% of patients have a potential hepatitis C virus infection.
(3) Polyclonal cryoglobulinemia (type III): Two or more clones of Ig in serum constitute IgM-IgG, IgM-IgG-IgA and other complexes, more common in chronic infections (such as HCV infection) And autoimmune diseases (30% to 50%), lymphoproliferative diseases (10% to 15%), 40% of patients with primary cryoglobulinemia, Abrahamian and other case-control analysis found that HCV-positive Liver transplant patients, 20% with type III cryoglobulinemia, clinically common with purpura and glomerulonephritis, pathological membrane proliferative glomerulonephritis.
2. Clinical manifestations of cryoglobulinemia
(1) Primary cryoglobulinemia is more common in young people and middle-aged people. Women are slightly more than men. When patients experience cold surface temperature decrease, cryoglobulin in the extremity vessels precipitates or is jellyd. Shape, block the capillaries, and cause ischemic necrosis and vasospasm in the blood vessel wall, purpura and cold urticaria on the skin are most common, some patients may have Raynaud's phenomenon, patients may have joint pain, hepatosplenomegaly, Lymph node enlargement, peripheral neuritis (such as paresthesia and numbness) and vasculitis syndrome, etc., individual patients may have cryoglobulinemia calf ulcer, mainly due to vasculitis of the skin.
(2) clinical manifestations of renal damage: acute renal damage is more common in type III cryoglobulinemia, symptoms like acute glomerulonephritis, some patients with acute renal failure.
Chronic renal damage is more common in type II cryoglobulinemia, with persistent asymptomatic proteinuria and hematuria and nephrotic syndrome as the main manifestations, with varying degrees of renal dysfunction and later development to chronic uremia.
Examine
Examination of renal damage in cryoglobulinemia
Serum protein electrophoresis
The gamma globulin is increased, the immunoglobulin (especially IgG, IgM) is increased, the rheumatoid factor is positive, the C3 is decreased, and the erythrocyte sedimentation rate is increased.
2. Determination of cryoglobulin
According to the precipitation of cold globulin at 4 ° C, polymerization at 25 ~ 30 ° C, 37 ° C dissolution characteristics, anti-coagulation with EDTA or sodium oxalate, blood was taken with a 37 ° C syringe, after centrifugation, the plasma was separated, a small amount of sodium azide was preserved, The plasma was divided into two Wintrobe sub-vessels, and the tube was placed in a refrigerator at 4 ° C. The control tube was placed in a 37 ° C incubator for 72 h. The tube was precipitated and the control tube was not precipitated positive. The cold globulin is quantitatively determined.
3. Optical microscope
In patients with acute renal failure, under the light microscope of kidney biopsy, it is generally found that there are extensive capillary proliferation or glomerular capillary damage in the glomeruli with large amount of subendothelial sediments and large deposits in the crescent. Round intraluminal thrombi, these are large subendothelial deposits, or deposition of cryoglobulin in the lumen, sometimes deposited in monocytes, and these lesions are found by non-specific esterase staining. Intracellular is very common, and 1/3 of the kidney biopsy specimens can be seen with obvious vasculitis.
4. Immunofluorescence microscope
It can be found in the capillary wall, the granular deposits of the mesangium and the C3, IgG and IgM mass deposits in the lumen. These deposits are immunologically similar to the circulating cryoglobulin, only A small amount of C1q deposition, there may be IgM deposition in the interstitium.
5. Electron microscope
Large deposits in the capillary wall and electron density deposits of the crystalline structure can be found.
Diagnosis
Diagnosis and diagnosis of renal damage in cryoglobulinemia
diagnosis
First of all, it should be affirmed whether the blood cold globulin is increased, making a diagnosis of cryoglobulinemia, clinical appearance of purpura and urticaria, or Raynaud's phenomenon, joint pain, liver, spleen, lymphadenopathy and peripheral neuritis. Performance, can determine the diagnosis of cryoglobulinemia, after which, further classification can be made; combined with clinical and laboratory to identify the cause, and then diagnose the primary and secondary cryoglobulinemia, such as with renal damage, The disease should be diagnosed in conjunction with laboratory findings and renal biopsy.
Differential diagnosis
1. Differentiation from glomerular disease as early as 1975, McIntosh et al. in 75 patients with glomerulonephritis after streptococcal infection and 16 patients with acute glomerulonephritis after non-streptococcal infection, in the serum within 1 month of onset Chronic globulin was found, glomerular deposits were mainly IgG-C3 or IgG-IgM-C3, 1 case contained fibrinogen, and 20% to 50% serum cryoglobulin in membrane proliferative glomerulonephritis type I Positive, C3 is mostly normal, in addition to the presence of IgM-IgG or IgM-IgA in the serum of patients with acute glomerulonephritis.
2. Primary and secondary cryoglobulinemia for identification of primary cryoglobulinemia refers to the presence of cryoglobulin in the blood, but no obvious cause can be found, patients with secondary cryoglobulinemia Have a clear cause.
In addition to multiple myeloma, primary macroglobulinemia and other lymphoproliferative diseases, such as allergic purpura, systemic lupus erythematosus, Sjogren's syndrome, shunt nephritis, necrotizing vasculitis and Cold globulin may also be present in the serum of some patients such as rheumatoid arthritis, and these diseases can cause kidney damage, and cold globulin is confirmed at the lesion.
