课件：IgA肾病结合内科.ppt

IgA 肾病 IgA nephropathy,Hebei medical university Xu qingyou,definition,IgA nephropathy is the most common glomerulonephritis throughout the world. Primary IgA nephropathy is characterized by deposition of the IgA antibody in the glomerulus.,definition,IgA nephropathy remains the one of the most common, if not the most common, glomerular lesions of all the forms of glomerulonephritis.,IgA nephropathy (also known as IgA nephritis, IgAN, Bergers disease) is a form of glomerulonephritis (inflammation of the glomeruli of the kidney).,definition,IgA nephropathy was initially described in the late 1960s by Berger and Hinglais, and patients were described on the basis of the finding of predominant IgA deposition(and ,to a lesser extent, other immunoglobulins) in the mesangium with a mesangial proliferation, and with clinical features that span the spectrum from asymptomatic hematuria to repidly progressive glomerulonephritis.,Berger J,Hinglais N. J Urol Nephrol 1968, 74: 694,definition,The distribution of IgA nephropathy varies in the different geographic regions throughout the world. It was the most common form of primary glomerular disease in Asia, evident in up to 30% to 40% of all biopsies, 20% in Europe, and 10% of all biopies performed for glomerular disease in North America.,30% to 40%,10%,20%,Signs and symptoms,The classic presentation (in 40-50% of the cases) is episodic frank hematuria which usually starts within a day or two of a non-specific upper respiratory tract infection (hence synpharyngitic) as opposed to post-streptococcal glomerulonephritis which occurs some time (weeks) after initial infection. Less commonly gastrointestinal or urinary infection can be the inciting agent. All of these infections have in common the activation of mucosal defenses and hence IgA antibody production. Loin pain can also occur. The gross hematuria resolves after a few days, though microscopic hematuria may persist. These episodes occur on an irregular basis every few months and in most patients eventually subsides (although it can take many years). Renal function usually remains normal, though rarely, acute renal failure may occur . This presentation is more common in younger adults.,Signs and symptoms,A smaller proportion (20-30%), usually the older population, have microscopic hematuria and proteinuria (less than 2 gram/day). These patients may not have any symptoms and are only clinically found if a doctor decides to take a urine sample.,Proteinuria 2g/day microscopic hematuria,Signs and symptoms,Very rarely (5% each), the presenting history is: Nephrotic syndrome (3-3.5 grams of protein loss in the urine, associated with a poorer prognosis) Acute renal failure (either as a complication of the frank hematuria, when it usually recovers, or due to rapidly progressive glomerulonephritis which often leads to chronic renal failure) Chronic renal failure (no previous symptoms, presents with anemia, hypertension and other symptoms of renal failure, in people who probably had longstanding undetected microscopic hematuria and/or proteinuria),Nephrotic syndrome,Acute renal failure,Chronic renal failure,Signs and symptoms,Reich HN, et al. J Am Soc Nephrol 2007, 18: 3177,蛋白尿g/d 6个月测定的均值,肾脏存活率,Diagnosis,In children and younger adults, the history and association with respiratory infection can raise the suspicion of IgA nephropathy.,Diagnosis,For an adult patient with isolated hematuria, tests such as ultrasound of the kidney and cystoscopy are usually done first to pinpoint the source of the bleeding. These tests would rule out kidney stones and bladder cancer, two other common urological causes of hematuria.,hematuria,Diagnosis,A kidney biopsy is necessary to confirm the diagnosis. The biopsy specimen shows proliferation of the mesangium, with IgA deposits on immunofluorescence and electron microscopy.,kidney biopsy,Diagnosis,Other blood tests done to aid in the diagnosis include CRP or ESR, complement levels, ANA, and LDH. Protein electrophoresis and immunoglobulin levels can show increased IgA in 50% of all patients.,Diagnosis,A urinalysis will show red blood cells, usually as red cell urinary casts. Proteinuria, usually less than 2 grams per day, also may be present. Other renal causes of isolated hematuria include thin basement membrane disease and Alport syndrome, the latter being a hereditary disease associated with hearing impairment and eye problems.,Morphology,Histologically, IgA nephropathy may show mesangial widening and focal and segmental inflammation. Diffuse mesangial proliferation or crescentic glomerulonephritis may also be present.,Immunoflourescence shows mesangial deposition of IgA often with C3 and properdin and smaller amounts of other immunoglobulins (IgG or IgM),Natural history,Complete remission, a normal urinalysis, occurs rarely in adults, in about 5% of cases. Thus, even in those with normal renal function after a decade or two, urinary abnormalities persist in the great majority. In contrast, 30 50% of children may have a normal urinalysis at the end of 10 years. However, given the very slow evolution of this disease, the longer term (20 30 years) outcome of such patients is not yet established.,a normal urinalysis,urinary abnormalities,a decade or two,Therapy,Patients with isolated hematuria, proteinuria 1 g/day and normal renal function have a benign course and are generally just followed up annually. In cases where tonsillitis is the precipitating factor for episodic hematuria, tonsillectomy has been claimed to reduce the frequency of those episodes. However, it does not reduce the incidence of progressive renal failure.,normal renal function,followed up,Therapy- steroids,A subset of IgA nephropathy patients, who have minimal change disease on light microscopy and clinically have nephrotic syndrome, show an exquisite response to steroids, behaving more or less like minimal change disease.,In other patients, the evidence for steroids is not compelling. Short courses of high dose steroids have been proven to lack benefit. However, in patients with preserved renal function and proteinuria (1-3.5 g/day), a recent prospective study has shown that 6 months regimen of steroids may lessen proteinuria and preserve renal function.,Therapy -Cyclophosphamide,Cyclophosphamide had been used in combination with anti-platelet/anticoagulants in unselected IgA nephropathy patients with conflicting results. Also, the side effect profile of this drug, including long term risk of malignancy and sterility, made it an unfavorable choice for use in young adults. However, one recent study, in a carefully selected high risk population of patients with declining GFR, showed that a combination of steroids and cyclophosphamide for the initial 3 months followed by azathioprine for a minimum of 2 years resulted in a significant preservation of renal function.Other agents such as mycophenolate mofetil, ciclosporin and mizoribine have also been tried with varying results.,Therapy- omega-3 fatty acids,A study from Mayo Clinic did show that long term treatment with omega-3