主任查房 武金城.ppt

主任查房,武金城 49/M 2012-5-16,病例特点,中年男性，隐袭起病，慢性病程 肾脏受累 大量蛋白尿、低白蛋白血症、肾功能受损 糖尿病、非活动性HBsAg携带,诊断与鉴别诊断ARF or A/C,急性肾衰竭,肾前性肾衰竭,肾性肾衰竭,肾后性肾衰竭,肾小球性,肾小管性,肾间质性,肾血管性,无证据,无证据,肾小球：,急进性肾小球肾炎 支持：蛋白尿 ANA、ANCA-PR3 （-）；无明显血尿,肾间质：,急性间质性肾炎、特发性急肾衰 支持点：有可疑用药史、蛋白尿、肾小管损伤证据 不支持点：无相应体征、血嗜酸细胞正常、蛋白尿量大,肾小管：,急性肾小管坏死 支持：用药史、有近端肾小管重吸收功能障碍 不支持：无明显少尿、无尿及多尿的病程，低比重尿,肾血管,肾动脉狭窄、血栓 肾静脉血栓 血栓性微血管病,肾脏本病,的诊断 大量蛋白尿(尿蛋白3.5/) 低蛋白血症(血浆白蛋白30/) 水肿 高脂血症,诊断思路,是否,否,原发性或继发性,是,继发性,原发性,推测病理诊断,病因诊断,有无并发症,常见病因及病理类型,DKD临床特点,J Am Soc Nephrol , 2010, 21: 556563,Diagram,Diagram,NDRD线索,Absence of diabetic retinopathy; Low or rapidly decreasing GFR; Rapidly increasing proteinuria or nephrotic syndrome; Refractory hypertension; Presence of active urinary sediment; Signs or symptoms of other systemic disease; 30% reduction in GFR within 2-3 months after initiation of an ACE inhibitor or ARB.,AJKD,VOL 49, NO 2, SUPPL 2, FEBRUARY 2007 /professionals/kdoqi/guideline_diabetes/guide1.htm,其他,糖尿病病史短 尿蛋白分子量测定特点,肾脏病理,Membranous Nephropathy（MN）,distinct clinicopathologic entity by David Jones in 1957 Nephrotic glomerulo nephritis. Am J Pathol. 1957;33:313-329. Circulating autoantibodies (immunoglobulin G4 and G1 subclasses) interacting with antigens native to or planted in the Glomerular capillary wall at the podocyte cell membranebasement membrane Interface generally are regarded as the fundamental pathobiological mechanism MN now is regarded as a podocytopathy,americanJournalofKidneyDiseases, Vol56,No1(July),2010:pp157-167,IgG subclasses,named according to their abundance in the serum: IgG1 comprises 60 to 70 percent of total IgG IgG2 comprises 20 to 30 percent IgG3 comprises 5 to 8 percent IgG4 comprises 1 to 4 percent,Serum IgG subclasses in normal adults. Monogr Allergy 1986; 19:100.,Doi T，Mayumi M，Kanatsu K，et alDistribution of IgG subclasses in membranous nephropathyClin Exp lmmunol，1984，58：57-62,IgG1、IgG3 通过Th1细胞分泌的细胞因子IL-2、IFN-r、TNF-发挥细胞毒作用 IgG1 and IgG3 fix C1q most effectively while IgG2 does so weakly. IgG4 通过Th2系统激活B细胞参与免疫反应 IgG4 does not bind complement at all,IgG subclass restriction (antibody responses to certain types of pathogens) : bacterial polysaccharide antigens, such as the capsular antigens of pneumococcus, are composed mainly of IgG2 molecules protein antigens and viral antigens are composed predominantly of IgG1 and IgG3 IgG4 incompletely understood, although the finding that antibody responses to chronic schistosomiasis and filariases are primarily composed of IgG4 molecules suggests that IgG4 may play a role in the immune response against parasitic disease,IMN患者肾组织中仅IgG4沉积或IgG4沉积为主， 可伴有IgG1沉积,1. Imai H，Hamai K，Komatsuda A，et alIgG subclasses in patients with membranoproliferative glomerulonephritis，membranous nephropathy，and lupus nephritisKidney Int，1997，51：270-276 2. Kuroki A，Shibata T，Honda H，et alGlomerular and serum IgG subclasses in diffuse proliferative lupus nephritis，membranous lupus nephritis，and idiopathic membranous nephropathyIntern Med，2002，41：936-942,提示IMN可能与多条免疫反应途径有关，但以Th2介导的体液免疫反应为主,M-Type Phospholipase A2 Receptor as Target Antigen in Idiopathic MN,M-PLA2R抗体-adult IMN antigen 存在于正常足细胞表面的膜蛋白，其在肾组织有高水平表达。 大多数特发性膜性肾病患者有抗PLA2R构象依赖性表位的抗体，是该病一种主要抗原。,M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathyJN EngI J Med，2009，361(7)：11-21,IMN患者血清中的抗PLA2R自身抗体主要为IgG4亚型,M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathyJN EngI J Med，2009，361(7)：11-21,病理上DKD与MN区分,FM 抗体种类、沉积成分 沉积部位 荧光图像 LM EM,亚急性小管间质病,IgG4-related systemic disease,Proposal for diagnostic criteria for IgG4-related kidney disease,Between 2004 and 2011, we identied 41 patients with IgG4-RKD in 5 University Hospital,Clin Exp Nephrol (2011) 15:615626,IgG4-associated idiopathic tubulointerstitial nephritis complicating autoimmune pancreatitis Nephrol Dial Transplant (2004) 19: 474476 IgG4-related Chronic Tubulointerstitial Nephritis without Autoimmune Pancreatitis and the Time Course of Renal Function Inter Med 49: 1593-1598, 2010,Characteristic tubulointerstitial nephritis in IgG4-related disease,well-demarcated borders between involved and uninvolved areas;,Human Pathology (2012) 43,536549,involvement of the cortex and medulla, often extending beyond the renal capsule and with occasional extension to retroperitoneal fibrosis;,Interstitial inflammatory cells comprising predominant lyplasma cells and lymphocytes,with a high prevalence of IgG4-positive cells often admixed with fibrosis;,peculiar features of Interstitial fibrosis resembling a “birds-eye” pattern comprising fibrosis among interplasma cell spaces;,Deposits visible by light and immunofluorescent microscopy in the tubular basement membrane,Bowman capsule, and interstitium that are restricted to the involved portion, sparing normal parts.,Membranoproliferative Glomerulonephritis-Like Glomerular Disease and Concurrent Tubulointerstitial Nephritis Complicating IgG4-Related Autoimmune Pancreatitis Inter Med 48: 157-162, 2009 IgG4-Related Tubulointerstitial Nephritis With MembranousNephropathy AmJKidneyDis.2011;58(2):320-324,Diagnosis of Autoimmune Pancreatitis: The Mayo Clinic Experience,On the basis of this experience we propose that diagnosis of AIP can be made in patients with 1 of these criteria: (1) diagnostic histology, (2) characteristic imaging on computed tomography and pancreatography with elevated serum IgG4 level, or (3) respon