1、Department of Nephrology, First Affiliated Hospital Sun Yat-sun University 陈 崴,Glomerular disease,outline,Anatomy and function General pathogenesis Clinical syndromes and presentation Specific glomerular diseases,Anatomy and function,Anatomy,Anatomy,Renal Function,Remove wastes Maintain homeostasis
2、Secrete EPO,Anatomy-nephron,Glomerular Anatomy,Capillary Lumen,Endothelial cell,Glomerular basement membrane,Epithelial cell,Podocytes,Structure of normal glomerular capillary,系膜细胞,系膜基质,内皮细胞,上皮细胞足突,General pathogenesis,What causes glomerular disease ?,Most are of immunologic origin, and caused by im
3、mune complexes !,Antibody mediated GN - Circulating Immune complex,Location: Mesangial and sub-endothelial,Antibody mediated GN - In-situ Immune complex,Location: GBM sub-epithelial,Antibody mediated GN - In-situ Immune complex (trapped Ag),Location: GBM sub-epithelial,pathogenesis,Glomerular Filtra
4、tion Barrier,Glomerular Filtration Barrier Injury,Fusion of foot process : Proteinuria GBM Injury : Hematuria/ Proteinuria,Classification of Glomerular Disease,Etiology,Pathology,Clinical Features,Clinical syndromes and presentation,Characteristics of Glomerular Diseases,Parameter,Glomerular,Tubuloi
5、nterstitial,ProteinuriaMW of ProteinRenal morphologyRBC Morphology,Massive+ 1.52.0g/d Large/Medium/SmallSymmetrydysmorphic,Small amount2+ 1.0g/d SmallAsymmetrynormal,Clinical syndromes and presentation,Latent GN,Nephrotic syndrome,Acute GN,RPGN,Chronic GN,镜下或肉眼血尿蛋白尿,畸形红细胞, 棘型红细胞,蛋白尿3.5g/d 低蛋白血症 高脂血症
6、 水肿,血尿 蛋白尿(1-3g/d) ARF 水肿 高血压 红细胞管型,急进的肾功能 恶化 血尿,蛋白尿 进行性少尿,无尿 红细胞管型 有或无系统症状,血尿 蛋白尿 高血压 肾功能 减退,How are glomurular diseases diagnosed ?,Usually by history, physical findings, Urinalysis and other laboratory data. Occasionally a renal biopsy must be performed !,Renal Biopsy Processing,Renal Biopsy Proc
7、essing,Renal Biopsy Processing,Renal Biopsy Processing,Pathology,PAS MASSON H&E PASM,Pathological classification of GN,轻微病变性肾小球肾炎minimal change glomerulonephritis 局灶节段性病变 focal segmental lesions 弥漫性肾小球肾炎 diffuse glomerulonephritis膜性肾病 membranous nephropathy 增生性肾炎 proliferative glomerulone-phritis 硬化
8、性肾炎 sclerosing glomerulonephritis 未分类性肾小球肾炎 unclassified glomerulo-nephritis,增生性肾炎 proliferative glomerulone-phritis 系膜增生性肾小球肾炎 mesangial proliferative GN毛细血管内增生性肾小球肾炎 endocapillary proliferative GN系膜毛细血管内增生性肾小球肾炎 mesan-gial capillary GN新月体肾炎 crecentic GN,Pathological classification of GN,Clinical s
9、yndromes of glomerular diseases,Asymptomatic hematuria/ or proteinuria Nephrotic syndrome Acute glomerular nephritis Rapidly progressive glomerular nephritis Chronic glomerular nephritis,Asymptomatic hematuria/ or proteinuria Latent nephritis,Mild chronic GN or recovery phase of acute GN Isolated mi
10、croscopic hematuria (Dysmorphic RBC) Isolated proteinuria No HBP, edema or Azotemia Treatment is similar to chronic GN,CASE I,11 year-old male History: Intermittent hematuria x 1 yearHx of recurrent pharyngitis Physical: tonsillitis Urinalysis: 15 RBC/HPF1 proteinRBC casts Lab Data: dysmorphic RBC,T
11、he Patient Has IgA nephropathy!,IgA Nephropathy,Most common GN Mesangioproliferative or other pathological types Predominent mesangial IgA deposit Persistent or episode of hematuria Exacerbate on infection 1/3 have elevated serum IgA,Clinical syndromes of glomerular diseases,Asymptomatic hematuria/
12、or proteinuria Nephrotic syndrome Acute glomerular nephritis Rapidly progressive glomerular nephritis Chronic glomerular nephritis,Nephrotic Syndrome,Insidious onset Manifestations Proteinuria 3.5g/d Hypoalbuminemia alb 30 g/l Edema Hyperlipidemia,Nephrotic syndrom-etiology(1),Primary Nephrotic synd
13、rom minimal change disease FSGSmembranous nephropathymembranoproliferative GNIgAN,Nephrotic syndrom-etiology(2),Secondary Nephrotic syndrom Autoimmunity:SLE, Infection: Hepatitis B or C,HIVTumor: solid carcinoma, lymphomaMetabolic: DM, AmyloidosisDrugs: NSAIDS,Nephrotic syndrom-epidemiology,Children
14、 Yong people Old people Primary MCD FSGS,MsGN MNMPGN Secondary HSP SLE DNHepatitis B HSP TumorInherited NS Hepatitis B MM , AL,14 year-old, male, high-school student History: No significant medical historyFatigue x 3 weeksEdema x 1 week Physical: Mild generalized edema Urinalysis: 4 proteinMany hyal
15、ine castsFew granular casts No RBCs or RBC casts Lab Data: proteinuria 4g/d , alb 20g/l,normal renal function, Hepatitis (-), Auto-immunity Ab (-) Renal biopsy,CASE II,The patient has Minimal change disease!,Electron Microscopy: effacement of foot processes,Introduction,Incidence:,Etiology:,Clinical
16、 Features:,Clinical Course:,Loss of net negative charge on capillary basement membrane.,Nephrotic syndrome. Prominent proteinuria & edema No hypertension,Sensitive to steroid, relapse may occur.,80% of nephrotic syndrome in children,Minimal Change Disease,CASE III,65 year-old, male, Smoke for 40 yea
17、rs History: Fatigue x 3 monthsCough and chest pain x 2 months Facial edema x 1 week Physical: edema, Urinalysis: protein + Lab Data: proteinuria 8g/d , alb 24g/l, normal renal function, Hepatitis (-), Auto-immunity Ab (-),Why is a thorough Clinical evaluation important in patients with the nephrotic
18、 syndrome !,Many such patients have an occult malignancy !,CASE III,Lung Carcinoma,CASE III,LM-PASM:”spikes” along the GBM,CASE III,IF: IgG deposition along GBM,CASE III,EM: subepithelial electron dense material,Its Clearly a case Of carcinoma related Membranous nephropathy !,CASE II-MN,Commonly occ
19、urred in middle&old-agedpeople Etiology：Primary Secondary ：Tumor-related, Hepatitis B related , Drugs - related Presentation: HT & Renal failure, Thrombosis,Introduction,Membranous Nephropathy,Incidence:,Etiology:,Path:,Clinical Course:,Immune complex disease. May associated with carcinomas, infecti
20、ons, drugs, and heavy metals.,Some adults develop ESRD.,Diffuse, uniform basement membrane thickening with subepithelial projections (“spikes”).,Commonly occurred in middle&old-aged people,How to treat the Nephrotic Syndrome?,Pathogenesis/Complication,Treatment of NS,Liver,Edema,Hypoalbuminemia,Glom
21、 inflammation,Proteinuria ,Permeability,Lipoprotein Synthesis,Blood Lipid,Primary,Secondary Causes,Treatment of Complication,Blood volume,Thrombosis,CV disease,ARF,Infection,Antithrombotic,Anti-infection,Diuretics/Dialysis,Statins,0.25mg/kg.d,Slow the speed of tapering,1mg/kg.d8w,0.5mg/kg.d,Taper 5m
22、g per week,How to use glucosteroids(1),Maintenance for 1 year,0.25mg/kg.d,Slow the speed of tapering,1mg/kg.d8w,0.5mg/kg.d,Taper 5mg per week,How to use glucosteroids(2),Maintenance for 1 year,Sufficient initial dose,0.25mg/kg.d,Slow the speed of tapering,1mg/kg.d8w,0.5mg/kg.d,Taper 5mg per week,How
23、 to use glucosteroids(3),Maintenance for 1 year,Sufficient initial dose,Slow tapering,0.25mg/kg.d,Slow the speed of tapering,1mg/kg.d8w,0.5mg/kg.d,Taper 5mg per week,How to use glucosteroids,Maintenance for 1 year,Sufficient initial dose,Slow tapering,Long maintenance,Clinical syndromes of glomerula
24、r diseases,Asymptomatic hematuria/ or proteinuria Nephrotic syndrome Acute glomerular nephritis Rapidly progressive glomerular nephritis Chronic glomerular nephritis,急性肾小球肾炎 Acute GN,History of streptococcus infection 2 weeks ago Acute onset Prominent hematuria and RBC casts ARF & HT Low C3，for 8wee
25、ks ESR increased，Anti-DNAseB（）,急性肾小球肾炎 Acute GN,急性肾小球肾炎 Acute GN,Clinical syndromes of glomerular diseases,Asymptomatic hematuria/ or proteinuria Nephrotic syndrome Acute glomerular nephritis Rapidly progressive glomerular nephritis Chronic glomerular nephritis,Rapid progressive GN,Similar to acute
26、GN on onset Rapid deterioration of renal function Cr , Oliguria and obvious macroscopic hematuria Crescent formation50% Need aggressive therapy(Large dose of steroid pulse therapyCTX；Plasmaphoresis),Rapid progressive GN,Rapid progressive GN,Clinical syndromes of glomerular diseases,Asymptomatic hema
27、turia/ or proteinuria Nephrotic syndrome Acute glomerular nephritis Rapidly progressive glomerular nephritis Chronic glomerular nephritis,Chronic glomerulonephritis,Proteinuria(3.5g/d) Hematuria Hypertension Edema Azotema(BUN/Cr),Chronic GN,NS,Treatment of Chronic GN,Reduce proteinuria Control hyper
28、tension ACE-I or AT II receptor blocker/antagonist(ARB) Low protein and low P diet for azotemia Avoid nephrotoxic agents Anti-platelet aggregation Also applicable to NS in remission or partial remission,Summary, glomerular permeability caused by primary or secondary etiology Immunosuppressvie (Stero
29、ids, cytotoxic agents and CsA) reduced permeability by suppression of glomerular inflammation Immunosuppressive is a double-edged sword (careful monitoring) ACEI/ARB reduces proteinuria in addition to lowing of blood pressure Control Blood pressure play a pivotal role in renal protection The only di
30、fference between chronic GN and NS is the extent of proteinuria, immunosuppressives are for reduction of proteinuria. Other treatments are similar,TAKE HOME MESSAGE ！,One important clinic syndrome of glomerular disease: Nephrotic syndrome ! Diagnosis is based on thorough clinic evaluation ! Renal biopsy is critical for diagnosis !,THANKS ！,,
