肾病综合征（英文）儿科课件

Nephrotic Syndrome Department of Prdiatrics, Tongji Hospital Nephrotic Syndrome Definition Etiology Pathology Pathophysiology Clinical Manifestation Laboratory Data Diagnosis Therapy and Prognosis Male 4 years and 6 months old Complaint of edema and oliguria Definition: Nephrotic Criteria Massive proteinuria ISKDC: 40mg/m2/hr CAN: + trice/2w or 50-100mg/kg/24hr Mendoza: Urine Protein/Cr 2.0 Hypoalbuminemia: 5.72mmol/L Edema Definition: Nephritic Criteria Hematuria: RBC +( 10 /HP), trice/2w Hypertension: 130/90 mmHg in children over 7y 120/80 mm Hg in 3-6y children 110/70 mm Hg in 6.4mmol/L, Cr 133umol/L Hypocomplementemia: C313y patients causesDIAMOND Secondary NS : DIAMOND Infection: APSGN, HBV, HIV,shunt nephropathy, reflux nephropathy, leprosy, syphilis, schistosomiasis, hydatid disease Drug,Toxic,Allegy: mercury, snake venom, vaccine, pellicillamine, Heroin,gold, NSAID, captopril, probenecid, volatile hydrocarbons Neoplasma: Hodgkins disease, carcinoma ( renal cell, lung, neuroblastoma, breast, and etc) Autoimmune or collagen-vascular diseases: SLE, Hashimotos thyroiditis, EMC, HSP, Vasculitis Genetic Disease: Alport syn., Fabry syn., Nail-patella syn., Sickle cell disease, Amyloidosis, Congenital nephropathy Metabolic disease: Diabetes mellitus Others: Chronic transplant rejection, congenital nephrosclerosis Pathology Primary NS: Minimal Change Nephropathy (MCN): 80% Mesangial proliferative glomerulonephritis (MsPGN): 10-12% Focal segmental glomerulosclerosis (FSGS): 5% Others: Membranous Nephropathy (MN) most common in adults Membrane proliferative glomerulonephritis (MPGN): 2-5% Cresent glomerulonephritis: rare, Crescent glomeruli 50% Secondary NS: dependent on causes, APSGN, MN, FSGS, MsPGN or MPGN Minimal Change Nephropathy (MCN ) Little or no microscopic abnormality Absence of immune complexes Effacement of epithelial foot process Occasionally mesangial hypercellurity MCN: normal in LM MCN: effacement of epithelial foot process in EM Mesangial proliferative glomerulonephritis (MsPGN) Mesangial proliferation and expansion IgG,C3 and sometimes IgA, IgM deposits in mesangial stalk Electron-dense deposits in mesangial or paramesangial areas MsPGN: Mesangial proliferation and expansion IgG and C3 deposits in mesangial Mesangial proliferative glomerulonephritis (MsPGN) Mesangial proliferation and expansion IgG,C3 and sometimes IgA, IgM deposits in mesangial stalk Electron-dense deposits in mesangial or paramesangial areas Focal segmental glomerulosclerosis (FSGS) Focal and segmental capillary collapse and mesangial sclerosis Deposits of IgM or C3 in the glomeruli Loss of visceral epithelial cell podocytes, duplication of the basal GBM lamina,separation of epithelial cell from GBM Membranous Nephropathy (MN) Diffuse GBM thickening, characteristic GBM spikes Subepithelial deposit of IgG and C3 Membrane proliferative glomerulonephritis (MPGN) Mesangial proliferation and expansion Subendothelial mesangial interposition, tram track apperance Mesangial and subendothelial deposits of IgG and C3 Pathophysiology of nephrotic syndrome MCN: Involvement of immune system No Ig or complement deposit Association between allegy and idiopathic NS Abnormalities of humural and cellular immunity: IgG, IgA, CD4/CD8 Relapse of NS triggered by a variety of minor infections Autologous remission after measles Induction of remission by corticosteroids and akylating agents MCN: pathogenesis of proteinuria Lymphacyte 29kd peptide glomerular polyanion proteinuria Con A lymphacytes 60-160kd GPF proteinuria lymphacytes 13-18kd SIRS proteinuria GPF: glomerular permeability factor SIRS: soluble immune response suppressor MCN: pathogenesis of edema FFNa, CH2O Edema Proteinuria Na reabsorption in distal renal tubules Na and water retention Edema Hypoalbuminemia intravascular oncotic pressure (25mmHg6-8mmHg) Fluid extravasation hypovolemia ADH and aldosterone Water and salt retension Edema MCN: pathogenesis of hypoalbuminemia Loss of protein from ultrafiltration Increased catabolism of protein in renal tubules Loss from intestine proved by 51Chromium-albumin tracing MCN: pathogenesis of hyperlipidemia Hypoalbuminemia hypatic synthesis of lipidhyperlipidemia Clinical Manifestation Simple nephrosis: 2-7y, massive edema in face and paraorbital areas, ascites, pleural effusion, loss of appetite, nausea and vomiting, inertia and lethargy Nephritic nephrosis: 7y, moderate edema, gross hematuria, hypertension Complications: Complications (1) Infection: URI, peritonitis, cellulitis and etc IgG, IgA, Complement WBC function Lack of Zn and other trace elements Hypercoagulable state and thrombosis Higher concentration of , Lower level of anticoagulant substance: antithrombin，protein S,protein C Overvigorous diuresis Higher blood viscosity, increased platelet aggregation Role of corticosteroids Complications (2) Electrolyte imbalance: hyponatrimia, hypokalemia, hypercalcemia Salt-depleted diet Overvigorous diuresis Extrarenal loss Protein-bound calcium loss from urine Steroids induced hypocalcemia ARF: pre-renal Hypovolemic shock Others: growth failure Laboratory Data (1) ESR: simple nephrosis 100mm/h, nephritic nephrosis IgM, C3 nephritic nephrosis IgMIgA, normal C3 simple nephrosis Laboratory Data (2) Renal function: usually normal Urine protein pattern: simple nephrosis albumin nephritic nephrosis IgG, albumin and others Ratio of UIgG/ U albumin simple nephrosis 1 Diagnosis and differential diagnosis Idiopathic or secondary MCN or non-MCN importance of renal biopsy Treatment of NS General principle Anticoagulation Corticosteroids Immunosuppressive agents Chinese traditional medicine General principle Low salt diet (2g/d), appropriate protein intake (2-3g/kg/d) Avoiding infection Diuresis: Thiazide DHCT 2mg/kg/d Antisterone 2-4mg/kg/d Dextran 10-20ml/kg followed by Lasix at 2mg/kg Anticoagulation Dipyridamole: 5mg/kg/d Heparin: 0.5-1mg/kg/d7-10d Warfarin: initial dose: 2.5mgTid3-5d Subsequent dose: 2.5-10mg/d based on PT Corticosteroids Short course: 2mg/kg/d pro(-) 1.5mg/kg/qod4w no taper, Course 8w, Relapse rate (1y)= 81% Standard course: 2mg/kg/d4w 2mg/kg/qod4w taper, Course 6m, Relapse rate (1y)= 61% Long course: 2mg/kg/d4-6w 2mg/kg/qod4- 6w taper, Course 9-12m, Relapse rate (1y)= 31% Steroids treatment response high response: 4wproteinuria(-) response: 8wproteinuria(-) partial response: 8wproteinuria(+/+) steroid dependent: responsive but require high dose relapse: proteinuria(-)proteinuria(+ or up) frequent relapse: relapse twice/6m or trice/1y Side effect of steroids Growth failure Hypertension posterior sublenticular cataracts Osteoporotic bone disease Gastric ulcerhematesis Immunosuppressive agents(1) CTX: 2-2.5mg/kg/d8-12w, maxium single dose 0.1, maxium cumulative 200- 250mg/kg Chlorambucil: 0.2mg/kg/d8-12w, maxium single dose 6mg, maxium cumulative dose 12-16mg/kg Cyclosporin A: 5-6mg