1、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 pr
2、oteinuria 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
3、 133umol/L Hypocomplementemia: C30.8/L,Definition,Nephritic Nephrosis: nephrotic criteria with at least one nephritic criteria Simple nephrosis: nephrotic criteria without nephritic criteria,Etiology,Congenital NS: rare Idiopathic NS: majority Secondary NS: many causes especially in 13y patients cau
4、sesDIAMOND,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: Hodgki
5、ns 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 diseas
6、e: 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 a
7、dultsMembrane 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 epith
8、elial foot process Occasionally mesangial hypercellurity,MCN: normal in LM,MCN: effacement of epithelial foot process in EM,Mesangial proliferative glomerulonephritis (MsPGN),Mesangial proliferation and expansionIgG,C3 and sometimes IgA, IgM deposits in mesangial stalkElectron-dense deposits in mesa
9、ngial or paramesangial areas,MsPGN: Mesangial proliferation and expansionIgG and C3 deposits in mesangial,Mesangial proliferative glomerulonephritis (MsPGN),Mesangial proliferation and expansionIgG,C3 and sometimes IgA, IgM deposits in mesangial stalkElectron-dense deposits in mesangial or paramesan
10、gial 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
11、),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,Pathophysiol
12、ogy 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
13、 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 proteinuriaGPF: glomerular permeability factorSIRS: soluble immune response suppressor,M
14、CN: 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 hypoalbum
15、inemia,Loss of protein from ultrafiltrationIncreased 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 ede
16、ma 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 etcIgG, IgA, Complement WBC fun
17、ction Lack of Zn and other trace elements Hypercoagulable state and thrombosisHigher concentration of ,Lower level of anticoagulant substance: antithrombin，protein S,protein COvervigorous diuresisHigher blood viscosity, increased platelet aggregationRole of corticosteroids,Complications (2),Electrol
18、yte imbalance: hyponatrimia, hypokalemia, hypercalcemiaSalt-depleted dietOvervigorous diuresisExtrarenal lossProtein-bound calcium loss from urineSteroids induced hypocalcemia ARF: pre-renal Hypovolemic shock Others: growth failure,Laboratory Data (1),ESR: simple nephrosis 100mm/h, nephritic nephros
19、is IgM, C3 nephritic nephrosisIgMIgA, 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 albuminsimple nephrosis 1,Diagnosis and differential diagnosis,Idiopathic o
20、r secondary MCN or non-MCNimportance 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/k
21、g/dAntisterone 2-4mg/kg/dDextran 10-20ml/kg followed by Lasix at 2mg/kg,Anticoagulation,Dipyridamole: 5mg/kg/d Heparin: 0.5-1mg/kg/d7-10d Warfarin: initial dose: 2.5mgTid3-5dSubsequent dose: 2.5-10mg/d based on PT,Corticosteroids,Short course: 2mg/kg/d pro(-) 1.5mg/kg/qod4w no taper, Course 8w, Rela
22、pse 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: 8wprotein
23、uria(+/+) 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,Immunosuppre
24、ssive 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/kg/d2-6m, keep blood concentration at 50-150ng/ml,Immunosuppressive agents(2),Vincristine: 0.07
25、5mg/kg weekly, maxium single dose2mg 6-TG(6-thioguanine): 2mg/kg/d8w, maxium single dose75mg nitrogen mustard: 0.1mg/kg/d4d, may be repeated 1 month later azathioprine: 1-2mg/kg/d8-12w,New immunosuppressive agents,Mycophenolate mofetil acid (MMF): Cellcept FK506: Prograf, Tacrolimus Rapamycin: Sirul
26、imus Simulect , basiliximab, daclizumab FYT-720、Gusperimus、SDS-RAD,Pulse therapy,Methylprednisolone: 15-30mg/kg3d Indication: refractory nephrosis, Lupus RPGN: cocktail protocolFSGS: Mendoza protocolMN: Ponticelli protocol,Prognosis,Generally good, especially for MCN MsPGN: good or poor FSGS: 50% to ESRF,Male 4 years and 6 months old Complaint of edema and oliguria,
