內科學教學課件：Nephrotic Syndrome

1、Nephrotic Syndrome (P633),a group of signs and symptoms, not a single disease (base on extent of proteinuria, not on etiology) 1. Features Large amount of proteinuria, 3.5g/d Hypoalbuminemia: serum albumin 30g/L Hyperlipidemia Edema - Massive proteinuria and hypoalbuminemia are necessary for diagnos

2、is.,2. Causes (1) Primary glomerular diseases Pathological classifications of NS: Minimal change disease (MCD) Membranous nephropathy (MN) Mesangial proliferative GN (MsPGN) Mesangial capillary GN (membrane proliferative GN, MPGN) Focal segmental glomerular sclerosis (FSGS),(2) Systemic diseases and

3、 other disorders: Metabolic disease-Diabetes Mellitus, amyloidosis Autoimmune disease-SLE, Henoch-Schonlein purpura Malignancy-Hodgkin disease, multiple myeloma, lymphoma, other cancers. Drugs- NSAIDs（non-steroidal antiinflammatory drugs） Hereditary disorder-Alports syndrome Allergens-bee sting, sna

4、ke bite, pollen Infections-SBE, HBV, HIV infection,Classifications and common causes for nephrotic syndrome,3. Pathophysiology （1）Proteinuria Electrical charge barrier disturbance: MCD, selective proteinuria Size barrier disturbance: non-selective proteinuria （2）Hypoalbuminemia Secondary to protein

5、loss in urine. Liver could not produce enough albumin to supplement. Increased albumin catabolism Loss of other proteins: IgG, metal-binding proteins, coagulation component, complement Hypercoagulable state, iron, copper, zinc deficiency, infection.,（3）Edema Proteinuriahypoalbuminemiaplasma oncotic

6、pressureedema Increased salt and water retention: from RAS （4）Hyperlipidemia: Increased hepatic synthesis of cholesterol, triglycerides and lipoproteins in the process of albumin synthesis. Reduced catabolism of these compounds.,4. Complications (1) Infection Malnutrition Disturbance of immune funct

7、ion(WBC function, complememt loss) Therapy of corticosteroid Sites: Pathogens: (2) Thromboembolic events Reduced effective blood volume Hyperlipidemia Altered clotting factors level Thrombosis embolus embolism Could be life-threatening.,(3) Acute renal failure Reduced renal perfusion Severe edema of

8、 renal interstitium Drug (harmful to kidney) therapy: Acute bilateral thrombosis of renal vein Could be idiopathic (4) Severe metabolic disturbance Malnutrition in protein metabolism hyperlipidemia,5.Treatments of Nephrotic Syndrome General management Rest in bed Diet: - Protein: 1.0g/(kg.d), rich i

9、n EAA (essential amino acid) - Enough energy: 30-35kcal/d - Low salt intake (3g/d) restriction of fluid intake,Diuresis and blood ultrafiltration PRINCIPLES：properly, combined, intermittently, carefully Diuretics: - dihydrochlorothiazide (DCT) - furosemide, bumetanide - spironolactone (potassium-spa

10、ring diuretics) Albumin infusion: colloid osmotic pressure Blood ultrafiltration Proteinuria controlACEI/ARB,Specific management (main treatment) Corticosteroid - Prednisone 1mg/(kg.d), orally, for 8 (12) weeks Adequate dosage , long course , dosage decreasing be taper. - Response to corticosteroid:

11、 sensitive, dependent, resistant Side effects of Corticosteroid : Metabolism(glucose, lipid), bone, immune system, cardiovascular (hypertension), mental disturbance, skin, .,Indications of cytotoxic agents (for primary NS): Membranous nephropathy (MN) Mesangial capillary GN (membrane proliferative G

12、N, MPGN) Focal segmental glomerular sclerosis (FSGS) Relapsing cases of Minimal change disease (MCD) and Mesangial proliferative GN (MsPGN),Cytotoxic agents and immunosuppressive drugs,Alkylating agents Cyclophosphamide (CTX) Immunophilin binding agents Cyclosporine (CsA), Tacrolimus (FK506), Rapamy

13、cin Purine synthesis inhibitors Azathioprine (AZA), Mycophenolate mofetil (MMF) Pyrimidine synthesis inhibitors Leflunomide（LEF） Others: 雷公藤,Cyclophosphamide（CTX）,Long history in the treatment for primary or secondary kidney disease Cheap Intravenouslly, total dosage is 6 8g. Side effect: bone marro

14、w suppression, liver funtion damage, hemorrhagic cystitis, sterility(male), etc.,Therapy for “chronic” hyperlipidemia Lipid-lowering drugs: HMG-CoA reductase inhibitors (Statin series), Simvastatin, pravastatin Anticoagulation therapy Start earlier in membranous nephropathy in cases with serum album

15、in 20g/L. - aspirin, dipyridamole, heparin, low molecular heparin. Treatment of complications Prevention is much more important than treatment.,Primary glomerular diseases Minimal change disease (MCD) Membranous nephropathy (MN) Mesangial proliferative GN (MsPGN)- IgA nephropathy Mesangial capillary

16、 GN (membrane proliferative GN, MPGN) Focal segmental glomerular sclerosis (FSGS) They are also different in age, sensitivity to treatment, clinical features and prognosis.,MINIMAL CHANGE DISEASE (MCD),Its most commonly seen in children but occasionally present in adult (elderly). Relatively abrupt

17、onset LM(-), FM(-), EM: foot process effacement. Hematuria is not common. No hypertension or renal failure. (except idiopathic ARF) Sensitive to steroid therapy Relapse easily. MCD in adults：,Focal Segmental Glomerular Sclerosis（FSGS）,Onset in youth and insidious Have more nephritic features(75 of t

18、he patients have hematuria） Hypertension and renal function damage are common. Renal biopsy: at least one glomerulus has segmental sclerosis Poor response to steroid Renal prognosis is relatively poor (30-50% ESRD),Membranous nephropathy (MN),Onset in older people, insidiously Nephrotic features (se

19、ldom with hematuria or hypertension） Renal biopsy: thickened BM, IgG & C3 subepithelial deposits. Renal prognosis is relatively good.( With nomal renal function for many years),IgA nephropathy（IgAN）,Its the commonest form of primary GN world-wide. Especially in Asia. (about 40% of the biopsy in China，1/3 of them will go to ESRD) characterized by deposition of IgA-containing immune deposits in the glomerular mesangium. (diagnosed only by renal biopsy) A v