Nephrotic Syndrome (NS) Qiang Yao Renal Division, Renji Hospital Shanghai 2nd Medical Universigy
Diagnosis: Pro ++++ • Proteinuria: >3.5g/d • Hypoalbuminemia: SAlb <30g/L • Edema; • Hyperlipidemia.
Hypoproteinemia • Albumin • Immunoglobulins • Metal binding proteins • Erythropoietin urinary loss • Transferrin • Complement deficiency • Coagulation components
Hyperlipidemia • Hypercholesterolemia • Hypertriglyceridemia • Low-density lipoproteins (LDL) • Very low- density lipoproteins (VLDL)
chemical composition of plasma lipoprotein (%) CM VLDL LDL HDL protein 2 10 20 45 lipide 98 90 80 55 triglyceride88 55 8 10 phospholipid 6 20 24 22 cholesterol total 4 15 48 23 free 1 5 8 6 ester 3 10 40 17 lipide/protein 40~50 9 4 1~1.5
Mechanisms of Hyperlipidemia • Increased hepatic synthesis of LDL, VLDL and lipoprotein (a) in response to hypoalbuminemia • Urinary loss of HDL • Enzymatic changes with abnormal lipid biosythesis and degradation
Edema Edema • Lower colloid osmotic pressure? 15mmHg H2O colloid osmotic pressure 26 mmHg
Edema • Water and sodium retention? • Does it related with renin-angiotensin-aldosterone system?
Glomerular diseases that cause NS–-- Minimal Change Glomerulopathy Epidemiology: • It is most common reason of NS in children, accounting for 80-90% of young patients with nephrotic syndrome , while only 20-25% in adults. • There appears to be a male preponderance, especially in children, in whom the male- to- female ratio is 2~3 :1
Glomerular diseases that cause NS–-- Minimal Change Glomerulopathy Pathology • No glomerular lesions by light microscopy • No staining with antisera specific for immunoglobulins or complement components. • Effacement of visceral epithelial cell foot processes
Glomerular diseases that cause NS–-- Minimal Change Glomerulopathy Clinical features: • The cardinal clinical feature of minimal change glomerulopathy in children is the relatively abrupt onset of proteinuria and development of the NS. • Hematuria, hypertension and impaired renal function are not common.
Glomerular diseases that cause NS–-- mesangial proliferative GN Epidemiology: • It is a common reason of NS in our country, accounting for 30% of primary nephrotic syndrome, higher than those in western.
Glomerular diseases that cause NS–-- mesangial proliferative GN Pathology • Diffuse proliferation of mesangial cells and ECM • Positive staining with IgA, IgG, IgM or C3 in mesangial area • Dense deposits in mesangial area
Glomerular diseases that cause NS–-- Mesangial Proliferative GN Clinical features: • 50% has infection before onset of renal disease. • Non-IgAN: 50% with NS, 70% with hematuria • IgAN:15% with NS, almost all with hematuria
Glomerular diseases that cause NS–-- Mesangial Capilary Glomerulonephritis Epidemiology: • It is accounting for 10% of nephrotic syndrome patients in our country .
Glomerular diseases that cause NS–-- Mesangial Capilary Glomerulonephritis Pathology • Severe diffuse proliferation of mesangial cells and ECM, demonstrating doubling and more complex replication of glomerular basement membranes • Peripheral granular to bandlike staining for C3 and IgG • Dense deposits in mesangial subendothelial area
Glomerular diseases that cause NS–-- Mesangial Capilary Glomerulonephritis Clinic feature: • 30% has infection before onset of renal disease (nephritic syndrome), half of them present as a nephrotic syndrome. • Almost all of patients with hematuria • Early onset of impairment of renal function, hypertension, anemia • Progressive procedure (10 year renal survival rate was less than 65%)
Glomerular diseases that cause NS–--Membranous Glomerulopathy Epidemilology • Idiopathic membranous glomerulopathy is the most common cause for nephrotic syndrome in adults
Pathology Subepithelial immune complex; projections of basement membrane; deposits surrounded by basement membrane; thickened basement membrane IgG and C3 positive staining in capillary Glomerular diseases that cause NS–--Membranous Glomerulopathy
Glomerular diseases that cause NS–-- Membranous Glomerulopathy Clinic feature: • 80% with NS • 5-10 years later, renal function declined • Renal vein thrombosis is not uncommon (4-52%)
Glomerular diseases that cause NS–-- Focal Segmental Glomerulosclerosis Epidemilology • Over the past two decades, there has been an increased incidence of FSGS, accounting for 10% in our country. • Some cases developed from minimal changes GN.
Pathology It is characterized by focal and segmental glomerular sclerosis Nonsclerotic glomeruli and segments usually have no staining for immunoglobulins or complement. Glomerular diseases that cause NS–--Focal Segmental Glomerulosclerosis
Glomerular diseases that cause NS–-- Focal Segmental Glomerulosclerosis Clinic feature: • NS • With hematuria • Hypertension and renal function declining are common
Diagnosis • Diagnosis: NS? Primary or secondary? Complications?
Differential diagnosis Primary Secondary children minimal change allergic purpura nephritis Teenagermesangial proliferative FSGS nephritis Middle age mesengial capillary SLE LN nephritis old age membranous myeloma, amyloidosis nephropathy
Complications • Infection malnutrition loss of immunoglobulins corticosteroids • Thrombosis coagulation, coricosteroids, PLT activity
Complications • Acute renal failure( ARF) Hypoalbuminemia Hypovolemia pre-renal azotemia • Dyslipidemia
Treatment Support care • Rest in bed; limitation of protein intake(0.8-1.0g/kg/d); limitation of salt intake (<3g/d) • Diuretic therapy • Diminishing proteinuria: ACEI and ARB
Treatment Inhibition of inflammation and immune response • Corticosteroid therapy (onset): for children: prednisone 60mg/m2/d for adult: prednisone 1mg/kg/d (<80mg/d) 4-6 weeks later , complete remission of proteinturia occurs, the dosage then decreased (10% every 1-2 weeks). • Be careful for the side effects of corticosteroid therapy
Prognosis: Patterns of response of cordicosteroids
Treatment • Cytotoxic drugs with corticosteroid: (for steroid dependent or steroid resistant) Cyclophosphamide (CTX): p.o. or intravenously Side effects: liver injury, inhibition of bone marrow, etc. • Cyclosporine (for those failed responsing to combination of steroid and cytotoxic drugs) Dose: 5mg/kg/d, bid, p.o. Side effects: renal and liver toxic injury, expensive, etc.
Treatment • Mycophenolate mofetil, MMF (for steroid dependent or steroid resistant) Dose:1.5-2g/d, bid, p.o. for 3-6 months, maintaining 0.5 year
Treatment • Minimal changes: sensitive to steroids; single drug; reuse when relapse; combined with cytotoxic drugs when resistant or dependent on steroids • Membranous GN: combine steroid with cytotoxic drugs or cyclosporin; avoid using drugs when Scr>354umol/L; for the patients with risks for progressing, otherwise, investigate 6 months (antihypertensive).
Treatment • FSGS: sensitive to steroids in 30-50% of patients; slow response to therapy; steroids therapy (onset) for 3-4 months; if not response until 6 month (resistant), then try cyclosporine. • Mesangial proliferative GN: no evidence show that adults will response to steroids; aspirin
Treatment Treatment for complications • Infection • Thrombosis • ARF（HD; cordicosteroids, diuresis, SB） • dyslipidemia