nephrotic syndrome (ns) qiang yao renal division, renji hospital shanghai 2nd medical universigy
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Nephrotic Syndrome (NS)
Qiang Yao
Renal Division, Renji Hospital
Shanghai 2nd Medical Universigy
Diagnosis:
Proteinuria: >3.5g/d Hypoalbuminemia: SAlb <30g/L Edema; Hyperlipidemia.
Pro ++++
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 HDLprotein 2 10 20 45lipide 98 90 80 55 triglyceride 88 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
Lower colloid osmotic pressure?
15mmHg H2O
colloid osmotic pressure 26 mmHg
Edema
Edema
Water and sodium retention?
Does it related with renin-angiotensin-aldosterone system?
How many pathological types causes nephrotic syndrome?
Glomerular diseases that cause NS–-- Minimal Change Glomerulopathy
Epidemiology: It is most common reason of NS in children, a
ccounting 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 lig
ht microscopy No staining with antisera sp
ecific 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 chang
e 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, a
ccounting for 30% of primary nephrotic syndrome, higher than those in western.
Glomerular diseases that cause NS–-- mesangial proliferative GN
Pathology Diffuse proliferation of mes
angial cells and ECM Positive staining with IgA, I
gG, 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 disea
se. 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 syndrom
e 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 disea
se (nephritic syndrome), half of them present as a nephrotic syndrome.
Almost all of patients with hematuria Early onset of impairment of renal function, h
ypertension, 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
Glomerular diseases that cause NS–-- Membranous Glomerulopathy
Pathology Subepithelial immune c
omplex; 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
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 a
n increased incidence of FSGS, accounting for 10% in our country.
Some cases developed from minimal changes GN.
Glomerular diseases that cause NS–-- Focal Segmental Glomerulosclerosis
Pathology It is characterized by fo
cal and segmental glomerular sclerosis
Nonsclerotic glomeruli and segments usually have no staining for immunoglobulins or complement.
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 Secondarychildren minimal change allergic purpura nephritis
Teenager mesangial 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
Patterns of response of cordicosteroids
Prognosis:
Primary responder, no relapse (steroid sensitive)
Primary responder with only one relapse in the first 6 mo after an initial response
Initial steroid response with two or more relapses within 6 mo (frequent relapse)
Initial steroid-induced remission with relapses during tapering of corticosteroid, or within 2 wk after their withdrawal (steroid dependent)
Steroid-induced remission, but no response to a subsequent relapse
No response to treatment (steroid resistant)
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 cyto
toxic 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