Nephrotic Syndrome (NS)

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 Yntroduction

= Etiology
= Pathophysiology
= Pathology and clinical feature
= Complications
= Diagnosis and differential diagnosis
= Treatment
 Diagnosis:

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= Proteinuria: >3.5g/d
= Hypoalbuminemia: SAlb <30g/L
= Edema;
= Hyperlipidemia.
 Hypoproteinemia

=

= Ymmunoglobulins
= 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
triglyceride üü 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

= Yncreased 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

= Water and sodium retention?

=
 !" #$ %!&
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How many pathological types causes
nephrotic syndrome?
 Vlomerular diseases that cause NS±--
Minimal Change Vlomerulopathy

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= Yt 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
 Vlomerular diseases that cause NS±--
Minimal Change Vlomerulopathy

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= No glomerular lesions by
light microscopy
= No staining with antisera
specific for
immunoglobulins or
complement components.
= Effacement of visceral
epithelial cell foot processes
 Vlomerular diseases that cause NS±--
Minimal Change Vlomerulopathy

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= 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.
 Vlomerular diseases that cause NS±--
mesangial proliferative VN

÷


= Yt is a common reason of NS in our country,
accounting for 30% of primary nephrotic syndrome,
higher than those in western.
 Vlomerular diseases that cause NS±--
mesangial proliferative VN

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= Diffuse proliferation of
mesangial cells and ECM
= Positive staining with YgA,
YgV, YgM or C3 in mesangial
area
= Dense deposits in mesangial
area
 Vlomerular diseases that cause NS±--
Mesangial Proliferative VN

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= 50% has infection before onset of renal disease.
= Non-YgAN: 50% with NS, 70% with hematuria
= YgAN:15% with NS, almost all with hematuria
 Vlomerular diseases that cause NS±--
Mesangial Capilary Vlomerulonephritis

÷


= Yt is accounting for 10% of nephrotic syndrome
patients in our country .
 Vlomerular diseases that cause NS±--
Mesangial Capilary Vlomerulonephritis

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= 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
YgV
= Dense deposits in mesangial
subendothelial area
 Vlomerular diseases that cause NS±--
Mesangial Capilary Vlomerulonephritis

i


 

= 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%)
 Vlomerular diseases that cause NS±--
Membranous Vlomerulopathy

÷


= Ydiopathic membranous glomerulopathy is the most
common cause for nephrotic syndrome in adults
 Vlomerular diseases that cause NS±--
Membranous Vlomerulopathy
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= Subepithelial immune
complex; projections of
basement membrane;
deposits surrounded by
basement membrane;
thickened basement
membrane
= YgV and C3 positive
staining in capillary
 Vlomerular diseases that cause NS±--
Membranous Vlomerulopathy

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= 80% with NS
= 5-10 years later, renal function declined
= Renal vein thrombosis is not uncommon (4-52%)
 Vlomerular diseases that cause NS±--
Focal Segmental Vlomerulosclerosis

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= Over the past two decades, there has been an
increased incidence of FSVS, accounting for 10% in
our country.
= Some cases developed from minimal changes VN.
 Vlomerular diseases that cause NS±--
Focal Segmental Vlomerulosclerosis
`

= Yt is characterized by
focal and segmental
glomerular sclerosis
= Nonsclerotic glomeruli
and segments usually
have no staining for
immunoglobulins or
complement.
Vlomerular diseases that cause NS±-- Focal
Segmental Vlomerulosclerosis

i


 

= 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
Teenager mesangial proliferative FSVS
nephritis
Middle age mesengial capillary SLE LN
nephritis
old age membranous myeloma, amyloidosis
nephropathy
 Complications

= Ynfection
malnutrition
loss of immunoglobulins
corticosteroids

= Thrombosis
coagulation, coricosteroids, PLT activity
 Complications

= Acute renal failure( ARF)

Hypoalbuminemia Hypovolemia pre-renal
azotemia

= Dyslipidemia
 Treatment

 
 
= Rest in bed; limitation of protein intake(0.8-
1.0g/kg/d); limitation of salt intake (<3g/d)

= Diuretic therapy

= Diminishing proteinuria: ACEY and ARB

 Treatment

Y





 

 





 


= 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

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 Treatment

= i










(for steroid dependent or steroid resistant)
Cyclophosphamide (CTX): p.o. or intravenously
Side effects: liver injury, inhibition of bone marrow, etc.

= i 


(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

= R 

 

RR
(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 VN: 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

= FSVS: 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 VN: no evidence show that
adults will response to steroids; aspirin
 Treatment

Treatment for complications

= Ynfection
= Thrombosis
= ARFÕHD; cordicosteroids, diuresis, SB
= dyslipidemia