Nephrotic Syndrome
Jaiganesh.M, M.D ( General
Medicine)
Asst. Professor, S.M.C.H
Classification
Nephrotic syndrome can be primary, or
secondary,
-- injury to glomeruli is an essential feature.
Primary causes of nephrotic syndrome include
Minimal-change nephropathy
Focal glomerulosclerosis
Membranous nephropathy
Hereditary nephropathies
Secondary causes of Nephrotic syndrome:
Diabetes mellitus
Lupus erythematosus
Amyloidosis and paraproteinemias
Viral infections (eg, hepatitis B, hepatitis
C, human immunodeficiency virus [HIV] ).
Nephritic and Nephrotic
Syndromes
Fibrillary and Immunotactoid
Glomerulopathies
Membrano proliferative
Glomerulonephritis
Lupus Nephritis
BASEMENT
MEMBRANE
Features
Protein +++
+
Proteinuria: >3.5g/d
Hypoalbuminemia: Serum Alb <30g/L
Edema;
Hyperlipidemia.
Hypoproteinemia
Albumin
Immunoglobulins
Metal binding proteins
Erythropoietin urinary loss
Transferrin
Complement deficiency
Coagulation components
Primary urine is formed through the
filtration of plasma fluid across the
glomerular barrier
the glomerular filtration rate (GFR) is
125 mL/min. The plasma flow rate (Qp)
is close to 700 mL/min.
The concentration of albumin in serum
is 40 g/L, -- while the estimated
concentration of albumin in primary
urine is 4 mg/L.
Hyperlipidemia
Hypercholesterolemia
Hypertriglyceridemia
Low-density lipoproteins (LDL)
Very low- density lipoproteins (VLDL)
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 biosythe
sis and degradation
Edema
Lower colloid osmotic pressure
15mmHg H2O
colloid osmotic pressure 26 mmHg
Edema
FACIAL PUFFINESS
Diagnosis:
Protein +++
+
Proteinuria: >3.5g/d
Hypoalbuminemia: Serum Alb <30g/L
Edema
Hyperlipidemia.
Pathological types causing n
ephrotic syndrome
1.Minimal Change Glomerulopathy
Epidemiology:
It is most common Type of NS in children,
accounting for 80-90% of young patients w
ith nephrotic syndrome .
Minimal Change Glomerulopathy
Pathology
No glomerular lesions by
light microscopy
No staining with antisera
specific for immunoglobul
ins or complement comp
onents.
Effacement of visceral e
pithelial cell foot process
es
ALBUMIN
ALBUMIIN
Minimal Change Glomerulopathy
Clinical features:
abrupt onset of proteinuria and develop
ment of the NS.
Hematuria, hypertension and impaired ren
al function are not common.
2.Mesangial proliferative GN
Epidemiology:
It is a common reason of NS in our country
, accounting for 30% of primary nephrotic
syndrome.
Mesangial proliferative GN
Pathology
Diffuse proliferation of mesa
ngial cells and ECM
Positive staining with IgA, Ig
G, IgM or C3 in mesangial ar
ea
Dense deposits in mesangi
al area
Dense deposits in mes
angial area
Mesangial Proliferative GN
Clinical features:
50% has infection before onset of renal di
sease.
Hematuria is common
3.Membranous Glomerulopathy
Epidemilology
Idiopathic membranous glomerulopathy is
the most common cause for nephrotic s
yndrome in adults
Membranous Glomerulopathy
Pathology
Subepithelial immun
e complex; projectio
ns of basement me
mbrane; thickened ba
sement membrane
IgG and C3 positive st
aining in capillary
Subepithelial immune complex; projections of basement m
embrane
SUB
EPITHELIAL
Membranous Glomerulopathy
Clinic feature:
5-10 years later, renal function declined
Renal vein thrombosis is common (4-52%)
Hematuria may occur
4. Focal Segmental Glomeruloscle
rosis
Epidemilology
Over the past two decades, there has bee
n an increased incidence of FSGS.
Afro americans, cocaine use and HIV
Focal Segmental Glomerulosclerosis
Pathology
It is characterized by foc
al and segmental glome
rular sclerosis
Nonsclerotic glomeruli a
nd segments usually ha
ve no staining for imm
unoglobulins or compl
ement.
Focal Segmental Glomerulosclero
sis
Clinic feature:
NS
With hematuria
Hypertension and renal function declining
are common
HOW TO DIAGNOSE
Diagnosis:
NS?
Primary or secondary?
Complications?
NEPHROTIC -- AGE
AGE PRIMARY SECONDARY
children minimal change allergic purpura
Teenager mesangial prolif FSGS
erative
Middle age mesengial capill SLE LN
ary N
old age Membranous N myeloma, amyloi
dosis
Urinalysis is the first test.
Nephrotic range proteinuria will be apparent
by 3+ or 4+ readings on the dipstick,
Waxy casts mark proteinuric renal disease.
-- glomerular filtration of lipoproteins -- the
uptake of these by the tubular cells that
shed off in urine.
The presence of more than 2 red blood
cells (RBCs) per high power field --
Microhematuria -- occur in membranous
nephropathy but not in minimal-change
nephropathy.
Urinary protein -- spot collection. A single,
spot urine ratio of urine protein to urine
creatinine is greater than 2.
24-hour period, starting at 7 am and
finishing the next day at the same time.
Normal < 150 mg of total protein /24-hour.
300-500 mg/ day will be dipstick test
positive
more than 3.5 gram/day is called
nephrotic range proteinuria
RENAL BIOPSY : TO KNOW THE TYPE
OF NEPHROTOC SYNDROME.
Complications
Infection
malnutrition
loss of immunoglobulins
corticosteroids - complications
Thrombosis
Complications
Acute renal failure( ARF)
Hypoalbuminemia Hypovolemia pre-renal
azotemia
Dyslipidemia
CKD
Treatment
Support care
Rest in bed;
limitation of protein intake(0.8-1.0g/kg/d); limitati
on of salt intake (<3g/d)
Diuretic therapy
Diminishing proteinuria: ACEI and ARB
Inhibition of inflammation and immune response
Corticosteroid therapy (onset):
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).
the side effects of corticosteroid therapy
Patterns of response TO STEROIDS
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)
No response to treatment (steroid resistant)
Cytotoxic drugs with corticosteroid:
(for steroid dependent or steroid resistant)
Cyclophosphamide (CTX): p.o. or intravenously
Side effects: liver injury, inhibition of bone marrow.
1-2 mg/kg/d PO; continue for 3-6 mo beyond r
emission
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.
Mycophenolate mofetil, MMF
(for steroid dependent or steroid resistant)
Dose:1.5-2g/d, bid, p.o. for 3-6 months, maintaining 0.5 ye
ar
Treatment
Minimal changes: sensitive to steroids; sin
gle drug; combined with cytotoxic drugs w
hen resistant or dependent on steroids
Membranous GN: combine steroid with cyt
otoxic drugs or cyclosporin;
FSGS: sensitive to steroids in 30-50% of p
atients; slow response to therapy; steroid
s therapy (onset) for 3-4 months; if not res
ponse until 6 month (resistant), then try cy
closporine.
Mesangial proliferative GN: no evidence s
how that adults will response to steroids; a
spirin
Treatment
Treatment for complications
Infection
Thrombosis
ARF （ HD; cordicosteroids, diuresis, S
B）
dyslipidemia
QUIZ
The most common complication of
minimal change disease is:
1.Infection
2.Hemorrhage
3.Side-effects of steroid therapy
4.End-stage renal disease
5.Renal vein thrombosis
ANS: 3 STEROID THERAPY.
Daily excretion of urinary protein…all are
true except
up to 150 mg /day is normal
300-500 mg/ day will be dipstick test
positive
more than 3.5 gram/day is called
nephrotic range proteinuria
between 0.5-2 gram/ day usually
indicates a glomerular source
ANS : 4 . Equivocal – glomerular or
tubular.
In Microalbuminuria ……all are true except
is defined as Albuminuria between 30-300
mg / day
Is defined as albuminuria between 20-200
microgram / minute
always protein dipstick negative
important in the follow up of type II not type I
diabetes mellitus
persistent proteinuria has been associated
with the development of atherosclerorsis
ANS: 5. IMPORTANT IN BOTH TYPES OF
DM
as persistent protienuria 30-300 mg / day or
between 20-200 microgram / minute
on 2 or more occasion -- 6 months apart
It is very powerful predictor for the future
development of overt diabetic nephropathy
and atherosclerosis.
A 40-year-old Afro american, obese man is
evaluated for hypertension, Medical history is
not significant.H/o drug abuse –present. There is
b/l pedal edema.
Glucose (fasting) N
creatinine N
Urinalysis 3+ protein, microhematuria +_
24-Hour urinary protein 2.8 g/24 h
Which of the following is the most likely
diagnosis?
1)IgA nephropathy
2)Minimal change disease
3)Membranous nephropathy
4)Glomerulopathy with secondary focal
segmental glomerulosclerosis.
ANS : 4. FSGS
Afro american
Cocaine
HIV
OBesity
What is the immune deposit pattern in
MEMBRANOUS NEPHROPATHY?
1.Subendothelial
2.Subepithelial
3.Mesangial
4.Intra membranous
ANS: 2.Subepithelial
Initial steroid-induced remission --- but relap
ses during tapering of corticosteroid, or wit
hin 2 wk after their withdrawal is termed:
1.steroid resistant
2.steroid sensitive
3.steroid dependent
4.steroid responsive
ANS : 3. (steroid dependent)
