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)