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1. NEPHROTIC
SYNDROME
Madan RatnaNeupane
Prashant Raj Bhatt

2. Introduction
Glomerular syndrome
It is a kidney disease with proteinuria,
hypoalbuminemia, and edema.
May affect adults and children, of both sexes and of
any race.
May occur in typical form or in association with
nephritic syndrome

3. Causes of Nephrotic
syndrome
Primary causes:
Minimal-change nephropathymore in children
Focal segmental glomerulosclerosis (FSGS) adults.
Membranous nephropathy
membranoproliferativeGN
Hereditary nephropathies
Secondary causes:
Diabetes mellitus
Lupus erythematous
Amyloidosis
Ingestion of drugs (gold, penicillamine, street heroin)
Viral infections (HepB, HepC, HIV)
Preeclampisa

4. Features……..
4 features of Nephrotic syndrome:
Heavy proteinuria(>3g/24hr) or a first morning
protein : creatinine ratio of>2 
Hypoalbuminemia(<2.5g/dl)
Generalized Edema
Hyperlipidemia and lipiduria

5. Pathogenesis
2 important pathogenesis:
Mechanism of glomerular injury
Proteinuria
Increase in the permeability of the glomerular capillary
wall which leads to massive proteinuria and
hypoalbuminemia.

6. Mechanism of proteinuria
Due to increased filtration of macromolecules (such as
albumin) across the glomerular capillary wall
Normally, filtration of macromolecules is restricted by
two mechanisms:
Charge selectivity
Size selectivity

7. Charge selectivity
Endothelial cells and GBM have net negative charge due
to polyanionssuch as heparansulfate proteoglycans
This creates a charge barrier to the filtration of large
anions such as albumin.
In minimal change disease-there is loss of anionic charge
Glomerular capillary wall is size-selective

8. Mechanism of edema formation
The decrease in intravascular volume decreases the renal
perfusion and RAAS system is activated. Also, release of ADH is
stimulated which contributes to edema formation.
•Massive urinary protein loss due to
increased filtration.
•Decrease in plasma oncotic pressure
•Trasnsudationof fluid from intravascular
compartment to interstitial space

9. How is lipid level elevated?
Hypoalbuminemia leads to stimulated generalized hepatic
protein synthesisSynthesis of lipoproteins is increased.
Also, there is decrease plasma level of lipoprotein lipase (due to
urinary loss) which leads to decreased lipid catabolism.
characteristic disorderincrease LDL, VLDL,and/or
intermediate-density lipoprotein (IDL) fractions, but nochange
ordecrease in HDLresultsincrease in the LDL/HDL cholesterol
ratio

10. Investigations
1.Urinalysis
2.Urine sediment examination
3.Urinary protein measurement
4.Serum albumin
5.Serologic studies for infection and immune
abnormalities
6.Renal ultrasonography
7.Renal biopsy
8.Lipid profile
9.RBS

11. Diagnosis
Laboratory findings
Urinalysis (protein 3+ to 4+)
Serum albumin (< 1gm/dl)
Milky appearance of plasma (hypercholesterolemia)
Decreased IgGand increased IgM
•Renal biopsy

12. Management of
NephroticSyndrome
A.General Measures
1.Initial treatment
-Dietary Na restriction
-Thiazidediuretics (bendroflumethiazide5mg daily)
-if unresponsive: Furosemide40-120mg daily + Amiloride
5mg daily with serum K+ monitored
2.
Normal protein intake
-avoid high protein diet (80-90 mg/daily)
3.
Albumin infusion
-indicated in diuretic resistant and oliguria and uremia in
the absence of severe glomerular damage
-combined with diuretics

13. 4. Hypercoagulablestates
-long term prophylactic anticoagulation desirable to prevent
from thromboembolicconditions.
-if renal vein thrombosis occurs, permanent anticoagulation is
required.
5. Sepsis
-suspectibilityto infection is increased due to loss of
immunoglobulins, so pneumococcal infection are particularly
common so pneumococcal vaccine given.
6. Lipid abnormalities
-increased risk of cardiovascular risks
-HMG CoAreductaseinhibitor
7. ACE inhibitors and/or angiotensinII receptor
-antiproteinuricpropertiesby lowering glomerular capillary
filtration pressure
-BP and renal function should be monitored regularly

14. B.Longtermmonitoring
Followupcareinpatientswithnephroticsyndromeincludes
1.Immunization(pneumococcal,influenzaandzoster
immunization)
2.Treatmentofrelapsesofsteroid-responsivenephrotic
syndrome(first2relapsestreatedsameasinitial
presentation;frequentrelapsestreatedwithprednisolone
0.1-0.5mg/kgonalternatedaysfor3-6monthsandthen
tapered)
3.Monitoringforsteroidtoxicity(monitorgrowthinchildren,
supplementalcalciumandvitD)
4.Monitoringofdiureticandangiotensinantagonistregimens

15. Minimal change disease(MCD)
Clinical features:-
Most common in children, particularly males
Oedema; facial in case of children
Selective proteinuria (smaller serum proteins)
No hypertension
Associated condition
Secondary forms of MCD may accompany certain
malignancies( Hodgkinsdisease and solid tumors)
A form of interstitial nephritis associated with NSAIDS

16. CONTD….
Pathogenesis:
Circulating cytokine, perhaps related to a T cell response
that alters capillary charge and podocyteintegrity
Primary abnormality of foot processes (podocyte) is also
postulated
the proteinuria has been attributed to a T-cell derived
factor that causes podocyte damage and effacement of
foot processes
Diagnosis
Kidneybiopsy-normalglomerulionlightmicroscopeand
negativeimmunofluorescence.
Electronmicroscopyshowseffacementoffootprocesses

17. Treatment
In adults: Prednisone at 1mg/kg/day may decrease proteinuria
in 8-16 weeks
Once in remission the dose tapered over 3 months then
discontinued
Relapse can occur in 75% of adults so reinstitution of
prednisone is often effective
If the patient is steroid dependent or resistant may need
cytotoxic drugs like cyclophosphamide(2mg/kg/d) or
chlorambucil(0.2mg/kg/d) or cyclosporine(5mg/kg/d)

18. Focal Segmental Glomerulosclerosis
Presents with nephrotic syndrome, hypertension and renal insufficiency
Pathology:
Obliterationofsegmentsofglomerulibyhyaline,PAS-positivematerial
MaybeduetoCirculatorypermeabilityfactorthatcausestheincreased
proteinleak.
Tubularatrophy,interstitialfibrosis
Secondary forms of FSGS are associated with obesity, HIV and iv drug abusers
Kidney biopsy reveals focal and segmental sclerosis of glomeruli under light
microscopy
The degree of interstitial fibrosis and tubular atrophy correlates with prognosis
Immunofluorescence shows staining for C3 and IgMin areas of sclerosis,
representing trapped immune deposits

19. Treatment
Prednisone of 1mg/kg/d for 16 weeks
Pts who relapse after a period of apparent responsiveness
may benefit from repeat course of steroids
Nonrespondersand relapsersmay respond to treatment
with cyclosporine 5mg/kg/d or cyclophosphamide or
mycophenolatemofetil

20. Membranous Nephropathy
Occurs mainly in adults predominantly in males
85% idiopathic
Secondary MN are associated with SLE, viral hepatitis,
syphilis, or solid organ malignancies
Clinical features
—Present with nephrotic syndrome or heavy proteinuria
though the renal function is normal or near normal
—Microscopic hematuria, hypertension and/or renal
impairment

21. CONTD…..
Immunofluorescenceshowsunifromgranularcapillarywall
depositsofIgGandcomplementC3
Alsomedicationslikepenicillamineandgoldalsocaninduce
thisdiseaseprocess
Kidneybiopsythickeningoftheglomerularbasement
membraneonlightmicroscopy,withspikesonsilverstain
showingareasofnormalbasementmembraneinterposed
betweensubepithelialdeposits(correlatewithIgGandC3on
immunofluorescence)

22. Treatment
Becauseofgenerallygoodprognosisspecifictherapy
shouldbereservedforpatientsathigherriskfor
progression(reducedGFRandage>50yrs,HTN)
Treatment: Prednisone(0 .5mg/kg/d)andcytotoxicagents
likechlorambucil(0.2mg/kg/day)orcyclophosphamide(2.5
mg/kg/day)onalternatingmonthsfor6-12months

23. Membranoproliferative
Glomerulonephropathy(MPGN)
exhibits a variety of clinical presentations, including acute
GN, nephrotic syndrome, and asymptomatic hematuria and
proteinuria
Hepatitis C (HCV) accounts for most cases of MPGN and is
often associated with cryoglobulinemia
Other secondary causes are: SLE , chronic infection and
various malignancies

24. CONTD……..
3 different subtypes: MPGN type I, II,III
Type I and IIIimmune complex mediated , both C3 and C4
are low
also occurs in assosciationwith Hepatitis B and C antigenemia,SLE,
infected arterioventricularshunt, and extra renal infection
Type IIk/a dense deposit disease
Fundamental abnormalityexcess complement activation
Autoantibodies against C3 covertasek/a Nephritic factor believedto
stabilize the enzyme and lead to uncontrolled cleavage of c3 and
activation of alternative pathway
Only C3 is low

25. Diagnosis
The kidney biopsy shows mesangialproliferation and
hypercellularityon light microscopy, with “lobulization” of
the glomerular tuft.
Mesangialinterpositioningwithin the glomerular
basement membrane can give a double-contour or “tram -
track” appearance on silver stain.
Immunofluorescence and electron microscopy can show
subendothelial(type I) or intramembranous (type II)
deposits.

26. Treatment
For adult idiopathic MPGN, treatment has not been
shown to improve disease-free survival, although the use
of corticosteroids in children likely stabilizes disease
Treatment of secondary form is targeted to the
underlying cause
If renal function is rapidly deteriorating in presence of
cryoglobinaemiaplasmapharesisstabilize the disease
Case report demonstrated possible efficacy of
Eculizimabin treatment of TypeIIMPGN

27. . Specific Measures
•Specific treatment of nephroticsyndrome depends on
the disease’s cause.
•High dose corticosteroid with Prednisolone60mg/m2 (max 80 mg/d)-4-6
weeks followed by 40 mg/m2 every other day-4-6 weeks
•-To prevent relapse: Cyclophosphamide 1.5-2mg/kg/d or ciclosporin3-
5mg/kg/d
Minimal change disease
•Prednisolone0.5-2mg/kg/d-6 months
•Ciclosporin-to reduce urinary protein excretion
•at dose to maintain serum level 150-300 ng/ml
•long term, as relapse after reducing or stopping
•Cyclophosphamide, chlorambucil, or azathioprinefor second line therapy.
Focal segmental
glomerulosclerosis
•Chlorambucil(0.2mg/kg/d in months 2,4, and 6) + oral prednisolone
0.4mg/kg/d (in 1,3 and 5 months), or
•Cyclophosphamide 1.5mg/kg/d for 6-12 months) + oral prednisolone
1mg/kg/d on alternate days for first 2 months
•Ciclosporin and mycophenolate with oral steroids
•Anti-CD20 antibodies (ritumixab)-improve renal fn, reduce proteinuria
Membranous
glomerulonephropathy

28. References
•Washingtonsmanualoftherapeutics33
rd
and34
th
edition
•Robinandcortansbasisofpathology,8
th
edition
•Kumarandclarkclinicalmedicine,8
th
edition

29. THANK YOU