Nephrotic syndrome refers to a clinical condition characterized by heavy proteinuria, hypoalbuminemia, edema, and hyperlipidemia. It is most commonly caused by minimal change disease in children and membranous nephropathy in adults. The pathogenesis involves structural or functional alterations of the glomerular basement membrane, leading to increased permeability and loss of plasma proteins in the urine. Long-term nephrotic syndrome can result in complications like hypercoagulability, lipid abnormalities, and progressive kidney damage.

1. Student :Dr Haridas Munde
Guide :Dr Meenal mam
Lab diagnosis Nephrotic syndrome
( Clinical part )

3. Glomerular filtration membrane ..

4. Nephrotic syndrome refers to a clinical complex that
includes
• Massive proteinuria with daily protein loss in the
urine of > 3.5 g or more in adults.
• hypoalbuminemia, with plasma albumin level less
than 3 g/dl
• Generelised edema most obvious clinical
manifistation
• hyperlipidemia, and lipiduria
NEPHROTIC SYNDROME

5. • 2 – 7 cases per 100,000 per year
• Higher in underdeveloped countries (South east
Asia)
• Occurs at all ages but is most prevalent in
children between the ages 1.5-6 years.
• It affects more boys than girls, 2:1 ratio
Incidence

7. genetics in NS

8. All causes of nephrotic syndrome share a common
pathophysiology.
Structural or physiochemical alteration in GBM
Derangement in capillary wall of glomeruli
Increased permeability to plasma proteins.
escape from plasma into glomerular filtrate.
pathophysiology

9. longstanding heavy proteinuria serum
serum albumin is decreased , resulting in hypoalbumenia
decrease in intravascular volume and decreased renal blood flow.
release of renin by JG cells
stimulates angiotension – aldosterone axis which promote retention of salt
and water by kidney.
odema
Cont..

10. • Effacement of
podocytes is now
thought to be the
primary pathology.
• -ve charge of the
basement membrane is
also important
stuctural vs physiochemical alteration.

11. • glomerular wall has two filtration barriers in
series;
inner :-charge dependent membrane;
more external, mainly size selective barrier
So Glomerular filter acts via two phenomenon
size selectivity
charge selectivity
Selectivity of proteinuria

12. • Excretion of relatively low M.W. protein
(Albumin or transferrin) is known as selective
proteinuria while
• if excretion is predominately high M.W. protein
(IgG, IgM or α2 macroglobulin) it is nonselective
proteinuria.
• It is also related to relative damage of
Glomerular filter.
Selectivity of proteinuria

13. • It is due to both the proteinuria and due to the
increase renal catabolism (in tubules).
• Infact hepatic albumin synthesis is increased
from 145±9mg/kg/day to 213±17mg/kg/day in
nephrotic patients.
• Transcriptiional regulation of human albumin
synthesis is not co-related with plasma oncotic
pressure or albumin concentration, but rather
with urinary albumin execration.
HYPOALBUMINEMIA

14. • As abnormal accumulation of interstitial fluid
and becomes obvious if in excess of 10% of B.W.
• Usually present as edema around
eyes
ankle
sacral pad
elbows
ascitis
pleural effusion.
EDEMA

15. hypoalbuminemia → decrease intravascular oncotic
pressure
↓
leakage of fluid from blood to interstitium
↓
↓ intravascular volume
↓
activates sympathetic N.S. and RAS and promote
vasopressin secretion & suppressing ANP release
↓
increase salt and water retension
↓
restore intravascular volume
↓
further leakage of fluid to interstitum.
Pathogenesis of Edema : underfill hypothesis :

16. • occurrence edema in many patients whom plasma
volume is expended
• RAA axis is suppressed
• High BP argues against hypovolemia and infact,
suggest hypervolemia.
This hyopthesis fail to explain ….

17. intrinsic defect of salt and water excretion in the
nephrotic kidney.
 Activation of the expression of Na+/H+exchanger3
(NHE3)
 Stimulation of the basolateral Na,K-ATPase pump
 Activation of the apical epithelial amiloride-
sensitive sodium channels (ENa+C))
primary renal salt and water retention
theory/ The “overfill” theory

21. • Presumed that hypoalbuminemia triggers the
increased synthesis of lipoproteins in liver.
• massive proteinuria causes loss of inhibitor of their
synthesis
• There is abnormal transport of circulating lipid
particles.
• Defective lipid catabolism has also important role.
• lipiduria – increased permiability of GBM to
lipoproteins
Hyperlipidemia & lipiduria

22.  LDL and cholesterol are increased in majority of
patients whereas
 VLDL and triglyceride tends to rise in patients with
severe disease.
Risk due to hyperlipidemia
relative risk for MI 5.5 fold ,
 coronary death 2.8 fold.
 It also increases progression of renal disease
CONT.

23. Increase urinary loss of antithrombin III.
Altered levels and/or activity of protein C & S.
 Hyperfibronogenemia due to increase
hepatic synthesis.
 Impaired fibrinolysis due to decrease
plasminogen.
HYPERCOAGULABILITY

24.  Patients may develop peripheral arterial or venous
thrombosis,
renal vein thrombosis and pulmonary embolism.
 Renal vein thrombosis (men >women) is very important
and common (up to 40% adults patients).
- Renal thrombosis usually associated with membranous
nephropathy, MPGN and amyloidosis.
Risk due to hypercoagulibity

25. • Also called as lipoid nephrosis or foot process
disease.
• Relatively benign disorder.
• most frequent cause of nephrotic syndrome in children
( 20% adults .80 % children).
• Hypertension and renal failure are very rare.
MINIMAL CHANGE DISEASE

26. • Idiopathic (majority)
• In association with ;
- Drug -NSAIDs, rifampin, interferon alpha.
- Systemic diseses -Hodgkin’s disease and other
lympho-proliferative malignancy.
- HIV infection.
MAJOR CAUSES OF MCD

27. • exact pathology is not known
• experimental studies - Proteinuria d/t circulating T
cell derived factor that cause podocyte damage
and effacement of foot proceesses.
• neither nature nor role in human study establshed
• Detection of a mutation in nephrin gene in
cases of congenital MCD has focused attention on
genetic basis.
Pathogenesis ..

28. • Primary FSGS comprises about 1/3 rd cases of NS
in adults.
Causes –
• Idiopathic ( majority)
• Secondary FSGS
-HIV nephropathy
-Heroin Nephropathy.
-Maladaptation to Nephron loss
-Secondary event in IgA nephropathy.
FOCAL SEGMENTAL
GLOMERULOSCLEROSIS

29.  pathogenesis of primary FSGS unknown.
 some suggest that MCD may transform into FSGS.
 Injury to podocyte is thought to represent the
initiating event of primary FSGS.
 as with MCD permeability increasing factors
produced by lymphocytes are also proposed.
 deposition of hyaline masses in glomeruli
represents the plasma proteins and lipids where
sclerosis develops.
Pathogenesis …FSGS

30. • Leading cause of idiopathic nephrotic syndrome in
adults (30 to 40%) with male to female ratio
of 2 :1.
 Age group 30 – 60 yrs
 it is characterized morphologically by presence of
sub-epithelial immunoglobulin containing deposits.
MEMBRANOUS NEPHROPATHY

31. • Idiopathic (majority)
• Infection- HBV , syphilis , schistosomiasis,
malaria.
• Malignant tumour – ca lung , colon ,
melanoma.
• Autoimmune diseases – SLE etc
• Inorganic salts – gold murcury .
• Drugs NSAID captopril penicilamaine
CUUSES….

32. • its is form of chronic immune complex
glomerulonephritis induced by antibodies reacting
in situ to endogenous or planted glomerural antigen.
• An endogenous podocyte antigen , phospholipid A 2
receptor is most often recognized by autoantibodies.
• Antigen antibody complexes causes capillary damage
by activation of complements ( c5b-c9 MAC0 without
inflamation ,
Pathogenesis

34. • 5-10 % cases of idiopathic nephrotic syndrome in
children and adults.
• some patients presents only hemaruria or
protenuria of non nephrotic range other exbits
combined nephrotic nephritic picture.
• MPGN type 1 – circulating immune complexes.
• Dense deposit disease- excessive complement
activation by c3 nephritic factor.
• principal mode presentation is nephrotic syndrome.
MEMBRANOPROLIFERATIVE
GLOMERULONEPHRITIS

35.  Most imp. Predictor - duration of disease.
 20 years prediction of nephropathy is
Type I DM have 30-40 %chances
Type II DM have 30-40 %chances
Risk factors
hyperglycemia,
systemic hypertension,
glomerular hypertension and' hyperfilteration, proteinuria,
cigarette smoking,
hyperlipidemia
DIABETIC NEPHROPATHY

36. • Hyperglycemia and insulin deficiency lead to
non enzymatic glycation of proteins in GBM.
• subsequent hemodynamic changes –
Increased GFR ,
Increased glomerular capillary pressure,
Glomerular hypertrophy,
Glomerulosclerosis.
• earliest finding – increased GFR .
Pathogenesis

37. • diagnosed on clinical grounds without a renal
biopsy.
• Supportive clues are
 presence of normal sized or enlarged kidneys,
 evidence, proliferative diabetic retinopathy,
and urinary sediments.
Retinopathy is found in 90 % - with type I DM
60% of patients type II DM

38. • Glomeruli are involved in 75 to 90% of patients.
• Hypertension is present in 20-25%.
• Renal size is usually normal or slightly enlarged.
• A minority of patients present with renal failure.
• Rectal biopsy and abdominal fat pad biopsy
reveal amyloid deposits in about 75% of patients
and may obviate the need for renal biopsy.
RENAL AMYLOIDOSIS

39. Finnish’ Type Nephrotic Syndrome
• Presents in first 3 months of life
c/f Anasarca, hypoalbuminaemia, oliguria
‘Antenatally detectable :
– Raised AFP in maternal serum and amniotic fluid
• Complications
– Failure o thrive
– Infections
– Hypothyroidism
– Renal Failure ( 2 – 3 yrs )
Congenital Nephrotic Syndrome

40. Complications