Nephrotic syndrome

Nephrotic syndrome
• Massive proteinuria > 3.5 g/day
• Hypoalbuminemia = hyperproteinurea.
• Edema: due to decreased osmotic Pressure of
blood ---> increased salt and water retention
• Hyperlipidemia
• Lipiduria
 Causes of Nephrotic syndrome
Causes Children Adults
Minimal change disease (MCD) 65% 10%
Focal segmental glomerulosclerosis (FSGS) 10% 35%
Membranous glomerulonephritis (MGN) 5% 30%
Membrano Proliferative GN (MPGN) 10% 10%
Secondary causes
DM , SLE & amyloidosis
Infections – HBV, HCV, malaria & HIV
Malignancy – HL, NHL
 Pathogenesis
• Structural & physiochemical alteration of GBM
– Increase permeability of plasma proteins
• 1. Injury to the foot processes of the visceral
epithelium.
• 2.The loss of the negative charges on the GBM.
 Hypoproteinemia

Plasma oncotic pressure is diminished

Shift of fluid from the vascular to the

interstitial compartment.
 Volume decreases

Activation of the renin–angiotensin–aldo-

sterone system

Na & water retension

 Complications
1.Infections
2.Electrolyte disturbances
3.Thromboembolism
4.Hypovolemic shook
5.Acute renal failure
 Minimal change disease
• Most common cause of nephrotic syndrome
in children.
• Peak incidence between 2-6 yrs
• Lipoid nephrosis/ nil disease
• Fusion of epithelial of foot processes
 Morphology
• LM – Normal
• IF – No immune complex deposition
• EM – Diffuse loss of foot processes
(diagnosis made only by EM)

Prognosis – very good

 MEMBRANOUS
GLOMERULONEPHRITIS (MGN)
• chronic immune-complex mediated disease
• Causes:
Idiopathic ( 85 % )
Autoimmune diseases ( LUPUS )
Infections ( Malaria & Hepatitis B )
Drugs ( NSAIDS )
Tumours ( lung and colon )
 Morphology
• LM - Diffuse thickening of the GBM & No
proliferation
• EM: Subepithelial GBM deposits with
effacement of foot processes.
• IF - Diffuse granular staining of IgG and C3
• Only 10% will progress to renal failure or die.
 FOCAL SEGMENTAL
GLOMERULO-SCLEROSIS
• Just like its name
– Focal
– Segmental
– Glomerulo-SCLEROSIS (NOT –itis)
• HIV, Heroine, Sickle Cell,
Obesity.
• Most common cause of ADULT
nephrotic syndrome
 Prognosis
• 20% will progress to renal failure or die.
• Response poorly to steroids.
MEMBRANOPROLIFERATIVE
GLOMERULONEPHRITIS
 Types
MPGN Type I: Characterized by deposition of
Ab-Ag complex in the GBM # activation of
complement system.
MPGN Type II: Characterized by severe
activation of complement system - C3 - and
formation of Ab against it.
• LM – 1. Mesangial cell proliferation,
2. BM thickening,
3. Mesangial interposition into the GBM,
giving appearance of tram-track like.
4. Leukocyte infiltration.

• EM -type I - Sub endothelial deposits

type II - Intramembranous dense deposits
(dense-deposit disease).
 Outcomes
• 50% will progress to renal failure or die.
 Chronic glomerulonephritis
• Glomerular diseases progress to a chronic
stage- Chronic GN
• End stage renal disease
• Difficult to identify the underlying primary
disease.
 Causes Progression rate
RPGN 90%
Membranous GN 50%
MPGN 50%
IgA nephropathy 30-50%
Focal glomerulosclerosis 50-80%
Post streptococcal GN 1-2%
Glomerular Diseases : Fate
 Gross
• Small granular and contracted kidney.
• Capsule is difficult to remove due to
adhesions.
 Microscopy
• Sclerosis of glomeruli
• Tubular atrophy
• Interstitial fibrosis
 Complications
• Uremic pericarditis & Gastroenteritis
• Secondary hyperparathyroidism
• LVH
 Case 2
• A 5yrs old girl presented with generalized
edema, puffiness of face and oliguria without
hematuria.
• O/E -There was Anasarca with bilateral pitting
edema of feet and periorbital region.
• BP was 110/80 mm Hg and pulse rate
86/minute.
 Lab tests revealed
• HB- 9gm%, TLC- 11000/cumm,
Platelet – 2.3 lakhs
• Urine - Heat coagulation test - 4+
• Urine microscopy – Presence of fat globules & occ
WBCs.
• Serum Cholesterol, VLDL and LDL increased.
• Renal function test – Urea – 36 mg/dl, creatinine
1.2 mg/dl
• Renal biopsy was normal.
1. What syndrome does the patient suffer from ?
2. List some of the causes of this syndrome ?
3. What is the most common biopsy finding ?
4. What are the complications of this condition ?
5. What other lab tests your like to do to confirm
the diagnosis ?
 Questions
• Essay
1. Classify glomerular diseases. Discuss the
pathogenesis of glomerular injury. Write
briefly about PSGN.
2. Nephrotic syndrome – Definition, causes &
pathogenesis. Write briefly about MCD.
3. Nephritic syndrome – Definition, causes &
pathogenesis. Write briefly about RPGN.
4. Write in detail about RCC
 SN
• Renal failure
• Chronic GN
• Acute GN
• Urinary casts
• Difference between nephritic syndrome & nephrotic
syndrome
• Good Pauster syndrome
• Granular & contracted kidney
• Nephrolithiasis
• Acute tubular necrosis
• Pyelonephritis
• Benign & malignant nephrosclerosis
• Charts –
Nephritic syndrome
Nephrotic syndrome
RCC
• Gross specimen
RCC, Pyelonephritis
• Microscopy
RCC ,Wilms tumor & Pyelonephritis