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Renal pathology the nephrotic syndrome- prof wadie
1. Renal Pathology
for medical students
The Nephrotic Syndrome
Professor Wadie M Y Elmadhoun
E-mail: wadie2222@yahoo.com
Kidney Pathology – Nephrotic Syndrome – Prof. Wadie 1
3. Intended Learning outcomes (ILOs)
• By the end of studying this lecture, students should be
able to:
1. Define the nephrotic syndrome and explain its
components, causes and pathogenesis.
2. Define and describe minimal change disease
3. Define and describe focal segmental
glomerulosclerosis.
4. Define and describe membranous
glomerulonephritis.
5. Define and describe membranoproliferative GN
6. List the complications of the nephrotic syndrome
Kidney Pathology – Nephrotic Syndrome – Prof. Wadie
3
4. Definition of the nephrotic syndrome
• A Manifestation of glomerular disease,
characterized by
• Heavy proteinuria leading to
• hypoalbuminaemia , and
• edema
• With/without hyperlipidemia and lipiduria.
Kidney Pathology – Nephrotic Syndrome – Prof. Wadie 4
5. Overview of causes and pathogenesis
• The causes of the NS are either:
1. Primary glomerular diseases (GN) or
2. Systemic diseases leading to glomerulopathy.
• The main point in pathogenesis is:
• Glomerular basement (GBM) damage by the
immune system results in loss of proteins
from circulation to urine.
Kidney Pathology – Nephrotic Syndrome – Prof. Wadie 5
6. Nephrotic Syndrome (NS)
• Massive proteinuria: 3.5 g/24hrs in adults,
• Hypoalbuminemia: below 2.5 g/dl.
• Edema: peri-orbital, or generalized. Due to decreased
oncotic pressure, leading to increased production of aldosterone.
• Hyperlipidemia: due to excessive free lipids + increased
hepatic production.
• Lipiduria: leak due to GBM damage.
Kidney Pathology – Nephrotic Syndrome – Prof. Wadie
12. The nephrotic syndrome: pathogenesis/etiology, pathological and clinical manifestations
GBM= Glomerular basement membrane, GN= glomerulonephritis,, FSGS= focal segmental glomerulosclerosis, MCD= Minimal change
disease, MGN= Membranous glomerulonephritis, MPGN= Membranoproliferative glomerulonephritis
12
Abnormal immune
responses against GBM
DM, HIV, HBV, Chemicals, …
Protein loss in urine
Less protein in circulation
EdemaInfections/ thrombosis/RF Hyperlipidemia & lipiduria
Glomerunephritis
& GBM
Damage
MPGNFSGS
MGNMCD
13. Minimal Change Disease (MCD)
• Accounts for 80% of all cases of the nephrotic
syndrome in children. About 10% in adults.
• Light microscope: Normal glomeruli, no changes.
• By electron microscope: loss of foot processes of
podocytes (effacement).
Kidney Pathology – Nephrotic Syndrome – Prof. Wadie 13
16. Minimal Change Glom.
(Lipoid Nephrosis)
• most common cause of nephrotic syndrome
in children
• effacement of foot processes
Kidney Pathology – Nephrotic Syndrome – Prof. Wadie
21. Clinical course of Minimal change disease
• Starts insidiously in an otherwise healthy
individual.
• 90% respond to predinsolone.
• Recurrent Proteinuria in 60% (steriod dependent).
• Less than 5% develop chronic renal failure in 25
years.
Kidney Pathology – Nephrotic Syndrome – Prof. Wadie 21
22. Focal Segmental
Glomerulo-sclerosis (FSGS)
• Just like its name:
- Focal: some, not all, glomeruli affected.
- Segmental: only segments, not whole,
glomerulus affected.
- Glomerulo-SCLEROSIS: fibrosis (NOT –itis)
• Is the Most common cause of
ADULT nephrotic syndrome.
• Associated with : HIV, Heroin,…
23. Focal segmental glomerulosclerosis
• FSGS constitutes 30-40% of nephrotic
syndrome (NS) in adults.
• and about 10% of NS in children.
• May be due to immunoglobulins and
complement immune responses.
• Onset is insidious.
• 50% develop renal failure in 10 years.
Kidney Pathology – Nephrotic Syndrome – Prof. Wadie 23
29. Membranous Glomerulonephritis
(MGN)
• Causes about 30% of nephrotic syndrome in adults,
but only 5% of NS in children.
• Associated with: Drugs, malignancies, SLE, Infections
• There is subepithelial deposition of Ag-Ab complexes.
• Indolent course.
• About 60% will continue to have persistent
proteinuria.
• 10% to 40% go on to renal insufficiency in 10 years.
35. Membranoproliferative
Glomerulonephritis (MPGN)
• Also known as
mesagiocapillary GN.
• Accounts for 10% of nephrotic
syndrome cases.
• GBM changes, subendothelial
deposits, mesangial
proliferation and
• Leukocyte infiltrations.
36. MPGN
• MPGN can be idiopathic or 2º e.g SLE,
viral/bacterial infections.
• There are 2 types:
1. Type I MPGN (80%): due to immune complex
deposition,
2. Type II MPGN: (dense deposit disease) due to
complement activation.
• MPGN is persistent and progresses to renal
failure.
Kidney Pathology – Nephrotic Syndrome – Prof. Wadie 36
44. Complications of nephrotic syndrome
• Infections
• Thrombosis
• Acute renal failure
• Chronic renal failure
• Steriod side effects.
Kidney Pathology – Nephrotic Syndrome – Prof. Wadie 44
45. Please
Have a careful look once again at
the following 2 repeated slides.
Kidney Pathology – Nephrotic Syndrome – Prof. Wadie 45
46. The nephrotic syndrome: pathogenesis/etiology, pathological and clinical manifestations
GBM= Glomerular basement membrane, GN= glomerulonephritis,, FSGS= focal segmental glomerulosclerosis, MCD= Minimal change
disease, MGN= Membranous glomerulonephritis, MPGN= Membranoproliferative glomerulonephritis
46
Abnormal immune
responses against GBM
DM, HIV, HBV, Chemicals, …
Protein loss in urine
Less protein in circulation
EdemaInfections/ thrombosis/RF Hyperlipidemia & lipiduria
Glomerunephritis
& GBM
Damage
MPGNFSGS
MGNMCD
47. ASSIGNMENT
• Can you write a comprehensive essay through
answering the following points:
1. Define the nephrotic syndrome and explain its
components, causes and pathogenesis.
2. Define and describe minimal change disease
3. Define and describe focal segmental
glomerulosclerosis.
4. Define and describe membraneous
glomerulonephritis.
5. Define and describe membranoproliferative GN.
6. List the complications of the nephrotic syndrome.
Kidney Pathology – Nephrotic Syndrome – Prof. Wadie
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48. Quiz 1
Kidney Pathology – Nephrotic Syndrome – Prof. Wadie
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• What is the cutoff for urine protein that
defines nephrotic syndrome in adults?
• Answer:
• > 3.5 g/24 hr
• 40 mg/m2/hr
• Urine protein: creatinine ratio of 2:1 or more.
• Early morning protein 3+/4+ on dipstick.
49. Quiz 2
• What is the level, in grams per dL, for serum
protein that is consistent with nephrotic
syndrome?
• Answer:
• Less than 2.5 g/dL
Kidney Pathology – Nephrotic Syndrome – Prof. Wadie
49
50. Quiz 3
• What is the difference between 1°
(primary) and 2° (secondary) nephrotic
syndromes?
• Answer:
• Primary - due to direct GBM and podocyte damage by
immune system;
• Secondary - damage occurs in the setting of a systemic
illness (eg, diabetes, SLE, HIV, amyloidosis,…)
Kidney Pathology – Nephrotic Syndrome – Prof. Wadie 50
51. Quiz 4
• Focal segmental glomerulosclerosis, minimal
change disease, membranous nephropathy:
are they 1° nephropathy, 2° nephropathy, or
both?
• Answer:
• All 3 may present as either a 1° or 2° disorder
Kidney Pathology – Nephrotic Syndrome – Prof. Wadie 51
52. Quiz 5
• The definition of nephrotic syndrome
includes:
A. Hypolipidemia
B. Lipiduria
C. 24 hour urine protein less than 2 grams.
D. hypertension
Kidney Pathology – Nephrotic Syndrome – Prof. Wadie 52
53. Quiz 6
• A patient exhibits diffuse edema. He voids 4 g
of protein per day and has hypoalbuminemia
and hyperlipidemia. What will glomerular
biopsy show?
• Answer:
• Podocyte disruption: loss of foot processes is a
hallmark of nephrotic syndrome
Kidney Pathology – Nephrotic Syndrome – Prof. Wadie 53
54. Quiz 7
• Give 5 examples of disorders that
present largely as nephrotic
syndrome.
• Answer:
• Focal segmental glomerulosclerosis,
membranous nephropathy, minimal
change disease, amyloidosis, and
diabetic glomerulonephropathy
Kidney Pathology – Nephrotic Syndrome – Prof. Wadie 54
55. Consider this illustration the major glomerular structures.
Demonstrate what morphological changes you expect to find in each
of the following glomerulopathies: MCD, FSGS, MGN, MPGN.
Hints: effacement, subendothelial/subepithelial deposits, proliferation, thickening, slerosis. 55
GBM
Capillary lumen
Mesangial
cell
Mesangial
cell