1. Minimal Change Disease/
Minimal Change Nephropathy
• Minimal change disease (MCD), also
known as
• Minimal Change Nephropathy
• lipoid nephrosis
• nil lesions or
• nil disease.

2. Minimal Change Disease/
Minimal Change Nephropathy
• Minimal change disease (MCD), also
known as
• Minimal Change Nephropathy
• lipoid nephrosis
• nil lesions or
• nil disease.

3. MCD
It refers to a histopathologic lesion in
the glomerulus that almost
always is associated with
nephrotic syndrome.

4. Lipoid Nephrosis
• The term lipoid nephrosis was used to
describe the finding of lipids in the
renal tubular cells
• as well as lipid-laden proximal tubular cells
or macrophages known as oval fat
bodies
in the urine.

5. Epidemiology
• Age: 1-7y (90%) & >80y
• Adults (10-15%)
• Teenager: 50% NS due to MCD
• Sex: Boys> Girls
• Association with Autoimmune disorders
• Association with Hematologic malignancies

6. Epidemiology
• Minimal Change Disease is most common in
very young children but can occur in older
children and adults (10-15%). It is by far the
most common cause of nephrotic syndrome
(NS) in children between the ages of 1 and 7,
accounting for the majority (about 90%) of
these diagnoses.

7. Lipoid Nephrosis-Epidemiology
• Among teenagers who develop
NS, it is caused by minimal
change disease about halfthe
time.

8. Epidemiology of MCD
Among children less than 10 years of age, boys
seem to be more likely to develop minimal
change disease than girls. Minimal change
disease is being seen with increasing
frequency in adults over the age of 80.

9. Epidemiology
• People with one or more autoimmune
disorders are at increased risk of developing
minimal change disease.
• Having minimal change disease also increases
the chances of developing other autoimmune
disorders.

10. Epidemiology of Lipoid Nephrosis
• MCD is associated with malignancies,
particularly hematologic malignancies,
such as Hodgkin’s disease, non-Hodgkin
lymphomas, or leukemias.
• Colorectal cancer-associated MCD is
uncommon and has been reported in only a
few cases to date.

11. Causes- Idiopathic
The cause is unknown, but the disease may
occur after or be related to:
• Allergic reaction (autoimmune etiology)
• Medication such as NSAID
• Tumors (Hematologic tumors)
• Vaccinations
• Viral infections (Such as EBV)

12. Pathology -Idiopathic
The pathology of minimal change disease is
unclear and is currently considered idiopathic
.
The pathology does not appear to involve
complement, immunoglobulins, or immune
complex deposition.

13. Factors which may involve in the Pathogenesis of MCD
• 1. Disorder of T-cell- secretion of cytokines.
• 2. Circulating T cell factor- Hemopexin
• 3. Endothelin 1
• 4. Nephrin
• 5. Dysferlin
• 6. CD 80
• 7.CTLA-4
• 8.PTPRO/ GLEPP1
• 9.HLA-DR 7
• 10. Synaptopodin

14. Mechanism of Nephrotic syndrome
• Rather, an altered cell-mediated immunologic
response the abnormal secretion of lymphokines
(cytokines13,12,4,18) by T cells (T lymphocytes)is
thought to reduce the production of anions in the
glomerular basement membrane, thereby
increasing the glomerular permeability to
serum albumin through a reduction of
electrostatic repulsion.

15. Mechanism of foot processes effacement
It is postulated that MCD is a disorder of T cells,
which release a cytokine (IL-12,4,13,18) that
injures the glomerular epithelial foot processes
podocytes swell up & foot processes effaced. This,
in turn, leads to a decreased synthesis of
polyanions.
Polyanion: a molecule or chemical complex having
negative charges at several sites

16. Pathology (Pathophysiology)
A circulating T-cell factor/permeability factor
(Hemopexin) causes podocyte cytoskeleton
disorganization leading to increased
glomerular capillary permeability and/or
changes (neutralize negative charges of
heparan sulfate) in glomerular basement
membrane heparan sulfate
glycosaminoglycans resulting in
proteinuria.

17. Pathology
•The loss of anionic charges
is also thought to favor
foot process fusion
(effacement).

18. Pathology
•IL-13 overexpression
can cause podocyte foot
process fusion
(effacement) and
proteinuria.

19. Hemopexin- beta-1B- glycoprotein
• Hemopexin also known as beta-1B-
glycoprotein is a protein that in humans is
encoded by the HPX gene and belongs to
hemopexin family of proteins

20. ARF- Endothelin-1
• In patients who develop acute renal failure,
endothelin 1 (This peptide is a potent vasoconstrictor
and is produced by vascular endothelial cells). expression is
greater in the glomeruli, vessels, and tubules
than in the nonacute renal failure group.

21. Congenital Nephrotic Syndrome & Nephrin
• The glomerular epithelial cells (podocytes)
and the slit diaphragm connecting the
podocyte foot processes play a primary role
in the development of proteinuria.
• Nephrin is a major component of the slit
diaphragm.

22. Congenital Nephrotic
syndrome & Nephrin
• The slit diaphragm is often missing in
MC nephrotic syndrome (MCD) kidneys.
The role of nephrin and the slit diaphragm in
MCD is not known. However, genetic variants
of a glomerular filter protein may play a role
in some patients with MCD.

23. Congenital Nephrotic syndrome & Nephrin
• Nephrin is a protein necessary for the proper
functioning of the renal filtration barrier.
Nephrin is a protein that is a structural
component of the slit diaphragm.
• A defect in the gene for nephrin, NPHS1, is
associated with
congenital nephrotic syndrome and causes
massive amounts of protein to be leaked into
the urine, or proteinuria.

24. Dysferlin
• A lack of glomerular dysferlin
expression is associated with minimal-
change nephropathy.
• Dysferlin also known as dystrophy-associated
fer-1-like protein is a protein that in humans is
encoded by the DYSF gene.
• Dysferlin is linked with skeletal muscle repair.

25. Dysferlin
• A defect in the DYSF gene, located on
chromosome 2p12-14, results in either of two
types of muscular dystrophy;
Miyoshi myopathy (MM) and
Limb-girdle muscular dystrophy type 2B
(LGMD2B).

26. CD 80 (B7-1)
• CD 80, a protein found in B cells and
responsible for T-cell activation, is
found to be increased in patients with
MCD.

27. Minimal change disease: a CD80
podocytopathy
• Recently, increased expression of CD80 (also
termed B7-1) on podocytes was identified as a
mechanism for proteinuria.
• CD80 is inhibited by binding to CTLA-4, which
is expressed on regulatory T cells.

28. CTLA-4 (Cytotoxic T-Lymphocyte Antigen 4), also
known as CD152 (Cluster of differentiation 152), is a
protein receptor that downregulates the immune
system.
• Interleukin-13 or microbial products via Toll-like
receptors could be factors that induceCD80
expression on podocytes.
• CTLA-4 appears to regulate CD80
expression in podocytes, and to be alteredin
minimal change disease patients.

29. CTLA-4 (Cytotoxic T-Lymphocyte Antigen 4)
• Proteinuria in minimal change disease is
caused by persistent CD80 expression in
podocytes,possibly initiated by stimulation of these
cells by antigens or cytokines.

30. Genetics
• Protein tyrosine phosphatase receptor type O
(PTPRO)- also known as
glomerular epithelial protein 1 (GLEPP1)
has been shown to be mutated in a number of
cases.

31. •Increased risk of MCD
in those with
possession of
HLA-DR7 allele

32. Synaptopodin & Response to Steroids
• Synaptopodin is a proline-rich protein intimately
associated with actin microfilaments present in the
foot processes of podocytes.
Greater synaptopodin expression in podocytes is
associated with a significantly better response to
steroid therapy. Thus, this marker could be used
in the future to help determine appropriate
therapy.

33. Pathology- Morphology
Light Microscopy:
• For years pathologists found no
changes when viewing specimens
under light microscopy; hence the
name minimal change disease/Nil
lesions/Nil disease.

34. Morphology
• Lipoid Nephrosis:
• Cells of the Proximal Tubule are often filled
with lipids but this is probably secondary
to resorption of lipoproteins which are
normally not filtered by a healthy glomerulus
(This is why this disease was originally called
"Lipoid Nephrosis")

35. Morphology
• Immunofluorescence
–No deposition of immune complexes

36. Pathology- Morphology
• Electron microscopy:
HALLMARKS
1.Diffuse loss of (diffuse & uniform effacement
of) visceral epithelial cells (podocyte) foot
processes,
2.Vacuolation, and
3. Growth of microvilli on the visceral
epithelial cells.
Occasional focal detachments.

38. MORPHOLOGY
Diffuse &
Uniform
Effacement
Of
Foot process

39. Effacement of foot processes
Diffuse
Loss of
Foot
processes
UNIFORM & DIFFUSE

40. Clinical features
• Nephrotic syndrome:
• Hyperproteinuria,
• Hypoalbuminemia,
• Edema,
• Hyperlipidemia,
• Lipidemia &
• Coagulopathy.

41. Prognosis
• Good.
• >90% respond to corticosteroids
• Proteinuria recurs in > 2/3 of cases
• Some of whom become steroid dependent
• < 5% develop CRF after 25 years.