The document discusses various glomerular diseases, focusing on nephritic syndrome and rapidly progressive glomerulonephritis (RPGN). It outlines the pathogenesis, clinical presentation, diagnostic evaluation, and treatment options for conditions like postinfectious glomerulonephritis and RPGN, emphasizing the importance of understanding these syndromes for effective management. Additionally, it highlights the need for ongoing research into their underlying mechanisms and potential novel therapies.

1. GLOMERULAR DISEASES
AND SYNDROMES
DR. SARA REZA

2. Specific learning objectives
By the end of this class, the students should be able to understand
the pathogenesis and clinical presentation of various glomerular
diseases.

5.  Which of the following characteristics is used to define a
nephritic syndrome?
A. Red Blood Cell casts in urine with a decreased BUN and
creatinine
B. Fatty casts in urine
C. Polyuria and hypotension
D. Protein in the urine (under 3.5 grams per day)

6. Nephritic Syndrome
 Clinical syndrome defined by
 Haematuria/ red cell casts
 Hypertension (mild)
 Oliguria
 Azotemia
 Proteinuria (<3g/24 hours)

7. CAUSES OF NEPHRITIC SYNDROME

8. Acute Postinfectious
(Poststreptococcal)
Glomerulonephritis
Acute postinfectious glomerulonephritis (GN) is a serious kidney
condition caused by an immune system response to a previous
infection, often streptococcal. This leads to inflammation and
damage within the glomeruli, the tiny filtration units of the
kidneys. While most cases resolve on their own, some can
progress to chronic kidney disease if not properly managed.
Understanding the underlying pathogenesis and clinical features
of this condition is crucial for effective diagnosis and treatment.

9. Pathogenesis of Postinfectious GN
1 Infection
Certain "nephritogenic" strains of streptococcal bacteria, as well as other
pathogens like pneumococcus and hepatitis viruses, can trigger an immune
response that leads to postinfectious GN.
2 Immune Complex Formation
Antibodies produced against bacterial antigens form immune complexes
that deposit in the glomeruli, activating the complement system and causing
inflammation.
3 Glomerular Injury
The immune complexes and complement activation lead to proliferation of
glomerular cells, leukocyte infiltration, and damage to the capillary walls,
resulting in the clinical features of postinfectious GN.

10. Histologic Features
Light Microscopy
Postinfectious GN is
characterized by diffuse
proliferation of glomerular
cells, including
endothelial, mesangial,
and infiltrating
inflammatory cells like
neutrophils. There may
also be necrosis of
capillary walls and
crescent formation in
severe cases.
Electron Microscopy
Electron microscopy
reveals immune complex
deposits, often in a
subepithelial "hump"
pattern, along the
glomerular basement
membrane. Mesangial
deposits may also be
present.
Immunofluorescence
Granular deposits of IgG
and complement
components are seen
along the capillary walls
and in the mesangium,
corresponding to the
immune complexes
visualized by electron
microscopy.

12. immunofluorescence microscopy
IgG, IgM, and C3 in in the mesangium and along the GBM

14. Clinical Presentation
1 Acute Nephritic Syndrome
The most common clinical presentation,
characterized by edema, hypertension,
and hematuria.
2 Proteinuria
Varying degrees of proteinuria,
occasionally severe enough to cause
nephrotic syndrome.
3 Complement Consumption
Decreased serum complement levels
during the active phase of the disease.
4 Serologic Markers
Elevated anti-streptolysin O (ASO)
antibody titers in poststreptococcal cases.

15. Prognosis and Outcomes
1 Acute Resolution
In most children with poststreptococcal GN, the condition resolves with
supportive care and the inflammation subsides over 2-3 months.
2 Rapid Progression
Some cases can develop rapidly progressive GN due to severe glomerular
injury and crescent formation, leading to rapid renal function decline.
3 Chronic Kidney Disease
In adults, 15-50% of cases progress to end-stage renal disease over years,
depending on the initial severity. Children have a lower risk of chronicity.

16. Treatment and Management
Supportive Care
The mainstay of treatment is supportive
care, including management of
hypertension, edema, and electrolyte
imbalances. Antibiotics may be used to
treat the underlying infection.
Immunosuppression
In severe or rapidly progressive cases,
immunosuppressive medications like
corticosteroids may be used to
suppress the aberrant immune
response.
Dialysis and Transplant
Patients who develop end-stage renal disease may require dialysis or kidney
transplantation as definitive treatment.

17. Prevention and Risk Factors
Streptococcal
Infections
Infection with certain
"nephritogenic" strains of
group A Streptococcus is
the most common trigger
for postinfectious GN.
Vaccination
Vaccination against
streptococcal and other
bacterial infections may
help prevent some cases of
postinfectious GN.
Good Hygiene
Proper hand hygiene and
prompt treatment of
streptococcal throat or skin
infections can reduce the
risk of postinfectious GN.

18. Future Directions and Research
Pathogenesis
Ongoing research aims to further elucidate the specific antigens and immune
mechanisms involved in the development of postinfectious GN.
Novel Therapies
Exploration of targeted immunomodulatory treatments to interrupt the
aberrant immune response and prevent progression to chronic kidney
disease.
Risk Stratification
Developing better predictive models to identify patients at high risk of
complications, informing individualized treatment approaches.

19. Rapidly Progressive
Glomerulonephritis
(RPGN)
Rapidly Progressive Glomerulonephritis (RPGN) is a clinical
syndrome characterized by the rapid loss of renal function, often
leading to kidney failure within weeks or months if left untreated.
It is typically associated with the presence of crescents, or
proliferative lesions outside the glomerular capillary loops, which
are a hallmark of this condition.

21. Causes of RPGN
Anti-GBM
Antibody-
Mediated
Also known as
Goodpasture's
disease, this form is
characterized by
linear deposits of IgG
and C3 along the
glomerular basement
membrane (GBM).
Patients may also
experience
pulmonary
hemorrhage.
Immune
Complex-
Mediated
Immune complexes
can accumulate in the
glomeruli, leading to
cellular proliferation
and crescent
formation. This can
occur in conditions
like post-
streptococcal
glomerulonephritis,
lupus, and IgA
nephropathy.
Pauci-Immune
In this form, there is a
lack of significant
immune complex
deposition or anti-
GBM antibodies. Anti-
neutrophil
cytoplasmic
antibodies (ANCA)
are often present,
and it may be a
component of
systemic vasculitis.

22. Pathological Features
1 Cellular Proliferation
Proliferation of epithelial cells
and migration of
monocytes/macrophages into
Bowman's space, forming the
characteristic crescent shape.
2 Glomerular Injury
Segmental capillary necrosis,
breaks in the GBM, and
deposition of fibrin in Bowman's
space, indicating severe
glomerular damage.
3 Immunofluorescence Patterns
Linear staining of IgG and C3 along the GBM in anti-GBM disease,
granular staining in immune complex-mediated GN, and negative staining
in pauci-immune GN.

24. Clinical Presentation
Rapid Onset
The onset of RPGN is similar to the
nephritic syndrome, but with more
pronounced oliguria and azotemia.
Proteinuria
Proteinuria may approach the nephrotic
range in some cases.
Dialysis or Transplant
Some patients become anuric and
require long-term dialysis or kidney
transplantation.
Prognosis
The prognosis is related to the
percentage of glomeruli involved, with a
better outlook for those with less than
80% crescent formation.

25. Treatment Approaches
1
Anti-GBM Antibody GN
Plasma exchange can be
beneficial in removing
pathogenic antibodies from the
circulation.
2 ANCA-Related GN
Plasma exchange may also be
helpful in some cases of pauci-
immune crescentic GN
associated with ANCA.
3
Immunosuppression
Corticosteroids and other
immunosuppressive agents are
often used to control the
underlying immune-mediated
process.

26. Pathogenesis of Crescent Formation
Glomerular Injury
Damage to the glomerular capillary walls and basement
membrane, often due to immune-mediated mechanisms.
Epithelial Proliferation
Proliferation of parietal epithelial cells lining Bowman's space,
forming the characteristic crescent shape.
Leukocyte Influx
Migration of monocytes, macrophages, and other inflammatory
cells into Bowman's space, contributing to crescent formation.

27. Diagnostic Evaluation
Serology
Testing for anti-GBM
antibodies and ANCA
can help differentiate
the underlying cause.
Kidney Biopsy
Histological
examination of the
kidney biopsy is
essential for diagnosis
and classification of
RPGN.
Imaging
Imaging studies, such
as ultrasound, may be
used to assess kidney
size and structure.

28. Prognosis and Outcomes
Crescent Involvement Prognosis
Less than 80% of glomeruli More favorable
Greater than 80% of glomeruli Less favorable
The prognosis for RPGN is largely determined by the extent of glomerular involvement, with
patients having crescents in less than 80% of glomeruli generally having a better outcome
than those with more extensive crescent formation. Early recognition and appropriate
treatment, including the use of plasmapheresis in select cases, can significantly improve the
chances of preserving kidney function and preventing the need for long-term dialysis or
transplantation.