1) Acute nephritic syndrome is characterized by sudden onset of hypertension, hematuria, mild to moderate proteinuria, and red blood cell casts. It is caused by acute glomerular inflammation and results in a fall in GFR and renal failure. 2) Rapidly progressive glomerulonephritis (RPGN) similarly presents with renal failure over weeks to months along with nephritic urinary sediment and proteinuria. 3) The main categories of acute nephritic syndrome and RPGN are immune complex mediated, anti-GBM antibody mediated, and pauci-immune mediated glomerulonephritis. A renal biopsy is needed for diagnosis.

1. ACUTE NEPHRITIC SYNDROME
AND RAPIDLY PROGRESSIVE
GLOMERULONEPHRITIS
Dr. D. ALEKHYA,
GENERAL MEDICINE POSTGRADUATE
MODERATOR: Dr. A.SRI SUSHMA,
GENERAL MEDICINE SENIOR RESIDENT

2. INTRODUCTION TO GLOMERULAR DISEASES:
• Classifications of glomerular diseases:
• Based on clinical syndromes
• Underlying renal pathology (including the percentage of glomeruli
involved)
• Mechanisms underlying the injury
• Sites of immune deposits
• Levels of serum complement
• And specific antibodies involved.

3. INTRODUCTION:
• Acute nephritic syndrome is clinical correlate of acute glomerular
inflammation
• It is characterised by sudden onset of hypertension, hematuria, mild to
moderate proteinuria, red blood cell casts, pyuria.
• Sudden onset of acute renal failure and oliguria(<400ml/day).
• Extensive inflammatory damage to glomeruli causes a fall in GFR and
eventually produces uremic symptoms with salt and water retention due to
low urinary sodium and high concentrated urine, leading to edema and
hypertension.
• The disease presentation may be acute or sub acute i.e, occurring over
days or weeks – acute; occurring over many months or years – chronic.

4. • Patients with glomerular disease may be classified into two groups:
1. Those with a clinical presentation of nephritic syndrome and
2. those with a clinical presentation of nephrotic syndrome
• Occasionally, a patient presents with features of both syndromes.
• Two additional points should be noted.
1. Systemic disease presenting as renal disease or
2. Renal disease presenting as systemic symptoms

5. Nephritic syndrome
Hypertension
Edema
Reduced glomerular filtration
rate
Active urinary sediment (red
cell casts)
Proteinuria < 3.5 g/24 hr
Nephrotic syndrome
Hypoalbuminemia
Oedema
Hyperlipidemia
Oval fat bodies in urine
Proteinuria > 3.5 g/24 hr

6. Nephritic syndrome
IgA nephropathy
Poststreptococcal GN
Idiopathic necrotizing GN
Anti-GBM disease
Nephrotic syndrome
Focal segmental
glomerulosclerosis
Membranous nephropathy
Minimal change disease
Membranoproliferative GN

7. Nephritic syndrome
• Systemic lupus erythematosus
• Vasculitis (ANCA-related):
Wegener granulomatosis
Microscopic polyarteritis
• Hypersensitivity vasculitis
• Henoch-Schönlein purpura
• Goodpasture syndrome
• Cryoglobulinemia
Nephrotic syndrome
• Diabetes mellitus
• Amyloidosis

8. • Glomerular diseases are classified as
• Primary
• Pathology is confined to the kidney
• Systemic features are a direct consequence of glomerular
dysfunction
• Usually, but not always, the term primary is synonymous with
idiopathic.
• Secondary
• Part of a multisystem disorder.

9. PATHOGENESIS – acute nephritic syndrome:
Inflammatory cells
infiltration and
infiltration of glomerular
tuft by neutrophils and
monocytes
Excessive proliferation of
glomerular cells
Obstruction to
glomerular capillary
lumen and decreases
renal blood flow
Decrease in GFR
Increased salt and water
retention by tubules
Extracellular fluid
volume expansion,
edema, hypertension

10. ACUTE NEPHRITIC SYNDROMES:
• Post streptococcal glomerulonephritis
• Subacute bacterial endocarditis
• lupus nephritis
• Anti GBM disease
• IgA nephropathy
• ANCA associated small vessel vasculitis
• Henoch schonlein purpura
• Cryoglobulinemia
• Membranoproliferative glomerulophritis
• C3 glomerulopathies
• Mesangioproliferative glomeruloneprhritis

11. RAPIDLY PROGRESSIVE
GLOMERULONEPHRITIS:
• RPGN is a clinical correlate of subacute glomerular inflammation
• Renal failure develops over weeks to months in association with:
Nephritic urinary sediment
Subnephrotic proteinuria
Variable oliguria
Hypervolemia
Edema
hypertension

12. ANTIBODY
MEDIATED
IMMUNE COMPLEX
MEDIATED
PAUCI-IMMUNE
MEDIATED
ACUTE
NEPHRITIC
SYNDROME
/RPGN
 ANTIBODY MEDIATED:
• Anti GBM disease
• Good pastures syndrome
 IMMUNE COMPLEX MEDIATED:
 Diseases associated with low C3 levels-
• PSGN
• Lupus nephritis
• Cryoglobulinemia
• Subacute bacterial endocarditis
 Diseases with normal C3-
• IgA nephropathy
• IgA vasculitis(HSP)
 PAUCI IMMUNE MEDIATED:
• Granulomatous polyangiitis(wegeners granulomatosis)
• Eosinophilic granulomatous polyangiitis(churg strauss
syndrome)
• Microscopic polyangitis

13. • Rapid diagnosis and prompt treatment are critical to avoid the
development of irreversible renal failure
• Renal biopsy remains the gold standard for diagnosis
• Immunofluorescence microscopy is particularly helpful and identifies three
major patterns of deposition of immunoglobulin that define three broad
diagnostic categories:
• Linear deposits of immunoglobulin along the glomerular basement
membrane(GBM) characteristic of anti-GBM disease
• Granular deposits of immunoglobulin is a hallmark of immune complex
glomerulonephritis
• Paucity or absence of immunoglobulin, so called as pauci immune
glomerulonephritis

14. • Most patients (>70%) with full blown acute nephritic syndrome have
immune complex glomerulonephritis
• Pauci immune glomerulonephritis is less commonly seen(30%)
• Anti GBM diease is very rarely seen(1%)

15. • Among the patients with RPGN, immune complex mediated
glomerulonephritis and pauci immune glomerulonephritis are equally
prevalent
• Anti GBM disease accounts for minority of cases (<10%)
• Three serological markers often predict the immunofluorescence
microscopy finding in nephritic syndrome and RPGN :
1. Serum C3 level
2. Anti GBM antibody and
3. Anti neutrophil cytoplasmic antibody(ANCA)
• The need for biopsy is dependent upon these markers

16. • Patients with acute nephritic syndrome and RPGN typically have
hypocomplementemia(low C3) and
• Negative anti GBM and ANCA serology
• 90-95% patients with anti GBM disease have circulating anti GBM
autoantibodies detectable ny immunoassay
• Serum complement levels are typically normal
• ANCA are usually not detected
• In patients with pauci immune glomerulonephritis have circulating
ANCA, normal serum complement levels, anti GBM titres negative

17. ELECTRON MICROSCOPY:
• The classic pathological correlate of RPGN is cresent formation
involving most glomeruli(cresentic glomerulonephritis)
• Cresents are half moon shaped lesios in bowmans space – composed
of proliferating parietal epithelial cells and infiltrating
monocytes(extracapillary proliferation)

19. Immune complex mediated
GN – granular deposition
Anti GBM disease –
ribbon like linear
deposits
Pauci immune GN
– paucity or no
deposits

20. TREATMENT – ANTI GBM DISEASE:
• Prior to the introduction of immunosuppressive therapy,
• Greater than 80% of patients with anti-GBM nephritis developed ESRD within
1 year
• Renal and patient survival have improved dramatically with early and
aggressive use of :
• Plasmapheresis,
• Glucocorticoids,
• Cyclophosphamide and
• Azathioprine

21. • In general, emergency plasmapheresis is performed daily or on alternate
days until anti-GBM antibodies are not detected in the circulation (usually
1 to 2 weeks).
• Prednisone - 1 mg/kg/day is started simultaneously, in combination with
either:
• Cyclophosphamide (2 to 3 mg/kg/day) or
• Azathioprine (1 to 2 mg/kg/day) to suppress new synthesis of anti-GBM antibodies
• The speed of initiation of therapy is a critical determinant of outcome.
• One-year renal survival approaches 90% if treatment is started before
serum creatinine exceeds (5 mg/dL) and falls to about 10% if renal failure is
more advanced.
• With ESRD, renal transplantation is a viable treatment option.

22. THANK YOU