A brief description of different kinds of kidney injury & it's immunological mechanism with special reference to glomerulonephritis

1. DR TARAK NATH CHATTOPADHYAY
MD PGT,GENRAL MEDICINE,BSMC&H

2.  The cause of immunologically mediated renal
disease is antigenic triggering of an immune
reaction.
 The list of associated antigens is extensive and
continually expanding. These antigens are
categorized as renal or non-renal and as self or
foreign .
 The causative antigen is often unknown.
Antigens

4.  To cause immunologically mediated renal
disease, an antigen must localize to the
kidney and trigger a local immune
inflammatory response.
 Renal antigens are inherently localized,
being constituent proteins of the kidney.
 Non-renal antigens require a mechanism for
depositing in the kidney.

5.  Type II hypersensitivity (Cytotoxic Antibody-
mediated )
 Type III hypersensitivity (Immune Complex-
mediated )
 Cell-mediated immunity (CD4+,CD8+ T)
 Immune hereditary factors (HLA)

6. Ags on the surface of target
cells
↓
Antibody→IgG, IgM
1. DAMAGE THE TARGET CELL
1) Activation of
complement
2) opsonization FcR
C3bR
3) ADCC
2. TARGET CELL DYSFUNCTION

7.  Prototype: Anti-GBM disease (Goodpasture's
disease)
 Renal damage is caused by linear deposition
of antibody specific for type IV collagen of
the GBM. The antibody attaches to its antigen
and activates the complement.
 Cytotoxic antibody localizes along the GBM in
a linear pattern with C.

9. Ag→body→IgG, IgM, IgA
↓
immune complexes (IC)
↓
soluble IC
↓
ICs are deposited from the circulation
into vascular basement membranes
①↓ ② ↓FcR
activation of complement plat. and basophils
↓
C3a, C5a →mast cell → release of vasoactive amines
↓ basophils
③ Neutrophils vasodilation
↓
lysosomal edema
enzymes→damage the tissue

10.  Immune complex localizes in the mesangium, glomerular capillary
wall, or renal interstitium as a lumpy-bumpy pattern.
 Small immune complexes are less likely to be deposited, and large
immune complexes are preferentially removed by RES minimizing
localization in the kidney.
 As circulating immune complexes are formed and antibody
production increases, the size of the circulating immune complex
increases:
 removal from the circulation by RES cells or
 localization in the mesangium or glomerular capillary wall.
 Various endogenous and exogenous substances may function as
antigen in immune complex formation.
 endogenous nuclear proteins in DNA-anti-dsDNA IC in lupus
nephritis,
streptococcal cell wall antigens in post-streptococcal
glomerulonephritis.

12. ‘Bumpy’ appearance
of immune complexes
deposited in the
glomerulus in SLE

15.  The prototype is the renal transplant.
 In nearly all non twin transplants, the kidney
presents nonself antigens that trigger an immune
(predominantly cell-mediated) response.
 If the host has been presensitized to antigens of
the renal graft, transplantation may trigger
hyperacute rejection , resulting in acute renal
ischemia, infarction, and transplant loss.
 Cell-mediated renal disease appears to play a part
in chronic poststreptococcal glomerulonephritis
(PSGN).

16. PSGN has been associated with HLA-B12
IgA nephropathy with HLA-B35 and HLA-DR4
Anti-GBM or Goodpasture's syndrome with HLA-
DR2
IMN（idiopathic membeanous nephropathy）
with HLA- II（DR3、DR2、DQ2、DQ1）
Minmal change nephrosis with HLA-DR7、DR9

17.  Renal biopsy and light microscopic examination
- best method for diagnosing immunologically
mediated renal disease, assessing prognosis, and
selecting treatment.
 Iimmunofluorescence microscopy using
fluorescein-labeled specific antibodies
 Electron microscopy for location of immune
complex, assessment of basement membrane

18.  Examining the urine for protein and formed elements
is often useful.
 Proteinuria is present in virtually all forms of
immunologically mediated renal disease.
 Nephrotic-range proteinuria usually suggests an
underlying immune mechanism, although nephrotic
syndrome may occur in nonimmune renal disease
(eg, diabetes mellitus).
 Acute cytotoxic-type injury of anti-GBM disease,
causes significant hematuria.
 Immune complex-type injury is associated with
hematuria and RBC casts..
 MPGN and membranous glomerulonephritis are
associated with significant proteinuria. MPGN usually
produces hematuria, but membranous
glomerulonephritis rarely does. Minimal-change
disease and focal sclerosing glomerulonephritis may
produce only proteinuria.

19.  Detect
 cytotoxic antibodies in type II renal disease (eg, anti-GBM antibodies,
anti-HLA antibodies).
 Circulating ANCA can be detected in ANCA-mediated renal disease .
 Altered levels of C proteins often differentiate types of
immunologically mediated renal disease.
 In classic pathway activation (eg, in SLE), consumption begins
with the early components, which are thereby depressed.
 The presence of C3 nephritic factor with depressed C3 but
normal Clq, C4, and C2 is virtually diagnostic of MPGN with
alternative pathway activation.
 Other helpful serologic analyses include:
 Rising antibody titers to streptococcal antigens in PSGN.
 Other postinfective glomerulonephritides eg, a positive test
for syphilis, hepatitis-associated antigen, or rising antibody
titers to other infective organisms..

20.  May help diagnose some forms of
immunologically mediated renal disease. For
example,
 PSGN has been associated with HLA-B12,
 IgA nephropathy with HLA-B35 and HLA-DR4, and
 Anti-GBM or Goodpasture's syndrome with HLA-
DR2.