2. INTRODUCTION
• Glomerulonephritis is a disease characterised by inflammation of
the glomerulus and its small blood vessels.
• It can occur in a variety of primary renal diseases and as well as in
many systemic diseases
• The disease is mainly immune complex mediated
• The glomerular involvement can be of following types
Focal – involvement of < 50 % of the tissue
Diffuse – involvement of > 50 % of the tissue
Segmental – changes confined to one or two lobules of the affected
glomeruli
3. ANATOMY OF GLOMERULUS
GLOMERULUS CONSISTS OF-
• Capillary network lined by
fenestrated endothelial cells
• Visceral and parietal epithelial
cells.
• Intervening basement membrane
It is also known as
filtration barrier
4. • Visceral epithelial cells
or podocytes have a slit
diaphragm that
consists of proteins
like nephrin,podocin
and actin.
• They impart a size
selective diffusion
barrier function to the
slit diaphragm to
5. OVERVIEW
• Glomerulonephritis is characterised by injury to the glomerular
filtration barrier leading to increase in the permeability .It leads to
renal loss of different proteins from our body.
• Along with albumin , globulin is also lost through kidney and this is
responsible for some complications , like-
Recurrent infections (due to loss of immunoglobulins)
Hypercoagulable state (due to loss of antithrombin 3)
6. PATHOPHYSIOLOGY
• Immune complex mediated
disease
• Involves either circulating
immune complex or antibodies
directed against glomerular ag
• On glomerular deposition it
leads to complement activation
and inflammatory cell
infiltration
• End result- membrane damage
causing increased permeability
8. LABORATORY WORKUP
• Complete haemogram- may show anaemia
• Renal function tests- features of renal impairment (raised creatinine)
• LFT- hypoalbuminaemia / hypoproteinaemia
• Serum C3 - may be low
• Autoimmune markers – ANA ,pANCA , cANCA
• ICTC , HbsAg , Anti HCV , MPDA
• VDRL
• SPEP – to rule out plasma cell disorder
9. Routine urinalysis-
• Haematuria
• RBC cast
• Dysmorphic RBC
• Proteinuria (>1-2 g/day)
Renal ultrasound – to look for kidney size , cortico-
medullary differentiation and renal echotexture.
10. • Kidney biopsy – it is done to know the histopathological
variant of glomerulonephritis and to plan therapy
accordingly. With the kidney biopsy specimen the
following are done-
Light microscopy
Immunofluroscence microscopy
Electron microscopy
Congo red stain to look for amyloid
• Chest x-ray – to look for associated pleural effusion or
13. POST STREPTOCOCCAL
GLOMERULONEPHRITIS
• Prototype of acute nephritic syndrome
• Usually occurs following an episode of beta haemolytic streptococcal infection of
skin or throat , only with nephritogenic strains ( M types 1,2,3,4,25,47,49).
• Time gap is 1-3 wk following throat infection and 2-6 wks following skin
infection.
• Causative strains produce streptococcal pyrogenic exotoxin b , that may be
responsible for immune complex formation and ultimate glomerular injury.
14. CLINICAL FEATURE
In developing countries it usually occurs among
children (2-14 yr) , but in developed countries it
usually occurs among elderly.
Patient usually present with
I. Oliguria
II. Haematuria or cola coloured urine
III.Hypertension
IV.Oedema – following an episode of streptococcal
infection
15. LABORATORY FINDING
• Complete haemogram – anaemia
• Urea/creatinine – may be elevated
• Urinalysis – haematuria ,RBC cast /dysmorphic RBC , proteinuria
• Serum complements – C3 level is usually temporarily low
• False positive RF factor or ANCA positivity
• Elevated ASO titre
• Streptococcal throat swab may be negative
• Anti- DNAse or anti- hyaluronidase positivity
• Sub epithelial hump on immunofluoroscence
16. TREATMENT AND OUTCOME
• Excellent prognosis
• Complete resolution occurs within 3-6 wks and
permanent renal failure occurs in < 1 % patients
• Treatment is mainly supportive with control of
oedema , hypertension .
• If acute renal failure occurs dialysis should be
instituted
• Antibiotic therapy should be given to all patients
• No role of immunosuppressive therapy even in
17. RPGN
• RPGN Is not a single disease , but it is a syndrome
characterised by
I. Features of nephritic syndrome
II. Rapid worsening of renal function
III.Presence of glomerular crescents on histopathology
IV.If left untreated death can occur from renal failure
• The glomerular injury in RPGN is also immunologically
mediated.
18. TYPES
RPGN
Type 1(Anti-GBM Antibody)
1. Idiopathic
2. Goodpauster syndrome)
Type 2 (Immune complex mediated)
1.PSGN
2.SLE
3.HSP
IgA nephropathy
Type 3 (pauci immune)
1. Idiopathic
2. ANCA associated
19. TREATMENT
• As disease course is fatal , so treatment is to be started at the
earliest opportunity . the treatment options are following
I. Renal replacement therapy for management of renal failure
II. Plasmapheresis for removal of causative auto antibodies
from body
III.High dose steroid therapy
IV.Cytotoxic drugs like cyclophosphamide
20. MEMBRANOPROLIFERATIVE
GLOMERULONEPHRITIS
• Immune mediated acute nephritic syndrome
• Associated with microscopic haematuria , hypertension , varying
degree of renal impairment , proteinuria
• Idiopathic MPGN usually presents in childhood or early young
adulthood
• It is of two types – type 1 & 2 . type 2 is characterised by presence of
autoantibody C3NeF in the serum that causes stabilization of C3
convertase leading to persistent low C 3 level ( dense deposit disease)
21. CLASSIFICATION
MPGN
TYPE 1
1.Idiopathic
2.HIV , Hep B,Hep C
3. SLE
4. Cryoglobulinaemia
5. CA lung
Breast
6.Plasma cell disease
TYPE 2 (DENSE DEPOSIT DISEASE)
1. Idiopathic
2 c3 nephritic factor associated
22. CLINICAL FEATURES
• Occurs in young population
• Presents with features of both nephrotic and nephritic
syndrome
• Slowly progressive unremitting course
• May present with features of RPGN
• 50% patients develop chronic kidney disease within 10 years
23. INVESTIGATIONS AND TREATMENT
• Investigations are similar to that of other causes of
glomerular disease including hep b , hep c , ICTC , serum
complements
• Kidney biopsy shows mesangial proliferation , diffuse
thickening of gbm leading to double contour or tram track
appearance
• Immunofluoroscence shows sub endothelial electron dense
deposits
• Treatment in idiopathic cases is by oral cyclophosphamide
or MMF with steroid
24.
25. MINIMAL CHANGE DISEASE
• Most common cause of nephrotic syndrome
among children.
• May occur among adult also in association with
Hodgkins lymphoma and NSAID use
• Exact cause not known , but it is thought to be
due to podocytopathy
• Animal model study shows that there occurs loss
of polyanionic charge around the podocytes that
leads to increased permeability of glomerular
26. • It is called minimal change disease because kidney
biopsy on light microscopy does not show any
abnormality.
• Immunofluoroscence also can not demonstrate any
electron dense deposits
• Electron microscopy shows diffuse effacement of foot
processes of podocytes
27. CLINICAL FEATURE
• Presents in young age with clinical features like
• Marked proteinuria (> 3.5g/day)
• Hypoalbuminaemia
• Oedema
• Hyperlipidaemia and lipiduria
• Atypical features are
I. Gross haematuria
II. Hypertension
III. Low complement
IV. Persistent renal impairment
28. INVESTIGATIONS
• Routine blood investigations are usually within normal
limit
• Serum complement normal
• Usually no feature of renal impairment
• Urinalysis shows nephrotic range proteinuria (
>3.5g/day)
• Usually haematuria absent
• In children kidney biopsy is usually not done unless there
is poor response to steroid therapy or steroid
29. TREATMENT
• Initial episode is usually treated by oral prednisolone 1
mg /kg /day for 4 weeks followed by slow taper over 6
months
• If there is poor response to steroid therapy or steroid
dependency then steroid sparing drugs are used like
mmf , cyclophosphamide , cyclosporine , tacrolimus.
• Children show excellent response with >90% children
show complete recovery , but response rate of adult
patients is slightly less.
30. MEMBRANOUS NEPHROPATHY
• Most common cause of nephrotic syndrome among adult
• Around 75% cases of membranous nephropathy are
primary and the rest is secondary
• Characterised by diffuse thickening along the glomerular
capillary wall due to sub epithelial accumulation of
immune complexes
• About 40% patients develop complete resolution and
around 10% patients develop ckd within 10 years
• Associated with increased tendency of renal vein
32. CLINICAL FEATURES
• Frothy urination
• Non selective nephrotic range proteinuria
• Oedema
• Microscopic haematuria and mild hypertension may be
associated
• Renal vein thrombosis is a complication
33. TREATMENT
• Control of proteinuria by ACE
inhibitor /ARB
• Blood pressure control
• Dyslipidaemia control
• Immunosuppressive therapy to
control proteinuria , also called
ponticelli regimen where patient
administered alternate monthly
steroid and cyclophosphamide
34. FOCAL SEGMENTAL GLOMERULOSCLEROSIS
• Most common cause of nephrotic syndrome among adults in USA.
• Histologically it is characterised by progressive glomerular
sclerosis
• Can also be divided into primary and secondary causes
• Occurs when there is any insult to kidney causing reduction in the
number of nephrons that leads to compensatory hyperfiltration in
the remaining nephrons and it causes glomerular hypertension
and ultimately glomerulosclerosis .
• Patients present with
1. Non selective nephrotic proteinuria
2. Hypertension
35.
36. TREATMENT
• Steroids and immunosuppressive drugs are effective only
in primary FSGS , but not in seondary FSGS.
• ACE inhibitor or ARB to be started for proteinuria control
• Blood pressure control
• Steroids are to be started as first line therapy at a dose
of 1 mg / kg for 4 weeks followed by gradual taper.
• If there is poor response to steroid therapy cyclosporin
may be tried.
37. IgA NEPHROPATHY
• One of the most common causes of glomerulonephritis
worldwide
• More common in men
• Usual age of presentation is 2nd-3rd decade
• Immune complex mediated glomerulonephritis
• Characterised by mesangial deposition of IgA and
mesangial cell proliferation
• It is thought to be in a continuous spectrum with HSP
38. CLINICAL FEATURE AND TREATMENT
• Usually it presents as recurrent episodes of gross
haematuria following an episode of URTI
• Can present as rapid worsening of renal failure , in the
form of RPGN
• Disease course is benign with majority of patients
achieving complete remission
• No universal agreement on treatment
• ACE inhibitor / ARB are used for proteinuria treatment
• Oral steroids and fish oil have been tried in many trials
39. DIABETIC NEPHROPATHY
• Leading cause of ESRD worldwide
• Occurs in both type 1 & type 2 DM
• Defined by presence of proteinuria > 500 mg / 24 hrs in
a patient with diabetic retinopathy and without any other
known kidney disease
• The characteristic morphologic changes are
1. Basement membrane thickening
2. Diffuse mesangial sclerosis
3. Nodular glomerulosclerosis
40. PATHOGENESIS
Step 1
•Chronic hyperglycaemia leads to production of advanced glycosylation end products (AGE )
Step 2
•They bind to cell surface receptors by non enzymatic glycosylation of proteins
Effects
•Accelerated atherosclerosis
•Endothelial dysfunction
•Glomerular injury
•Reduced NO
41. STAGES OF DIABETIC NEPHROPATHY
Glomerular hyperfiltration
Early glomerular lesion
Incipient nephropathy ( Microalbuminuria )
Overt diabetic nephropathy
ESRD
42. TREATMENT
• Strict control of BP
• Strict glycaemic control
• Short term protein restriction
and treatment of dyslipidaemia
• ACE inhibitor / ARB
• Renal replacement therapy
1. Haemodialysis
2. Renal transplant
• Experimental therapy like
Ruboxistaurine ( protein kinase
c inhibitor )
43. LUPUS NEPHRITIS
• Common and serious complication of patients with sle
• It occurs due to deposition of circulating immune
complexes
• 30 – 50 % patients with sle will have renal involvement
during initial presentation and 60 % will develop during
their disease course
• Common clinical features of lupus nephritis are
1. Proteinuria
2. Haematuria
3. Hypertension
45. TREATMENT
• Class 1 & 2 lupus nephritis do not require any extra
treatment other than management of lupus
• Class 3 & 4 lupus nephritis are treated with combination
of steroid and cytotoxic drugs , like cyclophosphamide
or MMF along with ACE inhibitor / ARB &
hydroxychloroquine
• Class 5 lupus nephritis usually are treated like that of
class 4 nephritis
• Class 6 lupus nephritis patients have a poor outcome
and they need a renal transplant
