glomerular diseases

GLOMERULAR DISEASES

GLOMERULONEPHRITIS(GN)
الدكتور خلدون ذنون- كلية طب نينوى -المرحلة الرابعة
Objectives
The student is supposed to understand the following:
1. Clinical pathology of (GN).
2. Clinical features of GN in general.
3. Methods of diagnosis of GN.
4. Summary of various types of GN.
5. Role of urine analysis and renal biopsy in diagnosis of GN.
6. Differentiation between nephritis and nephrosis.

General features of glomerular diseases and glomeulonephritis

Inflammatory & non inflammatory(glomerulopathy).
Causes of Glomerular damage: Immunological Metabolic e.g ( D.M., amyloidosis), Toxic (E.coli, NSAIDs) Infection (streptococcus, HIV, endocarditis).
Inherited
Most GN is immunological which is supported by:
- Anti-GBM (glomerular basement membrane) antibodies in Good
Pastures disease.
- Cellular immunity.
- Deposition of circulating immune complexes e.g SLE, or
formation of local immune complexes due to antibodies against
glomerular antigen or planted antigens in the Glomerulus
e.g viral & bacterial.
- Response to immunosuppressive drugs.
Site of glomerular injury: endothelium, GBM, mesangial cells & matrix, & podocytes.
Classification is mainly histopathological.
Glomerular diseases: acute and chronic.
Glomerular damage may result in: hematuria, proteinuria, diminished GFR, acute and chronic renal failure. In milder cases kidney function may remain normal and even in acute renal failure the kidney function may return to normal.
Presentation is either (nephrotic): is associated with significant proteinuria due to injury of podocytes, or nephritic: associated with hematuria mainly due to inflammation, glomerular basement membrane damage, and crescent formation. At times the presentation may be mixed.


Response to glomerular injury
Leucocyte infiltration.
Proliferation of mesangial & endothelial cells with epithelial cell (podocytes) changes.
Extracellular matrix changes.
Crescent formation.
Glomerular capillary thrombosis.
Glomerulosclerosis.

Acquired types of GN

MINIMAL CHANGE NEPHROPATHY
Occur at all ages, most common cause of nephrotic syndrome (NS) in children, in adults 25% of NS.
Normal histology by light microscopy, on EM fusion of podocyte foot processes, no immune deposition.
Associated with atopy,HLA-DR7, Hodgkins disease & NSAID.
Acute and often severe NS.
Proteinuria remits on high dose corticosteroid 1mg/kg/6weeks, some need maintenance steroid & cytotoxic drugs.
It does not progress to renal impairment.

FOCAL & SEGMENTAL GLOMERULOSCLEROSIS FSGS

Segmental scars in some glomeruli, no acute inflammation, podocyte foot process fusion.
Focal process, renal biopsy may look normal.
It is common in adults.
Primary: presents as idiopathic NS, may progress to renal failure, can recur after transplantation.
Secondary: associated with HIV, heroin, drugs, haemolytic uraemic syndrome, cholesterol embolism, & vasculitis.
Primary: no or poor response to steroides, some respond to steroid and cytotoxics.


MEMBRANOUS NEPHROPATHY
Most common cause of NS in adults.
Thickening of GBM, progress to glomerulosclerosis.
Granular subepithelial IgG deposits .
Antibodies to podocyte surface antigen, complement mediated.
Primary: mostly idiopathic associated with HLA-DR3. Secodary: drugs, heavy metals, HB virus, & malignancy.
Some cases may respond to prednisolone & cyclophosphamide.
1/3 remits spontaneously, 1/3 remain in NS & 1/3 show progressive loss of renal function.
IgA NEPHROPATHY
Most common cause of GN.
Present as macroscopic haematuria, asymptomatic urine abnormality, nephrotic syndrome, chronic renal impairment.
Haematuria is almost universal, proteinuria is usual, hypertension is very common.
(mesangial matrix & cells, focal segmental nephritis, mesangial IgA deposits.
Usually idiopathic & may be associated with liver disease.
Common cause of ESRF.
Acute exacerbation with gross haematuria associated with minor respiratory infection, latency from infection to nephritis a few days or less.
IgA nephropathy may progress rapidly with crescent formation.
Poor response to immunosuppressive therapy, B.P should be controlled.
Similar condition in children called Henoch schonlein purpura, also may follow respiratory tract infection, presented as skin vasculitis, abdominal pain due to GIT vasculitis, haematuria due to mild GN. In older children & adults the GN is more prominent. Renal biopsy: mesangial IgA deposits.

GN ASSOCIATED WITH INFECTIONS

Most commonly due to streptococcal infection, more common in children in developing world.
Other causes: Subacute bacterial endocarditis, hospital acquired infections, malaria, HB virus, HC virus, schistosomiasis & leishmaniasis.
Histopathology: proliferative, membranous or mesangiocapillary GN. FSGS with HIV.


ACUTE POST-STREPTOCOCCAL GN
Most commonly due to streptococcal infection, more common in children in developing world.
Latency is 10 days after throat infection which suggest immune mechanism.
Latency after skin infection is longer, only certain strains are responsible.
Diffuse proliferation of endothelial & mesangial cells with subendothelial immune deposits.
Acute nephritis of varying severity: Na retention & oedema, hypertension, oliguria, proteinuria, haematuria(red smoky urine.
Low serum C3,(ASO titre, culture of throat swab & skin lesion.
Renal function improves within 10-14 days.
Restrict fluid and salt intake, diuretics& hypotensive agents.
Renal lesion in almost all children & most adults will resolve completely.

MESANGIOCAPILLARY (MEMBRANOPROLIFERATIVE) GN

Type1: bacterial infection, HB virus, HC virus, cryoglobulinaemia.
TypeII (dense deposit disease): associated with C3 nephritic factor & partial lipodystrophy.

Good pastures disease (Anti GBM disease)

Crescentic nephritis, linear IgG deposit along GBM.
Associated with HLA-DR15.
Haemoptysis & haematuria.
Corticosteroid & cyclophosphamide, plasma exchange to remove antibodies.


LUPUS NEPHRITIS
Any histological type.
Immune deposits.
Low C3 complement.
Urine abnormality, nephritic, nephrotic, ARF, CRF.
Respond to steroid & cytotoxic drugs.

Rapidly progressive GN (crescentic nephritis)

( Crescent formation with rapid loss of renal function.
( Urine contains blood & protein.
( U/S normal size or large kidneys without obstruction.
( Systemic disease affecting other organs but not always.
( Causes:
. Systemic vasculitis . SLE . Goodpasteurs disease
. Aggressive phase of other GN e.g IGA nephropathy,
poststreptococcal GN.
( Diagnosis
ANCA, ANA, anti-GBM antibodies, complement,
immunoglobulin, renal biopsy.
( Management
. Immuno-suppression e.g cyclophosphamide & prednisolone.
. Supportive e.g dialysis.


Causes of GN associated with low serum complement
Post infectious GN
Infective endocarditis
Lupus nephritis
Cryoglobulinemia
Type 11 mesangiocapillary GN.

Inherited glomrular diseases A. Alports syndrome
It is an important cause of glomerular disease affecting adults.
Progressive degeneration of GBM.
Mainly due to mutation in COL4A5 gene.
Abnormalities of type I( basement membrane collagen.
Sensorineural deafness & occular abnormalities.
Most cases are x-linked disease, affected males progress from haematuria to ESRF in late teens or twenties, females are carriers & have haematuria with mild renal disease.
Some have autosomal recessive disease with microscopic haematuria.
Treatment: renal replacement therapy, allograft rejection may occur.

B. Thin GBM disease

Autosomal dominant, main cause of benign familial haematuria.
Glomeruli appear normal by light microscopy but on EM the GBM is abnormally thin.
Microscopic haematuria, no hypertension, no proteinuria, no(GFR.
Prognosis is good.










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