Glomerulonephritis

Nameesha Natasha Naidu

20130105
Reference

 Davidson’s Principle and Practice of Medicine

 Oxford Handbook of Clinical Medicine
 Inflammation of the glomeruli
Presentation

Nephrotic Syndrome Nephritic Syndrome

1. Proteinuria >3.5g/24h 1. Hematuria
2. Hypoalbuminemia <25g/l 2. Oedma and generalized fluid
3. Oedema retention

Severe hyperlipidemia (TC 3. Hypertension

>10mmol/l) is often present 4. Oliguria
 Causes
Primary Causes Secondary Causes
Nephrotic Sydrome: Nephrotic Sydrome:
 Membranous nephropathy  SLE(class V nephritis)
 Minimal Change  Diabetes
 FSGS  Amyloid
 Mesangiocapillary GN  Hepatitis B/C

Nephritic Syndrome: Nephritic Syndrome:

 IgA nephropathy  Post-streptococcal
 Mesangiocapillary GN  Vasculitis
 SLE
 Anti-GBM disease
 cryoglobulinemia
Types

 Minimal change nephropathy

 Focal segmental glomerulosclerosis
 Membranous glomerulonephritis
 Mesangiocapillary glomerulonephritis
 IgA nephropathy
 Post-streptococcal glomerulonephritis
 Henoch-Schonlein Purpura
 Anti-glomerular basement membrane disease
 Rapidly Progressive GN
 Minimal Change Nephropathy
 Reversible effacement of podocytes foot processes
 Presents with proteinuria or nephrotic syndrome
 Treatment: remits with high dose corticosteroid therapy (1mg/kg
prednisolone for 6 weeks)
 Some patients who respond incompletely or relapse frequently
need maintenance corticosteroids, cytotoxic therapy or other
agents
 Focal Segmental Glomerulosclerosis
 Can occur in all age groups
Primary FSGS: cause unknown
 Present with massive proteinuria and nephrotic syndrome
 Sclerosis in segments of the glomeruli
Secondary FSGS:
 Present with less proteinuria and sclerosis
 The focal scarring may reflect healing of previous focal glomerular injury such
as HUS, cholesterol embolism or vasculitis. Other secondary causes-HIV,
podocyte toxins and massive obesity.
 Treatment: high dose corticosteroid therapy(0.5-2mg/kg/day) but most patients
show little or no response
 Immunosuppressive drugs e.g ciclosporin used but efficacy uncertain
 Progression to CKD is common in patients who don’t respond to steroids and
the disease frequently recurs after renal transplantation
Membranous Glomerulonephritis
 Most common cause of nephrotic syndrome in adults
 Caused by autoantibodies directed at antigens expressed on the
surface of podocytes
 Biopsy: diffusely thickened GBM with IgG and C3 deposits in
immunofluroscence
 1/3 patients with idiopathic membranous glomerulonephritis undergo
spontaneous remission, 1/3 remain in a nephrotic state and 1/3 go on
to develop CKD
 Treatment: treat underling cause
 Give ACE-I and diuretics
 Short-term treatment with high dose corticosteroids and
cyclophosphamide may improve the nephrotic syndrome and long
term prognosis
Mesangiocapillary Glomerulonephritis
 Two types: immune complex mediated and complement mediated
 Increase in mesangial cellularity with thickening of glomerular
capillary walls and subendothelial deposition of immune complexes
and complements
 Causes: hepatitis C, SLE, monoclonal gammopathy and
abnormalities in complement pathway
 Presents with proteinuria and hematuria
 Biopsy: double contouring of the capillary walls(tram-tracks) and
thickened capillary basement membrane
 Treatment: treat underlying cause. Give ACEI/ARB to all.
 Immunosuppression with steroids and cyclophosphamide if rapid
progression of disease
 IgA Nephropathy
 One of the most common types of GN
 Presents with hematuria, hypertension and proteinuria
 In many cases there is slowly progressive loss of renal function leading to ESRD
 A particular hallmark in some individuals is acute self-limiting exacerbations, often
with gross haematuria, in association with minor respiratory infections.
 There is increased IgA which forms immune complexes and deposits in mesangial
cells
 IF shows IgA and C3 deposits and mesangial proliferation in renal biopsy
 The latency from clinical infection to nephritis is short
Treatment: BP control with ACE-I
 Immunosuppressant may slow decline in renal function in those with nephritic
presentation
 The management of less acute disease is largely directed towards the control of
BP in an attempt to prevent or retard progressive renal disease
 Henoch-Schonlein Purpura
 Characterised by systemic vasculitis that often arises in response to an
infectious trigger.
 Presents with purpuric rash on extensor surfaces(mostly legs), flitting
polyarthritis, abdominal pain and nephritis
 GN is usually indicated by hematuria
 Diagnosis is confirmed with + IF for IgA and C3 in skin/renal biopsy
 Treatment: same as IgA nephropathy
 Prognosis is good with spontaneous resolution but some develop ESRD
Systemic Lupus Erythematous
 1/3 patients with SLE will have evidence of renal disease with
vascular, glomerular and tubulointerstitial damage
 Requires early treatment
Antiglomerular Basement Membrane
Disease(Goodpasture’s disease)
 Caused by autoantibodies(IgG) to type IV collagen, an essential
component of GBM.
 Type IV collagen is also found in lungs and pulmonary hemorrhage
can occur especially in smokers.
 Present with hematuria/nephritic syndrome
 AKI may occur within days of onset of symptoms
 Treatment: plasma exchange, steroids and cytotoxics
 If started early, full recovery is possible and relapses are rare
Case

20year old male presents with

hematuria and puffiness of face, eyes
and trunk. On examination he was
found to be hypertensive(170/100)
with scrotal swelling. The patient gives
a history of pyoderma 5 weeks ago.
Post-streptococcal GN

 More common in children than adults

 Occurs 1-12 weeks after a sore throat or skin infection.
 A streptococcal antigen is deposited on the glomerulus, causing a
host reaction and immune complex formation
 Molecular mimicry also occurs
 Presents as nephritic syndrome(↓ GFR, proteinuria, hematuria and
oliguria)
 Treatment: improves spontaneously within 10-14days
 supportive (>95% patients renal function recovers)-fluid and salt
restriction with hypotensive agents.
Rapidly progressive glomerulonephritis
 Also known as crescentic glomerulonephritis
 Rapid loss of renal function over days to weeks.
 Most aggressive GN, potential to cause ESRD over days.
 Classified into 3 categories:
1. Immune complex disease e.g post-infections, SLE, IgA/HSP
2. Pauci-immune disease
3. Anti GBM disease e.g Goodpasture’s disease
 Clinical presentation: AKI with systemic features(fever, myalgia, weight loss,
hemoptysis). Pulmonary hemorrahge is the commonest cause of death
 Renal biopsy shows crescentric lesions
 Treatment: aggressive immunesuppression with high dose IV steroids and
cyclophosphamide + plasma exchange
Investigations for GN Management

 Blood: FBC, U&E, LFT, ESR,  ACE-I or ARB

immunoglobulins, autoantibodies,
ANA, anti-dsDNA, blood culture  Frusemide

 Urine: RBC cast  Statin to reduce cholesterol

 Dipstick urinalysis to check for ACR  Treat underlying cause

or PCR(ACR for men is <2.5 and  High dose steroids
for women <3.5)
 Supportive treatment
 Imaging: renal ultrasound, CXR
 Renal Biopsy