IgA Nephropathy and Henoch-Schonlein Disease Flashcards
Definition of IgA Nephropathy
IgA nephropathy (Berger disease) is a __ disorder characterised by deposition of __ in __ of glomerulus, leading to __ and __ of glomerulus and surrounding structure
IgAN can be __ or __
Glomerular
deposition of Immunoglobulin A in mesangial areas of glomerulus
Inflammation and damage
Primary IgAN (without cause) or secondary IgAN
What is the pathogenesis of IgAN?
- Dysregulation of mucosal-type IgA immune response resulting in production of aberrant IgA1
- Aberrant IgA1 forms immune complexes
- Failure of breakdown of aberrant immune complexes
- Deposition of immune complexes in glomerulus causes:
- Mesangial cell activation releases proinflammatory cytokines and profibrotic mediators affecting nearby structures
- Activation of local complement system
What other conditions is IgAN associated with?
(Secondary cause of IgAN)
- Idiopathic or familial
- Liver cirrhosis - alcohol induced, virus induced
- Coeliac disease
- HIV infection
- Inflammatory bowel disease
- Rheumatological diseases
- Minimal change disease
- Membranous nepropathy
- ANCA vasculitis
- Staphylococcus-related GN
How do patients with IgAN present?
- Asymptomatic, detected on routine UFEME microscopic haematuria +/- proteinuria
- Nephrotic range proteinuria
- Hypertension
- Recurrent gross haematuria after URTI (20-30% - children, young adult), with dull flank pain, low grade fever
- AKI - tubular obstruction by red cell casts
- Crescenteric GN
- CKD (20%) due to longstanding, undiagnosed disease
How do you differentiate between post-streptococcal GN vs IgAN?
Slower onset 10-14 days post-strep
Hypocomplementaemia
Elevated anti-streptococcal antibodies
Diagnosis of IgAN can be established by __, showing __ and __ on light microscopy; dominant or co-dominant deposition of __ and __ on IF microscopy
Kidney biopsy
Mesangial proliferation and matrix expansion on LM
IgA and complement on IFM
What are other postulated biomarkers to diagnose IgAN or monitor the activity of disease?
Postulated = not established in routine practice
- Serum IgA - elevated in 50% cases but non-specific, no prognostic value
- Serum galactose-deficient IgA1 (GD IgA1)
- GD IgA1 antibodies and immune complexes
When should a kidney biopsy be performed for suspected IgAN?
Although kidney biopsy may at least confirm diagnosis, decision for biopsy varies among nephrologists.
Not indicated
Asymptomatic patients with isolated haematuria or mild proteinuria < 500mg/day
(Histologic findings at this stage has higher risk to benefit, unlikely alter therapy)
Indicated
Unexplained creatinine above normal for age
Persistent/recurrent haematuria with nephrotic range proteinuria
Persistent/recurrent haematuria with UPCR > 0.05 g/mmol at least 4 weeks
Acute worsening of kidney function uncertain of ATN vs crescenteric IgAN
What is the prognosis of IgAN?
- Isolated haematuria and no proteinuria - low risk of progression if features do not change
- Proteinuria
- 0.5-1g/day - 20-30% require RRT within 20 to 25 years
- 2-3g/day - even higher - Children may develop spontaneous improvement in 5-30%
How can kidney biopsy findings predict outcome of IgAN?
(Oxford Classification MEST-C Criteria 2016)
Oxford Classification MEST-C Criteria
- Mesangial hypercellularity: <50% or >50% (score 0-1)
- Endocapillary hypercellularity: negative or positive (score 0-1)
- Segmental sclerosis: negative or positive (score 0-1)
- Tubular atrophy: <25%, 25-50%, >50% (score 0-2)
- Crescents: negative, 10-25%, > 25% (score 0-2)
What are the clinical features that are predictive of IgAN outcome?
- Sustained proteinuria over time
- Complete or partial remission of proteinuria
- MAP over time
- Level of impairment of kidney function
- +/- recurrent gross haematuria - conflicting data
When should you treat IgAN?
Isolated haematuria, no proteinuria, normal GFR do not require treatment - monitor every 6-12 months
Persistent proteinuria 500-1g/day
- Start ACEI or ARB: aim reduction to < 500mg/day
- +/- fish oil supplement - conflicting results
- Control BP tightly
(Japanese population confers tonsillectomy as a treatment, however the procedure is not entirely risk free, evidence of usefulness is weak)
When should immunosuppressive therapy be considered in IgAN?
- Persistent proteinuria despite optimal ACEI/ARB
- Nephrotic syndrome
- Accelerated decline in GFR
- Resistant or relapsed disease
Aim to stop IST when progression into advanced disease - glomerular sclerosis, interstitial fibrosis, eGFR < 30
(unless active crescenteric IgAN is found)
Does IgAN recur after transplantation?
Yes, ranging from histologic to full blown clinical phenotype
Rate of recurrence 10-50%
Graft loss < 5-10% within a decade of transplantation
(Thus transplantation remains the most optimal treatment)
Henoch-Schonlein purpura is a __ affecting __ due to __ deposits
It is now known as __
Incidence higher in __ (season) due to infections or allergies
Peak incidences at ages __, male __ female (__ ratio)
Revised International Chapel Hill Consensus Conference Nomenclature for Vasculitides 2012:
Classic tetrad: __, __, __, __ with biopsy __
Systemic leukocytoclastic vasculitis affecting small vessels, IgA immune deposits
Now known as IgA vasculitis
Fall and winter
Age 4-6, male > female (2:1 ratio)
Tetrad: skin rash (palpable purpura), abdominal pain, arthralgia, haematuria/proteinuria
Biopsy: IgA deposition
