assessment and management of iga nephropathy john feehally
DESCRIPTION
ASSESSMENT AND MANAGEMENT OF IgA NEPHROPATHY John Feehally. IgA NEPHROPATHY The commonest pattern of glomerulonephritis in the world. CLASSIFICATION OF GLOMERULONEPHRITIS. Histopathology. Clinical. Immune mechanisms. CLASSIFICATION OF GLOMERULONEPHRITIS. Histopathology. Clinical. - PowerPoint PPT PresentationTRANSCRIPT
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ASSESSMENT AND MANAGEMENT OFIgA NEPHROPATHY
John Feehally
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IgA NEPHROPATHY
The commonest pattern of glomerulonephritis in the world
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Histopathology Clinical Immune mechanisms
CLASSIFICATION OF GLOMERULONEPHRITIS
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Histopathology Clinical Immune mechanisms
CLASSIFICATION OF GLOMERULONEPHRITIS
Patterns established on light microscopy
Membranous
Membranoproliferative
Focal segmental glomerulosclerosis
etc……
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Histopathology Clinical Immune mechanisms
CLASSIFICATION OF GLOMERULONEPHRITIS
Patterns established on light microscopy
Membranous
Membranoproliferative
Focal segmental glomerulosclerosis
etc……‘Patterns’ not ‘diseases’
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IgA1 depositionIn the glomerular
mesangium
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IgA NEPHROPATHY
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ASSESSMENT AND MANAGEMENT OFIgA NEPHROPATHY
Is IgA nephropathy
a single ‘disease’ ?
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IgA NEPHROPATHY
A pattern of glomerulonephritis
with many variations
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Recurrent visible haematuria
Coincides with mucosal infection
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Nephrotic syndrome
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Asymptomatic
Haematuria / proteinuria
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CKD
ProteinuriaHypertension
Renal impairment
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HENOCH-SCHȌNLEIN NEPHRITIS
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Henoch-Schőnlein purpuraHenoch-Schőnlein purpura
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‘SECONDARY’ IgA NEPHROPATHY
COMMONLY REPORTED ASSOCIATIONS
Alcoholic liver diseaseCeliac disease
Ankylosing spondylitisReiter’s syndrome
UveitisDermatitis herpetiformis
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RECURRENT IgA NEPHROPATHY
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RECURRENT IgA NEPHROPATHY
Recurrence
38-60%
Graft dysfunction due to recurrence
15%
Graft loss due to recurrence
7%
Pooled published data – 5 year follow up
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RECURRENT IgA NEPHROPATHY
Recurrence
38-60%
Graft dysfunction due to recurrence
15%
Graft loss due to recurrence
7%
Pooled published data – 5 year follow up
Why does IgA nephropathy
NOT always recur ?
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4.7%
<5%
15-21%
Percentage of patients with
primary glomerular disease
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4.7%
<5%
15-21%Male > Female
Male = Female
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IgA NEPHROPATHY
Variations in:
Pathological pattern
Clinical pattern
Transplant recurrence
Epidemiological pattern
Pathogenesis
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IgA NEPHROPATHY
No proof that IgAN is a single ‘disease’
No proof that IgAN is the same ‘disease’ in all parts of the world
Not expect
a single pathogenic mechanism
to lead tomesangial IgA deposition
and injury
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ASSESSMENT AND MANAGEMENT OFIgA NEPHROPATHY
Can you predict which patients with IgA nephropathy
will get kidney failure?
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ASSESSMENT AND MANAGEMENT OFIgA NEPHROPATHY
Can you predict which patients with IgA nephropathy
will get kidney failure?
CLINICAL evidenceCLINICAL evidence
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Rodicio 1982
PROGNOSIS IN IgA NEPHROPATHY
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Rodicio 1982
PROGNOSIS IN IgA NEPHROPATHY
20% ESRD @ 20 years
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Chacko B et al. Nephrology 2005; 10: 496
IgA NEPHROPATHY IN INDIA
CMC Vellore 1994-2003
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Chacko B et al. Nephrology 2005; 10: 496
IgA NEPHROPATHY IN INDIA
CMC Vellore 1994-2003
478 adults
55% - Nephrotic syndrome at presentation
56% - Serum creatinine > 123 μmol/L at presentation
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Beukhof 1983
MACROSCOPIC HAEMATURIA AND PROGNOSIS IN IgA NEPHROPATHY
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LEAD TIME BIAS IN DIAGNOSIS OF IgA NEPHROPATHY
Geddes CC et al. NDT 2003; 18: 1541
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ISOLATED NON-VISIBLE HAEMATURIA IN IgA NEPHROPATHY
How benign is it ?
Cohort study – Toronto – 286 patients
Non-visiblehaematuria plus
Proteinuria < 0.2 g/24hr
Normal BP
Bartosik et al. AJKD 2001; 38: 728
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ISOLATED MICROSCOPIC HAEMATURIA IN IgA NEPHROPATHY
How benign is it ?
Cohort study – Toronto – 286 patients
Microscopic haematuria plus
Proteinuria < 0.2 g/24hr
Normal BP
10 year risk of deterioration in renal function
= ZERO
Bartosik et al. AJKD 2001; 38: 728
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ISOLATED NON-VISIBLE HAEMATURIA IN IgA NEPHROPATHY
How benign is it ?
Cohort study – Hong Kong
Non-visible haematuria plus Proteinuria < 0.4 g/24hr
Szeto C et al Am J Med 2001; 110:434
During 7 years follow up, 44% had a ‘clinical event’
33% proteinuria
26% hypertension
7% renal impairment
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OUTCOME AND AVERAGE FOLLOW-UP PROTEINURIA IN IgA NEPHROPATHY
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REMISSION OF PROTEINURIA IMPROVES PROGNOSIS IN IgA NEPHROPATHY
Reich H et al. JASN 2007; 18: 3177
Time-average proteinuria1 - < 1g/24h2 – 1-2 g/24h3 – 2-3g/24h4 - >3g/24h
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ASSESSMENT AND MANAGEMENT OFIgA NEPHROPATHY
Can you predict which patients with IgA nephropathy
will get kidney failure?
PATHOLOGICAL evidencePATHOLOGICAL evidence
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A CLINICO-PATHOLOGICAL CLASSIFICATION FOR IgA NEPHROPATHY
Does pathology add prognostic information
.. to clinical data at time of biopsy ?
.. to clinical data during follow up ?
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A CLINICO-PATHOLOGICAL CLASSIFICATION FOR IgA NEPHROPATHY
Does pathology add prognostic information
.. to clinical data at time of biopsy ?
.. to clinical data during follow up ?Perhaps the biopsy is only useful
to establish the diagnosis of IgAN ?
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PATHOLOGICAL CLASSIFICATIONS IN RENAL DISEASE
Are usually based on expert opinion
... and pre-conceived ideas of what lesions are important
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OXFORD CLASSIFICATION OF IgA NEPHROPATHY
A different way
Approach the problem with an open mind
With an international consensus group
• Study allall histological lesions
• Test reproducibility & independence
• Then test correlations with outcome
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SCORING OF SELECTED PATHOLOGY FEATURES
Mesangial hypercellularity - in > or <50% of glomeruli M0 or M1
Endocapillary hypercellularity – present/absent E0 or E1
Segmental sclerosis/adhesions – present/absent S0 or S1
Tubular atrophy/interstitial fibrosis – 0-25%, 26-50%, >50% T0 or T1 or T2
Each can be scored easily in routine clinical practice
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PREDICTIVE SIGNIFICANCE OF PATHOLOGY FEATURES IN IgA NEPHROPATHY
M E S T
Each adds predictive value to ….
Initial clinical features
Follow up clinical features
In all ages and races studied
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VALIDATION STUDIES FOR THE OXFORD CLASSIFICATION OF IgAN
M E S T
Macedonia2010
98 + + + +
USA2011
54 + + - +
Japan2011
161 children + + - +
France2011
183 - + + +
USA, Canada2011
187 adults & children
+ + + +
China2011
410 - + + +
Japan 2011
702 - - + +
Sweden2012
99 + + - +
Korea2012
197 + - + +
6/10 7/10 6/10 10/10
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WHAT NEXT ?
Validation studies
Work towards combining pathology and clinical elements
– to produce a single ‘risk score’
There is now the opportunity to design smaller, shorter RCTs
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ASSESSMENT AND MANAGEMENT OFIgA NEPHROPATHY
How good is the evidence to guide the treatment of
IgA nephropathy ?
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KI Supplements 2012 2(2): 1-274
CLINICAL PRACTICE GUIDELINE FOR GLOMERULONEPHRITIS
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Examples of Rating Guideline Recommendations
Level 1 We recommend….
Most patients should receive the recommended course of action
1A
Supported by evidence from high quality RCTs
Level 2 We suggest …
Different choices will be appropriate for different patients. Each patient needs help to arrive at a management decision appropriate for them
2D
No RCTsSupported by limited observational data
QUALITY of Supporting Evidence is shown as A, B, C or D
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Examples of Rating Guideline Recommendations
Level 1 We recommend….
Most patients should receive the recommended course of action
1A
Supported by evidence from high quality RCTs
Level 2 We suggest …
Different choices will be appropriate for different patients. Each patient needs help to arrive at a management decision appropriate for them
2D
No RCTsSupported by limited observational data
QUALITY of Supporting Evidence is shown as A, B, C or D
Of 10 recommendations or suggestions in the IgA Nephropathy guideline
Only 2 (20%) are 1A or 1B
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Clinical Practice Guideline for Glomerulonephritis
…. will not tell you what to do for every difficult patient in every situation
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Clinical Practice Guideline for Glomerulonephritis
…. will not tell you what to do for every difficult patient in every situation
The Guideline is not there to give you expert advice about an individual problem case
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Clinical Practice Guideline for Glomerulonephritis
…. will not tell us what to do for every difficult patient in every situation
….will remind us what we know
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Clinical Practice Guideline for Glomerulonephritis
…. will not tell us what to do for every difficult patient in every situation
….will remind us what we know
….will remind us what we do not know
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ASSESSMENT AND MANAGEMENT OFIgA NEPHROPATHY
“Should I treattreat this patient with IgA nephropathy ?”
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Non-visible haematuria
Visible haematuria
Nephrotic syndrome
Acute kidney injury
Proteinuria > 1g/day
Progressive fall in GFR
TREATMENT DECISIONS IN IgA NEPHROPATHY
Hypertension
Crescentic IgA nephropathy
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Microscopic haematuria
Macroscopic haematuria
Nephrotic syndrome
Acute kidney injury
Proteinuria > 1g/day
Progressive fall in GFR
TREATMENT DECISIONS IN IgA NEPHROPATHY
Hypertension
Crescentic IgA nephropathy
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TREATMENT RECOMMENDATIONS FOR IgA NEPHROPATHY
Recurrent Macroscopic Haematuria
No role for antibiotics
No role for tonsillectomy
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Microscopic haematuria
Macroscopic haematuria
Nephrotic syndrome
Acute kidney injury
Proteinuria > 1g/day
Progressive renal insufficiency
TREATMENT DECISIONS IN IgA NEPHROPATHY
Hypertension
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TREATMENT RECOMMENDATIONS FOR IgA NEPHROPATHY
Macroscopic Haematuria with acute renal failure
Renal biopsy is mandatory if not improve in 2-3 days with supportive measures
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AKI WITH VISIBLE HAEMATURIA IN IgA NEPHROPATHY
Moreno J et al. CJASN 2012; 7: 175
How common ?
AKI in 38% (4/11) of visible haematuria episodes (Praga 1985)Much less common in most other reports
How important are crescents ?Crescents often seen, but in <20% of glomeruli
and usually notnot the cause of AKI
9 published reports – 84 patients
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AKI WITH VISIBLE HAEMATURIA IN IgA NEPHROPATHY
Moreno J et al. CJASN 2012; 7: 175
Recovery of renal function ?
Most reports (29 patients) …
100% have complete recovery of renal function
Two reports (55 patients) – only 73% full recovery
9 published reports – 84 patients
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AKI WITH VISIBLE HAEMATURIA IN IgA NEPHROPATHY
Moreno J et al. CJASN 2012; 7: 175
Recovery of renal function ?
Full recovOne centre in Spain (52 patients)
Full recovery less likely:
Older ageDuration of visible haematuria (mean 15 vs 36 days)
Peak sCr (7.1 vs 309 mg/dL)
Tubular necrosisTubular red cell castsInterstitial; fibrosis
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TREATMENT RECOMMENDATIONS FOR IgA NEPHROPATHY
Acute Tubular Necrosis
Supportive measures only
Crescentic IgA nephropathy
Immunosuppression maymay be appropriate
Macroscopic Haematuria with acute renal failure
Renal biopsy is mandatory if not improve in 2-3 days with supportive measures
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Microscopic haematuria
Macroscopic haematuria
Nephrotic syndrome
Acute renal failure
Proteinuria > 1g/day
Progressive renal insufficiency
TREATMENT DECISIONS IN IgA NEPHROPATHY
Hypertension
Crescentic IgA nephropathy
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Renal outcome with best known treatment
CRESCENTIC GLOMERULONEPHRITIS
Renal survival
1 year 5 years
Systemic vasculitis 80% 75%
Goodpasture’s 70% 50%
Crescentic IgA nephropathy 50% 20%
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TREATMENT FOR CRESCENTIC IgA NEPHROPATHY
A number of recent optimistic reports -
Corticosteroids + Cyclophosphamide
Small : < 20 patients
Selection criteria variable
All are anecdotal
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TREATMENT FOR CRESCENTIC IgA NEPHROPATHY
Definition?
More than just a few crescents
Rapidly progressive renal failure
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TREATMENT FOR CRESCENTIC IgA NEPHROPATHY
Definition?
More than just a few crescents
Rapidly progressive renal failure
Which patients respond ?
Treat if crescents + other active glomerular damage
AND no chronic or irreversible changes
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TREATMENT FOR CRESCENTIC IgA NEPHROPATHY
If immunosuppression is indicated…
INDUCTION: Prednisolone 0.5-1mg/kg/dayCyclophosphamide 2mg/kg/day
MAINTENANCE: Prednisolone in reducing dosageAzathioprine 2mg/kg/day
[plasma exchange unproven]
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TREATMENT FOR CRESCENTIC IgA NEPHROPATHY
If immunosuppression is indicated…
INDUCTION: Prednisolone 0.5-1mg/kg/dayCyclophosphamide 2mg/kg/day
MAINTENANCE: Prednisolone in reducing dosageAzathioprine 2mg/kg/day
[plasma exchange unproven]
An RCT is badly needed
…. and will be difficult to achieve
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Microscopic haematuria
Macroscopic haematuria
Nephrotic syndrome
Acute renal failure
Proteinuria > 1g/day
Progressive renal insufficiency
TREATMENT DECISIONS IN IgA NEPHROPATHY
Hypertension
Crescentic IgA nephropathy
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NEPHROTIC-RANGE PROTEINURIA IN IgA NEPHROPATHY
Chen M et al. NDT 2011; 26: 1247
IgAN and nephrotic range proteinuria
N = 233
More More likely to have normoalbuminaemia than minimal change, FSGS, or membranous
Nephrotic-range proteinuria and serum albumin > 35 g/l
95.8% specificity for IgAN
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NEPHROTIC SYNDROME IN IgA NEPHROPATHY
Kim J-K et al. CJASN 2012; 7: 247
n = 100 – mean follow up 45 months
Complete remission 48%
Partial remission 32%
No remission 20%
Spontaneous remission 24%
PRIMARY END POINT - DOUBLE SERUM CREATININE
24%
More likely if partial or no remission
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NEPHROTIC SYNDROME IN IgA NEPHROPATHY
Kim J-K et al. CJASN 2012; 7: 247
n = 100
Mean follow up 45 months
p<0.001
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NEPHROTIC SYNDROME IN IgA NEPHROPATHY
Kim J-K et al. CJASN 2012; 7: 247
100
885
P<0.001
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NEPHROTIC SYNDROME + MICROSCOPIC HAEMATURIA
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NEPHROTIC SYNDROME + MICROSCOPIC HAEMATURIA
Corticosteroids: complete remission of nephrotic syndrome
Microscopic haematuria persists
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Two common glomerular diseases coincide……
Minimal change nephrotic syndrome IgA nephropathy
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NEPHROTIC SYNDROME IN IgA NEPHROPATHY
Minimal change
Mesangial hypercellularity
Glomerulosclerosis
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NEPHROTIC SYNDROME IN IgA NEPHROPATHY
n = 34
Prednisolone for 4 months: 40-60 mg daily halved after 8 weeks
Follow up 38 months
Lai - Clin Neph 1986; 26:174
Response of proteinuria
only in those with minor histological changes
Randomised controlled trial
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NEPHROTIC SYNDROME IN IgA NEPHROPATHY
Minimal change
Mesangial hypercellularity
Glomerulosclerosis
The response to corticosteroids in minimal change
does not justify their use
in all IgAN with nephrotic syndrome
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Microscopic haematuria
Macroscopic haematuria
Nephrotic syndrome
Acute kidney injury
Proteinuria > 1g/day
Progressive fall in GFR
TREATMENT DECISIONS IN IgA NEPHROPATHY
Hypertension
Crescentic IgA nephropathy
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Non-visible haematuria
Visible haematuria
Nephrotic syndrome
Acute kidney injury
Proteinuria > 1g/day
Progressive fall in GFR
TREATMENT DECISIONS IN IgA NEPHROPATHY
Hypertension
Crescentic IgA nephropathy
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PUBLISHED TREATMENT TRIALS IN IgA NEPHROPATHY
Often underpowered
Often insufficient follow up for ‘hard’ endpoints
Most use clinical entry criteria
Some have patients beyond ‘the point of no return’
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TREATMENT OPTIONS FOR PROGRESSIVE IgA NEPHROPATHY
Blood pressure control
Renin-angiotensin blockade
Corticosteroids
Other immunosuppressives
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TREATMENT OPTIONS FOR PROGRESSIVE IgA NEPHROPATHY
Blood pressure control
Renin-angiotensin blockade
Corticosteroids
Other immunosuppression
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TREATMENT RECOMMENDATIONS FOR IgA NEPHROPATHY
Target Blood Pressure
Proteinuria < 1g/24hr 130/80
Proteinuria > 1g/24hr 125/75
RAS Blockade
Proteinuria > 1g/24hr 125/75
Combination therapy ?
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EFFECT OF ACE INHIBITOR PLUS ARB ON PROTEINURIA IN IgA NEPHROPATHY: META-ANALYSIS
Cheng J et al. Int J Clin Pract 2012; 66: 917
6 studies – 109 patients
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EFFECT OF ACE INHIBITOR PLUS ARB ON PROTEINURIA IN IgA NEPHROPATHY: META-ANALYSIS
Cheng J et al. Int J Clin Pract 2012; 66: 917
NoNo effect on GFR
but
Study duration: 2-12 months
6 studies – 109 patients
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TREATMENT RECOMMENDATIONS FOR IgA NEPHROPATHY
Target Blood Pressure
Proteinuria < 1g/24hr 130/80
Proteinuria > 1g/24hr 125/75
RAS Blockade
Proteinuria > 1g/24hr 125/75
Combination therapy ?
SALT
RESTRICTION
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DIETARY SODIUM RESTRICTION AMPLIFIES EFFECTS OF RAS BLOCKADE ON PROTEINURIA
Slagman M et al. BMJ 2011
Lisinopril 40mg/day
Valsartan 320mg/day
Sodium intake 50 or 200 mmol/day
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DIETARY SODIUM RESTRICTION AMPLIFIES EFFECTS OF RAS BLOCKADE ON PROTEINURIA
Slagman M et al. BMJ 2011
Lisinopril 40mg/day
Valsartan 320mg/day
Sodium intake 50 or 200 mmol/day
Systolic BP
Diastolic BP
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TREATMENT RECOMMENDATIONS FOR IgA NEPHROPATHY
Proteinuria > 1g/day + hypertension
Only if
BP target achieved…
and proteinuria still >1g/24 hr
consider corticosteroids, immunosuppressive regimens …
What is the evidence these regimens are effective in these circumstances ?
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TREATMENT OPTIONS FOR PROGRESSIVE IgA NEPHROPATHY
Blood pressure control
Renin-angiotensin blockade
Corticosteroids
Other immunosuppression
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CORTICOSTEROID TREATMENT FOR IgA NEPHROPATHY
Pozzi C et al Lancet 1999; 353; 883 - JASN 2004; 15: 157
Survival without end point - doubling of serum creatinine
Randomised controlled trial – serum creatinine < 130 µmol/L
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n = 86
creatinine < 133 µmol/l - proteinuria 1-3.5g/24hr
Regimenmethylprednisolone 1g iv x3 at 1,3,5 months plusprednisolone 0.5 mg/kg/alt days for 6 months
No important side effects - no study ‘drop outs’
CORTICOSTEROID TREATMENT IN IgA NEPHROPATHY
Pozzi C et al Lancet 1999; 353; 883 - JASN 2004; 15: 157
Randomised controlled trial – serum creatinine < 133 µmol/L
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n= 103
2 year treatment regimen
Prednisolone 20mg od reducing to 5mg by 6 months
CORTICOSTEROID TREATMENT IN IgA NEPHROPATHY
Katafuchi AJKD 2003; 41:972
Antiproteinuric effect but no effect on renal function
Randomised controlled trial – serum creatinine < 133 µmol/L
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BLOOD PRESSURE CONTROL IN IgA NEPHROPATHY TRIALS
BP (mm Hg)
160
150
140
130
120
110
100
90
80
70
60
NKFRecommendation
125/75
Corticosteroids
Pozzi Katafuchi
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CORTICOSTEROIDS PLUS ACE INHIBITOR IN PROTEINURIC IgA NEPHROPATHY
Lv J et al. 2009 AJKD; 53: 26Manno C et al. NDT 2009; 24: 3694
TWO SIMILAR STUDIESProteinuria > 1g/24h - GFR > 50 ml/min
Continuous ACE inhibitor
+ oral CORTICOSTEROIDS for 6-8 months
Follow up: 2 years (China), 5 years (Italy)
Well maintained BP
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BLOOD PRESSURE CONTROL IN IgA NEPHROPATHY TRIALS
BP (mm Hg)
160
150
140
130
120
110
100
90
80
70
60
JNCRecommendation
125/75
Corticosteroids
Pozzi Katafuchi
Manno Lv
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CORTICOSTEROIDS PLUS ACE INHIBITOR IN PROTEINURIC IgA NEPHROPATHY
ESRD
STEROIDS CONTROL
ITALY 1/48 8/49
CHINA 1/30 7/33
Statisticallysignificant
Lv J et al. 2009 AJKD; 53: 26Manno C et al. NDT 2009; 24: 3694
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CORTICOSTEROIDS PLUS ACE INHIBITOR IN PROTEINURIC IgA NEPHROPATHY
STEROIDS CONTROL
ITALY 1/48 8/49
CHINA 1/30 7/33
Statisticallysignificant
But.. achieved ACE inhibitor dose rather low
Lv J et al. 2009 AJKD; 53: 26Manno C et al. NDT 2009; 24: 3694
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CORTICOSTEROIDS PLUS ACE INHIBITOR IN PROTEINURIC IgA NEPHROPATHY
STEROIDS CONTROL
ITALY 1/48 8/49
CHINA 1/30 7/33
Statisticallysignificant
But.. neither study had a ‘run-in‘ period
Lv J et al. 2009 AJKD; 53: 26Manno C et al. NDT 2009; 24: 3694
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TREATMENT OPTIONS FOR PROGRESSIVE IgA NEPHROPATHY
Blood pressure control
Renin-angiotensin blockade
Corticosteroids
Other immunosuppression
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IMMUNOSUPPRESSIVE TREATMENT FOR PROGRESSIVE IgA NEPHROPATHY
NO ROLE FOR
Cyclophosphamide
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BLOOD PRESSURE CONTROL IN IgA NEPHROPATHY TRIALS
BP (mm Hg)
160
150
140
130
120
110
100
90
80
70
60
JNCRecommendation
125/75
Ballardie
Corticosteroids+
Cyclophosphamide
Corticosteroids
Pozzi Katafuchi
Manno Lv
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IMMUNOSUPPRESSIVE TREATMENT FOR PROGRESSIVE IgA NEPHROPATHY
NO ROLE FOR
Cyclophosphamide
What about Mycophenolate
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BLOOD PRESSURE CONTROL IN IgA NEPHROPATHY TRIALS
BP (mm Hg)
160
150
140
130
120
110
100
90
80
70
60
JNCRecommendation
125/75
Ballardie
Corticosteroids+
Cyclophosphamide
Corticosteroids
Pozzi Katafuchi
Manno Lv
Mycophenolate
Maes
Tang
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MYCOPHENOLATE IN IgA NEPHROPATHY
Benefit BP achieved ACE inhibitors[number of patients]
BELGIUM
Maes 2004 [34] None 125/73 100%salt restricted
HONG KONG
Tang 2005 [40] ESRD 122/71 100%reduced
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TREATMENT RECOMMENDATIONS FOR IgA NEPHROPATHY
• The role of corticosteroids and immunosuppressives after tight BP control and maximal RAS blockade ?
• The effect of ancestry on treatment responses
Uncertainty
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Optimal supportive therapy for 6 months(ACEi, ARB, target BP < 125/75 mm Hg, Statin, etc.)
Optimal supportive
Responder
Non-Responder
Proteinuria >0.75 g/d
Run
-in P
hase
(6 M
onth
s)St
udy-
Phas
e(3
Yea
rs)
Optimal supportive + Immunosuppression
Drop-Out
RANDOMISATION
Study Design
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0
50
100
150
200
250
300
350
400
Recruitment-Update STOP IgAN - Status 28.2.2011 -
Follow-up
IgA
N p
atie
nts
Study patientsn=356
Randomisedn=127
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TREATMENT RECOMMENDATIONS FOR IgA NEPHROPATHY
We are still short of evidence …..
So there is room for your own opinion …..