ASSESSMENT AND MANAGEMENT OF IgA NEPHROPATHY John Feehally

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

Histopathology Clinical Immune mechanisms Patterns established on light microscopy Membranous Membranoproliferative Focal segmental glomerulosclerosis etc……

Histopathology Clinical Immune mechanisms Patterns established on light microscopy Membranous Membranoproliferative Focal segmental glomerulosclerosis etc…… ‘Patterns’ not ‘diseases’

In the glomerular mesangium
IgA1 deposition In the glomerular mesangium

IgA NEPHROPATHY

ASSESSMENT AND MANAGEMENT OF IgA NEPHROPATHY Is IgA nephropathy a single ‘disease’ ?

IgA NEPHROPATHY A pattern of glomerulonephritis with many variations

Recurrent visible haematuria Coincides with mucosal infection

Nephrotic syndrome

Haematuria / proteinuria
Asymptomatic Haematuria / proteinuria

CKD Proteinuria Hypertension Renal impairment

HENOCH-SCHȌNLEIN NEPHRITIS

Henoch-Schőnlein purpura

‘SECONDARY’ IgA NEPHROPATHY
COMMONLY REPORTED ASSOCIATIONS Alcoholic liver disease Celiac disease Ankylosing spondylitis Reiter’s syndrome Uveitis Dermatitis herpetiformis

RECURRENT IgA NEPHROPATHY

RECURRENT IgA NEPHROPATHY Pooled published data – 5 year follow up
Recurrence 38-60% Graft dysfunction due to recurrence 15% Graft loss due to recurrence 7%

RECURRENT IgA NEPHROPATHY
Pooled published data – 5 year follow up Recurrence 38-60% Graft dysfunction due to recurrence 15% Graft loss due to recurrence 7% Why does IgA nephropathy NOT always recur ?

Percentage of patients primary glomerular disease
15-21% 4.7% <5% Percentage of patients with primary glomerular disease

Male > Female Male = Female
15-21% Male > Female Male = Female 4.7% <5%

IgA NEPHROPATHY Variations in: Pathological pattern Clinical pattern Transplant recurrence Epidemiological pattern Pathogenesis

IgA NEPHROPATHY No proof that IgAN is a single ‘disease’
Not expect a single pathogenic mechanism to lead to mesangial IgA deposition and injury No proof that IgAN is a single ‘disease’ No proof that IgAN is the same ‘disease’ in all parts of the world

ASSESSMENT AND MANAGEMENT OF IgA NEPHROPATHY Can you predict which patients with IgA nephropathy will get kidney failure?

ASSESSMENT AND MANAGEMENT OF IgA NEPHROPATHY Can you predict which patients with IgA nephropathy will get kidney failure? CLINICAL evidence

PROGNOSIS IN IgA NEPHROPATHY
Rodicio 1982

PROGNOSIS IN IgA NEPHROPATHY
20% 20 years Rodicio 1982

IgA NEPHROPATHY IN INDIA
CMC Vellore Chacko B et al. Nephrology 2005; 10: 496

IgA NEPHROPATHY IN INDIA
CMC Vellore 478 adults 55% - Nephrotic syndrome at presentation 56% - Serum creatinine > 123 μmol/L at presentation Chacko B et al. Nephrology 2005; 10: 496

MACROSCOPIC HAEMATURIA AND PROGNOSIS
IN IgA NEPHROPATHY Beukhof 1983

LEAD TIME BIAS IN DIAGNOSIS OF IgA NEPHROPATHY
Geddes CC et al. NDT 2003; 18: 1541

How benign is it ? Cohort study – Toronto – 286 patients
ISOLATED NON-VISIBLE HAEMATURIA IN IgA NEPHROPATHY How benign is it ? Cohort study – Toronto – 286 patients Proteinuria < 0.2 g/24hr Normal BP Non-visible haematuria plus Bartosik et al. AJKD 2001; 38: 728

How benign is it ? Cohort study – Toronto – 286 patients
ISOLATED MICROSCOPIC HAEMATURIA IN IgA NEPHROPATHY How benign is it ? Cohort study – Toronto – 286 patients Proteinuria < 0.2 g/24hr Normal BP Microscopic haematuria plus 10 year risk of deterioration in renal function = ZERO Bartosik et al. AJKD 2001; 38: 728

How benign is it ? Cohort study – Hong Kong
ISOLATED NON-VISIBLE HAEMATURIA IN IgA NEPHROPATHY How benign is it ? Cohort study – Hong Kong Non-visible haematuria plus Proteinuria < 0.4 g/24hr During 7 years follow up, 44% had a ‘clinical event’ 33% proteinuria 26% hypertension 7% renal impairment Szeto C et al Am J Med 2001; 110:434

OUTCOME AND AVERAGE FOLLOW-UP PROTEINURIA
IN IgA NEPHROPATHY

REMISSION OF PROTEINURIA IMPROVES PROGNOSIS
IN IgA NEPHROPATHY Time-average proteinuria 1 - < 1g/24h 2 – 1-2 g/24h 3 – 2-3g/24h 4 - >3g/24h Reich H et al. JASN 2007; 18: 3177

ASSESSMENT AND MANAGEMENT OF IgA NEPHROPATHY Can you predict which patients with IgA nephropathy will get kidney failure? PATHOLOGICAL evidence

Does pathology add prognostic information
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 ?

Does pathology add prognostic information
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 ?

PATHOLOGICAL CLASSIFICATIONS IN RENAL DISEASE
Are usually based on expert opinion ... and pre-conceived ideas of what lesions are important

OXFORD CLASSIFICATION OF IgA NEPHROPATHY
A different way Approach the problem with an open mind With an international consensus group Study all histological lesions Test reproducibility & independence Then test correlations with outcome

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

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

FOR THE OXFORD CLASSIFICATION OF IgAN
VALIDATION STUDIES FOR THE OXFORD CLASSIFICATION OF IgAN M E S T Macedonia 2010 98 + USA 2011 54 - Japan 161 children France 183 USA, Canada 187 adults & children China 410 702 Sweden 2012 99 Korea 197 6/10 7/10 10/10

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

ASSESSMENT AND MANAGEMENT OF IgA NEPHROPATHY How good is the evidence to guide the treatment of IgA nephropathy ?

CLINICAL PRACTICE GUIDELINE FOR GLOMERULONEPHRITIS
KI Supplements (2): 1-274 CLINICAL PRACTICE GUIDELINE FOR GLOMERULONEPHRITIS

Examples of Rating Guideline Recommendations
QUALITY of Supporting Evidence is shown as A, B, C or D 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 RCTs Supported by limited observational data Guiding principles for the KDIGO guideline development process include: • Scientific and methodological rigor––The process will be evidence-based. The grading of the evidence and recommendations will adhere to the position statement of KDIGO on the grading evidence and recommendations for clinical practice guidelines. • Interdisciplinary approach––Work group members will be chosen for leadership in their respective fields, commitment to quality of care and expertise in clinical practice, with due consideration of international representation reflecting the mission statement of KDIGO. • Independence of work groups––The workgroup will have independence and final responsibility in the formulation of recommendations. This will assure an unbiased approach to guideline development, without influence of organizations or industry • Openness of the guideline development process––Following their initial review by KDIGO Executive Committee and Board of Directors, the draft guidelines will be subjected to an organizational and public review process that invites comment from international groups and professionals whom the guidelines will affect. Comments submitted at each phase of the review process will be carefully reviewed and considered by the Work Group prior to publication of the final guidelines. 50

Examples of Rating Guideline Recommendations
QUALITY of Supporting Evidence is shown as A, B, C or D 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 RCTs Supported by limited observational data Of 10 recommendations or suggestions in the IgA Nephropathy guideline Only 2 (20%) are 1A or 1B Guiding principles for the KDIGO guideline development process include: • Scientific and methodological rigor––The process will be evidence-based. The grading of the evidence and recommendations will adhere to the position statement of KDIGO on the grading evidence and recommendations for clinical practice guidelines. • Interdisciplinary approach––Work group members will be chosen for leadership in their respective fields, commitment to quality of care and expertise in clinical practice, with due consideration of international representation reflecting the mission statement of KDIGO. • Independence of work groups––The workgroup will have independence and final responsibility in the formulation of recommendations. This will assure an unbiased approach to guideline development, without influence of organizations or industry • Openness of the guideline development process––Following their initial review by KDIGO Executive Committee and Board of Directors, the draft guidelines will be subjected to an organizational and public review process that invites comment from international groups and professionals whom the guidelines will affect. Comments submitted at each phase of the review process will be carefully reviewed and considered by the Work Group prior to publication of the final guidelines. 51

Clinical Practice Guideline for Glomerulonephritis
…. will not tell you what to do for every difficult patient in every situation Guiding principles for the KDIGO guideline development process include: • Scientific and methodological rigor––The process will be evidence-based. The grading of the evidence and recommendations will adhere to the position statement of KDIGO on the grading evidence and recommendations for clinical practice guidelines. • Interdisciplinary approach––Work group members will be chosen for leadership in their respective fields, commitment to quality of care and expertise in clinical practice, with due consideration of international representation reflecting the mission statement of KDIGO. • Independence of work groups––The workgroup will have independence and final responsibility in the formulation of recommendations. This will assure an unbiased approach to guideline development, without influence of organizations or industry • Openness of the guideline development process––Following their initial review by KDIGO Executive Committee and Board of Directors, the draft guidelines will be subjected to an organizational and public review process that invites comment from international groups and professionals whom the guidelines will affect. Comments submitted at each phase of the review process will be carefully reviewed and considered by the Work Group prior to publication of the final guidelines. 52

…. 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 Guiding principles for the KDIGO guideline development process include: • Scientific and methodological rigor––The process will be evidence-based. The grading of the evidence and recommendations will adhere to the position statement of KDIGO on the grading evidence and recommendations for clinical practice guidelines. • Interdisciplinary approach––Work group members will be chosen for leadership in their respective fields, commitment to quality of care and expertise in clinical practice, with due consideration of international representation reflecting the mission statement of KDIGO. • Independence of work groups––The workgroup will have independence and final responsibility in the formulation of recommendations. This will assure an unbiased approach to guideline development, without influence of organizations or industry • Openness of the guideline development process––Following their initial review by KDIGO Executive Committee and Board of Directors, the draft guidelines will be subjected to an organizational and public review process that invites comment from international groups and professionals whom the guidelines will affect. Comments submitted at each phase of the review process will be carefully reviewed and considered by the Work Group prior to publication of the final guidelines. 53

…. will not tell us what to do for every difficult patient in every situation ….will remind us what we know Guiding principles for the KDIGO guideline development process include: • Scientific and methodological rigor––The process will be evidence-based. The grading of the evidence and recommendations will adhere to the position statement of KDIGO on the grading evidence and recommendations for clinical practice guidelines. • Interdisciplinary approach––Work group members will be chosen for leadership in their respective fields, commitment to quality of care and expertise in clinical practice, with due consideration of international representation reflecting the mission statement of KDIGO. • Independence of work groups––The workgroup will have independence and final responsibility in the formulation of recommendations. This will assure an unbiased approach to guideline development, without influence of organizations or industry • Openness of the guideline development process––Following their initial review by KDIGO Executive Committee and Board of Directors, the draft guidelines will be subjected to an organizational and public review process that invites comment from international groups and professionals whom the guidelines will affect. Comments submitted at each phase of the review process will be carefully reviewed and considered by the Work Group prior to publication of the final guidelines. 54

…. 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 Guiding principles for the KDIGO guideline development process include: • Scientific and methodological rigor––The process will be evidence-based. The grading of the evidence and recommendations will adhere to the position statement of KDIGO on the grading evidence and recommendations for clinical practice guidelines. • Interdisciplinary approach––Work group members will be chosen for leadership in their respective fields, commitment to quality of care and expertise in clinical practice, with due consideration of international representation reflecting the mission statement of KDIGO. • Independence of work groups––The workgroup will have independence and final responsibility in the formulation of recommendations. This will assure an unbiased approach to guideline development, without influence of organizations or industry • Openness of the guideline development process––Following their initial review by KDIGO Executive Committee and Board of Directors, the draft guidelines will be subjected to an organizational and public review process that invites comment from international groups and professionals whom the guidelines will affect. Comments submitted at each phase of the review process will be carefully reviewed and considered by the Work Group prior to publication of the final guidelines. 55

ASSESSMENT AND MANAGEMENT OF IgA NEPHROPATHY “Should I treat this patient with IgA nephropathy ?”

TREATMENT DECISIONS IN IgA NEPHROPATHY
Non-visible haematuria Visible haematuria Acute kidney injury Crescentic IgA nephropathy Proteinuria > 1g/day Nephrotic syndrome Hypertension Progressive fall in GFR

Microscopic haematuria Macroscopic haematuria Acute kidney injury Crescentic IgA nephropathy Proteinuria > 1g/day Nephrotic syndrome Hypertension Progressive fall in GFR

TREATMENT RECOMMENDATIONS FOR IgA NEPHROPATHY
Recurrent Macroscopic Haematuria No role for antibiotics No role for tonsillectomy

Microscopic haematuria Macroscopic haematuria Acute kidney injury Proteinuria > 1g/day Nephrotic syndrome Hypertension Progressive renal insufficiency

Macroscopic Haematuria with acute renal failure Renal biopsy is mandatory if not improve in 2-3 days with supportive measures

AKI WITH VISIBLE HAEMATURIA IN IgA NEPHROPATHY
9 published reports – 84 patients 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 not the cause of AKI Moreno J et al. CJASN 2012; 7: 175

9 published reports – 84 patients Recovery of renal function ? Most reports (29 patients) … 100% have complete recovery of renal function Two reports (55 patients) – only 73% full recovery Moreno J et al. CJASN 2012; 7: 175

Recovery of renal function ? Full recov One centre in Spain (52 patients) Full recovery less likely: Older age Duration of visible haematuria (mean 15 vs 36 days) Peak sCr (7.1 vs 309 mg/dL) Tubular necrosis Tubular red cell casts Interstitial; fibrosis Moreno J et al. CJASN 2012; 7: 175

Macroscopic Haematuria with acute renal failure Renal biopsy is mandatory if not improve in 2-3 days with supportive measures Acute Tubular Necrosis Supportive measures only Crescentic IgA nephropathy Immunosuppression may be appropriate

Microscopic haematuria Macroscopic haematuria Acute renal failure Crescentic IgA nephropathy Proteinuria > 1g/day Nephrotic syndrome Hypertension Progressive renal insufficiency

CRESCENTIC GLOMERULONEPHRITIS Renal outcome with best known treatment
Renal survival 1 year 5 years Systemic vasculitis 80% 75% Goodpasture’s 70% 50% Crescentic IgA nephropathy 50% 20%

TREATMENT FOR CRESCENTIC IgA NEPHROPATHY
A number of recent optimistic reports - Corticosteroids + Cyclophosphamide Small : < 20 patients Selection criteria variable All are anecdotal

Definition? More than just a few crescents Rapidly progressive renal failure

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

If immunosuppression is indicated… INDUCTION: Prednisolone 0.5-1mg/kg/day Cyclophosphamide 2mg/kg/day MAINTENANCE: Prednisolone in reducing dosage Azathioprine 2mg/kg/day [plasma exchange unproven]

If immunosuppression is indicated… INDUCTION: Prednisolone 0.5-1mg/kg/day Cyclophosphamide 2mg/kg/day MAINTENANCE: Prednisolone in reducing dosage Azathioprine 2mg/kg/day [plasma exchange unproven] An RCT is badly needed …. and will be difficult to achieve

Microscopic haematuria Macroscopic haematuria Acute renal failure Crescentic IgA nephropathy Proteinuria > 1g/day Nephrotic syndrome Hypertension Progressive renal insufficiency

NEPHROTIC-RANGE PROTEINURIA IN IgA NEPHROPATHY
IgAN and nephrotic range proteinuria N = 233 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 Chen M et al. NDT 2011; 26: 1247

NEPHROTIC SYNDROME IN IgA NEPHROPATHY
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 Kim J-K et al. CJASN 2012; 7: 247

Mean follow up 45 months p<0.001 Kim J-K et al. CJASN 2012; 7: 247

100 885 P<0.001 Kim J-K et al. CJASN 2012; 7: 247

NEPHROTIC SYNDROME + MICROSCOPIC HAEMATURIA

NEPHROTIC SYNDROME + MICROSCOPIC HAEMATURIA
Corticosteroids: complete remission of nephrotic syndrome Microscopic haematuria persists

Two common glomerular diseases coincide……
Minimal change nephrotic syndrome IgA nephropathy

NEPHROTIC SYNDROME IN IgA NEPHROPATHY Mesangial hypercellularity
Minimal change Mesangial hypercellularity Glomerulosclerosis

Randomised controlled trial n = 34 Prednisolone for 4 months: mg daily halved after 8 weeks Follow up 38 months Response of proteinuria only in those with minor histological changes Lai - Clin Neph 1986; 26:174

Minimal change Mesangial hypercellularity Glomerulosclerosis The response to corticosteroids in minimal change does not justify their use in all IgAN with nephrotic syndrome

Microscopic haematuria Macroscopic haematuria Acute kidney injury Crescentic IgA nephropathy Proteinuria > 1g/day Nephrotic syndrome Hypertension Progressive fall in GFR

Non-visible haematuria Visible haematuria Acute kidney injury Crescentic IgA nephropathy Proteinuria > 1g/day Nephrotic syndrome Hypertension Progressive fall in GFR

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’

TREATMENT OPTIONS FOR PROGRESSIVE IgA NEPHROPATHY
Blood pressure control Renin-angiotensin blockade Corticosteroids Other immunosuppressives

Blood pressure control Renin-angiotensin blockade Corticosteroids Other immunosuppression

Target Blood Pressure RAS Blockade
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 ?

EFFECT OF ACE INHIBITOR PLUS ARB ON PROTEINURIA
IN IgA NEPHROPATHY: META-ANALYSIS 6 studies – 109 patients Cheng J et al. Int J Clin Pract 2012; 66: 917

EFFECT OF ACE INHIBITOR PLUS ARB ON PROTEINURIA
IN IgA NEPHROPATHY: META-ANALYSIS 6 studies – 109 patients No effect on GFR but Study duration: 2-12 months Cheng J et al. Int J Clin Pract 2012; 66: 917

Target Blood Pressure SALT RESTRICTION RAS Blockade
TREATMENT RECOMMENDATIONS FOR IgA NEPHROPATHY Target Blood Pressure Proteinuria < 1g/24hr 130/80 Proteinuria > 1g/24hr 125/75 SALT RESTRICTION RAS Blockade Proteinuria > 1g/24hr 125/75 Combination therapy ?

DIETARY SODIUM RESTRICTION AMPLIFIES EFFECTS OF RAS BLOCKADE ON PROTEINURIA
Lisinopril 40mg/day Valsartan 320mg/day Sodium intake 50 or 200 mmol/day Slagman M et al. BMJ 2011

DIETARY SODIUM RESTRICTION AMPLIFIES EFFECTS OF RAS BLOCKADE ON PROTEINURIA
Lisinopril 40mg/day Valsartan 320mg/day Sodium intake 50 or 200 mmol/day Systolic BP Diastolic BP Slagman M et al. BMJ 2011

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 ?

CORTICOSTEROID TREATMENT FOR IgA NEPHROPATHY
Randomised controlled trial – serum creatinine < 130 µmol/L Survival without end point - doubling of serum creatinine Pozzi C et al Lancet 1999; 353; JASN 2004; 15: 157

CORTICOSTEROID TREATMENT IN IgA NEPHROPATHY
Randomised controlled trial – serum creatinine < 133 µmol/L n = 86 creatinine < 133 µmol/l - proteinuria 1-3.5g/24hr Regimen methylprednisolone 1g iv x3 at 1,3,5 months plus prednisolone 0.5 mg/kg/alt days for 6 months No important side effects - no study ‘drop outs’ Pozzi C et al Lancet 1999; 353; JASN 2004; 15: 157

CORTICOSTEROID TREATMENT IN IgA NEPHROPATHY n= 103
Randomised controlled trial – serum creatinine < 133 µmol/L n= 103 2 year treatment regimen Prednisolone 20mg od reducing to 5mg by 6 months Antiproteinuric effect but no effect on renal function Katafuchi AJKD 2003; 41:972

BLOOD PRESSURE CONTROL IN IgA NEPHROPATHY TRIALS
Corticosteroids Pozzi Katafuchi BP (mm Hg) 160 150 140 130 120 110 100 90 80 70 60 NKF Recommendation 125/75

CORTICOSTEROIDS PLUS ACE INHIBITOR IN PROTEINURIC IgA NEPHROPATHY
TWO SIMILAR STUDIES Proteinuria > 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 Lv J et al AJKD; 53: 26 Manno C et al. NDT 2009; 24: 3694

Corticosteroids Pozzi Katafuchi Manno Lv BP (mm Hg) 160 150 140 130 120 110 100 90 80 70 60 JNC Recommendation 125/75

CORTICOSTEROIDS PLUS ACE INHIBITOR IN PROTEINURIC IgA NEPHROPATHY
ESRD STEROIDS CONTROL ITALY / /49 CHINA 1/ /33 Statistically significant Lv J et al AJKD; 53: 26 Manno C et al. NDT 2009; 24: 3694

PROTEINURIC IgA NEPHROPATHY
CORTICOSTEROIDS PLUS ACE INHIBITOR IN PROTEINURIC IgA NEPHROPATHY STEROIDS CONTROL ITALY / /49 CHINA 1/ /33 Statistically significant But.. achieved ACE inhibitor dose rather low Lv J et al AJKD; 53: 26 Manno C et al. NDT 2009; 24: 3694

PROTEINURIC IgA NEPHROPATHY But.. neither study had a ‘run-in‘ period
CORTICOSTEROIDS PLUS ACE INHIBITOR IN PROTEINURIC IgA NEPHROPATHY STEROIDS CONTROL ITALY / /49 CHINA 1/ /33 Statistically significant But.. neither study had a ‘run-in‘ period Lv J et al AJKD; 53: 26 Manno C et al. NDT 2009; 24: 3694

IMMUNOSUPPRESSIVE TREATMENT FOR PROGRESSIVE IgA NEPHROPATHY
NO ROLE FOR Cyclophosphamide

Corticosteroids Pozzi Katafuchi Manno Lv BP (mm Hg) 160 150 140 130 120 110 100 90 80 70 60 Ballardie Corticosteroids + Cyclophosphamide JNC Recommendation 125/75

IMMUNOSUPPRESSIVE TREATMENT FOR PROGRESSIVE IgA NEPHROPATHY
NO ROLE FOR Cyclophosphamide What about Mycophenolate

Corticosteroids Pozzi Katafuchi Manno Lv Mycophenolate Maes Tang BP (mm Hg) 160 150 140 130 120 110 100 90 80 70 60 Ballardie Corticosteroids + Cyclophosphamide JNC Recommendation 125/75

MYCOPHENOLATE IN IgA NEPHROPATHY
Benefit BP achieved ACE inhibitors [number of patients] BELGIUM Maes [34] None 125/ % salt restricted HONG KONG Tang [40] ESRD 122/ % reduced

Uncertainty The role of corticosteroids and immunosuppressives after tight BP control and maximal RAS blockade ? The effect of ancestry on treatment responses

Study Design Optimal supportive therapy for 6 months Run-in Phase
(ACEi, ARB, target BP < 125/75 mm Hg, Statin, etc.) Run-in Phase (6 Months) Responder Drop-Out Non-Responder Proteinuria >0.75 g/d Study-Phase (3 Years) RANDOMISATION Optimal supportive Optimal supportive + Immunosuppression

Recruitment-Update STOP IgAN
- Status Study patients n=356 IgAN patients Randomised n=127 Follow-up

We are still short of evidence ….. So there is room for your own opinion …..

ASSESSMENT AND MANAGEMENT OF IgA NEPHROPATHY John Feehally

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