EVIDENCE BASED TREATMENT OF IgA NEPHROPATHY. Jonathan Barratt

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1 EVIDENCE BASED TREATMENT OF IgA NEPHROPATHY Jonathan Barratt

2 EVIDENCE BASED TREATMENT OF IgA NEPHROPATHY We do not have much evidence

3 EVIDENCE BASED TREATMENT OF IgA NEPHROPATHY We do not have much evidence. so there is plenty of room for opinion

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

5 TREATMENT DECISIONS IN IgA NEPHROPATHY GloMy 50 IgAN Allowed as long as not RPGN Microscopic haematuria Macroscopic haematuria Acute renal failure Crescentic IgA nephropathy Proteinuria > 1g/day PCR > 150 BP<130/80 RAS inhibition Nephrotic syndrome Hypertension Progressive renal insufficiency egfr > 20

6 IgA NEPHROPATHY

7 OXFORD CLASSIFICATION OF IgA NEPHROPATHY

8 OXFORD CLASSIFICATION OF IgA NEPHROPATHY

9 OXFORD CLASSIFICATION OF IgA NEPHROPATHY

10 GloMy Non-blinded RCT Standard care Myfortic 720 mg bd Pred 1mg/kg 0mg (10/52)

11 TREATMENT OPTIONS FOR PROGRESSIVE IgA NEPHROPATHY Corticosteroids Cyclophosphamide Mycophenolate Fish oil Blood pressure control

12 TREATMENT OPTIONS FOR PROGRESSIVE IgA NEPHROPATHY Corticosteroids Cyclophosphamide Mycophenolate Fish oil Blood pressure control

13 CORTICOSTEROID TREATMENT IN IgA NEPHROPATHY n = 86 Randomised controlled trial 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 Pozzi C et al Lancet 1999; 353; JASN 2004; 15: 157

14 CORTICOSTEROID TREATMENT FOR IgA NEPHROPATHY Survival without end point - doubling of serum creatinine Pozzi C et al Lancet 1999; 353; JASN 2004; 15: 157

15 CORTICOSTEROID TREATMENT IN IgA NEPHROPATHY n = 86 Randomised controlled trial 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

16 CORTICOSTEROID TREATMENT IN IgA NEPHROPATHY n = 103 Randomised controlled trial creatinine < 140 µmol/l 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

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19 TREATMENT OPTIONS FOR PROGRESSIVE IgA NEPHROPATHY Review of recently published randomised controlled trials Corticosteroids Cyclophosphamide Mycophenolate Fish oil Blood pressure control

20 MYCOPHENOLATE IN IgA NEPHROPATHY Randomised controlled trial N = 62 Proteinuria >2g/day Serum creatinine <350µmol/L Mycophenolate for 12 months All patients received corticosteroids Significant reduction in proteinuria maintained for 18 months No effect on renal function Chen 2002, Natl Med J China; 82:796

21 MYCOPHENOLATE IN IgA NEPHROPATHY Randomised controlled trial Belgium n = 34 Mean proteinuria 1.7g/day Mean CrCl 70mL/min Mycophenolate 2g/day for 36 months vs placebo Maes B et al Kidney Int 2004; 65: 1842

22 MYCOPHENOLATE IN IgA NEPHROPATHY Randomised controlled trial No effect on renal function Maes B et al Kidney Int 2004; 65: 1842

23 MYCOPHENOLATE IN IgA NEPHROPATHY Randomised controlled trial New York n = 25 Proteinuria 1-3 g/day Creatinine ~ 2.5 mg/dl Mycophenolate 2g/day 12 months vs placebo No benefit Frish G et al NDT 2005; 20: 2139

24 MYCOPHENOLATE IN IgA NEPHROPATHY Randomised controlled trial Hong Kong n = 40 Proteinuria 1-3 g/day Creatinine ~ 2.5 mg/dl Mycophenolate 2g/day 6 months vs placebo Proteinuria reduced Tang S et al. KI 2005; 68: 802

25 TREATMENT OPTIONS FOR PROGRESSIVE IgA NEPHROPATHY Review of recently published randomised controlled trials Corticosteroids Cyclophosphamide Mycophenolate Fish oil Blood pressure control

26 BP TREATMENT RECOMMENDATIONS FOR IgA NEPHROPATHY There is little RCT evidence in IgAN Target Blood Pressure ACR is 70 mg/mmol, or PCR 100 mg/mmol Systolic blood pressure: 130 mmhg (target range mmhg) and Diastolic blood pressure below 80 mmhg.

27 BLOOD PRESSURE CONTROL IN IgA NEPHROPATHY TRIALS Pozzi et al Corticosteroids

28 BLOOD PRESSURE CONTROL IN IgA NEPHROPATHY TRIALS Ballardie et al Corticosteroids + Cyclophosphamide Pozzi et al Corticosteroids

29 BLOOD PRESSURE CONTROL IN IgA NEPHROPATHY TRIALS Ballardie et al Corticosteroids + Cyclophosphamide Pozzi et al Corticosteroids Maes et al Mycophenolate

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31 148 patients (74 per Treatment) 3 year study

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34 Any Questions? Perhaps that pain wasn t your kidneys after all!