Henoch-Schönlein Purpura: Can we prevent nephritis and progression ? - PowerPoint PPT Presentation

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Henoch-Schönlein Purpura: Can we prevent nephritis and progression ?

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  1. Henoch-Schönlein Purpura:Can we prevent nephritis and progression ? Dr. Ayşe Öner Trakya University, Edirne / TURKEY ESPN 2008, LYON

  2. Can we prevent the progression of HSP nephritis? • Kidney damage is the principal prognostic determinant in Henoch-Schönlein purpura (HSP),affecting between 15-90% of the patients. • Of the children with Henoch-Schönlein Nephritis (HSN), more than 1-7% progress to end-stage renal failure • In long-term studies 19-20% develop ESRD in selected pts Koskimies et al. (1981)Arch Dis Child 56:482–484 Niaudet P et al (1993) Adv Nephrol 2: 121–140. Schärer K et al (1999). Pediatr Nephrol 13: 816–823 Tzard EJ Arch Dis Child Educ Pract Ed(2008);93:1-8

  3. Can we prevent the progression of Henoch-Schönlein nephritis ? 1- Do we need to treat every patient with HSN ? 2-Which group of patients would be more likely to suffer from long term morbidity ? 3- What the therapy should consist of? 4-How effective is the treatment in altering the clinical course of HSN in short and long- term ?

  4. Do we need to treat every patient with HSN ? • HSP children withrenal involvement Grade I Isolated microscopic hematuria Grade II Hematuria and mild proteinuria Grade III Acute nephritic syndrome Grade IV Proteinuria >1 gr/ day / or nephritic syndrome Grade V Acute nephritic syndrome /nephrotic syndrome

  5. Which group of patients with HSN would be more likely to suffer from long term morbidity ? Risk factors for developing CRF in children with HSN A- Clinical risk factors Age >7 Nephrotic syndrome Persistent proteinuria Initial renal insufficiency Nephrotic / nephritic syndrome High blood pressure Goldstein A R et al (1992) . Lancet 339:280–282 Shaerer K. Pediatr Nephrol (1999). 13: 816-2 Coppo R, 2006. Am J Kidney Did;47:993–1003. Mir S et al. Pediatr Nephrol (2007).22:1;67-70

  6. Which group of patients would be more likely to suffer from long term morbidity ? B- Hystological changes Grade IV- 55% patients Grade V 67% patients Crescentic GN (> 50%) 48 % patients CRF Tubulointerstitial changes ( chronic) Counahan R et al BMJ (1977) 2: 11-14 Goldstein AR et al .Lancet.1992;339:280-2 Niaudet P et al Ann Med Int ( 1994) 145: 577-80 Foster B et al J Pediatr (2000) 136: 370-5 CRF

  7. What the treatment of HSN should consist of? There is no consensus on therapy - Steroid alone ( oral or pulse ) - Steroid in combination with Cyclophosphamide Azathioprine Cyclosporine A Mycophenolate mofetil ACE-I Vit E - Plasmapheresis - IVIG Other: Antiplatelet agents Dipyridamole Factor XIII Wyatt RJ –HoggRJ.Pediatr Nephrol(2001) 156-167 Tzard EJ Arch Dis Child Educ Pract Ed(2008);93:1-8

  8. Different immunosuppressive and –modulative treatments and outcome in children with severe HSN MP: Pulse prednisolone, Az: azothioprine, CycA: Cyclosporine A; PP: Plasmapheresis, CP: Cyclophosphamide

  9. Different immunosuppressive and –modulative treatments and outcome in children with severe HSN MP: Pulse prednisolone, Az: azothioprine, CycA: Cyclosporine A; PP: Plasmapheresis, CP: Cyclophosphamide

  10. Does the treatment effect outcome in severe HSN ? • Early studies using per oral steroids for the treatment of HSN showed no benefit • No differences in outcomes between patients receiving corticosteroids, immunosuppressives or both and patients with no treatment • In a recent prospective study patients provided with only supportive treatment had a similar outcome to those treated with cyclophosphamide • Early treatment may also prevent the histological progression of the disease. Counahan R et al BMJ (1977) 2: 11-14 Tarshihs P et al Pediatr Nephrol (2004) 19:51-56 Tanaka H, (2003) Pediatr Nephrol 18: 347–350.

  11. Does the treatment effect outcome in severe HSN ? In the past HS nephritis → 15% of children with ESRD More recent HSN →1.8–3% of children with ESRD More aggressive treatment may have had a beneficial impact on the outcome. Narchi H.. Arch Dis Child2005;90:916–20. Meadow SR.Clinical Nephrology 1978;9:87–90. NiaudetP et al .Pediatr Nephrol 1998;12:238–43.

  12. Triple Therapy Protocol 1-MPZ (iv.pulse) (30mg/kg/day, 3 days), followed by oral prednisolone 45 mg/m2/day with tapering doses( over 3 months) 2. Oralcyclophosphamide, 2mg/kg/day, (2-3months) 3.Dipyridamole 5 mg/kg/day ( 6 months)

  13. The effect of Triple Therapy Protocol onrapidly progressive type of HSN in short-term follow-up period Follow-up Period:9-39 months 7 pts complete remission 4 pts partial remission 1 patient CRF Conclusion: Triple therapy prevent the Progresion of Rapidly Progresive type of Henoch Schönlein Nephritis in the early course of the disease

  14. The effect of Triple Therapy Protocol onRapidly Progressive Type of HSN inLong-Term Follow-up Period

  15. Case 1; İT • Age:12 years • Sex:male • Renal involvementat the first admission: Acute nephritic and nephrotic syndrome(Grade 5) • Edema-oliguria • hypertension • decreased GFR (14 ml/min per 1.73 m2) • proteinuria (4.8 g/m2 per day). • He fulfilled the clinical criteria of RPGN.

  16. Case 1;İT • Renal biopsy was not available. • Initation of treatment: > 2 months( after onset) • Treatment protocol: Triple therapy • He discharged with partial remission with a serum creatinine level of 2 mg/dl.

  17. Case 1; İT • He was lost to follow-up for 30 months. • He readmitted with acute nephritic and nephrotic syndrome, • Renal biopsy 60-75% fibroepithelial and fibrous crescents extensivefibrotic changes in tubulointerstitial tissue. • Duration of follow-up: 14 years Outcome: End stage renal failure(4 years after first admission CAPD-Renal transplantation- Graft rejection-Hemodialysis- EXITUS

  18. Case 2, KA Age: 11 years Male Renal involvementat the first admission: Acute nephritic and nephrotic syndrome (Grade 5) hypertension proteinuria (9.6 g/m2 per day) decreased GFR (25 ml/min per 1.73 m2) oliguria/acute periton dialysis

  19. Case 2, KA Renal biopsy 80% fibroepithelial and fibrous crescents, mild tubulo-interstitial fibrosis Initation of treatment: > 6 weeks Treatment:Triple therapy acute periton dialysis Follow-up: 16 years Outcome: Partial remission with persistent proteinuria (< 1 g/day)

  20. Case 3, Ş.Ç. • Age:14 years • Sex: female Acute nephritic and nephrotic syndrome (Grade 5) • edema • Hypertension • decreased GFR (36 ml/min /1.73 m2) • proteinuria (8.5 g/m2 /day).

  21. Case 3, Ş.Ç. • Renal biopsy Endo and extracapillary proliferative glomerulonephritis (60% epithelial and fibroepithelial crescents) • Initation of treatment: 5 weeks • Treatment:Triple therapy Outcome Complete remission • Duration of follow-up:16 years 2 pregnancies with transient hypertension and proteinuria having 2 healthy babies • Clinical status at the latest visit: Complete remission

  22. Case 4; G.Ö. Age: 8 years Sex: female Renal involvementat the first admission: Acute nephritic and nephrotic syndrome (Grade 5) gross hematuria decreased GFR (34 ml/min per 1.73 m2) proteinuria (4.2g/m2 per day) Initation of treatment: 5 weeks

  23. Case 4; G.Ö. • Treatment protocol: Triple therapy • Renal biopsy: 60 % epithelial crescent formation • Clinicalstatus(after 3 years of onset) • Complete remission

  24. Case 4; G.Ö. • 2006 ( After 8 years of remission) • She had complaint of macroscopic hematuria with concurrent pharyngitis • She developed nephritic/nephrotic syndrome No extrarenal symptoms • Serum Ig A level was high DİAGNOSIS: IgA nephropathy

  25. Treatment: MP pulse therapy (6 months) Cyclosporine A (3 mg/kg/day 18 months) ACE inh. (1 mg/kg/day) Dypiridamole (5 mg/kg/day ) Prophylaxy ( benzathine penicilline) She responded well to the therapy,went into remission ( after six months) Duration of follow-up:15 years REMISSION Case 4; G.Ö.

  26. Initial symptoms,hystological finding and timing of treatmentare very important in HSN Early agressive treatment is necessary for severe HSN (grade V-IV) Pregnancy is a very important risk factor and can be complicated by proteinuria and/or hypertension. HSP and Ig A nephropathy can be encountered consecutively in the same patient. What we learned from the long term follow up of these four patients?

  27. Patients • 398 patients with HSP • 156 patients (39.2%) with renal involvement were evaluated retrospectively. • 86 males / 70 females • mean age: 9.6 years • age range: 4-16years • 43 patients underwent renal biopsy.

  28. 156 Patientswere graded according to the degree of renal involvement.

  29. Histopathology of ISKDC classification in HSN Grade I: Minimal alterations Grade II: Mesangial proliferation Grade III a: Focal proliferation b: Diffuse <50 % crescent Grade IV a: Focal proliferation b: Diffuse 50-75 % crescent Grade V a: Focal proliferation b: Diffuse >75 % crescent Grade VI: MPGN like GN

  30. Renalbiopsy results in 43 patients

  31. Treatment modalities of 43 patients with renal biopsy

  32. Evaluation of outcome after treatment State A: No sign of renal involvement (healthy) State B: Minor urinary abnormalities microscopic hematuria, proteinuria State C: Active renal disease Proteinuria of 40 mg/m2/h HT, State D: Renal insufficiency Dialysis Transplantation Death Outcomes A+B were judged to represent a good outcome and C+D a poor outcome

  33. Follow-up of the patients • Follow-up period: • Mean: 303.5 months • Range: 1-16 years.

  34. Prognosis of the patients

  35. Prognosis of the patients

  36. Summary of the results • The prognosis of the patients with mild renal involvement (Grade 1-3) was better. • The patients having severe forms of nephritis (Grade 4-5) showed good prognosis with appropriate treatment. • The development of chronic renal failure is associted with clinical nephritic and nephrotic syndrome, and histopathological extensive crescent formation and especially fibrotic changes in crescents and tubulointerstitial tissue.

  37. Conclusion: • Initial presentation of renal involvement determines the prognosis in HSN • Triple therapy appears to be effective in preventing ofprogression of severe HSNespecially if started before the development of fibrotic changes in crescents and tubulointerstitial tissue. • In view of the small number of patients with severerenal disease multicentre/international studies arerequired to establish the role of immunosuppressivetherapy.

  38. TREATMENT RECOMMENDATİONS • Severe HSN Grade IV-V(Nephritic-Nephrotic Syndrome) Induction Therapy(Triple therapy) 1. I.V.pulse MPZ (30mg/kg/day, 3 days), followed by oral prednisolone in tapering doses 2. Oral cyclophosphamide, 2mg/kg/day, 2-3months 3. Dipyridamole 5 mg/kg/day Maintenance therapy ( 6 months) Oral prednisolone Dipyridamole 5 mg/kg/day ACEI Profilactive therapy (penicilline) • Mild grades HSN Grade I-II-III No spesific treatment supportive only. Hypertension ACEI

  39. Thank you