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HSP nephritis


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hsp nephritis

HSP nephritis

  1. 1. Henoch Schӧnlein Nephritis Ӧ
  2. 2. • Synonyms include anaphylactoid purpura, allergic vasculitis, leukocytoclastic vasculitis, and rheumatoid purpura.
  3. 3. • First description was by Heberden in 1806 • Schӧnlein first described the association of arthralgias and purpura, and he termed it ‘peliosis rheumatica’ in 1837. • Henoch (Schӧnlein’s student) described GI and renal manifestations in 1874 and 1899 respectively.
  4. 4. HSP in Children • Self limited • 20% long standing renal involvement. Of that 20%, 7% need HD • Children with renal involvement have a 35- 44% higher incidence of CKD in 24 year follow up. (Ronkainen J: The adult kidney 24 years after childhood HSP: retrospective cohort. Lancet 360: 666-670, 2002)
  5. 5. HSP in Adults • NO comparable incidence in adults • Overall 26% mortality in adults • Knowledge of natural history in adults is limited due to small series with short follow up. • More serious skin and joint involvement. • Renal disease is more frequent and more severe in adults, and more likely to progress. • Recurrence 10-40%, within 4 months. • Recurrence does not worsen prognosis.
  6. 6. Pathogenesis • Remains unknown; however, it is generally considered • Immune complex-mediated disease characterized by the presence of polymeric IgA1 (pIgA1)-containing immune complexes predominantly in dermal, gastrointestinal, and glomerular capillaries . • The pathognomonic granular IgA and C3 deposits in the mesangium are indistinguishable from those seen in IgA nephropathy
  7. 7. • C1GALT1 polymorphisms are associated with Henoch–Schönlein purpura nephritis • the G allele and GG genotype of 1365A/G were significantly increased in HSPN patients
  8. 8. Clinical feature • Rieu and Noel reported renal involvement in 33% of children and 63% of adults with HSP • A characteristic feature is hematuria- often is macroscopic but may be microscopic and either transient, persistent, or recurrent • Hematuria may accompany relapses of purpura or recur long after the extrarenal manifestations have resolved, often in association with upper respiratory infections • Usually, there is associated proteinuria of variable intensity, and the frequency of the nephrotic syndrome is also extremely variable. • Deterioration of GFR may occur, and azotemia or end-stage renal failure may ensue
  9. 9. Renal Involvement- Children • Only 1-5% progress to ESRD. • 10-50% of children get microscopic hematuria, mild GN, and proteinuria that resolves spontaneously. • Up to 33% recurrence in children, but symptoms are milder and shorter duration
  10. 10. Renal Involvement-Adults • 11% on HD • 10-30% ESRD at 15 years • 27% CrCl <50% • 50% persistent hematuria • 47% moderate proteinuria • 8% nephrotic range • 20% remission Evangeline, P: HSP in adults, Outcome and Prognosis factors, J Am Soc Nephrology 13:1271: 2002
  11. 11. Children versus Adults • 95 adults and 57 children, 5 year follow up • Crescents and nephrotic range proteinuria equal incidence • Residual CKD 31% in adults versus 24% children. • Adults 2x more likely to progress to HD/ESRD. (16 versus 7%) • Poor prognosis: >50% crescents, renal impairment at presentation, UP/C> 1.5 g/day, HTN Coppo R: Long term Prognosis of HSP nephritis in adults and children. Nephrol Dial Transplant 12: 2277-2283, 1997
  12. 12. Renal Transplant after HSP • 35% recurrence • 11% graft loss • Meulders et al
  13. 13. Diagnostic criteria Palpable purpura (mandatory) in the presence of at least one of the following four features: – Diffuse abdominal pain – Arthritis (acute) or arthralgia – Renal involvement (any haematuria and/or proteinuria) – Any biopsy showing predominant IgA deposition Ozen S et al Ann Rheu Dis 65:936-41, 2006 ,EULAR/PReS consensus criteria
  14. 14. What constitutes renal involvement? • Isolated Haematuria • Isolated Proteinuria • Nephrotic syndrome • Nephritic syndrome – Renal impairment – Hypertension Risk of long term renal impairment and duration of follow up recommended for Henoch-Schönlein purpura with normal or minimal urinary findings: a systematic review. Narchi H. Arch Dis Child 2005
  15. 15. What investigations if renal involvement? Primary Investigations U&E, HCO3, creatinine Albumin urine Protein:Creatinine urine dipstix and microscopy FBC Clotting screen Secondary Investigations Anti-streptococcal titre (ASOT) Antinuclear antibody (ANA) + dsDNA Antinuclear cytoplasmic antibody (ANCA) Complement – C3, C4 ESR CRP Renal ultrasound
  16. 16. HSP – Onset of nephritis Time of onset of urinary abnormalities after the diagnosis of HSP Weeks after HSP diagnosis 1 2 4 6 8 24 % 37 54 84 90 91 97 Narchi H Arch Dis Child 90:916-20, 2005
  17. 17. Indications for renal biopsy • Acute renal impairment/nephritic syndrome at presentation • Nephrotic syndrome with normal renal function persisting at 4 weeks • Nephrotic range proteinuria (urine protein/creatinine ratio, >250 mg/mmol) at 4–6 weeks (if not improving spontaneously) • Persistent proteinuria • urine protein/creatinine ratio >100 mg/mmol at >3 months particularly if diagnosis is not clear. Clinical practice: Diagnosis and management of Henoch–Schönlein purpura. McCarthy H & Tizard EJ. Eur J Pediatr (2010)
  18. 18. Henoch- Schönlein Nephritis histological classification – ISKDC Class Mesangial change Crescents Frequency % (n = 355) * I Minimal changes 8 II Pure mesangial proliferation 29 III a b focal diffuse mesangial proliferation mesangial proliferation <50% 43 IV a b focal diffuse mesangial proliferation mesangial proliferation 50 – 75% 12 V a b focal diffuse mesangial proliferation mesangial proliferation >75% 6 VI Membranoproliferative like glomerulonephritis 3 * Pooled data from Pathology of the Kidney, 6th Edition, Jennette et al. Philadelphia, Lippincott Williams & Wilkins, 2007.
  19. 19. Histology and the normal glomerulus
  20. 20. Normal glomerulus Moderate mesangial expansion – class 2 – ‘mild’. Mesangial proliferation and crescent formation Focal and segmental mesangial hypercellularity with associated capillary luminal leukocytes
  21. 21. • Immunofluorescence microscopy. There is granular staining for IgA in mesangial regions and segmentally along capillary walls. • which is often accompanied by C3, fibrinogen, and both light chains, and less frequently by IgG and/or IgM
  22. 22. • Electron microscopy. There are electron-dense deposits in the mesangium, and segmentally in subendothelial locations.
  23. 23. What treatments can be used for HSP Nephritis? • Immunosuppressants – Steroids • IV MP • po Prednisolone – Cyclophosphamide (CyP) – Ciclosporin – Plasma exchange – Rituximab? • ACEi
  24. 24. • No adequate evidence • No RCTs for treatment of HSP nephritis • The treatment of HSP nephritis is controversial, and recommendations are based on small, often uncontrolled series.
  25. 25. Current RHSC(G) guideline HSP Class Management I & II No immunosuppressant treatment routinely ACEi if persistent proteinuria III Pulse IV methylprednisolone 600mg/m2 for 3 days Oral prednisolone 60mg/m2 (max 60mg) for 1 month and taper Consider Cyclophosphamide 2.5mg/kg/day for 56 days ACEi if persistent proteinuria IV & V (VI) Pulse IV methylprednisolone 600mg/m2 for 3 days Oral prednisolone 60mg/m2 (max 60mg) for 1 month and taper Cyclophosphamide 2.5mg/kg/day for 56 days Consider Plasma exchange ACEi if persistent proteinuria
  26. 26. Will steroids prevent renal disease in HSP? • No! ChartapisakW, Opastirakul S, Willis NS, Craig JC, Hodson EM. ADC, 2008 and Cochrane review updated, 2010.
  27. 27. Will steroids improve outcome for acute mild renal symptoms? • RCT early steroid in HSP • Sub group analysis • 71 with renal symptoms in first month • More rapid resolution with steroids at 6 months – Ronkainen et al. J Ped 2006.
  28. 28. Recommended follow-up • BP & urine dipstix for – week 1-6 weekly – Week 7-24 monthly Narchi H Arch Dis Child 90:916-20, 2005
  29. 29. The adult kidney 24 years after childhood HSP: a retrospective cohort study. Clinical presentation at onset of Henoch - Schönlein purpura I no renal symptoms II proteinuria + haematuria, and no biopsy specimen or ISKDC biopsy grade I - II III renal symptoms > 1 month, nephritis or nephrosis, and ISKDC biopsy grade III or more Nephritis: haematuria and 2/3 symptoms: increase in serum creatinine, oliguria, hypertension. Nephrosis: proteinuria > 40 mg/m2/hr. Clinical outcome A healthy B minor urinary abnormalities (intermittent hypertension, proteinuria, haematuria) C active renal disease (hypertension, constant proteinuria) D end-stage renal disease (dialysis treatment or renal transplantation) Ronkainen et al. Lancet, 2002
  30. 30. The adult kidney 24 years after childhood HSP: a retrospective cohort study. Onset Grade Number of patients Good outcome A + B Poor Outcome C + D I 9 9 (100%) 0 II 18 16 (89%) 2 (11%) III 20 13 (65%) 7 (35%) • Clinical outcome after mean follow-up of 24·1 years, by symptoms at onset • Ronkainen et al. Lancet, 2002
  31. 31. Discuss with Nephrologist • Hypertension • Abnormal renal function • Macroscopic haematuria > 5 days • Persisting proteinuria
  32. 32. Summary • HSP is the commonest vasculitis of childhood • Renal involvement is frequent • Significant renal disease is less common but can develop up to 3 months from presentation • Early steroid therapy in HSP does not prevent nephritis • Treatment interventions for HSP nephritis are not well evidence based • Variations in long term outcomes may reflect changes in clinical practice over time • Prompt intervention in more severe nephritis with immunosuppression is still used • ACEi for persistent ‘chronic’ proteinuric nephropathy is recommended
  33. 33. • Thank you
  34. 34. Detection and referral of patients with Henoch–Schönlein purpura nephritis (adapted from local guidelines developed by Dr D Hothi and Bristol Paediatric Nephrologists). Tizard E J , Hamilton-Ayres M J J Arch Dis Child Educ Pract Ed 2008;93:1-8 Copyright © BMJ Publishing Group Ltd & Royal College of Paediatrics and Child Health. All rights reserved.