1. Case Presentation Dr Mohan Shenoy Consultant Paediatric Nephrologist Royal Manchester Children’s Hospital

2. History 6yr girl Presents with non blanching palpable purpuric rash over extensor surface of arms and legs Ankle pain

3. Examination Well child BP 106/60 Urine – NAD

4. HSP: Background Most common childhood vasculitis Incidence of HSP: 135-200 pmcp Highest among 4-6 year olds – 700 pmcp Stewart M et al, Eur J Pediatr 147:113-115, 1988 Gardner-Medwin J et al, Lancet 360:1197-202, 2002

5. HSP: 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

6. Evaluation of a child with HSP Weight Blood pressure Urine dipstix for blood and protein If dipstix positve for blood or protein: –Urine microscopy –Urine protein creatinine ratio –U&E, LFT

7. Investigations Only if diagnosis uncertain FBC Coagulation ASO titre C3 and C4 Igs ANA, ANCA

8. Case history So… In our patient with HSP with no renal manifestation, what follow-up and monitoring is required?

9. 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

10. Recommended follow-up BP & urine dipstix for –week 1-6 weekly –Week 7-24 monthly Discharge at 6 months if no urinary abnormality Narchi H Arch Dis Child 90:916-20, 2005

11. Can early steroid therapy prevent onset of HSP nephritis?

12. Early steroids to prevent onset of HSP nephritis A large UK prospective study 353 children randomised to steroids or placebo No difference in the incidence of proteinuria at 12 months –19/145 steroid vs 15/145 placebo Dudley J et al Pediatr Nephrol 22:1457, 2007

13. Cochrane review 2009

14. Therefore… Early steroid therapy to prevent onset of HSP nephritis cannot be recommended in children presenting with HSP

15. Case history Child presents 3 weeks later –Frank haematuria –Protein +++ –BP 110/70 –Not oedematous –Creat 45, albumin 34 –Urine protein creatinine ratio 285mg/mmol

16. HSPN - Presentation

17. Indications for Renal Biopsy Acute nephritis Nephrotic syndrome Persisting heavy proteinuria –Urine protein creatinine ratio >200mg/mmol for 2 weeks

18. Discuss with Nephrologist Hypertension Abnormal renal function Macroscopic haematuria > 5 days Persisting proteinuria

19. Case history Weekly review Upcr improves 154 and then 75mg/mmol BP and creatinine normal

20. Prognosis of HSP nephritis Significant variability Chronic kidney disease 2-20% 2% of children with ESKD in UK

21. Outcome of HSP nephritis Unselected study 270 children with HSP over 13 years Renal involvement at presentation – 20% Mean follow-up 8.3 years CKD in only 3 (1.1%) Stewart M et al, Eur J Pediatr 147:113-115, 1988

22. Clinical Presentation and Outcome Cameron JS et al Oxford Textbook of Clinical Nephrology

23. Biopsy grade and Outcome ISKDC Biopsy grade Cameron JS et al, Oxford Textbook of Clinical Nephrology

24. Long-term outcome of HSP nephritis 78 children with HSP nephritis Various immunosuppressive regimens F/U 23 years Active renal disease: 7.5% ESKD: 14% Goldstein et al Lancet 339:280–282, 1992

25. Outcome of HSP nephritis 16/44 pregnancies – proteinuria+/- hypertension 7 patients – deterioration following complete recovery at 5 year follow-up Goldstein et al Lancet 339:280–282, 1992

26. Take home messages No risk of CKD if urinalysis normal at 6 months In unselected patients, the risk of CKD < 2% Presentation with acute nephritis and nephrotic syndrome high risk of CKD Late deterioration in renal function can occur and all children with significant nephritis require life long monitoring