Nephrology presentation 28/3/2011

1. Nephrology presentation28/3/2011

2. History

3. 62 year male from Bethlehem referred with renal failure • 1/12 ago: Constitutional complaints No clear focus of infection Raised CRP and lymphopenia Normal renal function • He was treated symptomatically and discharged

4. However, one month later, his symptoms had not improved • On systemic enquiry - fleeting arthralgia of the large joints - myalgia of the arms and thighs with initiation of movement - he denied any ENT symptoms or skin rash - 35 pack year smoking history, diagnosed with emphysema, but never had any episodes of acute bronchospasm

5. Occupation: administrative work, some occasional welding • No previous history of note, i.e. hypertension, DM • No nephrotoxic drugs

6. Clinical examination

7. Vitals: BP 105/70, pulse 80/min • Gen: pale with no edema • CVS: loud P2 • Resp: hyperinflated with good bilateral air entry • Abdo: normal • CNS: normal • ENT: reddish uvula, no ulcers • Skin: no evidence of vasculitis / connective tissue disease

8. Special investigations

9. Urine • Urine dipstix: 3+ hematuria, 2+ proteinuria • Microscopy: active sediment • MCS: no evidence of infection • 24 hour collection: dU protein 0.5g

10. Blood investigations • FBC: Hb 8,4 / MCV 88 • U+E: urea 11,6 creatinine 299 • CRP 69 • ESR >90 • HIV (-) • Hepatitis B and C (-) • Protein electrophoresis normal • Complement normal • ANA (-) • cANCA (proteinase 3) > 100, pANCA (MPO) - negative • Anti-GBM - pending

11. Radiology • Renal ultrasound showed normal sized kidneys • CXR: hyperinflation, but clear • Shoulder x-ray: evidence of OA

12. Histology • Segmental necrotizing vaculitis • Few crescents • No granuloma formation • No eosinophillic infiltrates • No immune complexes

13. Small cell vasculitis and the kidney

14. Vasculitis is a clinicopathological process characterized by inflammation of and damage to the blood vessels • Affected vessels vary in size, type and location • Can occur as result of a primary process or secondary to another underlying disease • Given the numerous and varied types of vessels in the kidneys, renal disease is caused by a variety of systemic vasculitides.

15. Vasculitis Large sized vessels Small sized vessels • Takayasu’s - ANCA (+) • Giant cell arteritis - ANCA (-) Medium-sized vessels - Poly-arteritis nodosa - Kawasaki’s disease

17. Small vessel vasculitis ANCA (+) ANCA (-) HenlochShönleinpurpura Cryglobulinemic Connective tissue disorders Goodpasture’s disease Infection induced Hypersensitivity Paraneoplastic • Wegener’s granulomatosis • Microscopic poliangiitis • Renal limited vasculitis / ANCA GN • Churg Strauss syndrome • Drug induced

18. Anca (+)

19. Wegener’s granulomatosis • 5-10 / 1 000 000 • Granulomatous inflammation and necrotizing vasculitis affecting the nasal passages, airways and kidneys. • Common presentation include upper airway involvement – epistaxis, nasal crusting, hemoptysis, ulceration and deafness secondary to serious otitis media. • Inflammation of the retro-orbital tissue van cause proptosis and optic nerve compression • Untreated nasal discharge leads to bone and cartilage destruction • Migratory pulmonary inflitrates and nodules on CXR • Mostly cANCA(proteinase 3)

22. Microscopic poliangiitis • 8 / 1 000 000 • Necrotizing vasculitis affecting the capillaries, venules or arterioles • Typically presentation includes a rapidly progressive GN, often associated with alveolar haemorrhage • Cutaneous and GIT involvement • pANCA (+), but can be cANCA (+) • Considered as part of a clinical spectrum that includes Wegener’s and renal limited vasculitis

23. Renal limited vasculitis • Part of the spectrum including Wegener’s and microscopic poly-angiitis • No systemic involvement • Histology: necrotizing GN

24. The spectrum • Renal limited vasculitis - vasculitis with necrotizing GN - no systemic symptoms • Microscopic polyangiitis - vasculitis with necrotizing GN - systemic symptoms and involvement • Wegener’s granulomatosis - vasculitis with necrotizing GN - granuloma formation - systemic symptoms and involvement

25. Churgstrauss syndrome • Also known as allergic granulomatosis and angiitis • 1-3 / 1 000 000 • Histology similar to WG, but with eosinophillic infiltrates of the vessel walls • Prodromal period for years with allergic rhinitis, nasal polyposis and late-onset asthma • Triad of skin lesions, asymmetric mononeuritis multiplex and eosinophillia on a background of resistant asthma • Necrotizing GN • Mesenteric vascultitis • cANCA or pANCA

26. Anca (-)

27. Henlochshönleinpurpura • Characterized by deposition of IgA-containing immune complexes • Children and young adults • Purpura over the buttocks and lower legs, abdominal symptoms, arthritis following an URTI • GN can occur up to 4/52 after initial symptoms • Biopsy shows IgA deposition on IF • Generally good prognosis but adult presentation, hypertension, renal failure, significant proteinuria can progress to ESRF

29. Essential cryglobulinemicvasculitis • Characterized by the presence of cryoglobulins • Mix of complement and immunoglobulins, that precipitate in the cold • Type 2 (hep C) and 3 ass with vasculitis • Palpable purpura, athralgia, Raynaud’s phenomena, neuropathy • Immune complexes are deposited in the vessel walls

30. Hypersensitivity vasculitis • Some authors use this term to include HSP, mixed cryoglobulinemia, allergic vasculitis and serum sickness • Most properly used to refer to vasculitis occurring as a reaction to a known or suspected substance such as a drug. • Major finding is palpable purpura / petechiae – leucocytoclasticvasculitis on biopsy

31. Vasculitis secondary to connective tissue disorder • SLE, RA, relapsing polychondritis, Bechet’s disease • Organ involvement is determined by the underlying disease

32. Vascultitis secondary to viral infections • Hepatitis B, C • HIV, CMV, EBV, Parvo B19 • Clinical presentation can be similar to polyarteritisnodosa or microscopic poylangiitis • Even it is immune complex mediated, it must be distinguished form non-viral associated vasculitides, since the treatment is an anti-viral and not an anti-inflammatory regimen

33. The presence of a vasculitic disorder should be considered in any patient with an unexplained systemic illness • Patients often present with non-specific symptoms • However, there are a few clinical scenarios where a vascultic disorder should be looked for… - palpable purpura - pulmonary infiltrates and microscopic hematuria - chronic inflammatory sinusitus - mononeuritis multiplex - unexplained ischaemic events - glomerulonephritis

35. General Management of small vessel vasculitides • Primary - immunosuppressive therapy: steroids cyclophosphamide - Bactrim - plasma exchange in severe cases • Secondary - treat the underlying cause - antivirals - immunosuppression with connective tissue diseases - stop exposure to possible causative drugs

36. Back to our patient… • Glomerulonephritis with renal failure • cANCA • Asymptomatic “ emphysema” diagnosis, myalgia and arthalgia • No ENT symptoms • No resistant asthma • No eosinophillia • No skin involvement • No drug exposure • Renal biopsy: necrotizing GN few crescents no granulomata or eosinophillic infiltrates

37. Differential includes • Renal limited vascultitis / ANCA glomerulnephritis • Microscopic polyangiitis

38. Management • Started on prednisone 1mg/kg/day cyclophosphamide 2mg/kg/day bactrim ca, titralac, vit D • Follow-up in 10/7 for review

39. Thank you