NEPHROLOGY PRESENTATION

28/3/2011

HISTORY

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

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

HOWEVER, ONE MONTH LATER, HIS SYMPTOMS HAD NOT IMPROVED

Occupation: administrative work, some occasional welding

No previous history of note, i.e. hypertension, DMNo nephrotoxic drugs

CLINICAL EXAMINATION

Vitals: BP 105/70, pulse 80/minGen: pale with no edemaCVS: loud P2Resp: hyperinflated with good bilateral air entryAbdo: normalCNS: normalENT: reddish uvula, no ulcersSkin: no evidence of vasculitis / connective tissue disease

SPECIAL INVESTIGATIONS

Urine dipstix: 3+ hematuria, 2+ proteinuriaMicroscopy: active sedimentMCS: no evidence of infection24 hour collection: dU protein 0.5g

URINE

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

BLOOD INVESTIGATIONS

Renal ultrasound showed normal sized kidneysCXR: hyperinflation, but clearShoulder x-ray: evidence of OA

RADIOLOGY

Segmental necrotizing vaculitisFew crescentsNo granuloma formationNo eosinophillic infiltratesNo immune complexes

HISTOLOGY

SMALL CELL VASCULITIS AND

THE KIDNEY

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.

Vasculitis

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

ANCA (+)

Wegener’s granulomatosis

Microscopic poliangiitisRenal limited vasculitis

/ ANCA GNChurg Strauss

syndromeDrug induced

ANCA (-)

Henloch Shönlein purpura

CryglobulinemicConnective tissue

disordersGoodpasture’s diseaseInfection inducedHypersensitivityParaneoplastic

SMALL VESSEL VASCULITIS

ANCA (+)

5-10 / 1 000 000Granulomatous 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 CXRMostly cANCA(proteinase 3)

WEGENER’S GRANULOMATOSIS

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

MICROSCOPIC POLIANGIITIS

Part of the spectrum including Wegener’s and microscopic poly-angiitis

No systemic involvement

Histology: necrotizing GN

RENAL LIMITED VASCULITIS

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

THE SPECTRUM

Also known as allergic granulomatosis and angiitis1-3 / 1 000 000Histology similar to WG, but with eosinophillic infiltrates of

the vessel wallsProdromal period for years with allergic rhinitis, nasal

polyposis and late-onset asthmaTriad of skin lesions, asymmetric mononeuritis multiplex and

eosinophillia on a background of resistant asthmaNecrotizing GN Mesenteric vascultitiscANCA or pANCA

CHURG STRAUSS SYNDROME

ANCA (-)

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

HENLOCH SHÖNLEIN PURPURA

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

ESSENTIAL CRYGLOBULINEMIC 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 – leucocytoclastic vasculitis on biopsy

HYPERSENSITIVITY VASCULITIS

SLE, RA, relapsing polychondritis, Bechet’s diseaseOrgan involvement is determined by the underlying disease

VASCULITIS SECONDARY TO CONNECTIVE TISSUE DISORDER

Hepatitis B, CHIV, CMV, EBV, Parvo B19

Clinical presentation can be similar to polyarteritis nodosa 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

VASCULTITIS SECONDARY TO VIRAL INFECTIONS

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

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

GENERAL MANAGEMENT OF SMALL VESSEL VASCULITIDES

Glomerulonephritis with renal failurecANCAAsymptomatic “ emphysema” diagnosis, myalgia and arthalgia

No ENT symptomsNo resistant asthmaNo eosinophilliaNo skin involvementNo drug exposure

Renal biopsy: necrotizing GN few crescents no granulomata or eosinophillic infiltrates

BACK TO OUR PATIENT…

Renal limited vascultitis / ANCA glomerulnephritisMicroscopic polyangiitis

DIFFERENTIAL INCLUDES

Started on prednisone 1mg/kg/day cyclophosphamide 2mg/kg/day bactrim ca, titralac, vit D

Follow-up in 10/7 for review

MANAGEMENT

THANK YOU