15th July 2024

Background

Vasculitis is the presence of inflammatory leucocytes in vessel walls, often with fibrinoid necrosis. It occurs as either a primary autoimmune disorder or as a secondary manifestation of an underlying disease process. Systemic vasculitis is characterised by widespread organ involvement and is classified depending on the size of the blood vessel(s) involved. It is usually divided into large, medium and small vessel subtypes. Small vessel vasculitides have a particular propensity for affecting renal vasculature through their ability to cause focal necrotising glomerulonephritis.  This is with or without immune complex deposition (i.e. “immune” vs “pauci-immune”).

ANCA-associated small vessel vasculitides

Granulomatosis with polyangiitis (GPA), previously Wegener’s disease, is an autoimmune inflammatory process affecting the upper respiratory tract (epistaxis, sinusitis, nasal crusting), lungs (dyspnoea, haemoptysis) and kidneys (haematuria).  cANCA is positive in >90%, with the remainder mostly pANCA associated. A negative ANCA does not exclude vasculitis.  Rapidly progressive glomerulonephritis occurs, with urinalysis containing blood, protein and casts. The biopsy will show granulomas and epithelial crescents in Bowman’s capsule. Aggressive immunosuppression is needed to control renal involvement – cyclophosphamide (plus adjuvant steroid) should be offered to promote remission. Rituximab and/or plasma exchange may be required in relapsing or refractory cases.

Churg-Strauss syndrome (eosinophilic granulomatosis with polyangiitis) is often characterised by asthma, peripheral blood eosinophilia of >10%, sinusitis and mononeuritis multiplex. Involvement of the renal system is a feature of the “third-stage”, much rarer than in GPA and is a poor prognostic sign. Rapidly progressive glomerulonephritis is uncommon but may comprise a nephritic syndrome (hypertension, haematuria). 60% of patients are pANCA positive. High dose steroids alone are favoured in management, though additional immunosuppression with cyclophosphamide, azathioprine or IVIG may be required.

Microscopic polyangiitis is a further cause of acute renal-pulmonary syndrome. Lung involvement is rare, though it can be dramatic, in contrast to renal involvement, which can occur at any point in the disease course and is seen in around 80% of patients. Constitutional, gastrointestinal and skin symptoms are also common. Crescentic glomerulonephritis is seen on renal biopsy.  Treatment is similar to other ANCA mediated vasculitis.

Immune complex small vessel vasculitides

Cryoglobulinaemic vasculitis, Henoch-Schonlein purpura (IgA vasculitis) and anti-GBM disease fall under this umbrella.

Medium and large vessel vasculitides

With the exception of polyarteritis nodosa (PAN), medium and large vessel vasculitides do not generally give rise to glomerulonephritis.  Extra-cranial vascular involvement occurs in approximately 15% of patients with giant cell arteritis, but renal involvement is rare, and renovascular hypertension is uncommon.

In Takayasu arteritis (TA), stenosis of the main renal artery and/or its major branches can lead to renovascular hypertension.  This can be difficult to detect if there is co-existing subclavian stenosis, falsely lowering brachial blood pressure measurements.  TA is distinguished from fibromuscular dysplasia by presence of constitutional symptoms and elevated CRP and ESR. Most patients will have normal renal function and non-significant proteinuria/haematuria. Mild diffuse mesangial proliferative glomerulonephritis is very rarely seen in TA.

In contrast, renal involvement is common in polyarteritis nodosa, with more than two thirds of patients developing haematuria, proteinuria, hypertension and progressive renal dysfunction.  Vasculitis of the renal and interlobar arteries can cause micro-aneurysms, infarction and haematoma formation.