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The kidney in systemic vasculitis 

The kidney in systemic vasculitis

The kidney in systemic vasculitis

David Jayne


May 30, 2013: This chapter has been re-evaluated and remains up-to-date. No changes have been necessary.


Treatment: (1) Rituximab—discussion of recent clinical trials showing that this chimeric anti-CD20 monoclonal antibody is an effective alternative to cyclophosphamide for remission induction and preferable to further cyclophosphamide for relapsing or refractory disease. (2) Mycophenolate mofetil—evidence that this is less effective than azathioprine for relapse prevention. (3) Other new agents—deoxyspergualin shown to induce remission in refractory Wegener’s granulomatosis in two uncontrolled trials.

Updated on 25 May 2011. The previous version of this content can be found here.
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date: 28 April 2017

Systemic vasculitis can occur as a primary autoimmune disorder, or as a secondary manifestation of another disease process (e.g. related to infection, malignancy, chronic inflammatory disorder, or drugs). Primary systemic vasculitis is classified according to the predominant size of blood vessel involved and the presence of circulating antineutrophil cytoplasmic autoantibodies (ANCA). Incidence and prevalence rates are between 15 and 20 per million and 200 to 400 per million population, respectively. Vasculitic syndromes frequently involve the kidney, causing tissue infarction, loss of function and rapid progression to end stage renal disease within weeks or months.

Small-vessel vasculitides—Wegener’s granulomatosis (see Chapter 18.11.5), microscopic polyangiitis, and renal-limited vasculitis affect small vessels and are grouped together as the ANCA-associated vasculitides (AAV). Henoch–Schönlein purpura (see Chapter 21.8.1) and cryoglobulinaemia (see Chapter 21.10.4) also affect small vessels, but are ANCA negative.

Medium and larger vessel vasculitides—Churg–Strauss angiitis (30–50% are ANCA positive, see Chapter 18.11.5) and polyarteritis nodosa (ANCA negative) affect medium-sized vessels, as does Kawasaki’s disease (see Chapter 19.11.8). Giant cell arteritis (see Chapter 19.11.4) and Takayasu’s arteritis (see Chapter 16.14.4) affect larger vessels.

Aetiology and pathogenesis—the cause of primary systemic vasculitis is (by definition) unknown. The pathogenetic role of ANCA remains controversial because this pathology can occur without circulating ANCA, immune deposits are rarely present, and ANCA often persist without disease activity.

Pathology—the typical renal lesion of small vessel vasculitis is a glomerular capillaritis leading to segmental necrotizing glomerulonephritis with epithelioid crescent formation. Glomerular immune deposits are scanty or absent in AAV (‘pauci-immune’).

Clinical presentation—the diagnosis of vasculitis is often delayed for many months because initial symptoms such as fever, night sweats, polymyalgia, and weight loss are nonspecific. Patients with vasculitis present with: (1) persistent symptoms of constitutional disturbance; (2) nonrenal vasculitic manifestations, the nature of which may indicate a specific diagnosis, e.g. upper respiratory tract symptoms or signs (Wegener’s granulomatosis), ‘maturity-onset’ asthma (Churg–Strauss angiitis), or mononeuritis multiplex (polyarteritis nodosa); or (3) uraemia. AAV is the most common cause of rapidly progressive glomerulonephritis—crescentic glomerulonephritis with renal failure—and should be considered in any unexplained case of acute renal impairment, especially when associated with microscopic haematuria and proteinuria and the kidneys are of normal size on ultrasound examination. Patients with renal-limited vasculitis present with more advanced renal failure than those with extrarenal disease because they are asymptomatic until uraemia develops.

Diagnosis—this depends on the triad of clinical features, serology, and histology, and the exclusion of secondary causes. ANCA positivity, confirmed by a positive proteinase 3 ANCA (PR3-ANCA) or myeloperoxidase ANCA (MPO-ANCA), has a predictive value of over 95% for the diagnosis of AAV with renal involvement in a patient with suspected nephritis. The diagnosis of polyarteritis nodosa is usually made by demonstration of aneurysms of medium-sized muscular arteries on angiography, or when biopsy of affected tissue reveals fibrinoid necrosis of involved vessels, accompanied by a marked inflammatory response. Other investigations determine the extent and severity of systemic disease.

Management—combination therapy with cyclophosphamide and high-dose oral prednisolone leads to control of active disease in 90% of patients, but is complicated by toxicity, in particular, cytopenias and severe infection. Azathioprine or methotrexate in combination with low-dose prednisolone are used to maintain remission after 3 to 6 months in order to avoid the malignancy and other late toxicities associated with cyclophosphamide, and they may also be considered for the induction of remission in mild presentations without renal impairment. High-dose intravenous methylprednisolone is widely used for initial therapy for renal vasculitis, and plasma exchange improves the chances of renal recovery in patients with severe renal impairment. Careful follow-up of patients in experienced centres with regular monitoring of blood counts, biochemical indices, inflammatory markers (erythrocyte sedimentation rate and C-reactive protein), and ANCA permits the prevention and early detection of drug-related toxicity and infection, and the early diagnosis and treatment of disease relapse. Collaborative research networks have facilitated a sequence of randomized controlled trials and the development of evidence based treatment guidelines.

Disease relapse—this is seen in 50% of patients by 5 years and is more common in Wegener’s granulomatosis, in the presence of persisting ANCA positivity, and after withdrawal of immunosuppressive drugs. Agents used for relapsing or refractory disease include mycophenolate mofetil and leflunomide, high-dose intravenous immunoglobulin, and B-cell depletion with rituximab. Rituximab is an effective alternative to cyclophosphamide for remission induction and preferable to further cyclophosphamide for relapsing or refractory disease.

Prognosis—patient survival in AAV with renal involvement is 83% and 73% at 1 and 5 years, respectively, with a high serum creatinine at diagnosis, older age, and extensive extrarenal vasculitis indicating a poorer prognosis. Fifty per cent of those presenting with a serum creatinine greater than 500 μ‎mol/litre will be alive and off dialysis at 1 year of follow-up.

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