Introduction

Introduction

section 21  Disorders of the kidney and urinary tract 4988 21.10.2  The kidney in systemic vasculitis David Jayne ESSENTIALS Systemic vasculitis can occur as a primary autoimmune disorder, or as a secondary manifestation of another disease process (related to infection, malignancy, chronic inflammatory disorder, or drugs). Primary systemic vasculitis is classified according to the predominant size of the blood vessel involved and the presence of circulating antineutrophil cytoplasm 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 endstage renal disease within weeks or months. They account for 5% of cases of endstage renal failure. ANCA-​associated vasculitis (AAV) is the most common cause of renal vasculitis and has been the focus for most research. Management aims for an early diagnosis, recovery of renal function, and prevention of renal relapse. Small-​vessel vasculitides—​renal disease is common. There are two subgroups: AAV, which comprises three syndromes: granulomatosis with polyangiitis (GPA, formerly Wegener’s granulomatosis), micro- scopic polyangiitis (MPA), and eosinophilic granulomatosis with angiitis (EGPA, formerly Churg–​Strauss syndrome). The second sub- group is immune complex vasculitis and comprises IgA vasculitis (formerly Henoch–​Schönlein purpura), antiglomerular basement membrane disease, and cryoglobulinaemia: these are ANCA nega- tive and characterized by immune complex deposition. Medium-​ and larger-​vessel vasculitides—​renal disease is uncommon in the medium-​vessel disorders polyarteritis nodosa (ANCA nega- tive) and Kawasaki’s disease, and rare in the large-​vessel disorders, giant cell arteritis and Takayasu’s arteritis. Aetiology and pathogenesis—​there is a complex genetic contribution to AAV, and rare drug-​induced forms. Neutrophil dysregulation is as- sociated with ANCA and alternative complement pathway activation. Pathology—​the typical renal lesion of small-​vessel vasculitis is a neutrophil-​dominant glomerular capillaritis leading to segmental necrotizing glomerulonephritis with epithelioid crescent forma- tion. 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 indi- cate a specific diagnosis, for example, upper respiratory tract symp- toms or signs (GPA), ‘maturity-​onset’ asthma (EGPA), or mononeuritis multiplex (MPA); or (3)  features of renal insufficiency. 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, es- pecially when nonvisible haematuria with proteinuria is present 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 symptoms of renal insufficiency develop. Diagnosis—​this depends on the recognition of patterns of clinical features, supported by serology, histology, and imaging, and the ex- clusion 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 in- vestigations determine the extent and severity of systemic disease. Management—​combination therapy with cyclophosphamide or rituximab and high-​dose oral prednisolone leads to control of ac- tive disease in 80 to 90% of patients, but is complicated by toxicity, particularly cytopenias and infection. Azathioprine, methotrexate, or mycophenolate mofetil in combination with low-​dose prednisolone or rituximab are used to maintain remission after 3 to 6 months, and mycophenolate mofetil may also be considered for the induction of remission in MPO-​ANCA-​associated renal disease. High-​dose intravenous methylprednisolone is widely used as 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 moni- toring 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 re- lapse. Collaborative research networks have facilitated 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 PR3-​ANCA-​positive patients, in the presence of persisting ANCA positivity, and after withdrawal of immunosuppressive drugs. Rituximab is the first choice for relapsing or refractory disease: patients then require long-​term therapy as subsequent relapses are likely. 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. Introduction Renal involvement is common in primary systemic vasculitis af- fecting small blood vessels and is subdivided into those asso- ciated with antineutrophil cytoplasm autoantibodies (ANCA) (Table 21.10.2.1) (ANCA-​associated vasculitis (AAV): comprising granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA)) and those without ANCA but with immune complex deposition on