Course of paediatric ANCA-associated glomerulonephritis: advocating for an age-inclusive approach

Abstract

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of diseases characterised by systemic involvement of small-to-medium vessels with necrotising inflammation that, by virtue, can affect all organs. Even though the underlying pathophysiology is still not fully understood, a central role is devoted to autoantibodies against two major neutrophil proteins, either proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA), in granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). These autoantibodies are able to prime and activate neutrophils that, together with other inflammatory cells such as macrophages, monocytes and the complement system, lead to the observed endothelial injury. Both diseases, GPA and MPA, have a predilection for pulmonary and kidney involvement, with 58.6% and 82.2%1 of adults with AAV presenting with ANCA-glomerulonephritis (GN). The incidence of PR3-ANCA is highest in countries with higher latitudes, and PR3-ANCA vasculitis rarely occurs in Japan and China.2 A significant proportion of patients with ANCA-GN remain negative for ANCA but show signs of kidney disease, which is characterised by the absence or only a faint staining for immunoglobulins or complement. In children, the disease is ultra-rare, meaning precise estimates related to epidemiology are missing; however, the underlying disease pathophysiology is believed to be sufficiently similar to that of adults, with subtle differences reported in the frequency of organ involvement. For example, ANCA-GN in GPA seems to be more common in children than in adults, while a comparable frequency is reported in MPA (figure 1). The largest cohort studies reported from Northern America (40 centres), Europe (three centres) and Asia (two centres) revealed that GPA is almost four times as common as MPA.3 In children enrolled on the A Registry for Children with Vasculitis (ARChiVE) registry from 2004 to 2015, initial treatment among 231 children consisted of corticosteroids (96.5%), cyclophosphamide (75.8%), rituximab (12.1%) and plasma exchange …