Kidney disease in eosinophilic granulomatosis with polyangiitis: expect the unexpected

This editorial refers to ‘Renal involvement in eosinophilic granulomatosis with polyangiitis (EGPA): a multicentric retrospective study of 63 biopsy-proven cases’, by Cécile-Audrey Durel et al., on pages 359--365. Kidney involvement in ANCA-associated vasculitis has a significant impact on morbidity and mortality. While kidney involvement is present in a majority of patients with granulomatosis with polyangiitis and microscopic polyangiitis, the kidneys are likewise affected in around 30% of patients with eosinophilic granulomatosis with polyangiitis (EGPA) [1]. The incidence of EGPA ranges between 1 or 2 cases per million (0.5–4 among selected studies); however, there remains a dearth of studies focused on the kidney. Such paucity can be explained by the low incidence of EGPA and that patients are not treated by nephrologists in most centres. In this issue of Rheumatology, Durel et al. retrospectively collected data on patients (N = 63) with EGPA and kidney disease. In most cases (85.7%), kidney disease was confirmed concomitantly with an initial diagnosis of EGPA, thus revealing (1) an expected histopathological pattern with pauci-immune crescentic necrotizing glomerulonephritis (i.e. no or few immune deposits by immunofluorescence) and/or interstitial nephritis, and (2) an association with ANCA positivity. The remaining nine patients underwent biopsy after a median time of 8 years following initial diagnosis; among these, a proportion of unexpected histopathologic reports in cases with ‘late-onset kidney disease’, including findings consistent with membranous nephropathy and membranoproliferative glomerulonephritis (information concerning extra-renal disease activity was not present). Specifically, one out of five patients with membranous nephropathy showed positive glomerular phospholipase A2 receptor deposition [2], hence indicative of a primary form of membranous nephropathy. This finding points towards a shared genetic susceptibility between both autoimmune disorders, as HLA alleles are implicated in several autoimmune diseases (e.g. membranous nephropathy and EGPA) [3, 4]. It is important to note extant work has indicated an overlap syndrome between ANCA-associated vasculitis and IgG4-related disease [5, 6]. Moreover, membranous nephropathy and interstitial nephritis are the leading histopathologic features of kidney involvement in IgG4-related disease. Although the current study did not perform IgG4 staining of kidney biopsies and measurement of serum IgG4 levels, further research with a particular focus on concomitant occurrence of EGPA and membranous nephropathy is warranted.