Pauci-immune necrotizing glomerulonephritis is the most frequent cause of rapidly progressive glomerulonephritis and, in most cases, is associated with antineutrophil cytoplasmic antibodies (ANCA). It is either the renal manifestation of Wegener’s granulomatosis, microscopic polyangiitis of Churg-Strauss syndrome, or a renal-limited vasculitis. In this review, the histopathologic changes seen in renal biopsies of patients with pauci-immune glomerulonephritis are described. The authors also describe why the disease is sometimes limited to the kidneys, the clinical course of renal disease, treatment issues, how to deal with disease relapses, and how to prevent them from occurring. Furthermore, the necessity of renal biopsy and rebiopsy, the usefulness of rapid ANCA detection at diagnosis, and serial measurement of ANCA during follow-up are discussed. The effect of dialysis on the disease process and the possibility of renal transplantation after disease remission are also debated.
Pauci-immune necrotizing glomerulonephritis is a somewhat confusing term. Pauci originates from the Latin word paucus meaning little or few. It reflects the almost complete absence of immunoglobulin deposits (as assessed by immunofluorescence) when studying renal biopsies of a subgroup of patients with rapidly progressive glomerulonephritis. Historically, pauci-immune glomerulonephritis has been described as a form of glomerulonephritis with no evidence of linear immunoglobulin deposition (type I glomerulonephritis, as in Goodpasture disease) or immune complex deposition (type II glomerulonephritis, as in lupus nephritis). However, paucity of immune deposits does not imply that the immune system is not involved in the disease process; on the contrary, pauci-immune renal disease is believed to be a typical immune-mediated disease and is treated accordingly.
Pauci-immune renal disease can be renal-limited vasculitis (RLV) or the renal manifestations of microscopic polyangiitis (MPA), Wegener’s granulomatosis (WG), or Churg-Strauss syndrome (CSS). These diseases are designated as antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV). The latter 3 conditions are described in different articles in this issue (see the articles by Chung and Seo; Holle and colleagues; Baldini and colleagues elsewhere in this issue for further exploration of this topic). Renal involvement is frequent in AAV; depending on the cohort studied it varies between 71% and 88% for patients with WG and MPA. In CSS, renal involvement is around 25% of cases, with higher percentages for patients with positive ANCA.
In this review the histopathologic changes seen in renal biopsies of patients with pauci-immune glomerulonephritis are described. This article discusses why the disease is sometimes limited to the kidneys, the clinical course of renal involvement, treatment issues, how to deal with disease relapses, and strategies to prevent disease recurrence. Furthermore, the necessity of renal biopsy and repeat biopsy, the usefulness of rapid detection of ANCA for diagnosis, the relevance of serial measurement of ANCA during follow-up, the effect of dialysis on the disease process, and the issue of renal transplantation after disease remission are also discussed.
Renal pathology
The glomerular lesion in patients with systemic and renal-limited ANCA-associated diseases is identical, that is, crescentic glomerulonephritis characterized by necrotizing inflammation and paucity of immune deposits. The most frequently encountered histologic appearance is focal segmental glomerular fibrinoid necrosis with crescent formation and only mild hypercellularity, although neutrophils are modestly present at sites of necrosis ( Figs. 1 and 2 ). Periglomerular granulomatous inflammation, first described by Wegener in 1939, is seen in a small number of patients (see Fig. 1 ). Interstitial disease is present frequently, mostly characterized by a mild to severe interstitial infiltrate ( Figs. 3 and 4 ). The infiltrate consists mostly of mononuclear inflammatory cells and neutrophils to a lesser extent, and in up to 22% of biopsies a small number of eosinophils are also found. In a few cases, interstitial vasculitis can be found.
