The glomerular crescent: triggers, evolution, resolution, and implications for therapy - PubMed (original) (raw)

Review

The glomerular crescent: triggers, evolution, resolution, and implications for therapy

Lidia Anguiano et al. Curr Opin Nephrol Hypertens. 2020 May.

Abstract

Purpose of review: Crescents are classical histopathological lesions found in severe forms of rapidly progressive glomerulonephritis, also referred to as crescentic glomerulonephritis (CGN). Crescent formation is a consequence of diverse upstream pathomechanisms and unraveling these mechanisms is of great interest for improving the management of patients affected by CGN. Thus, in this review, we provide an update on the latest insight into the understanding on how crescents develop and how they resolve.

Recent findings: Cellular crescents develop from activated parietal epithelial cells (PECs) residing along Bowman's capsule and their formation has as a consequence the decline in glomerular filtration rate (GFR). Cellular crescents can be reversible, but when multilevel growth of PECs associate with an epithelial--mesenchymal transition-like change in cell phenotype, fibrous crescents form, and crescents become irreversible also in terms of GFR recovery. Different molecular pathways trigger the activation of PECs and are a prime therapeutics target in CGN. First, crescent formation requires also vascular injury causing ruptures in the glomerular basement membrane that trigger plasmatic coagulation within Bowman's space. This vascular necrosis can be triggered by different upstream mechanisms, such as small vessel vasculitides, immune complex glomerulonephritis, anti-GBM disease, and C3 glomerulonephritis, that all share complement activation but involve diverse upstream immune mechanisms outside the kidney accessible for therapeutic intervention.

Summary: Knowing the upstream mechanisms that triggered crescent formation provides a tool for the development of therapeutic interventions for CGN.

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Figures

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FIGURE 1

FIGURE 1

Evolution of crescent formation. The crescent is an unspecific histopathological lesion that can be triggered by a variety of different underlying disorders. This figure illustrates four of those and highlights first the extrarenal pathomechanisms leading to glomerular injury. The different patterns of immunoglobulin and complement deposits help to dissect these entities. Indeed, all of the aforementioned extrarenal drivers of injury to the glomerular microvasculature involve local complement activation as a shared molecular target for therapeutic interventions. Whenever, microvascular injury leads to rupture of the glomerular basement membrane (GBM), the leakage of plasma proteins drives parietal epithelial cell hyperplasia as the key cellular component of the crescent. Single nephron GFR decreases because of tuft collapse, rupture of the Bowman capsule, and influx of immune cells and fibroblasts are all secondary events that may or may not occur in individual glomeruli. Periglomerular immune cell infiltrates or fibrotic encasting of the activated parietal cells (fibrocellular crescents) are subsequent events that may affect the dynamics and prognosis of the disease. ANCA, antineutrophil cytoplasmic antibody; GFR = glomerular filtration rate; Ig, immunoglobulin; MPO, myeloperoxidase; PR3, proteinase 3.

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