1. Figure 1 Currently recognized factors that influence the development of scleroderma renal crisis
Figure 1 | Currently recognized factors that influence the development of scleroderma renal crisis. A combination of genetic (endothelin receptor (ER) polymorphisms), autoimmune (anti-RNA polymerase III antibodies (anti-RNAP III), immune cell activation and macrophage infiltration), external (glucocorticoid (GC) therapy) and/or cellular factors (altered cell proliferation, fibrosis, vascular damage and endothelial cell activation) can trigger scleroderma renal crisis (SRC), a rare renal complication of systemic sclerosis. Rapid treatment with angiotensin-converting-enzyme inhibitors can limit the progression of SRC to renal failure, indicating an involvement of the renin–angiotensin system in the pathogenesis of SRC. Elevated levels of circulating endothelin-1 and high expression of its receptors in SRC renal biopsy samples suggest that endothelin-1 is a key driver of SRC-associated renal failure. Despite a dose-dependent increased likelihood of SRC in patients treated with GCs, potentially owing to the effect of these agents on the inflammatory features of SSc, such as synovitis, arthralgias and tendon friction rubs, their role is unclear. CTGF, connective tissue growth factor; PDGF, platelet-derived growth factor; TGF-β, transforming growth factor-β; TH2, type 2 T helper cell TH17, type 17 T helper cell; VEGF, vascular endothelial growth factor. Microphotography reproduced with permission from Hindawi Publishing Corporation © Batal, I. et al. Int. J. Rheumatol. 2010, (2010).
Microphotography reproduced with permission from Hindawi Publishing
Corporation © Batal, I. et al. Int. J. Rheumatol. 2010, (2010).
Woodworth, T. G. et al. (2016) Scleroderma renal crisis and renal involvement in systemic sclerosis
Nat. Rev. Nephrol. doi: /nrneph