Abstract
Chronic kidney disease (CKD) is a health problem reaching epidemic proportions. There is no cure for CKD, and patients may progress to end-stage renal disease (ESRD). Peritoneal dialysis (PD) is a current replacement therapy option for ESRD patients until renal transplantation can be achieved. One important problem in long-term PD patients is peritoneal membrane failure. The mechanisms involved in peritoneal damage include activation of the inflammatory and immune responses, associated with submesothelial immune infiltrates, angiogenesis, loss of the mesothelial layer due to cell death and mesothelial to mesenchymal transition, and collagen accumulation in the submesothelial compact zone. These processes lead to fibrosis and loss of peritoneal membrane function. Peritoneal inflammation and membrane failure are strongly associated with additional problems in PD patients, mainly with a very high risk of cardiovascular disease. Among the inflammatory mediators involved in peritoneal damage, cytokine IL-17A has recently been proposed as a potential therapeutic target for chronic inflammatory diseases, including CKD. Although IL-17A is the hallmark cytokine of Th17 immune cells, many other cells can also produce or secrete IL-17A. In the peritoneum of PD patients, IL-17A-secreting cells comprise Th17 cells, γδ T cells, mast cells, and neutrophils. Experimental studies demonstrated that IL-17A blockade ameliorated peritoneal damage caused by exposure to PD fluids. This article provides a comprehensive review of recent advances on the role of IL-17A in peritoneal membrane injury during PD and other PD-associated complications.
Highlights
Chronic kidney disease (CKD) is a devastating disease that affects 5–7% of the worldwide population
In the peritoneal dialysate effluent (PDE) of end-stage renal disease (ESRD) patients exposed to different conventional peritoneal dialysis fluids (PDF), elevated proinflammatory cytokine levels, together with interleukin (IL)-17A, IL-6, IL-1β, Tumor necrosis factor-α (TNF-α), and TNF-like weak inducer of apoptosis (TWEAK), have been found [3,12,13,14,15,16,17], clearly showing the involvement of inflammation in peritoneal damage induced by PDF exposure
Further studies are needed to explore the mechanisms by which IL-17A promotes vascular endothelial growth factor (VEGF) expression, in peritoneum exposed to PDF as well as its contribution to angiogenesis in this context (Figure 2)
Summary
Chronic kidney disease (CKD) is a devastating disease that affects 5–7% of the worldwide population. These include increased peritoneal production of proinflammatory cytokines and advanced glycation end-products (AGEs) that induce cell death, proangiogenic factors such as vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1), and other profibrotic factors [8,9]. In the peritoneal dialysate effluent (PDE) of ESRD patients exposed to different conventional PDF, elevated proinflammatory cytokine levels, together with interleukin (IL)-17A, IL-6, IL-1β, Tumor necrosis factor-α (TNF-α), and TNF-like weak inducer of apoptosis (TWEAK), have been found [3,12,13,14,15,16,17], clearly showing the involvement of inflammation in peritoneal damage induced by PDF exposure Among these inflammatory mediators, cytokine IL-17A has recently been proposed as a potential therapeutic target for chronic inflammatory diseases [18,19]. We discuss the current data about IL-17A in ESRD patients on PD and in related preclinical studies, addressing the cellular responses and molecular mechanisms triggered by IL-17A and its potential contribution to peritoneal membrane pathophysiology (Figure 1)
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