Relaxin receptor deficiency promotes vascular inflammation and impairs outward remodeling in arteriovenous fistulas

What is it about?

Worldwide 2 million people who suffer from end-stage renal disease (ESRD) are being treated with hemodialysis. To be able to start hemodialysis, a proper functioning vascular access site is required. The placement of an arteriovenous fistula (AVF) is currently regarded as the best available option for vascular access. Yet, several clinical trials have shown that the frequency of AVF failure is approximately 40-60%, making vascular access related complications one of the most common causes of hospitalisation for hemodialysis patients. Despite the magnitude of this problem, there have been no major novel therapeutics in the field of hemodialysis access for the past decades. _x000D_ Relaxin is a hormone that can stimulate the enlargement of blood vessels, a desired effect in the setting of AVF as the blood vessels involved in AVF need to grow to allow safe cannulation. In this research project we looked on the role of relaxin axis as a potential therapeutic target to improve the usability of vascular access for hemodialysis._x000D_ We used a transgenic murine model in which relaxin signalling is disturbed. In these mice, we surgically created AVFs that closely mimic the human AVF setting. We observed that the disruption of relaxin signalling resulted in increased inflammation and accumulation of elastic fibres in AVF, which impaired the enlargement of the blood vessels involved. The results of our study illustrate the functional significance of the relaxin pathway in AVF remodelling. This implies that the relaxin pathway could be a novel target to promote longevity of AVFs for hemodialysis.

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