From Genes to Membrane Failure: Genetic Determinants of Peritoneal Dialysis Physiology and Outcomes

Peritoneal dialysis (PD) has long been an established modality of renal replacement therapy for patients with end-stage kidney disease (ESKD). Despite the modality’s advantages, significant inter-individual variability exists in peritoneal membrane transport characteristics, ultrafiltration capacity, and long-term technique survival. While PD therapy-related factors, such as dialysis solution composition, peritonitis episodes, and duration of therapy, contribute to these outcomes, genetic factors also play important roles in peritoneal membrane biology. Genetic studies have identified polymorphisms in genes involved in angiogenesis, inflammation, fibrosis, and endothelial function that influence PD outcomes. Variants in genes such as vascular endothelial growth factor, interleukin-6, transforming growth factor-β1, angiotensin-converting enzyme, endothelial nitric oxide synthase, and aquaporin-1 have all been reported to be associated with differences in peritoneal transport and susceptibility to membrane failure. These genetic discoveries provide significant insights into the pathways that lead to alterations in the PD membrane structure and function. This review article aims to explore current evidence on key genetic determinants of peritoneal membrane transport, inflammatory responses, and fibrotic transformation in PD, and to discuss their potential implications for personalised dialysis therapy and future research.