Unraveling the role of fibroblast-derived lysyl oxidase in AVF maturation failure

The National Institute of Diabetes and Digestive and Kidney Diseases awarded New Mexico State University $146,070 on September 2, 2026, under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847) to fund basic research into the role of fibroblast-derived lysyl oxidase in arteriovenous fistula maturation failure.

The research will elucidate the molecular and cellular mechanisms by which lysyl oxidase upregulation increases the risk of arteriovenous fistula failure in patients with chronic kidney disease. Up to 40 percent of arteriovenous fistulas currently require endovascular or surgical intervention to address stenosis, which impairs their function for hemodialysis. The award aims to identify novel therapeutic targets to prevent or reduce fistula failure and support the principal investigator's career development toward a tenure-track faculty position in the vascular division of the Department of Surgery at the Miller School of Medicine, University of Miami.

Performance occurs in Miami, Florida, with a period of performance through July 31, 2031. The program supports extramural basic and clinical biomedical research improving understanding of disease mechanisms and leading to improved prevention, diagnosis, and treatment of diabetes, digestive, and kidney diseases.

Abstract

End-stage kidney disease affects over 800,000 americans, with ~60% undergoing hemodialysis (HD). For these patients on HD, vascular access is critical, with three main types available: central venous catheter, arteriovenous graft, and arteriovenous fistula (AVF). Among these, the AVF is the preferred choice due to its superior longevity and lower risk of infection. However, avfs face significant challenges, as up to 40% require endovascular or surgical intervention to address stenosis, which impairs their ability to function for dialysis. These frequent interventions increase the risk of complications and hospitalizations, contributing to the high annual cost of maintaining vascular access, which exceeds $2 billion. Thus, there is an urgent need for novel anti-stenotic treatments to enhance AVF maturation and reduce failure rates. In fact, the successful completion of this study will allow me to uncover the role of fibroblast-specific LOX in the maturation and failure of arteriovenous fistulas (AVF). Specifically, I aim to elucidate the molecular and cellular mechanisms by which LOX upregulation increases the risk of AVF failure. Our preliminary data provides a robust foundation to explore LOX's role in modulating fibroblast phenotypes following AVF creation. I am confident that the outcomes of this K01 grant will help identify novel therapeutic targets to prevent or reduce AVF failure in patients with chronic kidney disease (CKD), potentially accelerating the development of innovative treatments. This award will also be instrumental in advancing my career goal of becoming an independent, well-funded scientist and securing a tenure-track faculty position within the vascular division of the department of surgery at the miller school of medicine, university of miami. My long-term research vision focuses on arterial and venous diseases, with a special emphasis on venous remodeling following surgical interventions such as AVF. Ultimately, my goal is to develop pharmacological and non-pharmacological therapies, including exercise training, to treat arterial and venous disorders and translate these discoveries into clinical practice to improve patient outcomes. By accomplishing the proposed aims and participating in the comprehensive training plan, I will strengthen my expertise in advanced imaging techniques, biostatistics, grant writing, transgenic mouse model management, and genomics. These skills will be critical in my path to scientific independence and will enable me to make significant contributions to the field.