Research Opportunities in Interventional Nephrology

Interventional nephrology is in the midst of an exponential growth phase, with data from the U.S. Renal Data System suggesting that at least 25 percent of total vascular access procedure costs are billed by nephrologists (1). Indeed, it is likely that the growth of interventional nephrology as a distinct discipline within nephrology has played an important role in the success of process-of-care initiatives, such as Fistula First, which has raised the arteriovenous fistula (AVF) prevalence rate from 34 percent in December 2003 at the start of this initiative to 59.5 percent as of August 2011 (2). Despite these positive indicators, however, dialysis vascular access dysfunction remains a huge clinical problem. Specifically, almost 80 percent of incident hemodialysis patients start with a tunneled dialysis catheter (TDC) (3), only 40 percent of AVFs are suitable for hemodialysis between 4 and 5 months after surgery (4), and the 1-year primary patency for polytetrafluoroethylene (PTFE) dialysis access grafts is only 23 percent (5). Clearly, we need to do better!

Although there are multiple biological and process-of-care reasons for these problems (610), we believe that an important underlying cause of these clinical problems is a relative lack of focused basic science, translational, clinical, and process-of-care (outcome) research in the field of dialysis vascular access.

In addition, the induction of formal, high-quality research initiatives into interventional nephrology programs in particular could potentially transform the standing of this distinct discipline within nephrology within both nephrology and internal medicine. Thus, research programs in this area could go a long way toward enhancing the standing of interventional nephrology in the eyes of nephrology program and division directors, and they could constitute an important step toward making interventional nephrology a true distinct discipline within nephrology akin to transplant nephrology. Such research programs could also help bring interventional nephrology into academic institutions. This is absolutely essential for the future of interventional nephrology. Sustained long-term growth of this distinct discipline will likely occur only if it has a solid base within academia while at the same time maintaining its close links with the community physician base that has allowed this specialty to grow so rapidly.

The first publication that attempted to identify core areas of research in vascular access was the 2006 Kidney Disease Outcomes Quality Initiative on vascular access (11), which identified several areas for possible research investigation, including patient preparation, selection and placement of hemodialysis access, cannulation of fistulae and grafts, detection of access dysfunction, treatment of fistula and graft complications, and prevention of catheter complications.

More recently, a survey sent out to the membership of the American Society of Diagnostic and Interventional Nephrology identified (a) arteriovenous fistula maturation, (b) process-of-care guidelines for the creation and maintenance of dialysis vascular access, and (c) PTFE graft stenosis as the three most pressing areas for research into dialysis vascular access, in the order described.

In addition, the ASN’s Interventional Nephrology Advisory Group of the American Society of Nephrology (INAG) in combination with the council of the American Society of Diagnostic and Interventional Nephrology recently submitted several areas for research investigation to the Kidney Research National Dialogue sponsored through the National Institute of Diabetes, Digestive and Kidney Diseases. In addition to the areas described previously, improvement in long-term dialysis outcomes, optimization of endovascular and surgical procedures, and the use of TDC coatings were highlighted as key areas for research activities in this field.

Clearly, there are many potential areas for research in this field and also at least some consensus on a priority ranking for investigative efforts. What is needed, however, is a mechanism to enable the research to be done successfully.

Although there are many approaches to investigative research in dialysis vascular access, the key issue in many ways is the establishment of a system or a process that encourages long-term research activity in this field. One approach, which has been espoused by INAG as a way to lay a firm foundation for a long-term commitment to research activity in this field, is to support the establishment of several academic dialysis access centers (ADACs). These centers will (a) establish basic or translational research programs focused on dialysis vascular access, (b) develop clinical research programs (both investigator initiated and industry sponsored), and (c) establish dedicated (1-year) interventional nephrology training programs where nephrology fellows will be trained not just to do procedures but also in the biology, epidemiology, and process of care of dialysis vascular access.

We believe that the establishment of such ADACs will not only increase the opportunities for well-funded high-quality research in this area but also play a key role in allowing interventional nephrology to grow, by establishing a place for this distinct discipline within nephrology within academic institutions. Finally, although these ADACs are likely to have a home within divisions of nephrology, it is critical that they retain a multidisciplinary nature, because dialysis vascular access dysfunction is by definition a multidisciplinary problem, which we believe can be solved only through a multidisciplinary and translational research effort.

In summary, we believe that this is the time to aggressively develop a formal structure for focused research into dialysis vascular access. We know the problems, and we are asking the questions that need to be asked. In addition, we are lucky that the past decade has seen phenomenal advances in bioengineering, drug delivery, nanotechnology, and cellular therapies, all of which could have a positive impact on dialysis vascular access. We need to apply these biological and technological advances (combined with outcomes and process-of-care research) to the clinical problem of dialysis vascular access so that we can improve on the care we provide our patients. The development of high-quality research programs focused on dialysis vascular access is essential for this to be achieved.

Notes

[1] Prabir Roy-Chaudhury, MD, PhD, is a professor of medicine in the division of nephrology and hypertension, University of Cincinnati, and Cincinnati VA Medical Center. He is a member of the ASN Interventional Nephrology Advisory Group.

References

1.U.S. Renal Data System.USRDS 2009 Annual Data Report: Atlas of End-Stage Renal Disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 2009.

2.Fistula First. 2011. http://www.fistulafirst.org.

3.U.S. Renal Data System. USRDS 2008 Annual Data Report: Atlas of End Stage Renal Disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 2008.

4.Dember LM, et al. Effect of clopidogrel on early failure of arteriovenous fistulas for hemodialysis: a randomized controlled trial. JAMA 2008; 299:2164–2171.

5.Dixon BS, et al. Effect of dipyridamole plus aspirin on hemodialysis graft patency. N Engl J Med 2009; 360:2191–2201.

6.Lee T, Roy-Chaudhury P. Advances and new frontiers in the pathophysiology of venous neointimal hyperplasia and dialysis access stenosis. Adv Chronic Kidney Dis 2009; 16:329–338.

7.Roy-Chaudhury P, Lee TC. Vascular stenosis: biology and interventions. Curr Opin Nephrol Hypertens 2007; 16:516–522.

8.Asif A, et al. Vascular mapping techniques: advantages and disadvantages. J Nephrol 2007; 20:299–303.

9.Roy-Chaudhury P, et al. Vascular access in hemodialysis: issues, management, and emerging concepts. Cardiol Clin 2005; 23:249–273.

10.Vargas PA, et al. Barriers to timely arteriovenous fistula creation: a study of providers and patients. Am J Kidney Dis 2011; 57:873–882.

11.Disease Outcomes Quality Initiative. Vascular access guidelines. Am J Kidney Dis 2006; 48:S177–S247.


February 2012 (Vol. 4, Number 2)