Sean Bagshaw's passion for both nephrology and critical care medicine led him to innovate in both fields with his project STARRT-AKI. (Photo: Laughing Dog Photography).
Is 'the sooner' really 'the better'? When it comes to treating acute kidney injury (AKI) in patients that are in the Intensive Care Unit, the right timing could save a life. In order to make a difference in the survival and quality of life of patients, Sean Bagshaw, recently renewed Canada Research Chair in Critical Care Nephrology, spearheads the STARRT-AKI study, which examines the effects of optimal time to start renal replacement therapy--also known as dialysis. Ron Wald, nephrologist at St. Michael's hospital in Toronto, is working closely with him.
"Over the last eight years we have been working on a program of research with the fundamental question 'When should we ideally start renal replacement therapy in critically ill patients with AKI?' Sounds like a simple question, but it's proven to be quite challenging to understand the nuances of how to best answer it," says Bagshaw.
In order to find that answer, Bagshaw's team has systematically reviewed the literature, surveyed expert opinions from nephrologists and intensivists from across Canada, and has conducted a series of preliminary studies in preparation for a large worldwide study of dialysis timing in critically ill patients with AKI.
Understanding acute kidney injury
Kidney failure may be the cause of severe health problems, but also an unfortunate side effect of being critically ill. The appearance of AKI responds to different factors that range from the patient's age to blood pressure, effects of toxins and surgery. "It can happen in the hospital as a consequence of the course of therapy they're receiving, the types of interventions they receive, or just the fact that patients come into hospitals being already very ill, and deteriorate while they're here," explains Bagshaw.
Studies identify sepsis as one of the main causes of kidney failure in the ICU. "More than 50 per cent of the patients we see here developing AKI have sepsis," says Bagshaw. Procedures like major surgery can contribute to it. In cardiac surgery, for example, patients get exposed to cardiopulmonary bypass (a heart-lung machine with which blood leaves the body and passes through a pump and an oxygenator before coming back into the patient). This process can take a toll on the kidneys, contributing to injury and loss of function after the surgery.
Although acute kidney injury may be caused by more than one factor, timely and effective treatment is key. Physicians initiate dialysis to support the kidneys and other organs that may be impacted by loss of kidney function, and therapy is more intensive when the patient is critically ill.
"Our kidneys normally work around the clock. When patients with chronic kidney failure receive dialysis therapy three times per week, they are getting supportive care but it's not like the real kidney function. In the ICU, we commonly use continuous renal replacement therapy machines that work almost 24 hours a day, seven days a week and coupled with other specialized technologies for patients whose kidneys have failed."
With STARRT-AKI, Bagshaw and his team are coordinating the trial in Canada, United States, Europe, Australia, New Zealand and China to determine if a strategy of early start to dialysis therapy in critically ill patients contributes to improved survival and recovery of kidney function.
Leading critical kidney care beyond borders
Bagshaw's expanding efforts have earned him the prestigious International Vicenza Award for Critical Care Nephrology this year, presented by the International Renal Research Institute of Vicenza to those who make significant contributions to this field of health care at a global scale.
Bagshaw started his work with the U of A in 2007. Always involved in critical care medicine, he developed an interest in acute kidney injury and associated therapies during his training in internal medicine. "It fascinated me to the point where, while I was in my training, I was uncertain of whether to pursue a career in critical care or nephrology," he remembers. "I was very much interested in both, and I tried to find a way to merge the two in what I thought would be a rewarding clinical career and maybe have an opportunity to make an academic contribution." After his training, he completed a postdoctoral fellowship for almost two years with Professor Rinaldo Bellomo, one of the most prominent academic leaders in critical care medicine, at the Austin Hospital in Melbourne, Australia.
The research team for STARRT-AKI has enrolled over 40 sites already to participate in their trial and are aiming for 100 sites from across the world including Canada, United Kingdom, Ireland, Australia, New Zealand, China, Belgium, Austria, Finland, Germany, France, Switzerland and Brazil, just to name a few.
Bagshaw's project has received generous funding from partners like the University Hospital Foundation from the beginning of his research, and several grants from Canadian Institutes of Health Research (CIHR), including an industry-partnered operating grant with CIHR and Baxter Healthcare Corporation.
Outside the Canadian borders, Bagshaw faces the challenges of running a large multi-national, multi-centre randomized control trial and helping secure funding from international organizations. "It's a large number of countries, centres and investigators, like running a small corporation. But it is very exciting at the same time," he adds.
The trial is expected to be completed in 2019. With so many participants focusing on one goal, Bagshaw will try to obtain a definitive answer to his research question and identify best practices, even if the result is not conclusive to benefit one specific approach to therapy.
"If we find earlier renal replacement therapy improves survival, it will be an easy recommendation for physicians. If we show there is no improvement of survival then it will have implications for how we utilize resources and focus on the economics of it," says Bagshaw. "So there are other tangible outcomes that, regardless of what the trial shows, will inform practice."