Raghavan Murugan, MD, MS Awarded Two R01 Grants from NIDDK for Team Science Projects

Professor Raghavan Murugan, MD, MS, with support from a team of investigators at the Center for Critical Care Nephrology and CRISMA, has been awarded two R01 grants, valued at more than $3.3 million, from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Both studies are team science collaborations with colleagues across the University of Pittsburgh and at the Mayo Clinic and Carnegie Mellon University.

The first project uses artificial intelligence to predict intradialytic hypotension in critically ill patients and determine optimal responses to clinical interventions. The second collaborative project is a randomized clinical trial that seeks to determine the best management approach for fluid removal in patients with acute kidney injury (AKI) who are receiving kidney replacement therapy.

Team Science Project #1: Artificial Intelligence Driven Acute Renal Replacement Therapy (AID-ART)

The AID-ART project will use sophisticated machine learning approaches for early prediction of intradialytic hypotension in critically ill patients. Artificial intelligence tools will analyze hundreds of subtle features from ICU patient monitors, including high-frequency waveform data and electronic medical records, to determine optimal responses to clinical interventions for acute kidney replacement therapy.

“Intradialytic hypotension is a major problem occurring in 30% of critically ill patients receiving kidney replacement therapy. This problem is unpredictable and associated with discontinuation of dialysis and fluid removal, ischemic organ injury, non-recovery of kidney function and mortality,” said Dr. Murugan, who is the multiple principal investigator and a professor of Critical Care Medicine and Clinical and Translational Science.

“Despite these poor outcomes, no standard clinical tool exists to identify patients at risk of intradialytic hypotension, in stark contrast to tools to monitor the function of several other organs in ICU patients,” said Gilles Clermont, MD, MSc, another multiple principal investigator and professor of Critical Care Medicine, Mathematics, Clinical and Translational Science, and Industrial Engineering at the University of Pittsburgh.

The third multiple principal investigator is Kianoush Kashani, MD, FASN, professor of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN. Other co-investigators in this multi-departmental, multi-institutional, and multi-organizational NIDDK grant are: Michael Pinsky, MD, Department of Critical Care Medicine; Robert Parker, PhD, University of Pittsburgh School of Engineering; Milos Hauskrecht, PhD, Pittsburgh School of Computer Science; Artur Dubrawski, PhD, Robotics Institute, Carnegie Mellon University School of Computer Science; and Vitaly Herasevich, MD, PhD, Department of Anesthesiology, Mayo Clinic, Rochester, MN.

Team Science Project #2: REstrictive versus LIberal rate of Extracorporeal Volume Removal Evaluation in Acute Kidney Injury (RELIEVE-AKI)

The RELIEVE-AKI project is a stepped-wedge cluster-randomized trial involving 144 critically ill patients with AKI, who are being treated with continuous kidney replacement therapy. Six intensive care units at the UPMC and Mayo Clinic hospital systems will be randomized 1:1 in which patients will receive either a restrictive or a liberal rate of fluid removal strategy.

“Two-thirds of AKI patients receiving kidney replacement therapy have fluid overload but we don’t know the optimal approach for fluid removal,” said Dr. Murugan. “A faster rate of fluid removal increases the risk of hemodynamic instability, cardiac arrhythmias, and ischemic organ injury, and conversely a slower rate of fluid removal prolongs exposure to fluid overload and its consequences. “

Multiple PI Kianoush Kashani, MD, MS, from the Mayo Clinic explained, “Complications during fluid removal remain high. They include the risk of intradialytic hypotension and cardiac arrhythmias that then require further interventions.”

This pragmatic clinical trial will be used to support the rationale, assess feasibility, and design a phase III multicenter randomized trial to examine the effects of alternative fluid removal strategies on patient-centered clinical outcomes.

University of Pittsburgh co-investigators are Paul Palevsky, MD, Renal and Electrolyte Division and Joyce Chang, PhD, Department of Medicine.