Sodium Nitrite Supplementation for Improving Physiological Function in Patients with Chronic Kidney Disease

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CANDIDATE: Matthew J. Rossman, Ph.D., is a postdoctoral fellow training in the integrative physiology of aging at the University of Colorado (CU) Boulder. In this K01 application, Dr. Rossman aims to determine the efficacy of a novel nitric oxide (NO) boosting compound, sodium nitrite, for improving vascular, motor (physical) and cognitive function in patients with chronic kidney disease (CKD). His immediate goal is to acquire the research training and professional skills necessary to transition to an independent, extramurally funded investigator. His long-­term goal is to establish his own research program with a focus on identifying novel, evidence-­based lifestyle and pharmacological interventions that prevent or delay the development of vascular, motor and cognitive dysfunction to reduce the risk of CVD and other comorbidities in CKD. CAREER DEVELOPMENT PLAN: Dr. Rossman’s career development plan consists of: 1) acquiring new research skills associated with the proposed research plan;; 2) training in renal physiology, CKD, motor and cognitive function, clinical trials and biostatistics through coursework and meetings with his mentorship team;; and 3) professional skill development through coursework;; attendance/presentations at weekly journal clubs, CU seminars and national scientific meetings;; and regular interactions with his mentor team. ENVIRONMENT: The environment for Dr. Rossman’s training plan will be outstanding. Dr. Rossman’s primary mentor Dr. Douglas Seals and his co-­mentor Dr. Michel Chonchol are internationally recognized, NIH funded scientists with strong records of successful mentoring in translational biomedical research pertaining to age-­ and disease-­related physiological dysfunction and CKD. Dr. Chonchol is also a board-­certified nephrologist and Director of Clinical Research in the Division of Renal Diseases and Hypertension at CU Denver. Consulting mentor Dr. McQueen is director of biostatistics at the CU Boulder Clinical & Translational Research Center and regularly provides mentoring/consulting to trainees and faculty conducting clinical trials. Consulting mentor Dr. Tamura is an associate professor at Stanford University with extensive experience assessing motor and cognitive function in patients with CKD. Consulting mentor Dr. Bryan is an expert in nitrite/NO biology and improving physiological function via nitrite supplementation. RESEARCH: CKD is a highly prevalent condition and CVD is the leading cause of death in patients with CKD. Increased CVD risk in CKD is largely attributable to the development of vascular dysfunction, primarily vascular endothelial dysfunction and large elastic artery stiffening. Reduced motor and cognitive function are also common in CKD and increase the risk of disability and mortality in these patients. Vascular, motor and cognitive dysfunction all are related to reduced NO bioavailability. Nitrite is a cytoprotective molecule and major storage form of NO with therapeutic potential for improving multiple domains of physiological dysfunction in CKD. The proposed research will test the efficacy of oral sodium nitrite therapy for improving vascular, motor and cognitive function in patients with CKD.