Kalani Raphael, MD (Division of Nephrology & Hypertention)

VA Merit Award
U.S. Department of Veterans Affairs

09/18/2018 – 09/17/2022

Acid-Base Balance of Kidney, Bone, and Muscle Health in Veterans with Preserved Renal function

High dietary acid intake has been associated with a number of adverse health consequences including kidney injury and impaired bone and muscle health. However, assessing dietary acid intake is largely done by reviewing food records, which are unreliable and not likely to be implemented by busy clinicians. Thus, it is difficult to identify individuals at risk for dietary acid mediated organ injury. The goal of this study is to determine if dietary acid intake, assessed by measuring urinary ammonium excretion, is associated with kidney injury and musculoskeletal health in Veterans with diabetes and/or hypertension. If higher ammonium excretion is associated with organ injury, then dietary acid mediated organ injury could be quantified by measuring urinary ammonium excretion. If so, urinary ammonium could be used to identify individuals with dietary acid mediated organ injury who might benefit from oral alkali and/or dietary interventions.

Monique Cho, MD (Division of Nephrology & Hypertension)

VA Merit Award
U.S. Department of Veterans Affairs

09/18/2018 – 09/17/2022

The Role of Functional Iron Deficiency in Systemic Complications of CKD

We will examine the association of hepcidin, a key iron regulator, with functional iron deficiency (FID) in chronic kidney disease (CKD) and determine if hepcidin and FID are associated with diabetic, kidney, and cardiovascular (CV) complications in patients with CKD. The study will involve detailed analyses of two sets of large databases from the national veteran’s data registry and Chronic Renal Insufficiency Cohort study. If our study confirms the association between hepcidin and FID with increased clinical risk, it will (1) broaden our understanding of FID to include metabolic, renal, and CV consequences instead of the singular focus on anemia, (2) promote development of a therapeutic focus based on the underlying physiological mechanism of FID by targeting the hepcidin pathway rather than exclusively relying on anemia treatment with intravenous iron therapy, which is associated increased CV risk, and (3) provide evidence to support the development of clinical trials to evaluate safety and efficacy of antihepcidin therapy, which is already in development for treatment of anemia, for the expanded clinical indications of ameliorating renal, diabetic, and CV risks in CKD.

Yan-Ting Shiu, PhD (Division of Nephrology & Hypertension)

VA Merit Award
U.S. Department of Veterans Affairs

09/18/2018 – 09/17/2022

Mechanisms of Imbalanced Inward and Outward Arteriovenous Fistula Remodeling

Hemodialysis is the preferred renal replacement modality for patients with end-stage renal disease (ESRD) in the U.S. and most developed countries. As the rate of growth of the ESRD population has continued to increase, an ever-increasing number of ESRD patients reply on hemodialysis to sustain their life. The vascular access is the “Achilles Heel” of the hemodialysis procedure. My project will help improve the understanding of the pathobiology of vascular access failure. The results of this project have significant potential to translate into an interventional project to improve the care of patients with kidney failure.

Robert Paine, MD (Division of Pulmonary Medicine)

VA Merit Award
U.S. Department of Veterans Affairs

09/18/2018 – 09/17/2022

Oxygen, Pulmonary Innate Immunity and Alveolar Epithelial Cell GM-CSF

The lung is our largest site of interaction with the outside word.  The alveolar epithelial cells that form the bulk of this surface are important players in the pulmonary innate immune response, in part by expression of granulocyte-macrophage colony stimulating factor (GM-CSF), a growth factor critical for normal functional maturation of lung macrophages.  We have found that regional hypoxia in the lung, as might be encountered in a wide variety of pathologic processes, suppresses epithelial cell expression of GM-CSF.  The goals of this project are to understand the consequences of this effect for host defense and to delineate the molecular mechanisms involved, focusing on the roles of hypoxia inducible factor (HIF) proteins, nitric oxide, and chromatin remodeling.  We anticipate that these studies will help identify novel targets to enhance pulmonary innate immunity in order to prevent or treat pneumonia in the setting of acute and chronic respiratory failure.

Matthew Rondina, MD (Division of General Internal Medicine)

VA Merit Award
U.S. Department of Veterans Affairs

09/18/2018 – 09/17/2022

Platelet Reprogramming During Inflammation

Thrombosis is a common complication of sepsis, contributing to adverse outcomes such as organ failure and death. Our project examines new pathophysiologic mechanisms of platelet reprogramming and thrombosis during sepsis.  We hope our findings ultimately help improve the care of Veterans who develop sepsis, and lead to new insights underpinning other thrombo-inflammatory diseases affecting the Veteran population.

Robert Paine, MD (Division of Pulmonary Medicine)

National Heart, Lung and Blood Institute/ National Institutes of Health

09/15/2017 – 05/31/2022

SPIROMICS II: Biological Underpinnings of COPD Heterogeneity and Progression

SPIROMICS is a multicenter study of 3,000 subjects that investigates the subpopulations and intermediate endpoints in chronic obstructive pulmonary disease (COPD).  The University of Utah was one of the six original SPIROMICS sites.  Key observations from SPIROMICS included characterization of a population of current and former smokers with COPD-like disease in the absence of airflow obstruction, discovery of an important relationship between the composition of airway mucous and disease activity, and new insights into the variability in the pattern of acute exacerbations of disease among individuals with COPD.  The NHLBI has now awarded a new grant, SPIROMICS II, that will work with this same cohort of patients to investigate further 1) smoking-related lung disease in individuals without airflow obstruction, 2) novel CT scan and mucous characteristics that identify distinctive pathologic phenotypes in COPD, 3) studies to determine the complex relationship between underlying host characteristics, events triggering acute exacerbations of COPD and the host response.  This state of the art human study integrates cutting edge radiographic techniques, molecular biology and physiology to elucidate the features that determine the variations in disease characteristics between individuals and to identify novel targets for therapeutic intervention to change the course of this disease.