Message from the Vice Chair for Research
July brings us Research Highlights from the Division of Nephrology. Currently led by interim chief Dr. Gerald Hladik, Nephrology at UNC—with its longstanding T32 training grant, longstanding P30 initiative to study glomerular diseases, its position at the center of the Cure Glomerulonephropathy Network and a growing cadre of young researchers—is the epitome of a Division where research and patient care combine to advance medicine. This Division has a habit of conscripting some of our very best residents into the field of Nephrology, and winning teaching awards year after year. This is a legacy of our Chair of Medicine, Dr. Falk, who this year will be honored with the 2016 “Astute Clinician” award from the NIH that recognizes that clinical insights lead to fundamental understanding of pathology, and novel approaches to treating disease. The Nephrology Division is this concept in action.
July introduces you to a few of our faculty doing research in kidney disease. Dr. Nachman is featured in the Chair’s Corner podcast this month on treating ANCA vasculitis with rituximab.
Janet Rubin, MD
Vice Chair for Research
Jenny Flythe, MD, MPH
Dr. Flythe is a nephrologist and clinical investigator focused on improving clinical outcomes and quality of life for individuals with dialysis-dependent end-stage kidney disease. She joined the UNC School of Medicine faculty in 2014 after completing her nephrology fellowship and public health training at Brigham and Women’s Hospital/ Massachusetts General Hospital and the Harvard School of Public Health. Her interest in research began in residency at Oregon Health & Science University, where she discovered that the dialysis care delivery system offered a unique intersection of her passions for complicated patients, intricate physiology, and health policy.
Her primary areas of expertise are in 3 major categories: 1) outcomes and epidemiological research; 2) qualitative research with a focus on patient engagement; and 3) helping to establish a national quality agenda for the dialysis delivery system. Her research focuses on fluid management, dialysis hemodynamics, and patient treatment preferences. Early in her career, Dr. Flythe identified the speed of fluid removal (ultrafiltration) during dialysis as a critical contributor to poor outcomes. This initial study helped spark renewed research interest in dialysis hemodynamics, a proposed Centers for Medicare and Medicaid Services (CMS) ultrafiltration rate clinical quality measure, and a national dialogue across dialysis industry and academic investigators regarding strategies to promote better fluid management practices.
Dr. Flythe’s qualitative research has highlighted a disconnect between the longer, slower dialysis treatments supported by research and the preferences of many patients for shorter, less intensive dialysis. This disconnect between patient wishes and actual care delivery led to her interest in patient engagement and patient-driven research priorities. She was recently awarded a Eugene Washington Engagement Award from the Patient-Centered Outcomes Research Institute (PCORI). The award brings together numerous dialysis community stakeholders to develop improved local dialysis facility infrastructure that will promote enhanced patient-centered outcomes research in the dialysis community.
Dr. Flythe is involved in the Kidney Health Initiative, a joint partnership between the Food and Drug Administration and the American Society of Nephrology, where she co-chairs a project focused on symptom management among dialysis patients. Outside of medicine, she enjoys exercising and spending time with her young daughter and fantastically supportive husband.
Keisha Gibson, MD, MPH
Dr. Gibson earned her medical degree at the UNC School of Medicine, where she also completed her fellowship training. During fellowship training, she earned a master’s degree at the UNC School of Public Health in Epidemiology. She joined the faculty at the UNC in 2008 as a member in the Division of Nephrology and Hypertension. While her clinical focus is on the care of children, adolescents, and young adults with kidney disease, Dr. Gibson’s research is focused on ethnic and socioeconomic disparities and their impact on outcomes in patients with glomerular diseases such as lupus and focal sclerosing glomerulonephritis.
Dr. Gibson is a co-investigator on several multicenter research studies in glomerular diseases. Since 2010, she has served as the co-Chair for the pediatric working group of the Nephrotic Syndrome Network Study (Neptune), a large multicenter longitudinal study of incident adult and pediatric patients with nephrotic syndrome sponsored by NIDDK, the University of Michigan and NephCure Kidney International. With UNC as a leading recruitment site, over 150 children and 400 adults with nephrotic syndrome have been enrolled in this study. By integrating molecular and clinical data in this well characterized cohort, this study aims to enhance the understanding the pathogenesis of these rare diseases that present as a common histological phenotype and advance innovation leading towards a precision medicine approach to treatment. Dr. Gibson has also expanded a registry and biorepository of DNA, RNA, and sera of both adult and pediatric patients with lupus nephritis and nephrotic syndromes under the umbrella of the Glomerular Disease Collaborative Network (GDCN). The GDCN is a collaborative network of over 300 physicians and the registry includes data from over 5000 patients with glomerular disease.
Dr Gibson’s current research focuses on the genotypic and clinical predictors of treatment response and long-term renal survival in African Americans affected by glomerular disease. Using whole exome sequencing, Dr. Gibson is working to identify novel risk alleles by comparing exomes from African American patients with glomerular disease that respond favorably to treatment and have good long-term renal survival compared to those who respond poorly and/or have progressive renal failure.
William "Will" Franklin Pendergraft III, MD, PhD
Dr. Pendergraft specializes in autoimmune glomerular disease and vasculitis. He completed graduate school and medical school at UNC, residency at UCSF and nephrology fellowship at the joint program between Brigham and Women's Hospital and Massachusetts General Hospital. He continues as a visiting postdoctoral scholar at the Broad Institute in Cambridge, MA.
Clinically and scientifically, Dr. Pendergraft’s expertise lies in nephrology with a specific focus on patients with inflammatory autoimmune diseases affecting the kidneys and he devotes a full-day clinic devoted to their care in the UNC Glomerulonephritis and Vasculitis Clinic. In particular, his clinical and translational research revolves around understanding the immunopathogenetic mechanisms underlying lupus nephritis and ANCA vasculitis.
Dr. Pendergraft is engaged in building a world-renowned lupus nephritis center here at UNC and has formed the Chapel Hill Alliance to Promote Excellence in Lupus (CHAPEL for short), which has patient care, education, research and clinical trial arms. The flagship product of CHAPEL is the Systems-Level Temporal Observation of Patients with Lupus (STOP SLE) study, which is the first of its kind study and is funded by a consortium between two pharmaceutical companies and in collaboration with The Broad Institute. STOP SLE recruits participants from the UNC Health Care system and uses high-tech and cutting-edge tools to identify predictors or biomarkers of disease and treatment response in patients with newly-diagnosed lupus nephritis. Dr. Pendergraft also directs all of the clinical trials at UNC focused on lupus nephritis, of which UNC has a large population, and his laboratory is engaged in clinical research seeking to understand rare variants of lupus nephritis. He collaborates in translational research in ANCA vasculitis under a long-standing NIDDK-funded program project grant with his main clinical mentor, Dr. Ronald J. Falk.
Interestingly, Dr. Pendergraft recently established a strong collaboration with the Carolinas Poison Control Center and its medical director, Dr. Michael Beuhler, to analyze exposures to nephrotoxins across the United States. The clinical aspects and outcomes of antifreeze exposures were recently published.
When not working in the laboratory or seeing patients, Will is involved in the medical school curriculum and the Physician Assistant Program. Outside of work, Will enjoys spending time with his three wonderful kids, volunteering at Glenwood Elementary School and working on his first fiction novel.
Vimal Derebail, MD, MPH
Dr. Derebail completed his undergraduate degree at Duke University and MD at the Medical College of Georgia. He completed his residency in Internal Medicine and fellowship in Nephrology at the University of North Carolina. As a fellow, he completed a master’s degree from the UNC Gillings School of Global Public Health. After completion of his fellowship, Dr. Derebail spent one year training with Dr. Nigel Key and UNC’s benign hematology group.
His research interests have developed from his experience in benign hematology. His work has primarily focused on the evaluation of sickle cell trait and sickle cell disease. He and his team, using data from both local and multinational cohort studies, have identified that sickle cell trait is associated with a greater risk of kidney disease. He has also studied kidney disease and overt sickle cell disease to understand the nature of renal pathophysiology, as well as to identify potential therapies to slow progression of kidney disease.
Drawing from his experience in hematology, Dr Derebail also studies hemostasis in patients with vasculitis and glomerular disease. Both of these disease states are associated with a heightened risk of deep venous thrombosis (DVT). He has worked to identify clinical risk factors for blood clots and develop a clinical tool to determine membranous nephropathy patients who have the greatest risk of DVT. He received a career development award from the Nephrotic Syndrome Study Network (NEPTUNE) and NephCure Kidney International to expand on this risk profile, in particular to understand how the hyperlipidemia associated with nephrotic syndrome might contribute to DVT risk.
In addition to his research efforts, Dr. Derebail maintains an active clinical schedule, attending on the inpatient Nephrology teaching and consultation services at UNC and in UNC’s outpatient dialysis units. He has served as medical director of Carolina Dialysis in Siler City, NC and is presently the medical director of home dialysis therapies based at Carolina Dialysis of Carrboro, NC. His home life remains equally active with his wife and three young daughters.
Patrick Nachman, MD
Dr. Nachman is part of a large and energetic team conducting research in glomerular disease and vasculitis that spans the spectrum of research “from bench to bedside.” Within this team, his efforts have primarily focused on translational and clinical research in Antineutrophil Cytoplasmic Autoantibody (ANCA)-associated vasculitis, and a number of glomerular diseases.
In ANCA-vasculitis, the team is working on several interrelated projects to assess whether epigenetic, molecular, cellular, and serologic factors identified at the Kidney Center lab are associated with disease activity and, more importantly, whether they can be used to better tailor immunosuppressive therapy to an individual’s needs. For example, some epigenetic and cellular markers may help identify people at low risk of disease relapse who may not need prolonged maintenance immunosuppression once they achieve a complete remission of vasculitis. Dr. Nachman also investigates risk factors for complications of immunosuppressive therapy and explores strategies to minimize them, notably in a multidisciplinary effort with Dr. Ashley Henderson in the Division of Pulmonary Medicine and Dr. Brent Senior in ENT Surgery.
Over the last 10 years, Dr. Nachman’s group has built a robust clinical research portfolio that includes investigator-initiated studies, industry-sponsored trials, as well as longitudinal cohort studies that dove-tail with our bench research program. Overall, the group now offers patients the opportunity to participate in clinical trials encompassing the major glomerular diseases, small vessel vasculitis, and lupus nephritis (led by Dr. William Pendergraft III.)
Dr. Nachman is particularly interested in addressing current hurdles to drug development for glomerular diseases and nephrology in general. This work includes defining surrogate endpoints in glomerular diseases, recognizing that the traditional “hard outcomes” are poorly suited for the design and implementation of clinical trials in these diseases. In collaboration with colleagues at the FDA and University of Toronto, he has recently published a “white paper” that critically assessed the use of proteinuria reduction as a surrogate endpoint in membranous nephropathy. This project laid a template for addressing the issues of surrogate endpoints in other glomerular diseases. As such, an international effort to better define surrogate endpoints in IgA Nephropathy (the world’s most common glomerular disease) was recently initiated with the endorsement and support by the Kidney Health Initiative.