Ronald J. Falk

Ronald Jonathan Falk, MD, FASN is the Allen Brewster Distinguished Professor of Medicine at the University of North Carolina-Chapel Hill.^[1] Since 1993, he has been chief of the UNC Division of Nephrology and Hypertension, and is also the co-founder and director of the UNC Kidney Center.^[2] He is currently the chair of UNC's department of Internal Medicine. Dr. Falk is a Past-President of the American Society of Nephrology^[3] (ASN).

Education

Falk attended college at Dartmouth College in Hanover, New Hampshire where he graduated Cum Laude with a Bachelor of Arts degree. He received his MD degree at the University of North Carolina-Chapel Hill, where he also completed his residency in internal medicine and completed a fellowship in nephrology. Soon thereafter, he completed a research fellowship in pediatric nephrology at the University of Minnesota Hospitals, in Minneapolis, Minnesota.^[4]

Professional Activities

Falk is former chair of the National Kidney Foundation’s council on glomerulonephritis (1995-1998). He has served in various capacities for ASN, including on the annual meeting program, training program directors, post-graduate education, and nomination committees. He was elected to the ASN council in 2006 and began his term as president on November 13, 2011. He was co-director of the glomerular disease course during Renal Week (now called Kidney Week) from 2000-2005 as well as a faculty member for the ASN Board Review and Renal WeekEnds (now called Highlights). Falk also served as deputy editor of NephSAP, an education journal for nephrologists. He initiated the ASN Kidney Week podcast series,which are on-site interviews that consistently rank as the most popular society podcasts. He is also a frequent host of ASN podcasts throughout the year.^[5]

Falk played an important role in securing a $61 million Clinical and Translational Science Award (CTSA) from the National Institutes of Health in 2008. UNC is one of only 60 universities in the country to receive a CTSA. Falk was instrumental in designing the North Carolina Translational and Clinical Sciences Institute (NC TraCS), which is the home of the CTSA at UNC. He continues to serve as the chair of the TraCS Institute Study Section, which reviews all grant pilot funding.^[6]

Falk also currently leads the UNC Solid Organ Transplant Program, a multidisciplinary clinical program that manages every step of the transplant process, from early identification of those in need of a new kidney, liver, heart, or lung to survive to their treatment, surgery, and recovery.

Falk has served as member or charter member and has served on or has chaired a number of National Institutes of Health (NIH) study sections, review and special emphasis panels, and advisory boards since 1997. He also serves as a member of several editorial boards, including those for the Journal of the American Society of Nephrology,^[7] Kidney International, and the American College of Physicians’ MKSAP series.

Research

Falk's research focuses on inflammatory and vascular kidney diseases (vasculitis and glomerulonephritis). During the 1980s, Falk teamed up with J. Charles Jennette, MD, currently the Kenneth M. Brinkhous Distinguished Professor and Chair of Pathology and Laboratory Medicine,^[8] to form the Glomerular Disease Collaborative Network (GDCN). This network was formed to coordinate kidney disease research by nephrologists throughout the southeastern United States and connect them with the UNC School of Medicine. The GDCN, which consists of more than 700 nephrologists from over 350 private practice nephrology offices, seeks to learn more about how glomerular diseases arise and progress, and ultimately to find the most effective treatment for patients with these diseases. Key to the GDCN is its ongoing enrollment and follow-up of patients in 16 specific glomerular disease registries. The registries allow nephrologists to identify patients at the onset of their disease and follow the course of their disease throughout their lifetime. Continual update of patients' medical records and contact information for the registries allows the GDCN to recruit patients for participation in a variety of more focused studies that may include the collection of blood and urine or the completion of questionnaires or telephone interviews. The registry is also used as a recruiting mechanism for treatment studies.

In 1994, Falk and Jennette convened an International Consensus Conference that yielded the Chapel Hill Nomenclature for Small Vessel Vasculitis^[9] that has now been adopted on a world-wide basis. Nearly two decades later, clinicians and scientists from numerous disciplines were invited to Chapel Hill to revisit the nomenclature and participate in the 15th International Vasculitis & ANCA workshop.^[10]

As an investigator, Falk studies kidney diseases caused by anti-neutrophil cytoplasmic autoantibodies (ANCAs), which are a major cause for the most common forms of aggressive glomerulonephritis and systemic vasculitis in adults. ANCAs are formed against antigens in the cytoplasm of neutrophil granulocytes (the most common type of white blood cell) and monocytes. Clinical lab tests for ANCAs are now common worldwide.

Falk and Jennette authored a landmark 1988 article^[11] in the New England Journal of Medicine reporting the discovery of a new class of autoantibodies called myeloperoxidase-specific antineutrophil cytoplasmic autoantibodies (MPO-ANCAs) that cause the most common form of aggressive immune-mediated inflammatory kidney disease.

In the early 1990s, further investigations by Falk and his collaborators revealed that ANCAs could actually cause disease. In 1990, his paper in the Proceedings of the National Academy of Sciences first suggested that ANCAs could be pathogenic^[12] and described how ANCAs cause substantial injury to endothelial cells that line small blood vessels.

Over the ensuing decade, Falk and his colleagues have more fully documented the pathogenicity of ANCAs, culminating in 2002 with an article^[13] that demonstrated in a mouse model that passively transferred anti-myeloperoxidase antibodies were capable of inducing pauci-immune necrotizing and crescentic glomerulonephritis. In 2004, this same group of investigators proposed a new theory of autoimmunity,^[14] called the theory of autoantigen complementarity, based on the observation from human studies that patients reacted with complementary peptides to proteinase 3 as well as the initial sense peptide. This theory has spawned a series of new observations that investigators are reporting in the literature.^[15]

In collaboration with genetic experts at UNC, Falk and his colleagues determined that ANCA autoantigen genes are activated or silenced through epigenetic control,^[16] that is, by factors that regulate gene expression without altering the underlying DNA sequence. These observations have a broader impact on numerous autoantibody-mediated diseases.

The discovery of a new ANCA antigen termed lysosomal associated membrane protein 2 (LAMP-2) stirred lot of excitement in the ANCA research community recently.^[17] The UNC research team set up a collaborative and comprehensive serological study to determine the prevalence of the antibodies against LAMP-2 antigen in ANCA glomerulonephritis patient cohorts. Sera samples were tested at both UNC-Kidney Center, NC, and at Massachusetts General Hospital, MA. In stark contrast to previous reports, anti-LAMP-2 autoantibodies were not present in patient cohorts at a frequency higher than found in the general population. The UNC group concluded that anti-LAMP-2 antibodies are identifiable, low titer, natural or induced antibodies occasionally found in the population and not a marker of disease.^[18]

The Falk lab recently identified HLA-DB1*15 as a genetic trait that is a risk factor PR3-ANCA disease in African-American patients with an odds ratio of 73.3 (p=2.3x10-9). They found that a disproportionate number of African America patients carried the DRB1*1501 allele of Caucasian descent, rather than the DRB1*1503 allele of African descent. The DRB1*1501 allele was also significant in Caucasian patients with an odds ratio of 2.2 (p=0.007). In a validation study, supported by the Vasculitis Clinical Research Consortium (VCRC), 7/9 African American PR3-ANCA patients carried a DRB1*15 allele giving an overall odds ratio of 35.9 (p=3.0x10-11) that this allele is a risk factor for this group.^[19]

Kidney Outreach Programs

Falk organized and continues to conduct a weekly multidisciplinary vasculitis and glomerular disease outpatient clinic that is one of the largest in the United States. In 2005, Falk became co-founder and director of the UNC Kidney Center (UNCKC). The overall mission of the UNCKC is to reduce the burden of chronic kidney disease through discovery about the pathophysiology and therapeutics of the disease; through the development and assessment of educational programs about kidney disease for North Carolinians and their primary care physicians and by providing physicians and citizens access to information about the causes and treatments of kidney disease.^[20] The UNCKC provides a multidisciplinary and multischool approach to research pertaining to kidney disease spanning the gamut from basic molecular biology and genetics to broad epidemiological studies and clinical treatment trials.

Through the Kidney Education Outreach Program (KEOP), Falk launched a patient education outreach campaign in 2006 with the slogan, “Remember to ask: ‘Hey Doc, how are my kidneys?’” Targeted education initiatives include billboard and television media campaigns, community-based interactive information sessions, and the KEOP Filter newsletter. The Mobile Outreach Unit has now conducted over 100 screenings in 38 North Carolina counties.

In 2008, the UNCKC received a generous donation from Shirley Gilman to create the Allan Brewster Memorial Fund. This fund has been used to expand the KEOP's community-based awareness campaign to increase North Carolinians’ knowledge about the importance of organ donation and the role of kidney transplantation in achieving improved clinical outcomes and quality of life for persons at risk for or experiencing kidney failure. In 2011, UNC opened four pre-transplant satellite clinics to cover the western and eastern areas of the state. These clinics are conducted in conjunction with local private practices and include a full transplant evaluation by one of UNC’s transplant nephrologists. A nurse practitioner is on hand to provide education on living donation, pre-emptive transplantation, and the importance of managing comorbidities to optimize transplant outcomes. The overall goal of the satellite clinics is to make sure every patient interested in a kidney transplant is evaluated and listed.

Using iTunes®, Falk and his fellow nephrologists in the UNC Kidney Center have recorded many podcasts covering kidney disease topics that are available through iTunes®. Detailed patient education materials about kidney disease have also been developed and are available through the UNC Kidney Center Health Library at http://www.unckidneycenter.org/kidneyhealthlibrary.html.

Awards and Honors

Falk was the recipient of the Hartford Foundation Fellowship in 1985 and the Jefferson Pilot Fellowship Award in 1986. He was inducted into the American Society of Clinical Investigation in 1993 and into the American Clinical and Climatologic Association in 2000, when he also received their Theodore E. Woodward Award. Falk was appointed the Doc J. Thurston Distinguished Professor in the University of North Carolina School of Medicine in July, 1994 and was honored as the first Allen Brewster Distinguished Professor of Medicine in 2011. He has been recognized as one of the “Best Doctors in America” every year since 1992 and is the recipient of a number of invited lectureships, including the prestigious Norma Berryhill Distinguished Lecture ^[21] in 2011. He was also the president of the American Society of Nephrology in 2012.

References