To improve efficiency and increase collaborative efforts among groups of investigators at institutions with established comprehensive kidney research bases, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) established the George M. O'Brien Research Centers Program in 1987. This network of research centers brings together investigators from relevant disciplines in a manner that enhances and extends the effectiveness of research related to kidney disease and its complications. The overall goal of the centers has been recently expanded to bring together, in a cooperative, multidisciplinary and integrative manner, basic science and clinical investigators to enrich the effectiveness of research into causes, treatment, and cure of ESRD.
The current George M. O'Brien Kidney Research Centers are located at University of Texas Health Sciences Center, San Antonio; Vanderbilt University Medical Center, Nashville; Baylor College of Medicine, Houston; Indiana University, Indianapolis; Albert Einstein College of Medicine, Bronx, NY; University of Iowa, Iowa City; University of Michigan, Ann Arbor.
Challenges for Research
Improving clinical outcomes through the application of human genomic information is a major challenge facing biomedical researchers today. Nevertheless, since the human genome was mapped, new laboratory methods and technologies have rapidly proliferated, and they should generate routine discovery of new genes and identification of their biological relevancy.
However, the understanding of normal cellular processes and the progression of kidney disease will require more than the delineation of an array of complex protein-protein interacting pathways. These pathways are aberrantly modified in disease states and reflected in the subtle protein changes in the cell. Such changes in protein expression are likely to be translated into changes in cell growth, differentiation, and programmed cell death or apoptosis.
At the end of 1999, based on the most current data derived from the 2000 Annual United States Renal Data System (USRDS) Report, 344,094 patients were being treated for end-stage renal disease (ESRD) and 89,252 new patients began ESRD treatment in 1999. The incidence of ESRD continues to mount and is projected to rise to over 170,000 by 2010.
Minority populations suffer a disproportionate share of kidney disease, especially diabetes-the most commonly reported cause of ESRD-and hypertension. ESRD continues to be a disease that affects African Americans (32 percent of treated ESRD patients) and Native Americans at a rate three to five times greater than the rate of Caucasian Americans. The medical, social, and financial implications of this disease continue to make ESRD a major public health and public policy problem. ESRD patients account for less than 1 percent of all Medicare beneficiaries, but accrue almost 6 percent of the program expenditures, $12.7 billion in 1999.
Chronic kidney disease has no cure, and progression to kidney failure for many may be slowed if the disease is diagnosed and managed early. Considerable progress is already being made in understanding the basic physiology and pathophysiology of the normal and affected renal systems. Further unraveling of the mechanisms behind the processes that lead to progressive deterioration in the function of these systems "is a work in progress."
Nevertheless, major advances have been made in the management of the clinical consequences of those processes. For example, during the past decade, sustained and intensified research efforts have led to the refinement of dialysis; the improvement of vascular access techniques; and higher rates of allograft survival. Also, prior racial differences between African Americans and Caucasians in one-year patient and graft survival have disappeared.
Another common form of kidney disease, which affects an estimated 5 percent of people who are hospitalized, is acute renal failure (ARF), secondary to ischemia. ARF is an important clinical problem. When hemodialysis is required for patients with ARF, the mortality rate increases to more than 60 percent, and ARF-associated medical expenses are estimated at $8 billion per year. Although important advances have been made in understanding ARF in animals, translating that knowledge from experimental models to humans is complicated by the heterogeneity of ARF. Consequently, animal models have fallen far short of the goals set for reducing the morbidity and mortality of this disease.
The Road Ahead
Interrelated, basic research subprojects, each with high scientific merit and clear research objectives, have been the hallmarks of the O'Brien Kidney Research Centers Program. In the aggregate, the subprojects will continue to be directed toward developing fundamental knowledge that will lead to greater understanding of kidney disease processes and to the design of curative or preventive strategies. New to the program, however, is the inclusion of a research development and pilot and feasibility (P&F) projects component.
The current goals of the George M. O'Brien Kidney Research Centers Program are as follows:
- Continue to attract new scientific expertise into the study of the basic mechanisms of kidney diseases and disorders
- Encourage multidisciplinary research focused on the causes of these diseases
- Explore new basic areas that may have clinical research application
- Generate developmental research (DR)/pilot and feasibility (P&F) studies of two years duration, which will lead to new and innovative approaches to studies of kidney disease and the eventual submission of competitive investigator-initiated R01 research grant applications.
The mounting complexities associated with the studies of disease processes will likely require investigations in cell and molecular biology, biochemistry, physiology, genomics and proteomics, epidemiology, immunology, and pathology. In addition, research will likely focus on topical areas such as diabetic nephropathy or other endocrine and metabolic disorders, hypertension in kidney disease, hereditary renal disease, immunologic renal disease, acute renal failure, and nephrotoxic cell injury.
Core Facilities
Core facilities in an O'Brien Kidney Research Center are shared resources that enhance productivity or in other ways benefit a group of investigators working to accomplish the stated goals of the center. Cores usually fall into one of four categories:
- Provision of a technology that lends itself to automation or preparation in large batches (e.g., radioimmunoassay and tissue culture)
- Complex instrumentation (e.g., electron microscopy or mass spectrometry)
- Animal preparation and care
- Technical assistance and training (e.g., molecular biology).
Examples of core resources are as follows:
- Molecular biology core to supply oligonucleotides and provide automated DNA-sequencing capability
- Animal models core to develop, breed, and maintain animal models for diseases of interest, which can then be used to improve understanding of the human forms of the disease
- Tissue culture core for the harvest, cultivation, and handling of large numbers of cells
- Other cores needed to characterize gene transfer systems
Developmental Research/Pilot and Feasibility Projects
The Developmental Research/Pilot and Feasibility (DR/P&F) Program will provide modest support for innovative initiatives with the potential to advance progress in understanding cellular and molecular mechanisms that cause renal disease. This program is directed at both new investigators and established investigators who wish to explore the feasibility of a novel approach to a problem in this area.
Project Officer: Marva Moxey-Mims, M.D., 301-594-7717.
