The Basic and Clinical Science Research Programs are integral to the daily activities in the division. The division's outstanding established clinical care programs are complemented by asking, "Can we improve patient care through research?" Division research programs and training activities fall into four major, overlapping areas:
Members of the division and close collaborators are actively engaged in basic science and clinical research of diabetic kidney disease, the most common cause of chronic and end stage renal disease in the United States. Basic science research focuses on new discoveries in cellular and molecular mechanisms of proteinuria, inflammation, and fibrosis in diabetic kidney disease, using a cell culture, animal model and human biopsy approach. Drs. Alpers and Shankland study models of diabetic kidney disease. Drs. Afkarian and Tuttle are translating molecular findings into clinical practice. Several large clinical research projects and trials utilize data from major epidemiology health studies that are headed by faculty at the UW and are currently being used by faculty and trainees in our program. These include the:
- Epidemiology of Diabetes Intervention and Complications (EDIC) study
- Women's Health Initiative (WHI)
- Multi-Ethnic Study of Atherosclerosis (MESA) to examine diabetes-related dyslipidemia, central obesity related to intensive insulin therapy and the potential role of vitamin D metabolism in the prevention of diabetes
- Diabetes Prevention Program Outcomes Study (DDOPS)
- Long-term follow up of the Diabetes Prevention Program (DPP) cohort
- Look Ahead (Action for Health in Diabetes) study
- Database for the Japanese-American Community Diabetes Study
- NIDDK-funded Diabetes Endocrinology Research Center with core facilities (cellular and molecular imaging, mass spectrometry, molecular genetics and others)
- NIH funded Mouse Metabolic Phenotyping Center that supports diabetes- and obesity-related research
- New Diabetes/Obesity Center of Excellence at the UW
A longstanding strength of the renal division has been the study of molecular and cellular mechanisms of glomerular injury and how this translates to proteinuria and kidney scarring. Dr. Shankland currently studies this topic and holds the prestigious position of Established Investigator of the American Heart Association. Dr. Caroline Marshall received a Robert Wood Johnson grant to examine how DNA damage of podocytes leads to proteinuria and glomerulosclerosis. Dr. Charles Alpers is well funded to study animal models of glomerular injury and podocyte diseases. Available to several cores and resources, including the Center for Expression Arrays, proteomics and FACS analysis. On the clinical side, Dr. Ashley Jefferson is a co-PI of the Focal Segemental Glomerulosclerosis NIH-funded grant (PI is Sandra Watkins, MD, Peditric Nephrology), and Dr. Ian de Boer is engaging in a clinical trial to test the hypothesis that ATRA enhances kidney survival in proteinuric patients as we have shown in experimental models. Dr. Pichler has a particular research interest in glomerular disease in patients with liver disease and has collected the largest-known kidney biopsy repository in these patients for study. Dr. Connie Davis is actively studying recurrence of glomerular disease in transplanted patients, with current emphasis on the association of rapamycin therapy with de novo FSGS. Dr. Nelson is an investigator of the multi-center Nephrotic Syndrom Study Network (NEPTUNE). Dr. Duffield studies kidney inflammation and stem cell biology.
Basic science research in vascular biology includes the labs of Dr. Nicosia (Pathology) and Dr. Giachelli (Bioengineering). Dr. Nicosia's research examines key mechanisms of angiogenesis, including angiopoietins and vascular endothelial growth factors, using animal models. Dr. Giachelli, a world expert in in-vitro calcification models, was the first to demonstrate a direct mineralizing role of serum phosphate on vascular smooth muscle cells and serves as a model for future translational research. Dr. Giachelli is currently serving as a mentor for one of our renal fellows, Wei Ling Lau. Dr. Kimberly Muczynski, MD, PhD, studies anti-endothelial cell antibodies in disease.
Dr. Kestenbaum studies dystrophic vascular calcification in CKD. He recently competed a large ancillary study to the MESA study to examine the association of serum mineral metabolism markers with longitudinal changes in coronary calcium in MESA participants with CKD. Dr. Kestenbaum and Dr. de Boer work closely with Dr. Siscovick (Epidemiology), an internationally known cardiovascular epidemiologist and senior investigator in MESA, CHS, and the Coronary Artery Risk Development in Young Adults (CARDIA) study. Together, they serve as members of a number of collaborative working groups within these studies, including those for renal, diabetes, and mineral metabolism. Dr. de Boer collaborates closely with Dr. Probstfield (Cardiology), a major leader in hypertension clinical trials, including ALLTHAT and HOPE. Dr. Ahmad is an active participant in clinical hypertension trials in patients with normal and abnormal kidney function, including dialysis patients. Finally, the Clinical Nutrition Research Unit includes 80 investigators with research interests in lipids, atherosclerosis, and diabetes.
Chronic Kidney Disease (CKD) leads to devastating clinical complications including cardiovascular disease, anemia and bone disease. The UW Division of Nephrology has had a storied history of excellence in the study of CKD complications. Dr. Sherrard and Dr. Andress pioneered the study of metabolic bone disease in dialysis patients, and the late Dr. Joseph Eschbach was responsible for the clinical introduction of recombinant human erythropoietin. Excellence in the study of CKD complications continues within the division. Dr. O'Hare is a leader in the epidemiology of peripheral vascular disease (PVD) complications of CKD. Recently she examined cystatin C, an alternative marker of kidney function, as an early indicator of PVD. Dr. Kestenbaum has published serveral articles describing cardiovascular and fracture outcomes following surgical parahyroidectomy. Dr. de Boer has published important new data describing early changes in serum lipids, measured by MRI in CKD patients. He is currently studying vitamin D and ATRA therapies as potential novel means to reduce proteinuria and slow progression of CKD. Together, Dr. Young, Dr. O'Hare and Dr. Rodriguez have published extensively on the role of race in cardiovascular complications of CKD. Central to moving forward in the field of clinical CKD is the collection of prospective data. Dr. Kestenbaum established the Seattle Kidney Study (SKS) in 2004 and has enrolled more than 550 CKD patients from clinical sites within UW. Dr. Davis and Dr. Ajit Limaey (Laboratory Medicine) are leaders in the study of BK Nephropathy, an important cause of graft failure, and Dr. Leca is currently investigating the complications of treatment of BK nephropathy with leflunomide.