Professor and Chair, Department of Physiology
Director, Center of Biomedical Research Excellence in Renal Biology
Urinary angiotensinogen as a novel biomarker for intrarenal angiotensin activity in type 1 diabetes
Luis Gabriel Navar received his Ph.D. in 1966 at the University of Mississippi under the direction of Dr. Arthur Guyton. He served on the faculty of the University of Mississippi and the University of Alabama at Birmingham before joining Tulane in 1988. He is Director of the Center for Biomedical Research Excellence in Hypertension and Renal Biology and Professor and Chair of the Department of Physiology. Dr. Navar has concentrated his research on the hormonal and paracrine mechanisms that regulate renal hemodynamics, glomerular filtration rate, and sodium reabsorption, and their relationships to the pathophysiology of hypertension and diabetes. His work has been recognized and lauded by his peers, as evidenced by numerous awards. Dr. Navar has had leadership roles serving as Councilor and President in the American Physiological Society (APS) and President of the Association of Chairs of Departments of Physiology and was Chair of the Council for High Blood Pressure. Dr. Navar has also been President of the Interamerican Society of Hypertension. He served on the Council of Academic Societies of the AAMC as well as on numerous peer review groups and study sections for the NIH, the VA, and the AHA. He has also served as Associate Editor for the American Journal of Physiology and Hypertension.
Angiotensinogen (AGT) is the only known substrate for renin, which is the rate-limiting enzyme of the renin-angiotensin system (RAS). Upregulation of intrarenal AGT levels leads to increased angiotensin peptide formation and consequent renal injury. Enhanced intrarenal AGT mRNA and/or protein levels have been observed in diabetic animals suggesting that intrarenal AGT plays an important role in the development and progression of diabetic nephropathy. While there is evidence that the intrarenal RAS is stimulated in diabetes mellitus, there are no means currently available to directly quantitate the magnitude of the activation of the intrarenal RAS. We previously reported that urinary excretion rates of AGT provide a specific index of intrarenal RAS status in angiotensin II-dependent hypertension. We recently developed a direct method to measure urinary AGT in humans using human AGT enzyme-linked immunosorbent assays (ELISA). Using this technology developed in our laboratory, we are evaluating the urinary AGT levels in juveniles and young adults with type 1 diabetes mellitus (T1 DM). The overall hypothesis is that urinary AGT levels serve as a novel early biomarker of the intrarenal RAS status and potentially serve as a predictor of the risks for developing renal injury. Our studies are being performed in order to determine the urinary AGT levels in juvenile control subjects and patients with T1 DM in order to determine if urinary AGT levels are higher In T1 DM juveniles compared to that in age-and gender-matched control subjects in a prospective study. This study will also determine if urinary AGT levels are higher in T1 DM juveniles with nephropathy compared to that in T1 DM juveniles without nephropathy. The long term goal is to demonstrate that the high baseline of urinary AGT levels in T1 DM juveniles are causally linked to the progression of renal dysfunction and further increases in urinary AGT levels. If the aims of the proposed study are successful, the intrarenal RAS can be monitored by measuring urinary AGT levels in patients and could provide a specific rationale for placing patients at risk on blockers of the RAS. Therefore, this research project has the potential to achieve significant impact for individualized patient management in patients with type 1 diabetes using urinary AGT as a biomarker to optimize treatments with RAS blockades, and the success of this proposed study can lead to improved health and economic burden of chronic kidney disease and cardiovascular disease in the US.
Akemi Sato, PhD – Medical Research Specialist
Weijian Shao, PhD – Medical Research Specialist
Ryo Sato, PhD – Research Scientist
Kayoko Miyada, PhD – Postdoctoral Fellow
Dale Seth – Lab Supervisor
Michael Cypress – Graduate Student
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