Affiliate Investigator, Chronic Disease, Ottawa Hospital Research Institute
Professor of Medicine, Division of Nephrology and Kidney Research Centre, University of Ottawa
Biographical Sketch:
Dr. Levine has studied in vivo kidney tubular function in disease models for more than three decades. From 1980-1997, he was Head of the Division of Nephrology of the University of Ottawa and the Ottawa General Hospital. He fostered kidney research in Ottawa, with his own in vivo work emphasizing responses of living tubules to kidney disease. Currently, his work in the Kidney Research Centre focuses on mechanisms of deterioration of kidney tubular transport in diabetic renal failure a huge public health problem. Dr. Levine has had virtually uninterrupted support from MRC/CIHR for 40 years-until the year 2009. He is also the author of over 90 major publications.
Research Interests
- Pathogenesis of diabetic nephropathy: in vivo techniques for micropuncture and microperfusion studies re: the role nitric oxide and other systems in diabetic gene targeted mice.
- the modulation of distal nephron proton pump and other transporters/receptors by systemic acid base imbalance, diabetes, and renal failure by the use of combined in vivo micropuncture and microperfusion techniques with electron microscopic intracellular localization (immunogold) of transporters/receptors; also using concomitant Western analyses for transporter protein expression.
- development of techniques for in vivo ultramicro and intratubular nitric oxide profiling in real time in normal, nephrectomized and diabetic rats.
Major Research Activities:
His laboratory has been the first:
1. To measure absolute bicarbonate reabsorptive rates in single nephrons (1971).
2. To demonstrate in vivo that there is net bicarbonate secretion in the nephron (1988).
3. To demonstrate direct effects of angiotensin II on distal tubule bicarbonate reabsorption as well as those of other hormones (1994-1996).
4. To define the characteristics of bicarbonate and electrolyte transport in surviving distal tubules after kidney ablation (1997-2001).
5. To measure distal nephrons transport in a model of diabetic nephropathy with and without renal ablation (2000).
6. To directly measure nitric oxide in real time in tubular fluid in normal and 5/6 nephrectomized living rats (2001).
7. To measure, in vivo, single nephron glomerular filtration rate (SNGFR) in any mouse model of diabetes mellitus; to show a dependency of this SNGFR on kidney neuronal nitric oxide synthase activity in the Type 2 diabetic (leptin receptor defective) db/db mouse (2004-2006).
Major Awards/Affiliations
He chaired the Ontario Ministry of Health working group on kidney failure resource allocation. He has been President of the Canadian Society of Nephrology and Science Policy Secretary of the Canadian Society for Clinical Investigation. He has chaired or been a member of numerous scientific committees, both nationally and internationally. He was designated "Person of the Year" by the Italian Canadian Business & Professional Association of Ottawa (1987), "Researcher of the Year" by the University of Ottawa (1989), and Researcher of the Year by the Ottawa General Hospital (1992). Dr. Levine was awarded the first "Kidney Foundation Medal for Research Excellence" in 1996. In 2003, he was awarded the J. David Grimes Career Achievement Award by the Ottawa Hospital Research Institute. He was elected to the American Society for Clinical Investigation in 1980 and he was the ASCI's University of Ottawa representative for several years. Working on behalf of the CSCI and CSN, he has been a strong advocate for Canadian health research, and has appeared before parliamentary committees. He was founder and Editor of Research News, a quarterly magazine devoted to research development in the Faculty. He has extensive grant review and editorial experience, being associated with 4 major journals, and on Kidney International's editorial board for 18 years.
Current Funding Sources:
CIHR: "Nitric Oxide Angiotensin Modulation of Glomerular Hyperfiltration and Glomerulosclerosis in Gene-Targeted Mouse Models of Diabetes Studied In Vivo." ($700,000, 2004-2009)
RECENT PUBLICATIONS:
Genetics in kidney disease: How much do we want to know? R. Kielstein and H.-M. Sass. Am. J. Kid. Dis. 39(3): 637-652, 2002. (D.Z. Levine, Editor)
Real time microelectrode measurement of nitric oxide in kidney tubular fluid in vivo. D.Z. Levine and M. Iacovitti. Sensors 2003, 3: 314-320.
Paracrine factors in tubuloglomerular feedback: Adenosine, ATP and Nitric Oxide. J. Schnermann and D.Z. Levine. Annu. Rev. Physiol., 2003, 65: 501-29.
Short-term modulation of distal tubule fluid nitric oxide in vivo by loop NaCl reabsorption. D.Z. Levine, K.D. Burns, J. Jaffey and M. Iacovitti. Kidney Int. 2004, 65: 184-189.
Hyperfiltration, nitric oxide, and diabetic nephropathy.Levine DZ. Curr Hypertens Rep. 2006 May;8(2):153-7.
PMID: 16672149 [PubMed - in process]
Real-time measurement of kidney tubule fluid nitric oxide concentrations in early diabetes: Disparate changes in different rodent models. Levine DZ, Iacovitti M.
Nitric Oxide. 2006 Aug;15(1):87-92. Epub 2006 Feb 28.
PMID: 16510300 [PubMed - in process]
Modulation of single-nephron GFR in the db/db mouse model of type 2 diabetes mellitus. Levine DZ, Iacovitti M, Robertson SJ, Mokhtar GA.
Am J Physiol Regul Integr Comp Physiol. 2006 Apr;290(4):R975-81. Epub 2005 Dec 8.
PMID: 16339386 [PubMed - indexed for MEDLINE]