eBriefing

Chronic Kidney Disease: Inflammation and Oxidative Stress in Pathogenesis and Clinical Course

Chronic Kidney Disease
Reported by
Jennifer Cable

Posted April 16, 2012

Presented By

Overview

Chronic kidney disease (CKD) is a progressive loss of kidney function that generally results from type 2 diabetes and hypertension. While current treatments can maintain kidney function and slow the progression of disease, there is nothing available that improves kidney function. In December 2011, researchers from academia and industry met at the New York Academy of Sciences for the symposium Chronic Kidney Disease: Inflammation and Oxidative Stress in Pathogenesis and Clinical Course to discuss an emerging approach toward CKD—targeting inflammation. The seminar was presented by the Academy, Fistula First, the Journal of Clinical Investigation, and Genzyme. The speakers presented an overview of the role of oxidative stress and inflammation in CKD, highlighting the current unmet needs in the diagnosis and treatment of CKD and presenting promising results for a new diagnostic marker of CKD as well as a new drug that improves kidney function by inhibiting pro-inflammatory pathways.

Use the tabs above to find a meeting report and multimedia from this event.

 

Presentations available from:
Jonathan Barasch, MD, PhD (Columbia University Medical Center)
Colin Meyer, MD (Reata Pharmaceuticals, Inc.)
ND Vaziri, MD (University of California, Irvine)
David Warnock, MD (University of Alabama at Birmingham)
George Zavoico, PhD (MLV)
Panel Discussion


Grant Support

Genzyme Corporation

Websites

National Kidney Foundation
Nonprofit health organization dedicated to preventing kidney and urinary tract diseases.

National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI)
Provides evidence-based clinical practice guidelines for all stages of CKD.

REGARDS Study
Information about the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study including participants, researchers, and current findings.


Journal Articles

Jonathan Barasch

Bao G, Clifton M, Hoette TM, et al. Iron traffics in circulation bound to a siderocalin (Ngal)-catechol complex. Nat. Chem. Biol. 2010;6(8):602-609.

Mishra J, Dent C, Tarabishi R, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 2005;365(9466):1231-1238.

Mori K, Lee HT, Rapoport D, et al. Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury. J. Clin. Invest. 2005;115(3):610-621.

Nickolas TL, O'Rourke MJ, Yang J, et al. Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury. Ann. Intern. Med. 2008;148(11):810-819.

Paragas N, Nickolas TL, Wyatt C, et al. Urinary NGAL marks cystic disease in HIV-associated nephropathy. J. Am. Soc. Nephrol. 2009;20(8):1687-1692.

Paragas N, Qiu A, Zhang Q, et al. The Ngal reporter mouse detects the response of the kidney to injury in real time. Nat. Med. 2011;17(2):216-222.

Parravicini E, Nemerofsky SL, Michelson KA, et al. Urinary neutrophil gelatinase-associated lipocalin is a promising biomarker for late onset culture-positive sepsis in very low birth weight infants. Pediatr. Res. 2010;67(6):636-640.

Viau A, El Karoui K, Laouari D, et al. Lipocalin 2 is essential for chronic kidney disease progression in mice and humans. J. Clin. Invest. 2010;120(11):4065-4076.

Colin Meyer

Auletta JJ, Alabran JL, Kim BG, et al. The synthetic triterpenoid, CDDO-Me, modulates the proinflammatory response to in vivo lipopolysaccharide challenge. J. Interferon Cytokine Res. 2010;30(7):497-508.

Fornoni A, Ijaz A, Tejada T, et al. Role of inflammation in diabetic nephropathy. Curr. Diabetes Rev. 2008;4(1):10-17.

Kim HJ and Vaziri ND. Contribution of impaired Nrf2-Keap1 pathway to oxidative stress and inflammation in chronic renal failure. Am. J. Physiol. Renal Physiol. 2010;298(3):F662-F671.

Kobayashi M, Li L, Iwamoto N, et al. The antioxidant defense system Keap1-Nrf2 comprises a multiple sensing mechanism for responding to a wide range of chemical compounds. Mol. Cell Bio. 2009;29(2):493-502.

Mezzano S, Aros C, Droguett A, et al. NF-kappaB activation and overexpression of regulated genes in human diabetic nephropathy. Nephrol. Dial. Transplant. 2004;19(10):2505-2512.

Pergola PE, Krauth M, Huff JW, et al. Effect of bardoxolone methyl on kidney function in patients with T2D and Stage 3b-4 CKD. Am. J. Nephrol. 2010;33(5):469-476.

Pergola PE, Raskin P, Toto RD, et al. Bardoxolone methyl and kidney function in CDK with type 2 diabetes. N. Engl. J. Med. 2010;365(4):327-336.

Schmid H, Boucherot A, Yasuda Y, et al. Modular activation of nuclear factor-kappaB transcriptional programs in human diabetic nephropathy. Diabetes 2006:55(11):2993-3003.

Tanaka Y, Aleksunes LM, Goedken MJ, et al. Coordinated induction of Nrf2 target genes protects against iron nitrilotriacetate (FeNTA)-induced nephrotoxicity. Toxicol. Appl. Pharmacol. 2008;231(3):364-373.

Tan Y, Ichikawa T, Li J, et al. Diabetic downregulation of Nrf2 activity via ERK contributes to oxidative stress-induced insulin resistance in cardiac cells in vitro and in vivo. Diabetes 2011;60(2):625-633.

Zheng H, Whitman SA, Wu W, et al. Therapeutic potential of Nrf2 activators in streptozotocin-induced diabetic nephropathy. Diabetes 2011;60(11):3055-3066.

Zoccali C. Endothelial dysfunction in CKD: a new player in town? Nephrol. Dial. Transplant. 2008;23(3):783-785.

ND Vaziri

Oxidative stress in kidney disease

Kim HJ and Vaziri ND. Contribution of impaired Nrf2-Keap1 pathway to oxidative stress and inflammation in chronic renal failure. Am. J. Physiol. Renal Physiol. 2009;298:F662-F671.

Vaziri ND, Dicus M, Ho ND, et al. Oxidative stress and dysregulation of superoxide dismutase and NADPH oxidase in renal insufficiency. Kidney Int. 2003;63:179-185.

Yoon JW, Pahl MV, and Vaziri ND. Spontaneous leukocyte activation and oxygen-free radical generation in end-stage renal disease. Kidney Int. 2007;71(2):167-172.

HDL and LDL in oxidative stress and inflammation

Moradi H, Pahl MV, Elahimehr R, et al. Impaired antioxidant activity of high-density lipoprotein in chronic kidney disease. Transl. Res. 2009;153(2):77-85.

Vaziri ND, Navab K, Gollapudi P, et al. Salutary effects of hemodialysis on low-density lipoprotein proinflammatory and high-density lipoprotein anti-inflammatory properties in patient with end-stage renal disease. J. Natl. Med. Assoc. 2011;103(6):524-533.

Uremia and intestinal barrier dysfunction

de Almeida Duarte JB, de Aguilar-Nascimento JE, Nascimento M, et al. Bacterial translocation in experimental uremia. Urol. Res. 2004;32(4):266-270.

Magnusson M, Magnusson KE, Sundqvist T, et al. Impaired intestinal barrier function measured by differently sized polyethylene glycols in patients with chronic renal failure. Gut 1991;32(7):754-759.

Magnusson M, Magnusson KE, Sundqvist T, et al. Increased intestinal permeability to differently sized polyethylene glycols in uremic rats: effects of low- and high-protein diets. Nehpron 1990;56(3):306-311.

Szeto CC, Kwan BC, Chow KM, et al. Endotoxemia is related to systemic inflammation and atherosclerosis in peritoneal dialysis patients. Clin. J. Am. Soc. Nephrol. 2008;3(2):431-436.

Vaziri ND, Dure-Smith B, Miller R, et al. Pathology of gastrointestinal tract in chronic hemodialysis patients: an autopsy study of 78 cases. Am. J. Gastroenterol. 1985;80(8):608-611.

Vaziri ND, Yuan J, Rahimi A, et al. Disintegration of colonic epithelial tight junction in uremia: a likely cause of CKD-associated inflammation. Nephrol. Dial. Transplant. 2011; Epub.

David Warnock

Astor BC, Matsushita K, Gansevoort RT, et al. Lower estimated glomerular filtration rate and higher albuminuria are associated with mortality and end-stage renal disease. A collaborative meta-analysis of kidney disease population cohorts. Kidney Int. 2011;79(12):1331-1340.

Go AS, Chertow GM, Fan D, et al. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N. Engl. J. Med. 2004;351(13):1296-1305.

Howard VJ, Cushman M, Pulley L, et al. The reasons for geographic and racial differences in stroke study: objectives and design. Neuroepidemiology 2005;25(3):135-143.

Warnock DG, Muntner P, McCullough PA, et al. Kidney function, albuminuria, and all-cause mortality in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study. Am. J. Kidney Dis. 2010;56(5):861-871.

Organizers

Colin Meyer, MD

Reata Pharmaceuticals, Inc.
e-mail | website | publications

Colin Meyer is the Vice President, Product Development of Reata Pharmaceuticals and joined the company as its second employee. Meyer's primary role is to develop and implement strategies to move product candidates expeditiously through all stages of development. His duties include overseeing preclinical development, clinical pharmacology, and working with Reata's senior leadership team to design and implement development strategies for drug candidates. Meyer received a BS in chemistry with specialization in biochemistry and a BA in biology from the University of Virginia. He received an MD from the University of Texas Southwestern Medical School and an MBA from Southern Methodist University Cox School of Business.

George Zavoico, PhD

MLV
e-mail | website | publications

George B. Zavoico is Managing Director, Research, and a Senior Equity Research Analyst at MLV, a boutique investment bank and institutional broker-dealer based in New York. He has over 6 years of experience as a life sciences analyst writing research on publicly traded equities. Prior to MLV, he was an equity analyst with Westport Capital Markets and Cantor Fitzgerald. Prior to working as an analyst, Zavoico established his own consulting company serving the biotech and pharmaceutical industries by providing competitive intelligence and marketing research, due diligence services, and guidance in regulatory affairs. He also wrote extensively on healthcare and the biotech and pharmaceutical industries for periodicals targeting the general public and industry executives. Zavoico began his career as a Senior Research Scientist at Bristol-Myers Squibb Co., moving on to management positions at Alexion Pharmaceuticals, Inc. and T Cell Sciences, Inc. (now Celldex Therapeutics, Inc). He has a BS in Biology from St. Lawrence University and PhD in Physiology from the University of Virginia and has held post-doctoral positions at the University of Connecticut Health Sciences Center and Brigham and Women's Hospital and Harvard Medical School.

Jennifer Henry, PhD

The New York Academy of Sciences
e-mail

Jennifer Henry received her PhD in plant molecular biology from the University of Melbourne, Australia, with Paul Taylor at the University of Melbourne and Phil Larkin at CSIRO Plant Industry in Canberra, specializing in the genetic engineering of transgenic crops. She was then appointed as Associate Editor, then Editor, of Functional Plant Biology at CSIRO Publishing. She moved to New York for her appointment as a Publishing Manager in the Academic Journals division at Nature Publishing Group, where she was responsible for the publication of biomedical journals in nephrology, clinical pharmacology, hypertension, dermatology, and oncology. Henry joined the Academy in 2009 as Director of Life Sciences and organizes 35 – 40 seminars each year. She is responsible for developing scientific content in coordination with the various life sciences Discussion Group steering committees, under the auspices of the Academy's Frontiers of Science program. She also generates alliances with outside organizations interested in the programmatic content.


Speakers

Jonathan M. Barasch, MD, PhD

Columbia University Medical Center
e-mail | website | publications

Jonathan Barasch studied organic and biochemistry at Dartmouth College and then completed medical and graduate studies at Columbia where he is now an Associate Professor of Medicine and Cell Biology. He studies growth factors in the embryonic and adult kidney, focusing on iron transport.

ND Vaziri, MD

University of California, Irvine
e-mail | website | publications

Nosratola "Nick" D. Vaziri is emeritus professor of medicine, physiology and biophysics at the University of California, Irvine, Schools of Medicine and Biological Science. He is former chair of the Department of Medicine and past president of the School of Medicine's academic senate at the University of California Irvine. He is a Master and a Laureate of the American College of Physicians, past president of the Western Association of Physicians, past president of the American Paraplegia Society, and recipient of numerous prestigious awards. He serves on the editorial board of several scientific journals. Vaziri has authored close to 500 original papers and 150 invited book chapters, reviews, and editorials. He has made seminal contributions to the understanding of the molecular mechanisms of lipid disorders, oxidative stress, and inflammation in chronic renal disease.

David Warnock, MD

University of Alabama at Birmingham
e-mail | website | publications

David Warnock's research focuses on the factors, genetic and environmental, that contribute to hypertension and chronic kidney disease. The spectrum extends from basic studies of salt and water transport systems to population based studies of the prevalence of CKD and the association with stroke and heart disease. Another focus is inherited disorders of renal function, with a current emphasis on the renal manifestations of Fabry disease. Warnock received a BA from the University of California at Berkeley and received his MD from the University of California, San Francisco. His clinical training was completed at the University of California, San Francisco, including a 1-year research fellowship with Isidore Edelman in the Cardiovascular Research Institute. Following a fellowship with Maurice Burg at the NIH, Warnock returned to UCSF as a faculty member. He served as the Section Chief at the San Francisco VA Medical Center during the last 5 years of his appointment at UCSF. Following a sabbatical with Bernard Rossier at the Institute of Pharmacology in Lausanne, Switzerland, Warnock was recruited to UAB. Warnock's research interests include acid-base physiology, sodium transport mechanisms, chronic kidney disease, diabetes and kidney disease, and inherited renal diseases.

Colin Meyer, MD

Reata Pharmaceuticals, Inc.
e-mail | website | publications


Jennifer Cable, PhD

Jennifer Cable resides in New York City, where she experiments with different methods and outlets to communicate science. She enjoys bringing science to scientists and nonscientists alike. She writes for Nature Structural and Molecular Biology, Bitesize Bio, Under the Microscope, and the Nature New York blog. She received a PhD from the University of North Carolina at Chapel Hill for her research in investigating the structure/function relationship of proteins.