Articles in PresS. Am J Physiol Renal Physiol (September 18, 2014). doi:10.1152/ajprenal.00506.2014

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EDITORIAL FOCUS

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Caveat Emptor: If you have PKD be careful of what you drink?

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Robert Bacallao, MD

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Division of Nephrology, Richard Roudebush VAMC and Indiana University School of Medicine, R2-221, 950 West Walnut St., Indianapolis, IN 46202

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Email: [email protected] Tel: 317-278-0471

Copyright © 2014 by the American Physiological Society.

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In this issue, work by Vincent Gattone examines a potential confounding variable in the treatment of autosomal dominant polycystic kidney disease. Dr. Gattone was the first to describe a role for V2 receptor antagonist as a way to decrease cyst growth in the setting of polycystic kidney disease. His original work was performed in the pcy murine model of PKD a non-orthologous model of PKD (3) . Subsequent work extended this original observation to an orthologous model and subsequently V2 receptor antagonism showed some clinical efficacy in the TEMPO study (5, 6). Since patients with ADPKD have defective urinary concentrating ability, these patients are prone to elevated vasopressin levels and have increased urinary cAMP (1). Based on these observations it has been suggested that increasing water intake can suppress vasopressin (4). However water is seldom pure and in some cases contaminants at a level considered safe may unduly affect at risk populations.

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The paper published in this edition of AJP-renal examines whether a common potable water contaminant, dichloroacetate, can increase cyst growth in the PCK rat model of polycystic kidney disease. Dichoroacetate is formed when chlorine covalently combines with acetate in solution. The EPA has a maximum allowable concentration of 60 ug/L in drinking water (2), so this is a common chemical component of drinking water and it could possibly affect people with subtle alterations in metabolism. Clearly further work is needed to fully identify the risks of permissible water contaminants to people with underlying genetic disorders.

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This work is also the final scientific effort of Vincent H Gattone. Dr. Gattone passed away on January 21, 2014, finally succumbing to cancer. Vince earned a Bachelor of Science degree in Chemistry from Ursinus College, followed by a Masters degree in Academic Pathology from George Washington University. Subsequently Vince earned his PhD in Medical Sciences from the Medical College of Ohio in 1980. In late 1980 he came to Indiana University. Following his post-doctoral experience he took a faculty position at Pennsylvania State University and then joined the Department of Anatomy and Cell Biology at the University of Kansas University Medical School. It was at KUSM, where Vince was to begin the work that in many respects became the focus of his scientific career. While he was at KUSM, Vince demonstrated that a vasopressin receptor-2 antagonist could ameliorate cystic disease in a non-orthologous model of murine polycystic kidney disease. Subsequent work demonstrated similar efficacy in an orthologous model and now these agents are being tested in human studies.

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In 2000, Dr. Gattone joined the faculty of Cell Biology and Anatomy at Indiana University. While I had known Vince from our conversations at annual American Society of Nephrology meetings, when he came to Indiana University we began to work closely together, spurred by a common interest in polycystic kidney disease, medical education and Italian food. Like many fellow scientists working on polycystic kidney disease, I found Vince to be unfailingly supportive and helpful. He had a unique ability to connect people and ideas. Vince was especially dedicated to encouraging young investigators.

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The manuscript published in this issue of AJP-Renal in many respects demonstrates many aspects of Vince’s research focus. In clinical medicine we speak of patient centered care, Vince

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conducted patient centered research. It is this feature of his work that was noted by the committee awarding the Lillian Kaplan Award, an international award given for excellence in scientific research on Polycystic Kidney Disease. The award acknowledged a lifetime of pioneering work on the pathogenesis and treatment of polycystic kidney disease.

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Dr. Gattone is survived by his wife and five children. Every member of his family had fond memories of being swept up in Vince’s scientific quests. All were introduced early to the laboratory and data collection. No holiday was complete without a visit to the laboratory. Vince’s dedication to his scientific work was shared by his family and reflected his view that science is a communal affair.

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When Vince was diagnosed with cancer, he discovered that our medical school curriculum lacked coursework addressing the needs of patients facing terminal illness. Vince contacted the curriculum committee and worked with our palliative care group to create course content. During a time in which may people would withdraw, Vince embraced the insights he could relate to others about his condition. He allowed researchers unfettered access to his life and reflections as a terminally ill colleague. His humanity, grace and fellowship will be greatly missed.

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1. Devuyst O, and Torres VE. Osmoregulation, vasopressin, and cAMP signaling in autosomal dominant polycystic kidney disease. Curr Opin Nephrol Hypertens 22: 459-470, 2013. 2. Donohue JM, Galal-Gorchev H, Brattin W, Liccione JJ, and Altshuler KB. Toxicological Review of Dichloroacetic Acid. EPA 635/R-03/007, www.epa.gov/iris: U.S. Environmental Protection Agency, 2003, p. 1-102. 3. Gattone VH, Maser RL, Branden MG, Tiam C, and Resenberg J. Collecting duct gene expression and effect of an AVP-V2 receptor antagonist on the progression of PKD in pcy mice. Journal of the American Society of Nephrology 9: 18A, 1998. 4. Torres VE, Bankir L, and Grantham JJ. A Case of Water in the Treatment of Polycystic Kidney Disease. Clinical Journal of the American Society of Nephrology 4: 11401159, 2009. 5. Torres VE, Chapman AB, Devuyst O, Gansevoort RT, Grantham JJ, Higashihara E, Perrone RD, Krasa HB, Ouyang J, Czerwiec FS, and Investigators TT. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med 367: 2407-2418, 2012. 6. Wang X, Gattone V, 2nd, Harris PC, and Torres VE. Effectiveness of vasopressin V2 receptor antagonists OPC-31260 and OPC-41061 on polycystic kidney disease development in the PCK rat.[see comment]. Journal of the American Society of Nephrology 16: 846-851, 2005.

Caveat emptor: if you have PKD, be careful of what you drink?

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