John Paul Middleton | Scholars@Duke

John Paul Middleton
Professor of Medicine

I. More than 20 million people in the United States have chronic kidney disease (CKD), and these people carry an enormous medical burden. Patients with CKD suffer from the metabolic sequelae of poor kidney function, hypertension, progressive worsening of glomerular filtration rate (GFR), and from disproportionate cardiovascular diseases. Therefore, a large number of people can benefit from early recognition of CKD, improved understanding of the metabolic and cardiovascular responses to CKD, and by limiting progressive decline of GFR.

II. Current research efforts aim to improve understanding of the association among traditional and novel cardiovascular risks and kidney disease. Ultimately the goal of the ongoing research will be to improve the management of the unique cardiovascular complications that occur in the patients with chronic kidney disease and to reduce the risk of developing advanced CKD.

III. Clinical trials underway at Duke include prospective trials in diabetic nephropathy, end-stage kidney disease, and in focal segmental glomerulosclerosis (FSGS. In addition, Dr. Middleton serves on the Steering Committee for the NIH Clinical Trial in Focal Segmental Glomerulosclerosis (FSGS). Dr. Middleton and his group is also performing retrospective trials with large clinical databases to determine etiology of and outcomes from sudden cardiac arrest in patients with advanced CKD.

IV. Recent studies have helped identify interventions to reduce progression of hypertensive nephrosclerosis and diabetic nephropathy. The research group has also determined exposures that augment the cardiovascular risk of chronic kidney disease, including CKD that is maintained on hemodialysis.

V. Key words: chronic kidney disease CKD), hypertension, glomerular disease, progression of chronic kidney disease (CKD), cardiovascular complications of chronic kidney disease (CKD), hemodialysis, cardiovascular risk

Current Appointments & Affiliations

Professor of Medicine, Medicine, Nephrology, Medicine 2020

Contact Information

2424 Erwin Road, Suite 605, Durham, NC 27705
Duke Box 2747, Durham, NC 27705
j.p.middleton@duke.edu (919) 660-6860

Background
Education, Training, & Certifications
- Fellow in Nephrology, Medicine, Duke University 1986 - 1989
- Medical Resident, Medicine, University of Texas, Medical Branch at Galveston 1983 - 1986
- M.D., Virginia Commonwealth University 1983
Previous Appointments & Affiliations
- Associate Professor of Medicine, Medicine, Nephrology, Medicine 2007 - 2020
- Associate Professor of Medicine, Medicine, Nephrology, Medicine 2004 - 2007
- Instructor, Temporary in the Department of Medicine, Medicine, Nephrology, Medicine 2003 - 2004
- Assistant Professor of Medicine, Medicine, Nephrology, Medicine 1990 - 1996
Expertise
Subject Headings
Research
Selected Grants
- Patiromer Efficacy to Reduce Episodic Hyperkalemia in End Stage Renal Disease Patients Treated with Hemodialysis (PEARL-HD) awarded by Vifor Pharma, Inc 2019 - 2024
- A Prospective, RanDomized, Multi-Center, Open-Label, Cross-Over Study of Sodium Zirconium Cyclosilicate to Control Interdialytic HyperkalemiA Following Augmentation of DialysatePotassium: Efficacy to Reduce the Incidence of Post-Dialysis Atrial Fib awarded by NephroNET, Inc 2022 - 2023
- Duke Training Grant in Nephrology awarded by National Institutes of Health 1995 - 2023
- A Randomized Trial of Fistula vs. Graft Arteriovenous Vascular Access in Older Adults with End-Stage Kidney Disease on Hemodialysis: The AV ACCESS Trial awarded by Wake Forest University School Of Medicine 2021 - 2023
- Preventing Cognitive Decline by Reducing BP Target Trial (PCOT) awarded by University of Texas - Southwestern 2020 - 2021
- Protocol No. 28431754DNE3001: "A Randomized, Double-blind, Event-driven, Placebo-controlled, Multicenter Study of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Subjects With Type 2 Diabetes Mellitus and Diabetic Nephropathy" awarded by Janssen Research & Development, LLC 2014 - 2019
- Oral Sodium Bicarbonate to Slow Chronic Kidney Disease Progression awarded by University of Utah 2017 - 2018
- Data Coordinating Center for Pilot Studies of Candidate Therapies for CKD awarded by Cleveland Clinic Lerner College of Medicine 2013 - 2018
- NephroGenex Protocol PRY-311 : A Phase 3 Randomized, Double-Blind,Placebo-Controlled, Multi-Center Study to Evaluate the Safety and Efficacy of Pyridorin (pyridoxamine dihydrochloride) in Subjects With Nephropathy Due to Type 2 Diabetes. awarded by Medpace, Inc 2014 - 2018
- Risk Factors for Sudden Cardiac Death in Patients with Chronic Kidney Disease awarded by National Institutes of Health 2014 - 2017
- Computational Approach To Personalized Anemia Management awarded by University of Louisville 2012 - 2016
- BMS CV202-010-0055 awarded by Bristol-Myers Squibb 2013 - 2015
- IPA - Kimberly B. Gitter awarded by Veterans Administration Medical Center 2008 - 2010
- Hemodialysis Vascular Access Clinical Trials Consortium awarded by National Institutes of Health 2000 - 2009
External Relationships
- AstraZeneca
- National Institutes of Health
- NephroNet
- Novo Nordisk
- Raleigh Radiology
- Relypsa/Vifor
Publications & Artistic Works
Selected Publications
- Academic Articles
  - Esagian, Stepan Michran, Dimitrios Spinos, Anastasia Vasilopoulou, Nikolaos Syrigos, Muath Bishawi, Ruediger Wilhelm Lehrich, John Paul Middleton, Paul Vincent Suhocki, Theodore Nick Pappas, and Konstantinos P. Economopoulos. “Influence of peritoneal dialysis catheter type on complications and long-term outcomes: an updated systematic review and meta-analysis.” J Nephrol 34, no. 6 (December 2021): 1973–87. https://doi.org/10.1007/s40620-021-01016-y.
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  - Esagian, Stepan M., Georgios A. Sideris, Muath Bishawi, Ioannis A. Ziogas, Ruediger W. Lehrich, John P. Middleton, Paul V. Suhocki, Theodore N. Pappas, and Konstantinos P. Economopoulos. “Surgical versus percutaneous catheter placement for peritoneal dialysis: an updated systematic review and meta-analysis.” J Nephrol 34, no. 5 (October 2021): 1681–96. https://doi.org/10.1007/s40620-020-00896-w.
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  - Zhou, Zien, Meg J. Jardine, Qiang Li, Brendon L. Neuen, Christopher P. Cannon, Dick de Zeeuw, Robert Edwards, et al. “Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis.” Stroke 52, no. 5 (May 2021): 1545–56. https://doi.org/10.1161/STROKEAHA.120.031623.
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  - Srivastava, Anand, Xuan Cai, Jungwha Lee, Wei Li, Brett Larive, Cynthia Kendrick, Jennifer J. Gassman, et al. “Kidney Functional Magnetic Resonance Imaging and Change in eGFR in Individuals with CKD.” Clin J Am Soc Nephrol 15, no. 6 (June 8, 2020): 776–83. https://doi.org/10.2215/CJN.13201019.
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  - Raphael, Kalani L., Tamara Isakova, Joachim H. Ix, Dominic S. Raj, Myles Wolf, Linda F. Fried, Jennifer J. Gassman, et al. “A Randomized Trial Comparing the Safety, Adherence, and Pharmacodynamics Profiles of Two Doses of Sodium Bicarbonate in CKD: the BASE Pilot Trial.” J Am Soc Nephrol 31, no. 1 (January 2020): 161–74. https://doi.org/10.1681/ASN.2019030287.
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  - Ix, Joachim H., Tamara Isakova, Brett Larive, Kalani L. Raphael, Dominic S. Raj, Alfred K. Cheung, Stuart M. Sprague, et al. “Effects of Nicotinamide and Lanthanum Carbonate on Serum Phosphate and Fibroblast Growth Factor-23 in CKD: The COMBINE Trial.” J Am Soc Nephrol 30, no. 6 (June 2019): 1096–1108. https://doi.org/10.1681/ASN.2018101058.
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  - Edmonston, Daniel, Jessica D. Morris, and John P. Middleton. “Working Toward an Improved Understanding of Chronic Cardiorenal Syndrome Type 4.” Adv Chronic Kidney Dis 25, no. 5 (September 2018): 454–67. https://doi.org/10.1053/j.ackd.2018.08.010.
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  - Pun, Patrick H., and John P. Middleton. “Dialysate Potassium, Dialysate Magnesium, and Hemodialysis Risk.” J Am Soc Nephrol 28, no. 12 (December 2017): 3441–51. https://doi.org/10.1681/ASN.2017060640.
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  - Pun, Patrick H., Benjamin A. Goldstein, John A. Gallis, John P. Middleton, and Laura P. Svetkey. “Serum Potassium Levels and Risk of Sudden Cardiac Death Among Patients With Chronic Kidney Disease and Significant Coronary Artery Disease.” Kidney Int Rep 2, no. 6 (November 2017): 1122–31. https://doi.org/10.1016/j.ekir.2017.07.001.
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  - Middleton, John P., and Myles Wolf. “Second Chances to Improve ESRD Outcomes With a Second-Generation Calcimimetic.” Jama 317, no. 2 (January 10, 2017): 139–41. https://doi.org/10.1001/jama.2016.18631.
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  - Pun, Patrick H., Safa Abdalla, Geoffrey A. Block, Glenn M. Chertow, Ricardo Correa-Rotter, Bastian Dehmel, Tilman B. Drüeke, et al. “Cinacalcet, dialysate calcium concentration, and cardiovascular events in the EVOLVE trial.” Hemodial Int 20, no. 3 (July 2016): 421–31. https://doi.org/10.1111/hdi.12382.
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  - Suthar, Samantha Dias, and John P. Middleton. “Clinical Outcomes in Dialysis Patients: Prospects for Improvement with Aldosterone Receptor Antagonists.” Semin Dial 29, no. 1 (2016): 52–61. https://doi.org/10.1111/sdi.12421.
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  - Van Buren, Peter N., Julia B. Lewis, Jamie P. Dwyer, Tom Greene, John Middleton, Mohammed Sika, Kausik Umanath, et al. “The Phosphate Binder Ferric Citrate and Mineral Metabolism and Inflammatory Markers in Maintenance Dialysis Patients: Results From Prespecified Analyses of a Randomized Clinical Trial.” Am J Kidney Dis 66, no. 3 (September 2015): 479–88. https://doi.org/10.1053/j.ajkd.2015.03.013.
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  - Moe, Sharon M., Glenn M. Chertow, Patrick S. Parfrey, Yumi Kubo, Geoffrey A. Block, Ricardo Correa-Rotter, Tilman B. Drüeke, et al. “Cinacalcet, Fibroblast Growth Factor-23, and Cardiovascular Disease in Hemodialysis: The Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial.” Circulation 132, no. 1 (July 7, 2015): 27–39. https://doi.org/10.1161/CIRCULATIONAHA.114.013876.
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  - Pun, Patrick H., Anne S. Hellkamp, Gillian D. Sanders, John P. Middleton, Stephen C. Hammill, Hussein R. Al-Khalidi, Lesley H. Curtis, Gregg C. Fonarow, and Sana M. Al-Khatib. “Primary prevention implantable cardioverter defibrillators in end-stage kidney disease patients on dialysis: a matched cohort study.” Nephrol Dial Transplant 30, no. 5 (May 2015): 829–35. https://doi.org/10.1093/ndt/gfu274.
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  - Middleton, John P., and Uptal D. Patel. “The need for collaboration to improve cardiovascular outcomes in patients with CKD.” Adv Chronic Kidney Dis 21, no. 6 (November 2014): 456–59. https://doi.org/10.1053/j.ackd.2014.08.007.
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  - Middleton, John P., and Ruediger W. Lehrich. “Prescriptions for dietary sodium in patients with chronic kidney disease: how will this shake out?” Kidney Int 86, no. 3 (September 2014): 457–59. https://doi.org/10.1038/ki.2014.124.
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  - Surana, Sikander P., Patrick H. Pun, Sai Ram Keithi-Reddy, Steven M. Spiegel, John P. Middleton, and Ajay K. Singh. “Sudden cardiac arrest in ESRD patients.” Clin Nephrol 81, no. 2 (February 2014): 121–31. https://doi.org/10.5414/CN107667.
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  - Zeeuw, Dick de, Tadao Akizawa, Paul Audhya, George L. Bakris, Melanie Chin, Heidi Christ-Schmidt, Angie Goldsberry, et al. “Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease.” N Engl J Med 369, no. 26 (December 26, 2013): 2492–2503. https://doi.org/10.1056/NEJMoa1306033.
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  - Pun, Patrick H., John R. Horton, and John P. Middleton. “Dialysate calcium concentration and the risk of sudden cardiac arrest in hemodialysis patients.” Clin J Am Soc Nephrol 8, no. 5 (May 2013): 797–803. https://doi.org/10.2215/CJN.10000912.
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  - Hurwitz, Herbert I., Pamela S. Douglas, John P. Middleton, George W. Sledge, David H. Johnson, David A. Reardon, Dafeng Chen, and Oliver Rosen. “Analysis of early hypertension and clinical outcome with bevacizumab: results from seven phase III studies.” Oncologist 18, no. 3 (2013): 273–80. https://doi.org/10.1634/theoncologist.2012-0339.
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  - Malone, Andrew F., Matthew A. Sparks, David N. Howell, John Paul Middleton, Stephen R. Smith, and Ruediger W. Lehrich. “IgG4-related tubulointerstitial nephritis associated with chronic lymphocytic leukemia.” J Nephrol 26, no. 6 (2013): 1195–98. https://doi.org/10.5301/jn.5000298.
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  - Pun, Patrick H., Debra Schumm, Gillian D. Sanders, Deborah Hickey, John P. Middleton, Nancy Clapp-Channing, and Sana M. Al-Khatib. “A pilot study using an implantable device to characterize cardiac arrhythmias in hemodialysis patients: implications for future research.” Ann Noninvasive Electrocardiol 17, no. 2 (April 2012): 159. https://doi.org/10.1111/j.1542-474X.2012.00491.x.
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  - Middleton, John P., and Steven D. Crowley. “Prehypertension and chronic kidney disease: the ox or the plow?” Kidney Int 81, no. 3 (February 2012): 229–32. https://doi.org/10.1038/ki.2011.393.
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  - Pun, Patrick H., Charles A. Herzog, and John P. Middleton. “Improving ascertainment of sudden cardiac death in patients with end stage renal disease.” Clin J Am Soc Nephrol 7, no. 1 (January 2012): 116–22. https://doi.org/10.2215/CJN.02820311.
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  - Pun, Patrick H., and John P. Middleton. “Sudden cardiac death in hemodialysis patients: a comprehensive care approach to reduce risk.” Blood Purif 33, no. 1–3 (2012): 183–89. https://doi.org/10.1159/000334154.
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  - Gipson, Debbie S., Howard Trachtman, Frederick J. Kaskel, Tom H. Greene, Milena K. Radeva, Jennifer J. Gassman, Marva M. Moxey-Mims, et al. “Clinical trial of focal segmental glomerulosclerosis in children and young adults.” Kidney Int 80, no. 8 (October 2011): 868–78. https://doi.org/10.1038/ki.2011.195.
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  - Pun, P. H., and J. P. Middleton. “The authors reply:.” Kidney International 79, no. 11 (June 1, 2011): 1259. https://doi.org/10.1038/ki.2011.71.
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  - Singh, Kamaljit, Robert K. Niven, Timothy J. Senden, Michael L. Turner, Adrian P. Sheppard, Jill P. Middleton, and Mark A. Knackstedt. “Remobilization of residual non-aqueous phase liquid in porous media by freeze-thaw cycles.” Environ Sci Technol 45, no. 8 (April 15, 2011): 3473–78. https://doi.org/10.1021/es200151g.
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  - Gipson, Debbie S., Howard Trachtman, Frederick J. Kaskel, Milena K. Radeva, Jennifer Gassman, Tom H. Greene, Marva M. Moxey-Mims, et al. “Clinical trials treating focal segmental glomerulosclerosis should measure patient quality of life.” Kidney Int 79, no. 6 (March 2011): 678–85. https://doi.org/10.1038/ki.2010.485.
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  - Pun, Patrick H., Ruediger W. Lehrich, Emily F. Honeycutt, Charles A. Herzog, and John P. Middleton. “Modifiable risk factors associated with sudden cardiac arrest within hemodialysis clinics.” Kidney Int 79, no. 2 (January 2011): 218–27. https://doi.org/10.1038/ki.2010.315.
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  - Middleton, John P. “Predisposition to arrhythmias: electrolytes, uremic fibrosis, other factors.” Semin Dial 24, no. 3 (2011): 287–89. https://doi.org/10.1111/j.1525-139X.2011.00866.x.
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  - Sharp Collaborative Group, Carlos L. “Study of Heart and Renal Protection (SHARP): randomized trial to assess the effects of lowering low-density lipoprotein cholesterol among 9,438 patients with chronic kidney disease.” Am Heart J 160, no. 5 (November 2010): 785-794.e10. https://doi.org/10.1016/j.ahj.2010.08.012.
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  - Hurwitz, H., P. S. Douglas, J. P. Middleton, G. W. Sledge, D. H. Johnson, D. A. Reardon, D. Chen, and O. Rosen. “Analysis of early hypertension (HTN) and clinical outcome with bevacizumab (BV).” Journal of Clinical Oncology 28, no. 15 (May 20, 2010).
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  - Middleton, John P., and Patrick H. Pun. “Hypertension, chronic kidney disease, and the development of cardiovascular risk: a joint primacy.” Kidney Int 77, no. 9 (May 2010): 753–55. https://doi.org/10.1038/ki.2010.19.
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  - Pun, P. H., E. F. Honeycutt, S. M. Al-Khatib, and J. P. Middleton. “The authors reply.” Kidney International 77, no. 7 (January 1, 2010): 648–49. https://doi.org/10.1038/ki.2009.536.
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  - Bhatnagar, Vibha, Erin P. Garcia, Daniel T. O’Connor, Victoria H. Brophy, John Alcaraz, Erin Richard, George L. Bakris, et al. “CYP3A4 and CYP3A5 polymorphisms and blood pressure response to amlodipine among African-American men and women with early hypertensive renal disease.” Am J Nephrol 31, no. 2 (2010): 95–103. https://doi.org/10.1159/000258688.
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  - Pun, Patrick H., Thomas R. Smarz, Emily F. Honeycutt, Linda K. Shaw, Sana M. Al-Khatib, and John P. Middleton. “Chronic kidney disease is associated with increased risk of sudden cardiac death among patients with coronary artery disease.” Kidney Int 76, no. 6 (September 2009): 652–58. https://doi.org/10.1038/ki.2009.219.
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  - Bhatnagar, Vibha, Daniel T. O’Connor, Victoria H. Brophy, Nicholas J. Schork, Erin Richard, Rany M. Salem, Caroline M. Nievergelt, et al. “G-protein-coupled receptor kinase 4 polymorphisms and blood pressure response to metoprolol among African Americans: sex-specificity and interactions.” Am J Hypertens 22, no. 3 (March 2009): 332–38. https://doi.org/10.1038/ajh.2008.341.
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  - Li, Yanhong, Joëlle Y. Friedman, Betsy F. O’Neal, Matthew J. Hohenboken, Robert I. Griffiths, Martin E. Stryjewski, John P. Middleton, et al. “Outcomes of Staphylococcus aureus infection in hemodialysis-dependent patients.” Clin J Am Soc Nephrol 4, no. 2 (February 2009): 428–34. https://doi.org/10.2215/CJN.03760708.
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  - Sinsakul, Marvin, Mohammed Sika, Roger Rodby, John Middleton, Yu Shyr, Heidi Chen, Ernest Han, et al. “A randomized trial of a 6-week course of celecoxib on proteinuria in diabetic kidney disease.” Am J Kidney Dis 50, no. 6 (December 2007): 946–51. https://doi.org/10.1053/j.ajkd.2007.09.005.
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  - Bhatnagar, Vibha, Daniel T. O’Connor, Nicholas J. Schork, Rany M. Salem, Caroline M. Nievergelt, Brinda K. Rana, Douglas W. Smith, et al. “Angiotensin-converting enzyme gene polymorphism predicts the time-course of blood pressure response to angiotensin converting enzyme inhibition in the AASK trial.” J Hypertens 25, no. 10 (October 2007): 2082–92. https://doi.org/10.1097/HJH.0b013e3282b9720e.
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  - Pun, Patrick H., Ruediger W. Lehrich, Stephen R. Smith, and John P. Middleton. “Predictors of survival after cardiac arrest in outpatient hemodialysis clinics.” Clin J Am Soc Nephrol 2, no. 3 (May 2007): 491–500. https://doi.org/10.2215/CJN.02360706.
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  - Hogg, Ronald, John Middleton, and V Matti Vehaskari. “Focal segmental glomerulosclerosis--epidemiology aspects in children and adults.” Pediatr Nephrol 22, no. 2 (February 2007): 183–86. https://doi.org/10.1007/s00467-006-0370-5.
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  - Lehrich, Ruediger W., Patrick H. Pun, Nadine D. Tanenbaum, Stephen R. Smith, and John P. Middleton. “Automated external defibrillators and survival from cardiac arrest in the outpatient hemodialysis clinic.” J Am Soc Nephrol 18, no. 1 (January 2007): 312–20. https://doi.org/10.1681/ASN.2006040392.
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  - Norris, Keith, Jacque Bourgoigne, Jennifer Gassman, Lee Hebert, John Middleton, Robert A. Phillips, Otelio Randall, et al. “Cardiovascular outcomes in the African American Study of Kidney Disease and Hypertension (AASK) Trial.” Am J Kidney Dis 48, no. 5 (November 2006): 739–51. https://doi.org/10.1053/j.ajkd.2006.08.004.
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  - Dixon, B. S., G. J. Beck, L. M. Dember, T. A. Depner, J. J. Gassman, T. Greene, J. Himmelfarb, et al. “Erratum: Design of the Dialysis Access Consortium (DAC) aggrenox prevention of access stenosis trial (Clinical Trials 2 (400-412)).” Clinical Trials 3, no. 2 (June 9, 2006): 160. https://doi.org/10.1191/1740774506cn146xx.
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  - Winn, Michelle P., Nikki Daskalakis, Robert F. Spurney, and John P. Middleton. “Unexpected role of TRPC6 channel in familial nephrotic syndrome: does it have clinical implications?” J Am Soc Nephrol 17, no. 2 (February 2006): 378–87. https://doi.org/10.1681/ASN.2005090962.
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  - Tanenbaum, N. D., D. N. Howell, J. P. Middleton, and R. F. Spurney. “Lambda light chain deposition disease in a renal allograft.” Transplant Proc 37, no. 10 (December 2005): 4289–92. https://doi.org/10.1016/j.transproceed.2005.10.030.
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  - Lea, Janice, Tom Greene, Lee Hebert, Michael Lipkowitz, Shaul Massry, John Middleton, Stephen G. Rostand, Edgar Miller, Winifred Smith, and George L. Bakris. “The relationship between magnitude of proteinuria reduction and risk of end-stage renal disease: results of the African American study of kidney disease and hypertension.” Arch Intern Med 165, no. 8 (April 25, 2005): 947–53. https://doi.org/10.1001/archinte.165.8.947.
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  - Dember, Laura M., James S. Kaufman, Gerald J. Beck, Bradley S. Dixon, Jennifer J. Gassman, Tom Greene, Jonathan Himmelfarb, et al. “Design of the Dialysis Access Consortium (DAC) Clopidogrel Prevention of Early AV Fistula Thrombosis Trial.” Clin Trials 2, no. 5 (2005): 413–22. https://doi.org/10.1191/1740774505cn118oa.
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  - Dixon, Bradley S., Gerald J. Beck, Laura M. Dember, Thomas A. Depner, Jennifer J. Gassman, Tom Greene, Jonathan Himmelfarb, et al. “Design of the Dialysis Access Consortium (DAC) Aggrenox Prevention Of Access Stenosis Trial.” Clin Trials 2, no. 5 (2005): 400–412. https://doi.org/10.1191/1740774505cn110oa.
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  - Appel, Lawrence J., John Middleton, Edgar R. Miller, Michael Lipkowitz, Keith Norris, Lawrence Y. Agodoa, George Bakris, et al. “The rationale and design of the AASK cohort study.” J Am Soc Nephrol 14, no. 7 Suppl 2 (July 2003): S166–72. https://doi.org/10.1097/01.asn.0000070081.15137.c0.
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  - Lea, Janice P., Denyse T. Brown, Michael Lipkowitz, John Middleton, Keith Norris, and Keith AASK Study Group. “Preventing renal dysfunction in patients with hypertension: clinical implications from the early AASK Trial results.” Am J Cardiovasc Drugs 3, no. 3 (2003): 193–200. https://doi.org/10.2165/00129784-200303030-00005.
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  - Wright, Jackson T., George Bakris, Tom Greene, Larry Y. Agodoa, Lawrence J. Appel, Jeanne Charleston, DeAnna Cheek, et al. “Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial.” Jama 288, no. 19 (November 20, 2002): 2421–31. https://doi.org/10.1001/jama.288.19.2421.
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  - Peri, U. N., A. Z. Fenves, and J. P. Middleton. “Improving survival of octogenarian patients selected for haemodialysis.” Nephrol Dial Transplant 16, no. 11 (November 2001): 2201–6. https://doi.org/10.1093/ndt/16.11.2201.
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  - Lewis, J., L. Agodoa, D. Cheek, T. Greene, J. Middleton, D. O’Connor, A. Ojo, et al. “Comparison of cross-sectional renal function measurements in African Americans with hypertensive nephrosclerosis and of primary formulas to estimate glomerular filtration rate.” Am J Kidney Dis 38, no. 4 (October 2001): 744–53. https://doi.org/10.1053/ajkd.2001.27691.
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  - Agodoa, L. Y., L. Appel, G. L. Bakris, G. Beck, J. Bourgoignie, J. P. Briggs, J. Charleston, et al. “Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial.” Jama 285, no. 21 (June 6, 2001): 2719–28. https://doi.org/10.1001/jama.285.21.2719.
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  - Schwartz, M. M., E. J. Lewis, T. Leonard-Martin, J. B. Lewis, and D. Batlle. “Renal pathology patterns in type II diabetes mellitus: relationship with retinopathy. The Collaborative Study Group.” Nephrol Dial Transplant 13, no. 10 (October 1998): 2547–52. https://doi.org/10.1093/ndt/13.10.2547.
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  - Middleton, J. P. “Ischemic disease of the kidney: how and why to consider revascularization.” J Nephrol 11, no. 3 (1998): 123–36.
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  - Middleton, J. P. “Direct regulation of the Na,K pump by signal transduction mechanisms.” Miner Electrolyte Metab 22, no. 5–6 (1996): 293–302.
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  - SPURNEY, R. F., J. P. MIDDLETON, J. R. RAYMOND, and T. M. COFFMAN. “MODULATION OF THROMBOXANE RECEPTOR ACTIVATION IN RAT GLOMERULAR MESANGIAL CELLS.” American Journal of Physiology 267, no. 3 (September 1, 1994): F467–78.
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  - Quarles, L. D., J. E. Hartle, J. P. Middleton, J. Zhang, J. M. Arthur, and J. R. Raymond. “Aluminum-induced DNA synthesis in osteoblasts: mediation by a G-protein coupled cation sensing mechanism.” J Cell Biochem 56, no. 1 (September 1994): 106–17. https://doi.org/10.1002/jcb.240560115.
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  - Spurney, R. F., J. P. Middleton, J. R. Raymond, and T. M. Coffman. “Modulation of thromboxane receptor activation in rat glomerular mesangial cells.” Am J Physiol 267, no. 3 Pt 2 (September 1994): F467–78. https://doi.org/10.1152/ajprenal.1994.267.3.F467.
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  - McGill, J. M., S. Basavappa, A. W. Mangel, G. H. Shimokura, J. P. Middleton, and J. G. Fitz. “Adenosine triphosphate activates ion permeabilities in biliary epithelial cells.” Gastroenterology 107, no. 1 (July 1994): 236–43. https://doi.org/10.1016/0016-5085(94)90082-5.
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  - Fitz, J. G., A. H. Sostman, and J. P. Middleton. “Regulation of cation channels in liver cells by intracellular calcium and protein kinase C.” American Journal of Physiology Gastrointestinal and Liver Physiology 266, no. 4 29-4 (May 24, 1994).
  - FITZ, J. G., A. H. SOSTMAN, and J. P. MIDDLETON. “REGULATION OF CATION CHANNELS IN LIVER-CELLS BY INTRACELLULAR CALCIUM AND PROTEIN-KINASE-C.” American Journal of Physiology 266, no. 4 (April 1, 1994): G677–84.
    Link to Item
  - Fitz, J. G., A. H. Sostman, and J. P. Middleton. “Regulation of cation channels in liver cells by intracellular calcium and protein kinase C.” Am J Physiol 266, no. 4 Pt 1 (April 1994): G677–84. https://doi.org/10.1152/ajpgi.1994.266.4.G677.
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  - Spurney, R. F., J. P. Middleton, J. R. Raymond, and T. M. Coffman. “Modulation of thromboxane receptor activation in rat glomerular mesangial cells.” Am.J.Physiol. 267, no. 3 part 2 (January 1, 1994).
  - Middleton, J. P., W. A. Khan, G. Collinsworth, Y. A. Hannun, and R. M. Medford. “Heterogeneity of protein kinase C-mediated rapid regulation of Na/K-ATPase in kidney epithelial cells.” J Biol Chem 268, no. 21 (July 25, 1993): 15958–64.
    Link to Item
  - Bates, M. D., C. L. Olsen, B. N. Becker, F. J. Albers, J. P. Middleton, J. G. Mulheron, S. L. Jin, M. Conti, and J. R. Raymond. “Elevation of cAMP is required for down-regulation, but not agonist-induced desensitization, of endogenous dopamine D1 receptors in opossum kidney cells. Studies in cells that stably express a rat cAMP phosphodiesterase (rPDE3) cDNA.” J Biol Chem 268, no. 20 (July 15, 1993): 14757–63.
    Link to Item
  - Basavappa, S., J. Middleton, A. W. Mangel, J. M. McGill, J. A. Cohn, and J. G. Fitz. “Cl- and K+ transport in human biliary cell lines.” Gastroenterology 104, no. 6 (June 1993): 1796–1805. https://doi.org/10.1016/0016-5085(93)90661-u.
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  - MANGEL, A. W., N. D. SNOW, M. A. MISUKONIS, S. BASAVAPPA, J. P. MIDDLETON, J. G. FITZ, and R. A. LIDDLE. “CALCIUM-DEPENDENT REGULATION OF CHOLECYSTOKININ SECRETION AND POTASSIUM CURRENTS IN STC-1 CELLS.” American Journal of Physiology 264, no. 6 (June 1, 1993): G1031–36.
    Link to Item
  - Mangel, A. W., N. D. Snow, M. A. Misukonis, S. Basavappa, J. P. Middleton, J. G. Fitz, and R. A. Liddle. “Calcium-dependent regulation of cholecystokinin secretion and potassium currents in STC-1 cells.” Am J Physiol 264, no. 6 Pt 1 (June 1993): G1031–36. https://doi.org/10.1152/ajpgi.1993.264.6.G1031.
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  - Middleton, J. P., A. W. Mangel, S. Basavappa, and J. G. Fitz. “Nucleotide receptors regulate membrane ion transport in renal epithelial cells.” Am J Physiol 264, no. 5 Pt 2 (May 1993): F867–73. https://doi.org/10.1152/ajprenal.1993.264.5.F867.
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  - Quarles, L. D., D. M. Haupt, G. Davidai, and J. P. Middleton. “Prostaglandin F2 alpha-induced mitogenesis in MC3T3-E1 osteoblasts: role of protein kinase-C-mediated tyrosine phosphorylation.” Endocrinology 132, no. 4 (April 1993): 1505–13. https://doi.org/10.1210/endo.132.4.8462449.
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  - Basavappa, S., J. Middleton, A. W. Mangel, J. M. Mcgill, J. A. Cohn, and J. G. Fitz. “Cl^- and K⁺ transport in human biliary cell lines.” Gastroenterology 104, no. 6 (1993): 1796–1805.
  - Becker, B. N., T. W. Gettys, J. P. Middleton, C. L. Olsen, F. J. Albers, S. L. Lee, B. L. Fanburg, and J. R. Raymond. “8-hydroxy-2-(di-n-propylamino)tetralin-responsive 5-hydroxytryptamine4-like receptor expressed in bovine pulmonary artery smooth muscle cells.” Mol Pharmacol 42, no. 5 (November 1992): 817–25.
    Link to Item
  - Fan, P. Y., M. Haas, and J. P. Middleton. “Identification of a regulated Na/K/Cl cotransport system in a distal nephron cell line.” Biochim Biophys Acta 1111, no. 1 (October 19, 1992): 75–80. https://doi.org/10.1016/0005-2736(92)90276-r.
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  - Raymond, J. R., F. J. Albers, and J. P. Middleton. “Functional expression of human 5-HT1A receptors and differential coupling to second messengers in CHO cells.” Naunyn Schmiedebergs Arch Pharmacol 346, no. 2 (August 1992): 127–37. https://doi.org/10.1007/BF00165293.
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  - Collins, D. M., M. B. Lambert, J. P. Middleton, R. K. Proctor, C. J. Davidson, G. E. Newman, and S. J. Schwab. “Fistula dysfunction: effect on rapid hemodialysis.” Kidney Int 41, no. 5 (May 1992): 1292–96. https://doi.org/10.1038/ki.1992.192.
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  - Schwinn, D. A., S. O. Page, J. P. Middleton, W. Lorenz, S. B. Liggett, K. Yamamoto, E. G. Lapetina, M. G. Caron, R. J. Lefkowitz, and S. Cotecchia. “The alpha 1C-adrenergic receptor: characterization of signal transduction pathways and mammalian tissue heterogeneity.” Mol Pharmacol 40, no. 5 (November 1991): 619–26.
    Link to Item
  - Raymond, J. R., F. J. Albers, J. P. Middleton, R. J. Lefkowitz, M. G. Caron, L. M. Obeid, and V. W. Dennis. “5-HT1A and histamine H1 receptors in HeLa cells stimulate phosphoinositide hydrolysis and phosphate uptake via distinct G protein pools.” J Biol Chem 266, no. 1 (January 5, 1991): 372–79.
    Link to Item
  - Schwinn, D. A., S. O. Page, J. P. Middleton, W. Lorenz, S. B. Liggett, K. Yamamoto, E. G. Lapetina, M. G. Caron, R. J. Lefkowitz, and S. Cotecchia. “The α_1C-adrenergic receptor: Characterization of signal transduction pathways and mammalian tissue heterogeneity.” Molecular Pharmacology 40, no. 5 (1991): 619–26.
  - Schwinn, D. A., S. O. Page, J. P. Middleton, W. Lorenz, S. B. Liggett, K. Yamamoto, E. G. Lapetina, M. G. Caron, R. J. Lefkowitz, and S. Cotecchia. “The α(1C)-adrenergic receptor: Characterization of signal transduction pathways and mammalian tissue heterogeneity.” Molecular Pharmacology 40, no. 5 (January 1, 1991): 619–26.
  - Middleton, J. P., J. R. Raymond, A. R. Whorton, and V. W. Dennis. “Short-term regulation of Na+/K+ adenosine triphosphatase by recombinant human serotonin 5-HT1A receptor expressed in HeLa cells.” J Clin Invest 86, no. 6 (December 1990): 1799–1805. https://doi.org/10.1172/JCI114909.
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  - Middleton, J. P., F. J. Albers, V. W. Dennis, and J. R. Raymond. “Thapsigargin demonstrates calcium-dependent regulation of phosphate uptake in HeLa cells.” Am J Physiol 259, no. 4 Pt 2 (October 1990): F727–31. https://doi.org/10.1152/ajprenal.1990.259.4.F727.
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  - RAYMOND, J. R., J. P. MIDDLETON, and V. W. DENNIS. “HELA-CELLS EXPRESS CAMP-INHIBITABLE SODIUM-DEPENDENT PHOSPHATE-UPTAKE.” American Journal of Physiology 258, no. 2 (February 1, 1990): F433–37.
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  - Raymond, J. R., J. P. Middleton, and V. W. Dennis. “HeLa cells express cAMP-inhibitable sodium-dependent phosphate uptake.” Am J Physiol 258, no. 2 Pt 2 (February 1990): F433–37. https://doi.org/10.1152/ajprenal.1990.258.2.F433.
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  - MIDDLETON, J. P., J. R. RAYMOND, A. FARGIN, A. R. WHORTON, M. G. CARON, R. J. LEFKOWITZ, and V. W. DENNIS. “RECOMBINANT HUMAN 5-HT1A RECEPTOR IN HELA-CELLS STIMULATES NA+/K+ ATPASE ACTIVITY VIA A CALCIUM-DEPENDENT MECHANISM.” Kidney International 37, no. 1 (January 1, 1990): 567–567.
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  - RAYMOND, J. R., A. FARGIN, J. P. MIDDLETON, J. GRAFF, D. M. HAUPT, M. G. CARON, R. J. LEFKOWITZ, and V. W. DENNIS. “THE CLONED HUMAN 5-HT1A RECEPTOR EXPRESSED IN HELA-CELLS STIMULATES SODIUM-DEPENDENT PHOSPHATE-TRANSPORT (SDPT) VIA PROTEIN KINASE-C (PKC).” Kidney International 37, no. 1 (January 1, 1990): 202–202.
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  - Raymond, J. R., A. Fargin, J. P. Middleton, J. M. Graff, D. M. Haupt, M. G. Caron, R. J. Lefkowitz, and V. W. Dennis. “The human 5-HT1A receptor expressed in HeLa cells stimulates sodium-dependent phosphate uptake via protein kinase C.” J Biol Chem 264, no. 36 (December 25, 1989): 21943–50.
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  - MIDDLETON, J. P., C. B. DUNHAM, J. J. ONORATO, D. A. SENS, and V. W. DENNIS. “PROTEIN KINASE-A, CYTOSOLIC CALCIUM, AND PHOSPHATE-UPTAKE IN HUMAN PROXIMAL RENAL-CELLS.” American Journal of Physiology 257, no. 4 (October 1, 1989): F631–38.
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  - Middleton, J. P., C. B. Dunham, J. J. Onorato, D. A. Sens, and V. W. Dennis. “Protein kinase A, cytosolic calcium, and phosphate uptake in human proximal renal cells.” Am J Physiol 257, no. 4 Pt 2 (October 1989): F631–38. https://doi.org/10.1152/ajprenal.1989.257.4.F631.
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  - Schwab, S. J., L. D. Quarles, J. P. Middleton, R. H. Cohan, M. Saeed, and V. W. Dennis. “Hemodialysis-associated subclavian vein stenosis.” Kidney Int 33, no. 6 (June 1988): 1156–59. https://doi.org/10.1038/ki.1988.124.
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  - Middleton, J. P., and J. C. Wolper. “Hepatic biloma complicating sickle cell disease. A case report and a review of the literature.” Gastroenterology 86, no. 4 (April 1984): 743–44.
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- Other Articles
  - MIddleton, J. P., and R. W. Lehrich. “NephSAP: End-Stage Renal Disease and Dialysis.” Nephsap. ASN, November 1, 2014.
- Conference Papers
  - McCullough, Peter, Matthew Weir, Emil degoma, Qing Zuraw, Amit Sharma, Wenli Luo, and John Middleton. “VADADUSTAT DOES NOT PROLONG CORRECTED QT INTERVAL IN A THOROUGH QTC STUDY IN HEALTHY SUBJECTS.” In Nephrology Dialysis Transplantation, 32:582–582. OXFORD UNIV PRESS, 2017.
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  - Farber, Alik, Tze-Woei Tan, Bo Hu, Laura M. Dember, Gerald J. Beck, Bradley S. Dixon, John W. Kusek, Harold I. Feldman, Harold I. Dialysis Access Consortium (DAC) Study Group, and Harold I. Dialysis Access Consortium DAC Study Group. “The effect of location and configuration on forearm and upper arm hemodialysis arteriovenous grafts.” In J Vasc Surg, 62:1258–64, 2015. https://doi.org/10.1016/j.jvs.2015.06.132.
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  - Raasch, E., P. Pun, A. Starr, I. Klem, and J. P. Middleton. “CHRONIC KIDNEY DISEASE, RISK OF CARDIAC ARREST, AND MYOCARDIAL FIBROSIS.” In Journal of Investigative Medicine, 58:431–431. LIPPINCOTT WILLIAMS & WILKINS, 2010.
    Link to Item
  - Pun, P. H., R. W. Lehrich, S. R. Smith, and J. P. Middleton. “Predictors of survival following sudden cardiac arrest in outpatient hemodialysis clinics.” In Journal of Investigative Medicine, 54:S298–S298. B C DECKER INC, 2006.
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  - Dixon, B. S., T. Greene, G. J. Beck, L. M. Dember, J. J. Gassman, J. Himmelfarb, L. G. Hunsicker, et al. “Dialysis access consortium (DAC) trial design: Sustained-release dipyridamole plus aspirin (D/A) to prevent graft failure.” In Journal of the American Society of Nephrology, 13:232A-232A. LIPPINCOTT WILLIAMS & WILKINS, 2002.
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  - Middleton, J. P., V. G. McDermott, D. G. Schumm, and S. J. Schwab. “Surgical thrombectomy and revision improves survival of hemodialysis (HD) vascular access.” In Journal of the American Society of Nephrology, 7:A0838–A0838. WILLIAMS & WILKINS, 1996.
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  - MIDDLETON, J. P. “DIFFERENTIAL SHORT-TERM REGULATION OF NA/K ATPASE POPULATIONS IN RENAL EPITHELIAL-CELLS.” In Journal of the American Society of Nephrology, 5:294–294. WILLIAMS & WILKINS, 1994.
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  - MIDDLETON, J. P., S. CADY, E. OSTLUND, A. APERIA, and B. D. COWLEY. “A CALCIUM-INDEPENDENT PROTEIN-KINASE-C (PKC) EXPRESSED IN AUTOSOMAL-DOMINANT POLYCYSTIC KIDNEY-DISEASE (ADPKD) SPECIFICALLY INHIBITS NA/K ATPASE.” In Journal of the American Society of Nephrology, 5:294–294. WILLIAMS & WILKINS, 1994.
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  - SPURNEY, R. F., T. M. COFFMAN, and J. P. MIDDLETON. “THROMBOXANE-A(2)[TXA(2)] ACTIVATES PROTEIN KINASE-C-ALPHA, AND KINASE-C-DELTA IN RAT GLOMERULAR MESANGIAL CELLS.” In Journal of the American Society of Nephrology, 5:731–731. WILLIAMS & WILKINS, 1994.
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  - BASAVAPPA, S., A. W. MANGEL, J. M. MCGILL, J. P. MIDDLETON, and J. G. FITZ. “CALCIUM-DEPENDENCE OF ATP-ACTIVATED ION PERMEABILITY IN A HUMAN BILIARY CELL-LINE.” In Gastroenterology, 104:A874–A874. W B SAUNDERS CO, 1993.
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  - MIDDLETON, J. P. “PHOSPHORYLATION OF ALPHA-1 ISOFORM OF NA/K ATPASE IN INTACT RAT-KIDNEY CELLS BY PROTEIN-KINASE-C.” In Clinical Research, 41:A141–A141. SLACK INC, 1993.
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  - QUARLES, L. D., R. CATON, and J. P. MIDDLETON. “PROSTAGLANDIN-F2-ALPHA-INDUCED TYROSINE PHOSPHORYLATION IN MC3T3-E1 OSTEOBLASTS - MITOGENIC ROLE.” In Clinical Research, 40:A340–A340. SLACK INC, 1992.
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  - RAYMOND, J. R., C. L. OLSEN, F. J. ALBERS, J. P. MIDDLETON, B. N. BECKER, and M. D. BATES. “STABLE FUNCTIONAL EXPRESSION OF RAT PHOSPHODIESTERASE TYPE-3 GENE IN OK CELLS DOES NOT ALTER SHORT-TERM HOMOLOGOUS DESENSITIZATION OF NATIVE DOPAMINE-DA1 RECEPTORS.” In Clinical Research, 40:A217–A217. SLACK INC, 1992.
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  - ALBERS, F. J., J. R. RAYMOND, V. W. DENNIS, and J. P. MIDDLETON. “AMPLIFICATION OF CYCLIC-AMP SIGNALING CASCADE IN OPOSSUM KIDNEY (OK) CELLS.” In Clinical Research, 39:A180–A180. SLACK INC, 1991.
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  - RAYMOND, J. R., and J. P. MIDDLETON. “RECOMBINANT HUMAN SEROTONIN 5-HT1A RECEPTORS EXPRESSED IN CHO CELLS COUPLE TO MULTIPLE SIGNAL TRANSDUCTION PATHWAYS.” In Clinical Research, 39:A358–A358. SLACK INC, 1991.
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  - ALBERS, F. J., J. P. MIDDLETON, V. W. DENNIS, and J. R. RAYMOND. “SOMATOSTATIN STIMULATES SODIUM-DEPENDENT PHOSPHATE-UPTAKE IN HELA-CELLS - EVIDENCE FOR A REGULATORY PATHWAY INDEPENDENT OF THE INHIBITION OF ADENYLATE-CYCLASE.” In Clinical Research, 38:A370–A370. SLACK INC, 1990.
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  - MIDDLETON, J. P., J. R. RAYMOND, A. R. WHORTON, and V. W. DENNIS. “THE CLONED HUMAN 5-HT1A RECEPTOR EXPRESSED IN HELA-CELLS STIMULATES NA+/K+ ATPASE VIA ACTIVATION OF VOLTAGE-SENSITIVE CALCIUM CHANNELS.” In Clinical Research, 38:A442–A442. SLACK INC, 1990.
    Link to Item
  - RAYMOND, J. R., J. P. MIDDLETON, F. J. ALBERS, and V. W. DENNIS. “THAPSIGARGIN STIMULATES SODIUM-DEPENDENT PHOSPHATE-UPTAKE IN HELA-CELLS - EVIDENCE FOR A REGULATORY ROLE OF C-2+ WHICH IS INDEPENDENT OF PROTEIN KINASE-C.” In Clinical Research, 38:A245–A245. SLACK INC, 1990.
    Link to Item
  - ALBERS, F. J., J. R. RAYMOND, J. P. MIDDLETON, and V. W. DENNIS. “HISTAMINE-H1 RECEPTORS STIMULATE SODIUM-DEPENDENT PHOSPHATE-UPTAKE VIA A PERTUSSIS TOXIN-INSENSITIVE G-PROTEIN AND PROTEIN KINASE-C IN HELA-CELLS.” In Kidney International, 37:453–453. BLACKWELL SCIENCE INC, 1990.
    Link to Item
  - DENNIS, V. W., J. P. MIDDLETON, F. J. ALBERS, and J. R. RAYMOND. “PROTEIN KINASE-A (PKA) AND PROTEIN KINASE-C (PKC) HAVE OPPOSITE EFFECTS ON PHOSPHATE-TRANSPORT IN HELA-CELLS.” In Kidney International, 37:456–456. BLACKWELL SCIENCE INC, 1990.
    Link to Item
  - DENNIS, V. W., D. A. SENS, and J. P. MIDDLETON. “HUMAN PROXIMAL RENAL-CELLS IN CULTURE - HORMONAL EFFECTS ON PHOSPHATE-TRANSPORT.” In Kidney International, 35:391–391. BLACKWELL SCIENCE INC, 1989.
    Link to Item
  - MIDDLETON, J. P., J. J. ONORATO, C. B. DUNHAM, D. A. SENS, and V. W. DENNIS. “COMPARISON OF CYCLIC-AMP PATHWAYS IN HUMAN AND OPOSSUM PROXIMAL RENAL-CELLS.” In Kidney International, 35:178–178. BLACKWELL SCIENCE INC, 1989.
    Link to Item
  - ONORATO, J. J., J. P. MIDDLETON, and V. W. DENNIS. “INHIBITION OF PTH-STIMULATED ADENYLATE-CYCLASE IN PROXIMAL TUBULE CELLS - EVIDENCE FOR AMPLIFICATION OF CYCLIC-AMP.” In Kidney International, 35:180–180. BLACKWELL SCIENCE INC, 1989.
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