Research

Commercially available intravenous (IV) iron formulations are complex colloidal suspensions of iron oxide-carbohydrate nanoparticles. High IV iron doses have been associated with higher mortality and infection rates that may be due, in part, to labile iron release and oxidative stress. The currently available formulations are exhibit heterogeneity in their physicochemical characteristics yet little work has been done to evaluate differential toxicity profiles among these agents. Dr. Pai’s clinical and translational research program was among the first to comparatively measure labile iron release form IV iron formulations in vivo and evaluate oxidative stress induction and bacterial growth. This body of work lead to application of techniques for bioequivalence evaluation of generic IV iron formulations. Dr. Pai’s work in this translational paradigm has bridged a critical gap between clinicians and nanomedicine science.

• Charytan DM, Pai AB, Chan CT, Coyne DW, Hung AM, Kovesdy CP, Fishbane S, On behalf of the American Society of Nephrology Dialysis Advisory Group. Considerations and Challenges in Defining the Optimal Utilization of Iron in Dialysis-Dependent Chronic Kidney Disease. J Am Soc Nephrol. 2015;26(6):1238-1247 PMID:25542967
• Conner TA, McQuade CR, Olp J, Pai AB. Effect of Intravenous Vitamin C  on Reactive Oxygen Species Generation, Cytokine Activation and Oxidative Stress in Hemodialysis (HD) Patients Receiving Intravenous Iron Sucrose (IS). Biometals. 2012 Oct;25(5):961-9 PMID: 22706571
• Pai AB, McQuade C, Olp J. Hicks P, Conner T.  Non-transferrin Bound Iron (NTBI), Cytokine Activation and Intracellular Reactive Oxygen Species Generation in hemodialysis (HD) Patients Receiving Iron Dextran (ID) or Iron Sucrose (IS). Biometals 2011; Jan 13 PMID: 21229380
• Gupta A, Zhuo J, Zha J, Reddy S, Olp J, Pai AB. Effect of different intravenous iron preparations on lymphocyte intracellular reactive oxygen species generation and subpopulation survival. BMC Nephrology 2010:11;16 PMID: 20716362
• Pai AB, Nielson JC, Kausz A, Miller P, Owen J. Plasma Pharmacokinetics of two consecutive doses of ferumoxytol in Healthy Subjects. Clin Pharmacol Ther 2010;June 30:1-5 PMID: 20592725
• Pai AB, Harford A, Boyd AV, McQuade C, Norenberg JP,  Zager P. Comparison of oxidative stress markers in hemodialysis patients following administration of iron dextran, sodium ferric gluconate and iron sucrose. Pharmacotherapy 2007;27:343-350 PMID: 17316146 

Reduced kidney function affects the safety profile of countless medications. Many adverse drug events caused by medications that are not used correctly in chronic kidney disease can be avoided. One significant example of this is the avoidance of non-steroidal anti-inflammatory drugs (NSAIDs) in patients at high risk for community-acquired acute kidney injury. Dr Pai has studied multiple pragmatic ways to improve education of providers and patients to reduce NSAID use in high risk patients. Dr. Pai’s work in this arena has led to research funding from the FDA and national appointments to develop educational programs and materials for providers and patients.

• Jang S, Prokopienko AJ, Grabe DW, Cerulli J, Fox C, Vassalotti J, Pai AB. NSAID-Avoidance Education in Community Pharmacies for Patients at High Risk for Acute Kidney Injury, Upstate New York, 2011. Prev Chronic Dis. 2014 Dec 18;11:E220
• Pai AB. Keeping Kidneys Safe: The Pharmacist’s Role in NSAID Avoidance in High-Risk Patients. J Am Pharm Assoc (2003). 2015 Jan 1;55(1):e15-25
• Gilmartin C, Pai AB, Hughes D, Hilal N. Risky business: Lessons from medication misadventures in chronic kidney disease. Physician Assist Clinic 2016;1:55-76

Pharmacists are highly accessible and under utilized health care providers. Medication management and patient adherence are fundamental challenges in achieving good outcomes in chronic disease states. Dr. Pai's work in this area focuses of pharmacists as disrupters in the current health care system structure. Dr. Pai conducted the only randomized, controlled clinical trial of provision of medication management by a pharmacist compared to standard of care in hemodialysis patients. This has served as the springboard for dialysis providers to provide these services to their patients.

• Pai AB, Cardone KE, Manley HJ, St. Peter W, Shaffer R, Somers M, Mehrotra R. Medication Reconciliation and Therapy Management in Dialysis-Dependent Patients: Need for a Systematic Approach. Clin  J Am Soc Nephrol. Invited Commentary. 2013 Nov;8(11):1988-99
• Manley HJ, Pai AB. Integrated Pharmacy Services: a necessary component for ESRD patient care. Am J Kidney Dis 2013; Sep;62(3):445-7 PMID: 23972057
• Pai AB, Depczynski JC, Martinez I, Boyd A, Khan N, Manley HJ. Reduced drug use hospitalization rates in patients undergoing hemodialysis who received pharmaceutical care-a 2 year randomized, controlled study.  Pharmacotherapy. 2009;29(12):1433-1440 PMID: 19947803