Thomas D. Nolin, PharmD, PhD is a tenured Associate Professor in the Department of Pharmacy & Therapeutics, and in the Department of Medicine Renal-Electrolyte Division at the University of Pittsburgh. He is an NIH funded investigator whose primary research focuses on developing an understanding of the impact of kidney disease and renal replacement therapy (RRT) on nonrenal metabolism and transport pathways and corresponding effects on drug exposure and response. Dr. Nolin has a strong record of interdisciplinary and interinstitutional collaborations with regulatory, pharmaceutical industry, and academic scientists in the conduct of clinical-translational studies exploring pharmacokinetics/pharmacodynamics and consequent drug dosing requirements in patients with kidney disease. He served as chair of the Kidney Health Initiative workgroup to assess pharmacokinetics during RRT and as co-chair of the Extracorporeal Treatments in Poisoning (EXTRIP) Workgroup. Dr. Nolin has published over 100 manuscripts and book chapters and has presented more than 120 scientific abstracts and invited talks. He serves on the editorial board of the American Journal of Kidney Diseases and as an Editor of the textbook Pharmacotherapy: A Pathophysiological Approach. Dr. Nolin is a Fellow of the American College of Clinical Pharmacy, the American College of Clinical Pharmacology, and of the American Society of Nephrology.
The research focus of the Nolin laboratory includes characterizing the impact of kidney disease and renal replacement therapy on drug exposure (clinical pharmacokinetics) and response (pharmacodynamics), evaluating the functional expression of drug metabolizing enzymes and transporters, and developing novel quantitative analytical techniques. My primary research focuses on studying the effect of kidney disease on pathways of nonrenal drug clearance, particularly those mediated by drug metabolizing enzymes and active transporters. The long-range goal of our research is to identify the mechanisms by which kidney disease contributes to alterations in these drug elimination pathways, to understand the impact of these alterations on drug response and patient outcomes, and ultimately, to use this information in the development of strategies to optimize drug use in patients with kidney disease.
SELECTED PEER REVIEWED PUBLICATIONS (2015-2018)
1. Tortorici MA, Cutler D, Hazra A, Nolin TD, Rowland-Yeo K, Venkatakrishnan K. Emerging areas of research in the assessment of pharmacokinetics in patients with chronic kidney disease. J Clin Pharmacol 2015;55(3)241-50. PMID: 25501531.
2. Ocque AJ, Stubbs JR, Nolin TD. Development and validation of an UHPLC-MS/MS method for the simultaneous determination of trimethylamine N-oxide, choline, and betaine in human plasma and urine. J Pharm Biomed Anal 2015;109:128-135. PMID: 25767908.
3. Nolin TD. A synopsis of clinical pharmacokinetic alterations in advanced CKD. Semin Dial 2015;28(4):325-329. PMCID: PMC4496305.
4. Naud J, Dumayne C, Nolin TD, Leblond FA, Pichette V. Drug pharmacokinetics in renal failure: What’s new? [Article in French] Néphrol Thér 2015;11(3):144-51. PMID: 25861715.
5. Walsh DW, Nolin TD, Friedman PA. Drug transporters and Na+/H+ exchange regulatory factor PSD-95/drosophila discs large/ZO-1 proteins. Pharmacol Rev 2015;67(3):656-680. PMCID: PMC4485015.
6. Alshogran OY, Urquhart BL, Nolin TD. Downregulation of hepatic carbonyl reductase type 1 in end-stage renal disease. Drug Metab Lett 2015;9(2):111-118. PMID: 26282591.
7. Pai AB, Grabe DW, Eisele G, Haqqie S, Patel H, Prokopienko AJ, Nolin TD, Kubotera N. Changes in plasma levels of asymmetric dimethylarginine in chronic kidney disease patients treated for 8 weeks with the vitamin D receptor agonist paricalcitol. J Res Development 2015;3(2):1000129. doi: 10.4172/jrd.1000129.
8. de Caestecker M, Humphreys BD, Liu KD, Fissell WH, Cerda J, Nolin TD, Askenazi D, Mour G, Harrell FE, Pullen N, Okusa M, Faubel S, for the Acute Kidney Injury Advisory Group of the American Society of Nephrology. Bridging translation by improving preclinical study design in AKI. J Am Soc Nephrol 2015;26(12):2905-16. PMID 26538634.
9. Roberts DM, Yates C, Megarbane B, Winchester JF, Maclaren R, Gosselin S, Nolin TD, Levergne V, Hoffman RS, Ghannoum M. Recommendations for the role of extracorporeal treatments in the management of acute methanol poisoning: A systematic review and consensus statement. Crit Care Med 2015;43(2):461-72. PMID: 25493973.
10. Decker BS, Goldfarb DS, Dargan PI, Friesen M, Gosselin S, Hoffman RS, Levergne V, Nolin TD, Ghannoum M. Extracorporeal treatment for lithium poisoning: Systematic review and recommendations from the EXTRIP Workgroup. Clin J Am Soc Nephrol 2015;10(5):875-887. PMCID: PMC4422246.
11. Ghannoum M, Wiegand TJ, Liu KD, Calello DP, Godin M, Lavergne V, Gosselin S, Nolin TD, Hoffman RS. Extracorporeal treatment for theophylline poisoning: Systematic review and recommendations from the EXTRIP Workgroup. Clin Toxicol (Phila) 2015;53(4):215-229. PMID: 25715736.
12. Calello DP, Liu KD, Wiegand TJ, Roberts DM, Lavergne V, Gosselin S, Hoffman RS, Nolin TD, Ghannoum M. Extracorporeal treatment for metformin poisoning: Systematic review and recommendations from the Extracorporeal Treatments in Poisoning Workgroup. Crit Care Med 2015;43(8):1716-30. PMID: 25860205.
13. Juurlink DN, Gosselin S, Kielstein JT, Ghannoum M, Lavergne V, Nolin TD, Hoffman RS. Extracorporeal treatment for salicylate poisoning: Systematic review and recommendations from the EXTRIP Workgroup. Ann Emerg Med 2015;66(2):165-81. PMID: 25986310.
14. Ghannoum M, Laliberté M, Nolin TD, Mactier R, Lavergne V, Hoffman RS, Gosselin S. Extracorporeal treatment for valproic acid poisoning: Systematic review and recommendations from the EXTRIP Workgroup. Clin Toxicol (Phila) 2015;53(5):454-65. PMID: 25950372.
15. Hudson JQ, Nolin TD. Estimated GFR and cystatin C for drug dosing: Moving beyond proof of concept to clinical translation? Am J Kidney Dis 2015;65(4):534-536. PMID: 25542411.
16. Wilson FP, Nolin TD, Berns JS. Drugs, dialysis, decisions, and data: A walk through the minefield of nephropharmacology. Semin Dial 2015;28(4):323-324. PMID: 25929704.
17. Alshogran OY, Ocque AJ, Leblond FA, Pichette V, Nolin TD. Validation and application of a simple UHPLC-MS/MS method for enantiospecific determination of warfarin in human urine. J Chromatogr Sci 2016;54(4):554-60. PMCID: PMC4885390.
18. Stubbs JR, House JA, Ocque AJ, Zhang S, Johnson C, Kimber C, Schmidt K, Gupta A, Wetmore JB, Nolin TD, Spertus JA, Yu AS. Serum trimethylamine-N-oxide is elevated in CKD and correlates with coronary atherosclerosis burden. J Am Soc Nephrol 2016;27(1):305-13. PMCID: PMC4696571.
19. Yoshida K, Sun B, Zhang L, Zhao P, Abernethy D, Nolin TD, Rostami-Hodjegan A, Zineh I, Huang SM. Systematic and quantitative assessment of the effect of chronic kidney disease on CYP2D6 and CYP3A4/5. Clin Pharmacol Ther. 2016;100(1):75-87. PMCID: PMC5024330.
20. Vijayan A, Faubel S, Askenazi DJ, Cerda J, Fissell WH, Heung M, Humphreys BD, Koyner JL, Liu KD, Mour G, Nolin TD, Bihorac A, for the Acute Kidney Injury Advisory Group of the American Society of Nephrology. Clinical use of the urine biomarker [TIMP-2] × [IGFBP7] for acute kidney injury risk assessment. Am J Kidney Dis. 2016;68(1):19-28. PMCID: PMC4921267.
21. Roumelioti ME, Nolin T, Unruh ML, Argyropoulos C. Revisiting the middle molecule hypothesis of uremic toxicity: A systematic review of beta 2 microglobulin population kinetics and large scale modeling of hemodialysis trials in silico. PLoS One 2016;11(4):e0153157. PMCID: PMC4824495.
22. Anseeuw K, Mowry JB, Burdmann EA, Ghannoum M, Hoffman RS, Gosselin S, Lavergne V, Nolin TD. Extracorporeal treatment in phenytoin poisoning: Systematic review and recommendations from the EXTRIP (Extracorporeal Treatment in Poisoning) Workgroup. Am J Kidney Dis 2016;67(2):187-97. PMID: 26578149.
23. Mowry JB, Burdmann EA, Anseeuw K, Ayoub P, Ghannoum M, Hoffman RS, Lavergne V, Nolin TD, Gosselin S. Extracorporeal treatment for digoxin poisoning: Systematic review and recommendations from the EXTRIP Workgroup. Clin Toxicol (Phila) 2016;54(2):103-14. PMID: 26795743.
24. Nolin TD. Vancomycin and the risk of AKI: Now clearer than Mississippi mud. Clin J Am Soc Nephrol 2016;11(12):2101-2103. PMCID: PMC5142077.
25. Alshogran OY, Nolin TD. Implications of kidney disease on metabolic reduction. Curr Drug Metab 2016;17(7):663-72. PMID: 27262337.
26. Hagos FT, Daood MJ, Ocque JA, Nolin TD, Bayir H, Poloyac SM, Kochanek PM, Clark RSB, Empey PE. Probenecid, an organic anion transporter 1 and 3 inhibitor, increases plasma and brain exposure of N-acetylcysteine. Xenobiotica 2017;47(4):346-53. PMCID: PMC5572076.
27. Clark RSB, Empey PE, Bayir H, Rosario BL, Poloyac SM, Kochanel PM, Nolin TD, Au AK, Horvat CM, Wisniewski SR, Bell MJ. Phase I randomized clinical trial of N-acetylcysteine in combination with an adjuvant probenecid for treatment of severe traumatic brain injury in children. PLoS One 2017;12(7):e0180280. PMCID: PMC5501440.
28. Ermer T, Kopp C, Asplin JR, Granja I, Perazella MA, Reichel M, Nolin TD, Eckardt KU, Aronson PS, Finkelstein FO, Knauf F. Impact of regular or extended hemodialysis and hemodialfiltration on plasma oxalate concentrations in patients with end-stage renal disease. Kidney Int Rep 2017;2(6):1050-58. PMCID: PMC5733827.
29. Prokopienko AJ, Nolin TD. Microbiota-derived uremic retention solutes: Perpetrators of altered nonrenal drug clearance in kidney disease. Expert Rev Clin Pharmacol 2018;11(1):71-82. PMID: 28905671.
30. Tan ML, Yoshida K, Zhao P, Zhang L, Nolin TD, Piquette-Miller M, Galetin A, Huang SM. Effect of chronic kidney disease on nonrenal elimination pathways: A systematic assessment of CYP1A2, CYP2C8, CYP2C9, CYP2C19 and OATP. Clin Pharmacol Ther 2018;103(5):854-67. PMCID: PMC5947523.
31. Roumelioti ME, Trietley G, Nolin TD, Ng YH, Xu Z, Alaini A, Figueroa R, Unruh ML, Argyropoulos CP. Beta-2 microglobulin clearance in high-flux dialysis and convective dialysis modalities: A meta-analysis of published studies. Nephrol Dial Transplant 2018;33(6):1025-39. PMID: 29186592.
32. Hudson JQ, Nolin TD. Pragmatic use of kidney function estimates for drug dosing: The tide is turning. Adv Chronic Kidney Dis 2018;25(1):14-20. PMID: 29499882.
33. Choi YJ, Zhou D, Barbosa ACS, Niu Y, Guan X, Xu M, Ren S, Nolin TD, Liu Y, Xie W. Activation of constitutive androstane receptor ameliorates renal ischemia-reperfusion induced kidney and liver injury. Mol Pharmacol 2018;93(3):239-50. PMID: 29351922.
34. Ghannoum M, Hoffman RS, Gosselin S, Nolin TD, Levergne V, Roberts DM. Use of extracorporeal treatments in the management of poisonings. Kidney Int 2018 June 26 Epub. PMID: 29958694.
35. Nolin TD, Perazella MA. Introduction to Nephropharmacology for the Clinician: A new CJASN series. Clin J Am Soc Nephrol 2018 Apr 16 Epub. PMID: 29661769.
36. Johnson C, Prokopienko AJ, West RE III, Nolin TD, Stubbs JR. Decreased kidney function is associated with enhanced hepatic flavin monooxygenase activity and increased circulating trimethylamine N-oxide concentrations in mice. Drug Metab Dispos. 2018 Jun 18 Epub. PMID: 29915157.
SELECTED PRESENTATIONS (2015-2018)
1. “Opportunities for Improved Medication Safety in Patients with Decreased Kidney Function.” Maine Medical Center, Department of Medicine Grand Rounds, Portland, ME, September 2, 2015.
2. “Nonrenal Drug Clearance in CKD: Searching for the Path Less Traveled.” Maine Medical Center, Department of Medicine Division of Nephrology Noon Conference, Portland, ME, September 2, 2015.
3. “Drug Dose Adjustment of Non-Renally Eliminated Drugs in CKD Patients – What is the Evidence?” Keynote Lecture at 14th NephroPharmacology Meeting, Heidelberg, Germany, October 10, 2015.
4. “CRRT Pharmacokinetics: A New Chapter.” American Society of Nephrology Annual Meeting, Kidney Week 2015, San Diego, CA, November 5, 2015.
5. “Use of Kidney Function Estimates for Drug Dosing: Does One Equation Fit All?” University of Pittsburgh, School of Medicine, Department of Pathology Seminar in Laboratory Medicine, November 16, 2015.
6. “Nonrenal Drug Clearance in CKD: Searching for the Path Less Traveled.” University of Kansas Medical Center, School of Medicine, Division of Nephrology and Hypertension and the Kidney Institute Sullivan Conference, Kansas City, KS, March 4, 2016.
7. “Nonrenal Clearance in CKD.” National Kidney Foundation 2016 Spring Clinical Meeting, Boston, MA, April 27, 2016.
8. “ADME in CKD: Overview of Pharmacokinetic Alterations in Kidney Disease”. American Society of Nephrology Annual Meeting, Kidney Week 2016, Chicago, IL, November 16, 2016.
9. “Clinical Cases in CRRT and IHD.” American Society of Nephrology Annual Meeting, Kidney Week 2016, Chicago, IL, November 16, 2016.
10. “Drug Dosing in Patients Receiving RRT for AKI.” National Kidney Foundation 2017 Spring Clinical Meeting, Orlando, FL, April 21, 2017.
11. “ADME in Kidney Impairment: Searching for the Path Less Traveled.” U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Clinical Pharmacology, Silver Spring, MD, May 8, 2017.
12. “Use of Kidney Function Estimates for Drug Dosing: Does One Equation Fit All?” U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Clinical Pharmacology, Silver Spring, MD, May 15, 2017.
13. “Renal Replacement Therapy: Overview of PK in Intermittent and Continuous Modalities.” U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Clinical Pharmacology, Silver Spring, MD, July 16, 2017.