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Pharmacotherapeutic considerations for chronic pain in chronic kidney and end-stage renal disease

Authors Mathew RO, Bettinger JJ, Wegrzyn EL, Fudin J 

Received 20 October 2016

Accepted for publication 28 October 2016

Published 8 December 2016 Volume 2016:9 Pages 1191—1195


Checked for plagiarism Yes

Editor who approved publication: Dr Michael Schatman

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Roy O Mathew,1 Jeffrey J Bettinger,2 Erica L Wegrzyn,3 Jeffrey Fudin3,4

1Department of Medicine, Wm. Jennings Bryan Dorn VA Medical Center, Columbia, SC, 2Department of Professional Practice, Albany College of Pharmacy and Health Sciences, 3Department of Pharmacy, Albany Stratton VA Medical Center, Albany, 4Scientific and Clinical Affairs, Remitigate, LLC, Delmar, NY, USA

In hemodialysis (HD) patients, the prevalence of chronic pain can be up to 92%.1 A survey of HD patients found 55% reported a severe pain episode in the previous 24 hours.2 Furthermore, ~75% of HD patients report inadequate pain management.2 Despite these shocking statistics there is no universally accepted guideline for the treatment of pain in HD patients. Nevertheless, poorly managed pain in HD patients promulgates psychological disturbances, impaired sleep, decreased dialysis compliance, and an overall decline in quality of life.1


Jeffrey Fudin is associated with the following: Astra Zeneca (Speakers Bureau, Advisory Board), Clarity (Consultant), DepoMed (Advisory Board, Speakers Bureau), Endo (Consultant, Speakers Bureau), Kaléo (Speakers Bureau, Advisory Board), Kashiv Pharma (Advisory Board), KemPharm (Consultant), Pernix Therapeutics (Speaker), Remitigate, LLC (Owner), and Scilex Pharmaceuticals (Consultant). This article is the sole work of the authors, and stated opinions/assertions do not reflect the opinion of employers, employee affiliates, and/or pharmaceutical companies listed. It was not prepared as part of the authors’ duty as federal employees. The authors report no other conflicts of interest in this work.



Brkovic T, Burilovic E, Puljak L. Prevalence and severity of pain in adult end-stage renal disease patients on chronic intermittent hemodialysis: a systematic review. Patient Prefer Adherence. 2016;10:1131–1150.


Davison SN. Pain in hemodialysis patients: prevalence, cause, severity, and management. Am J Kidney Dis. 2003;42(6):1239–1247.


Nolin TD. A synopsis of clinical pharmacokinetic alterations in advanced CKD. Semin Dial. 2015;28(4):325–329.


Gabardi S, Abramson S. Drug dosing in chronic kidney disease. Med Clin North Am. 2005;89(3):649–687.


Nolin TD. Altered nonrenal drug clearance in ESRD. Curr Opin Nephrol Hypertens. 2008;17(6):555–559.


Reidenberg MM, Drayer DE. Alteration of drug-protein binding in renal disease. Clin Pharmacokinet. 1984;9(suppl 1):18–26.


St Peter WL, Redic-Kill KA, Halstenson CE. Clinical pharmacokinetics of antibiotics in patients with impaired renal function. Clin Pharmacokinet. 1992;22(3):169–210.


Yeung CK, Shen DD, Thummel KE, Himmelfarb J. Effects of chronic kidney disease and uremia on hepatic drug metabolism and transport. Kidney Int. 2014;85(3):522–528.


Atkinson TJ, Fudin J, Wegrzyn EL, Bettinger JJ. Dialysis, opioids, and pain management: Where’s the evidence? Pract Pain Manag. 2014;14(8):49–57.


Zedler B, Saunders W, Joyce A, et al. Validation of a screening risk index for overdose or serious prescription opioid-induced respiratory depression prescription opioid use and deaths from overdose or opioid-induced respiratory depression. Presented at the 2015 AAPM Annual Meeting. March 2015.


Murtagh FE, Chai MO, Donohoe P, Edmonds PM, Higginson IJ. The use of opioid analgesia in end-stage renal disease patients managed without dialysis: recommendations for practice. J Pain Palliat Care Pharmacother. 2007;21(2):5–16.


Whelton A. Renal and related cardiovascular effects of conventional and COX-2-specific NSAIDs and non-NSAID analgesics. Am J Ther. 2000;7(2):63–74.


Perneger TV, Whelton PK, Klag MJ. Risk of kidney failure associated with the use of acetaminophen, aspirin, and nonsteroidal antiinflammatory drugs. N Engl J Med. 1994;331(25):1675–1679.


Williams AW, Dwyer AC, Eddy AA, et al. Critical and honest conversations: the evidence behind the “Choosing Wisely” campaign recommendations by the American Society of Nephrology. Clin J Am Soc Nephrol. 2012;7(10):1664–1672.


Whelton A. Nephrotoxicity of nonsteroidal anti-inflammatory drugs: physiologic foundations and clinical implications. Am J Med. 1999;106(5B):13S–24S.


Wasse H, Gillen DL, Ball AM, et al. Risk factors for upper gastrointestinal bleeding among end-stage renal disease patients. Kidney Int. 2003;64(4):1455–1461.


Chandna SM, Farrington K. Residual renal function: considerations on its importance and preservation in dialysis patients. Semin Dial. 2004;17(3):196–201.


Curhan GC, Knight EL, Rosner B, Hankinson SE, Stampfer MJ. Lifetime nonnarcotic analgesic use and decline in renal function in women. Arch Intern Med. 2004;164(14):1519–1524.


Sindrup SH, Otto M, Finnerup NB, Jensen TS. Antidepressants in the treatment of neuropathic pain. Basic Clin Pharmacol Toxicol. 2005;96(6):399–409.


Tracy B, Sean Morrison R. Pain management in older adults. Clin Ther. 2013;35(11):1659–1668.


By the American Geriatrics Society Beers Criteria Update Expert P. American Geriatrics Society 2015 updated Beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015;63(11):2227–2246.


Nagler EV, Webster AC, Vanholder R, Zoccali C. Antidepressants for depression in stage 3-5 chronic kidney disease: a systematic review of pharmacokinetics, efficacy and safety with recommendations by European Renal Best Practice (ERBP). Nephrol Dial Transplant. 2012;27(10):3736–3745.


Lobo ED, Heathman M, Kuan HY, et al. Effects of varying degrees of renal impairment on the pharmacokinetics of duloxetine: analysis of a single-dose phase I study and pooled steady-state data from phase II/III trials. Clin Pharmacokinet. 2010;49(5):311–321.


Haanpaa ML, Gourlay GK, Kent JL, Miaskowski C, Raja SN, Schmader KE, Wells CD. Treatment considerations for patients with neuropathic pain and other medical comorbidities. Mayo Clin Proc. 2010;85(3 suppl):S15–S25.


Pristiq (desvenlafaxine succinate); Package Insert [Internet]. Bethesda, MD: DailyMed; [updated 2016].


Savella (milnacipran hydrochloride); Package Insert [Internet]. Bethesda, MD: DailyMed; [updated Jan 31, 2015].


Fetzima (levomilnacipran); Package Insert [Internet]. Bethesda, MD: DailyMed; [updated July 21, 2014].


Sills GJ. The mechanisms of action of gabapentin and pregabalin. Curr Opin Pharmacol. 2006;6(1):108–113. Epub Dec 22, 2005.


Aronoff GM. Handbook on Pharmacological Management of Chronic Pain. Charlotte, NC: Wavecrest Publishing; 2005.


Neurontin; Package Insert [Internet]. Bethesda, MD: DailyMed; [updated Nov 11, 2015].


Lyrica; Package Insert [Internet]. Bethesda, MD: DailyMed; [updated Jun 23, 2016].


Carbamazepine; Package Insert [Internet]. Bethesda, MD: DailyMed; [updated Jan 28, 2008].


Kral LA, Ghafoor VL. Pain and its management: neuropathic pain and postherpetic neuralgia. Chapter 7. In: Brian K. Alldredge, Robin L. Corelli, Michael E. Ernst, B. Joseph Gugliemo, Pamala A. Jacobson, Wayne A. Kradjan, Bradley R. Williams, editors. Koda-Kimble & Young’s Applied Therapeutics: The Clinical Use of Drugs. 10th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2013:126–130.


Bernus I, Dickinson RG, Hooper WD, Eadie MJ. The mechanism of the carbamazepine-valproate interaction in humans. Br J Clin Pharmacol. 1997;44:21–27.


Al-Quliti KW. Update on neuropathic pain treatment for trigeminal neuralgia: the pharmacological and surgical options. Neurosciences. 2015;20(2):107–114.


Oxcarbazepine; Package Insert [Internet]. Bethesda, MD: DailyMed; [updated Jul 21, 2014].

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