Journal of Clinical Lipidology
Volume 6, Issue 1 , Pages 19-26 , January 2012

Evaluation of the incidence and risk factors for development of fenofibrate-associated nephrotoxicity

  • Rebecca L. Attridge, PharmD, MSc

      Affiliations

    • University of the Incarnate Word, 4301 Broadway CPO#99, San Antonio, TX 78209, USA
    • University of Texas at Austin, Austin, TX, USA
    • University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
    • Corresponding Author InformationCorresponding author.
    • ,
  • William D. Linn, PharmD

      Affiliations

    • University of the Incarnate Word, 4301 Broadway CPO#99, San Antonio, TX 78209, USA
    • University of Texas at Austin, Austin, TX, USA
    • ,
  • Laurajo Ryan, PharmD, MSc

      Affiliations

    • University of Texas at Austin, Austin, TX, USA
    • University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
    • ,
  • Jim Koeller, MSc

      Affiliations

    • University of Texas at Austin, Austin, TX, USA
    • University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
    • ,
  • Christopher R. Frei, PharmD, MSc

      Affiliations

    • University of Texas at Austin, Austin, TX, USA
    • University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

Received 20 May 2011 ,Accepted 30 August 2011.

References 

  1. Broeders N, Knoop C, Antoine M, Tielemans C, Abramowicz D. Fibrate-induced increase in blood urea and creatinine: is gemfibrozil the only innocuous agent?. Nephrol Dial Transplant. 2000;15:1993–1999
  2. Angeles C, Lane BP, Miller F, Nord EP. Fenofibrate-associated reversible acute allograft dysfunction in 3 renal transplant recipients: biopsy evidence of tubular toxicity. Am J Kidney Dis. 2004;44:543–550
  3. Lipscombe J, Lewis GF, Cattran D, Bargman JM. Deterioration in renal function associated with fibrate therapy. Clin Nephrol. 2001;55:39–44
  4. McQuade CR, Griego J, Anderson J, Pai AB. Elevated serum creatinine levels associated with fenofibrate therapy. Am J Health Syst Pharm. 2008;65:138–141
  5. Nissen SE, Nicholls SJ, Wolski K, et al. Effects of a potent and selective PPAR-alpha agonist in patients with atherogenic dyslipidemia or hypercholesterolemia: two randomized controlled trials. JAMA. 2007;297:1362–1373
  6. Ritter JL, Nabulsi S. Fenofibrate-Induced elevation in serum creatinine. Pharmacotherapy. 2001;21:1145–1149
  7. Ansquer JC, Dalton RN, Causse E, Crimet D, Malicot KL, Foucher C. Effect of fenofibrate on kidney function: a 6-week randomized crossover trial in healthy people. Am J Kidney Dis. 2008;51:904–913
  8. Hottelart C, El Esper N, Rose F, Achard J-M, Fournier A. Fenofibrate increases creatininemia by increasing metabolic production of creatinine. Nephron. 2002;92:536–541
  9. Antara package insert. Emeryville: Oscient Pharmaceutical; 2007;
  10. Tricor package insert. Chicago: Abbott Pharmaceutical; 2007;
  11. Pannu N. An overview of drug-induced acute kidney injury. Crit Care Med. 2008;36:S216–S23
  12. Schetz M, Dasta J, Goldstein S, Golper T. Drug-induced acute kidney injury. Curr Opin Crit Care. 2005;11:555–565
  13. Mehta RL, Kellum JA, Shah SV, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11:R31
  14. National Kidney Foundation: K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Am J Kidney Dis. 2002;39:S1–S266
  15. Keech A, Simes RJ, Barter P, et al. FIELD study investigators Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet. 2005;366:1849–1861
  16. The ACCORD Study Group. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010;362:1563–1574
  17. Keating GM, Croom KF. Fenofibrate: a review of its use in primary dyslipidaemia, the metabolic syndrome and type 2 diabetes mellitus. Drugs. 2007;67:121–153
  18. Tarif N, Bakris GL. Preservation of renal function: the spectrum of effects by calcium-channel blockers. Nephrol Dial Transplant. 1997;12:2244–2250
  19. Bailie GR, Uhlig K, Levey AS. Clinical practice guidelines in nephrology: evaluation, classification, and stratification of chronic kidney disease. Pharmacotherapy. 2005;25:491–502
  20. Stevens LA, Greene T, Levey AS. Surrogate end points for clinical trials of kidney disease progression. Clin J Am Soc Nephrol. 2006;1:874–884
  21. Abbott KC, Bakris G. Renal effects of antihypertensive medications: an overview. J Clin Pharmacol. 1993;33:392–399
  22. Bakris GL. The effects of calcium antagonists on renal hemodynamics, urinary protein excretion, and glomerular morphology in diabetic states. J Am Soc Nephrol. 1991;2:S21–S29
  23. Griffin KA, Picken M, Bakris GL, Bidani AK. Comparative effects of selective T- and L-type calcium channel blockers in the remnant kidney model. Hypertension. 2001;37:1268–1272
  24. Hayashi K, Wakino S, Sugano N, Ozawa Y, Homma K. Ca2+ channel subtypes and pharmacology in the kidney. Circ Res. 2007;100:342–353
  25. Robles NR. Calcium antagonists and renal failure progression. Ren Fail. 2008;30:247–255
  26. Bakris GL, Griffin KA, Picken MM, Bidani AK. Combined effects of an angiotensin converting enzyme inhibitor and a calcium antagonist on renal injury. J Hypertens. 1997;15:1181–1185
  27. Gashti CN, Bakris GL. The role of calcium antagonists in chronic kidney disease. Curr Opin Nephrol Hypertens. 2004;13:155–161
  28. Sarafidis PA, Khosla N, Bakris GL. Antihypertensive therapy in the presence of proteinuria. Am J Kidney Dis. 2007;49:12–26
  29. Nathan S, Pepine CJ, Bakris GL. Calcium antagonists: effects on cardio-renal risk in hypertensive patients. Hypertension. 2005;46:637–642
  30. Chen YJ, Quilley J. Fenofibrate treatment of diabetic rats reduces nitrosative stress, renal cyclooxygenase-2 expression, and enhanced renal prostaglandin release. J Pharmacol Exp Ther. 2008;324:658–663
  31. Wilson MW, Lay LT, Chow CK, Tai HH, Robertson LW, Glauert HP. Altered hepatic eicosanoid concentrations in rats treated with the peroxisome proliferators ciprofibrate and perfluorodecanoic acid. Arch Toxicol. 1995;69:491–497
  32. Varghese Z, Moorhead JF, Ruan XZ. The PPARalpha ligand fenofibrate: meeting multiple targets in diabetic nephropathy. Kidney Int. 2006;69:1490–1391
  33. Zhao X, Quigley JE, Yuan J, Wang MH, Zhou Y, Imig JD. PPAR-alpha activator fenofibrate increases renal CYP-derived eicosanoid synthesis and improves endothelial dilator function in obese Zucker rats. Am J Physiol Heart Circ Physiol. 2006;290:H2187–H2195
  34. Muller DN, Theuer J, Shagdarsuren E, et al. A peroxisome proliferator-activated receptor-alpha activator induces renal CYP2C23 activity and protects from angiotensin II-induced renal injury. Am J Pathol. 2004;164:521–532
  35. Alonso-Galicia M, Frohlich B, Roman RJ. Induction of P450 activity improves pressure-natriuresis in Dahl S rats. Hypertension. 1998;31:232–236
  36. Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011;364:797–805

PII: S1933-2874(11)00708-2

doi: 10.1016/j.jacl.2011.08.008

Journal of Clinical Lipidology
Volume 6, Issue 1 , Pages 19-26 , January 2012

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