Reversibility of fenofibrate therapy-induced renal function impairment in ACCORD type 2 diabetic participants

Josyf C. Mychaleckyj, Timothy Craven, Uma Nayak, John Buse, John R. Crouse, Marshall Elam, Kent Kirchner, Daniel Lorber, Santica Marcovina, William Sivitz, Joann Sperl-Hillen, Denise E. Bonds, Henry N. Ginsberg

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Abstract

OBJECTIVE - To assess the reversibility of the elevation of serum creatinine levels in patients with diabetes after 5 years of continuous on-trial fenofibrate therapy. RESEARCH DESIGN AND METHODS - An on-drug/off-drug ancillary study to the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid Trial to investigate posttrial changes in serum creatinine and cystatin C. Eligible participants were recruited into a prospective, nested, three-group study based on retrospective on-trial serum creatinine levels: fenofibrate case subjects (n = 321, ≥20% increase after 3 months of therapy); fenofibrate control subjects (n = 175, ≤2% increase); and placebo control subjects (n = 565). Serum creatinine and cystatin C were measured at trial end and 6-8 weeks after discontinuation of trial therapy. RESULTS - At trial end, case subjects had the highest adjusted serum creatinine (± SE) mg/dL (1.11 ± 0.02) and the lowest adjusted estimated glomerular filtration rate (eGFR) (± SE) mL/min/1.73 m 2 (68.4 ± 1.0) versus control subjects (1.01 ± 0.02; 74.8 ± 1.3) and placebo subjects (0.98 ± 0.01; 77.8 ± 0.7). After 51 days off-drug, serum creatinine in case subjects was still higher (0.97 ± 0.02) and eGFR still lower (77.8 ± 1.0) than control subjects (0.90 ± 0.02; 81.8 ± 1.3) but not different from placebo subjects (0.99 ± 0.01; 76.6 ± 0.7). Changes in serum cystatin C recapitulated the serum creatinine changes. CONCLUSIONS - Participants with significant initial on-trial increases in serum creatinine (≥20%) returned to the same level of renal function as participants receiving placebo while participants who had ≤2% increase in serum creatinine had net preservation of renal function compared with the same unselected placebo reference group. The fenofibrate-associated on-trial increases in serum creatinine were reversible, and the reversal was complete after 51 days off-drug. The similarity of the cystatin C results suggests that the mechanism of this change is not specific for serum creatinine.

Original languageEnglish (US)
Pages (from-to)1008-1014
Number of pages7
JournalDiabetes care
Volume35
Issue number5
DOIs
StatePublished - May 1 2012

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Fenofibrate
Type 2 Diabetes Mellitus
Creatinine
Kidney
Serum
Cystatin C
Placebos
Therapeutics
Glomerular Filtration Rate
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Cite this

Mychaleckyj, J. C., Craven, T., Nayak, U., Buse, J., Crouse, J. R., Elam, M., ... Ginsberg, H. N. (2012). Reversibility of fenofibrate therapy-induced renal function impairment in ACCORD type 2 diabetic participants. Diabetes care, 35(5), 1008-1014. https://doi.org/10.2337/dc11-1811

Reversibility of fenofibrate therapy-induced renal function impairment in ACCORD type 2 diabetic participants. / Mychaleckyj, Josyf C.; Craven, Timothy; Nayak, Uma; Buse, John; Crouse, John R.; Elam, Marshall; Kirchner, Kent; Lorber, Daniel; Marcovina, Santica; Sivitz, William; Sperl-Hillen, Joann; Bonds, Denise E.; Ginsberg, Henry N.

In: Diabetes care, Vol. 35, No. 5, 01.05.2012, p. 1008-1014.

Research output: Contribution to journalArticle

Mychaleckyj, JC, Craven, T, Nayak, U, Buse, J, Crouse, JR, Elam, M, Kirchner, K, Lorber, D, Marcovina, S, Sivitz, W, Sperl-Hillen, J, Bonds, DE & Ginsberg, HN 2012, 'Reversibility of fenofibrate therapy-induced renal function impairment in ACCORD type 2 diabetic participants', Diabetes care, vol. 35, no. 5, pp. 1008-1014. https://doi.org/10.2337/dc11-1811
Mychaleckyj, Josyf C. ; Craven, Timothy ; Nayak, Uma ; Buse, John ; Crouse, John R. ; Elam, Marshall ; Kirchner, Kent ; Lorber, Daniel ; Marcovina, Santica ; Sivitz, William ; Sperl-Hillen, Joann ; Bonds, Denise E. ; Ginsberg, Henry N. / Reversibility of fenofibrate therapy-induced renal function impairment in ACCORD type 2 diabetic participants. In: Diabetes care. 2012 ; Vol. 35, No. 5. pp. 1008-1014.
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AU - Mychaleckyj, Josyf C.

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AU - Buse, John

AU - Crouse, John R.

AU - Elam, Marshall

AU - Kirchner, Kent

AU - Lorber, Daniel

AU - Marcovina, Santica

AU - Sivitz, William

AU - Sperl-Hillen, Joann

AU - Bonds, Denise E.

AU - Ginsberg, Henry N.

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N2 - OBJECTIVE - To assess the reversibility of the elevation of serum creatinine levels in patients with diabetes after 5 years of continuous on-trial fenofibrate therapy. RESEARCH DESIGN AND METHODS - An on-drug/off-drug ancillary study to the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid Trial to investigate posttrial changes in serum creatinine and cystatin C. Eligible participants were recruited into a prospective, nested, three-group study based on retrospective on-trial serum creatinine levels: fenofibrate case subjects (n = 321, ≥20% increase after 3 months of therapy); fenofibrate control subjects (n = 175, ≤2% increase); and placebo control subjects (n = 565). Serum creatinine and cystatin C were measured at trial end and 6-8 weeks after discontinuation of trial therapy. RESULTS - At trial end, case subjects had the highest adjusted serum creatinine (± SE) mg/dL (1.11 ± 0.02) and the lowest adjusted estimated glomerular filtration rate (eGFR) (± SE) mL/min/1.73 m 2 (68.4 ± 1.0) versus control subjects (1.01 ± 0.02; 74.8 ± 1.3) and placebo subjects (0.98 ± 0.01; 77.8 ± 0.7). After 51 days off-drug, serum creatinine in case subjects was still higher (0.97 ± 0.02) and eGFR still lower (77.8 ± 1.0) than control subjects (0.90 ± 0.02; 81.8 ± 1.3) but not different from placebo subjects (0.99 ± 0.01; 76.6 ± 0.7). Changes in serum cystatin C recapitulated the serum creatinine changes. CONCLUSIONS - Participants with significant initial on-trial increases in serum creatinine (≥20%) returned to the same level of renal function as participants receiving placebo while participants who had ≤2% increase in serum creatinine had net preservation of renal function compared with the same unselected placebo reference group. The fenofibrate-associated on-trial increases in serum creatinine were reversible, and the reversal was complete after 51 days off-drug. The similarity of the cystatin C results suggests that the mechanism of this change is not specific for serum creatinine.

AB - OBJECTIVE - To assess the reversibility of the elevation of serum creatinine levels in patients with diabetes after 5 years of continuous on-trial fenofibrate therapy. RESEARCH DESIGN AND METHODS - An on-drug/off-drug ancillary study to the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid Trial to investigate posttrial changes in serum creatinine and cystatin C. Eligible participants were recruited into a prospective, nested, three-group study based on retrospective on-trial serum creatinine levels: fenofibrate case subjects (n = 321, ≥20% increase after 3 months of therapy); fenofibrate control subjects (n = 175, ≤2% increase); and placebo control subjects (n = 565). Serum creatinine and cystatin C were measured at trial end and 6-8 weeks after discontinuation of trial therapy. RESULTS - At trial end, case subjects had the highest adjusted serum creatinine (± SE) mg/dL (1.11 ± 0.02) and the lowest adjusted estimated glomerular filtration rate (eGFR) (± SE) mL/min/1.73 m 2 (68.4 ± 1.0) versus control subjects (1.01 ± 0.02; 74.8 ± 1.3) and placebo subjects (0.98 ± 0.01; 77.8 ± 0.7). After 51 days off-drug, serum creatinine in case subjects was still higher (0.97 ± 0.02) and eGFR still lower (77.8 ± 1.0) than control subjects (0.90 ± 0.02; 81.8 ± 1.3) but not different from placebo subjects (0.99 ± 0.01; 76.6 ± 0.7). Changes in serum cystatin C recapitulated the serum creatinine changes. CONCLUSIONS - Participants with significant initial on-trial increases in serum creatinine (≥20%) returned to the same level of renal function as participants receiving placebo while participants who had ≤2% increase in serum creatinine had net preservation of renal function compared with the same unselected placebo reference group. The fenofibrate-associated on-trial increases in serum creatinine were reversible, and the reversal was complete after 51 days off-drug. The similarity of the cystatin C results suggests that the mechanism of this change is not specific for serum creatinine.

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