Associations of Fenofibrate Therapy With Incidence and Progression of CKD in Patients With Type 2 Diabetes

Rebecca Suzanne Frazier, Rupal C Mehta, Xuan Cai, Julia Lee, Sara Napoli, Timothy Craven, Jennifer A Tuazon, Adam William Safdi, Julia Scialla, Katalin Susztak, Tamara Isakova

Research output: Contribution to journalArticle

Abstract

Introduction: Abnormalities in lipid metabolism may contribute to the development and progression of chronic kidney disease (CKD) in patients with type 2 diabetes. Fenofibrate induces early and reversible reduction in estimated glomerular filtration rate (eGFR), but it may have protective effects on microvascular complications of diabetes. We hypothesized that randomization to fenofibrate versus placebo would be associated with beneficial long-term effects on kidney outcomes in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial participants. Methods: We conducted a post hoc analysis in the ACCORD Lipid Trial to examine the association of randomization to fenofibrate versus placebo with change in eGFR and with time-to-development of microalbuminuria, macroalbuminuria, CKD, and kidney failure. Results: We analyzed 2636 participants in the fenofibrate arm and 2632 in the placebo arm. During a median follow-up of 4 years, treatment with fenofibrate was associated with lower rate of eGFR decline (−0.28 ml/min per 1.73 m2 per year in the fenofibrate group vs. −1.25 ml/min per 1.73 m2 per year in the placebo group, P < 0.01) and with lower incidence of microalbuminuria (hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.43–0.72, P < 0.001) and macroalbuminuria (HR 0.72, 95% CI 0.57–0.91, P < 0.001). There was no difference in incidence of CKD (HR 0.92, 95% CI 0.74–1.15, P = 0.46) and/or kidney failure (HR 0.95, 95% CI 0.68–1.33, P = 0.76). Conclusion: Compared with placebo, randomization to fenofibrate was associated with lower rates of incident albuminuria and a slower eGFR decline, but no difference in incidence of CKD or kidney failure in ACCORD participants.

Original languageEnglish (US)
Pages (from-to)94-102
Number of pages9
JournalKidney International Reports
Volume4
Issue number1
DOIs
StatePublished - Jan 1 2019

Fingerprint

Fenofibrate
Chronic Renal Insufficiency
Type 2 Diabetes Mellitus
Glomerular Filtration Rate
Incidence
Placebos
Random Allocation
Confidence Intervals
Renal Insufficiency
Therapeutics
Albuminuria
Diabetes Complications
Lipid Metabolism
Kidney
Lipids

Keywords

  • albuminuria
  • chronic kidney disease
  • diabetic nephropathy
  • fenofibrate
  • kidney failure

ASJC Scopus subject areas

  • Nephrology

Cite this

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title = "Associations of Fenofibrate Therapy With Incidence and Progression of CKD in Patients With Type 2 Diabetes",
abstract = "Introduction: Abnormalities in lipid metabolism may contribute to the development and progression of chronic kidney disease (CKD) in patients with type 2 diabetes. Fenofibrate induces early and reversible reduction in estimated glomerular filtration rate (eGFR), but it may have protective effects on microvascular complications of diabetes. We hypothesized that randomization to fenofibrate versus placebo would be associated with beneficial long-term effects on kidney outcomes in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial participants. Methods: We conducted a post hoc analysis in the ACCORD Lipid Trial to examine the association of randomization to fenofibrate versus placebo with change in eGFR and with time-to-development of microalbuminuria, macroalbuminuria, CKD, and kidney failure. Results: We analyzed 2636 participants in the fenofibrate arm and 2632 in the placebo arm. During a median follow-up of 4 years, treatment with fenofibrate was associated with lower rate of eGFR decline (−0.28 ml/min per 1.73 m2 per year in the fenofibrate group vs. −1.25 ml/min per 1.73 m2 per year in the placebo group, P < 0.01) and with lower incidence of microalbuminuria (hazard ratio [HR] 0.56, 95{\%} confidence interval [CI] 0.43–0.72, P < 0.001) and macroalbuminuria (HR 0.72, 95{\%} CI 0.57–0.91, P < 0.001). There was no difference in incidence of CKD (HR 0.92, 95{\%} CI 0.74–1.15, P = 0.46) and/or kidney failure (HR 0.95, 95{\%} CI 0.68–1.33, P = 0.76). Conclusion: Compared with placebo, randomization to fenofibrate was associated with lower rates of incident albuminuria and a slower eGFR decline, but no difference in incidence of CKD or kidney failure in ACCORD participants.",
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Associations of Fenofibrate Therapy With Incidence and Progression of CKD in Patients With Type 2 Diabetes. / Frazier, Rebecca Suzanne; Mehta, Rupal C; Cai, Xuan; Lee, Julia; Napoli, Sara; Craven, Timothy; Tuazon, Jennifer A; Safdi, Adam William; Scialla, Julia; Susztak, Katalin; Isakova, Tamara.

In: Kidney International Reports, Vol. 4, No. 1, 01.01.2019, p. 94-102.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Associations of Fenofibrate Therapy With Incidence and Progression of CKD in Patients With Type 2 Diabetes

AU - Frazier, Rebecca Suzanne

AU - Mehta, Rupal C

AU - Cai, Xuan

AU - Lee, Julia

AU - Napoli, Sara

AU - Craven, Timothy

AU - Tuazon, Jennifer A

AU - Safdi, Adam William

AU - Scialla, Julia

AU - Susztak, Katalin

AU - Isakova, Tamara

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Introduction: Abnormalities in lipid metabolism may contribute to the development and progression of chronic kidney disease (CKD) in patients with type 2 diabetes. Fenofibrate induces early and reversible reduction in estimated glomerular filtration rate (eGFR), but it may have protective effects on microvascular complications of diabetes. We hypothesized that randomization to fenofibrate versus placebo would be associated with beneficial long-term effects on kidney outcomes in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial participants. Methods: We conducted a post hoc analysis in the ACCORD Lipid Trial to examine the association of randomization to fenofibrate versus placebo with change in eGFR and with time-to-development of microalbuminuria, macroalbuminuria, CKD, and kidney failure. Results: We analyzed 2636 participants in the fenofibrate arm and 2632 in the placebo arm. During a median follow-up of 4 years, treatment with fenofibrate was associated with lower rate of eGFR decline (−0.28 ml/min per 1.73 m2 per year in the fenofibrate group vs. −1.25 ml/min per 1.73 m2 per year in the placebo group, P < 0.01) and with lower incidence of microalbuminuria (hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.43–0.72, P < 0.001) and macroalbuminuria (HR 0.72, 95% CI 0.57–0.91, P < 0.001). There was no difference in incidence of CKD (HR 0.92, 95% CI 0.74–1.15, P = 0.46) and/or kidney failure (HR 0.95, 95% CI 0.68–1.33, P = 0.76). Conclusion: Compared with placebo, randomization to fenofibrate was associated with lower rates of incident albuminuria and a slower eGFR decline, but no difference in incidence of CKD or kidney failure in ACCORD participants.

AB - Introduction: Abnormalities in lipid metabolism may contribute to the development and progression of chronic kidney disease (CKD) in patients with type 2 diabetes. Fenofibrate induces early and reversible reduction in estimated glomerular filtration rate (eGFR), but it may have protective effects on microvascular complications of diabetes. We hypothesized that randomization to fenofibrate versus placebo would be associated with beneficial long-term effects on kidney outcomes in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial participants. Methods: We conducted a post hoc analysis in the ACCORD Lipid Trial to examine the association of randomization to fenofibrate versus placebo with change in eGFR and with time-to-development of microalbuminuria, macroalbuminuria, CKD, and kidney failure. Results: We analyzed 2636 participants in the fenofibrate arm and 2632 in the placebo arm. During a median follow-up of 4 years, treatment with fenofibrate was associated with lower rate of eGFR decline (−0.28 ml/min per 1.73 m2 per year in the fenofibrate group vs. −1.25 ml/min per 1.73 m2 per year in the placebo group, P < 0.01) and with lower incidence of microalbuminuria (hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.43–0.72, P < 0.001) and macroalbuminuria (HR 0.72, 95% CI 0.57–0.91, P < 0.001). There was no difference in incidence of CKD (HR 0.92, 95% CI 0.74–1.15, P = 0.46) and/or kidney failure (HR 0.95, 95% CI 0.68–1.33, P = 0.76). Conclusion: Compared with placebo, randomization to fenofibrate was associated with lower rates of incident albuminuria and a slower eGFR decline, but no difference in incidence of CKD or kidney failure in ACCORD participants.

KW - albuminuria

KW - chronic kidney disease

KW - diabetic nephropathy

KW - fenofibrate

KW - kidney failure

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