Kidney Week

Abstract: TH-PO1067

The Acute Kidney Function Change with Fenofibrate Is Not Damaging: A Post Hoc Analysis of the FIELD Trial

Session Information

• CKD: Therapeutic Advances
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Gallagher, Alexandra, St George Hospital Department of Renal Medicine, Kogarah, New South Wales, Australia

Alexandra Gallagher, MBBS

• O'Connell, Rachel L., NHMRC Clinical Trials Centre, Camperdown, New South Wales, Australia

Rachel L. O'Connell, PhD

• Mangos, George, St George Hospital Department of Renal Medicine, Kogarah, New South Wales, Australia

George Mangos, MD, MBBS

• Smyth, Brendan, St George Hospital Department of Renal Medicine, Kogarah, New South Wales, Australia

Brendan Smyth, MBBS, PhD

• Keech, Anthony C., Department of Cardiology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia

Anthony C. Keech

• Jardine, Meg, Concord Repatriation General Hospital, Concord, New South Wales, Australia

Meg Jardine, MBBS, PhD

Group or Team Name

• The FIELD Investigators.

Background

Several agents known to protect against chronic kidney disease have been associated with an initial decline in the estimated Glomerular Filtration Rate (eGFR). Studies on sodium-glucose cotransporter-2 inhibitors have shown that these initial eGFR dips are not harmful, although the analyses were conducted after randomization. Fenofibrate, on the other hand, leads to an acute, reversible eGFR decline through non-glomerular mechanisms. In a trial where the acute eGFR response to fenofibrate was assessed before randomization, the aim was to test whether this initial acute eGFR decline could predict potential benefits.

Methods

The FIELD trial randomised adults to fenofibrate or placebo. All participants were exposed to an active run-in. The Acute Fenofibrate Response (AFR) was measured and categorised as nil, mild, moderate, or large (increase/no change, 0-10%, 10-20%, >20% eGFR decline). Subgroup analyses were conducted for several cardiovascular outcomes, mortality, a clinical kidney endpoint (doubling serum creatinine, eGFR <15ml/min/1.73m², renal related death, or kidney replacement therapy), and total (baseline to study close) and chronic (4 months post-randomisation to study close) eGFR slopes, with heterogeneity assessed using a test of trend.

Results

In 9777 participants, fenofibrate therapy did not reduce coronary events with no evidence of treatment modification by acute eGFR decline category (overall HR 0.89 [95% CI 0.75 to 1.05]); nil, mild, moderate, and large acute decline: 1.08, 0.77, 1.02 and 0.82 respectively, p-trend 0.997). AFR category did not predict harm for clinical kidney, total cardiovascular events (Figure 1) nor for total microvascular events, or all-cause mortality (p-trend 0.46 and 0.95, respectively). Subgroups of greater AFR experienced more improvement on chronic eGFR slope, and the reverse trend for total slope (p-trend <0.0001 and 0.01, respectively).

Conclusion

There was no evidence that greater acute eGFR decline leads to fenofibrate-associated harm for a range of clinically meaningful endpoints.