Kidney Week

Abstract: FR-PO1134

Performance of eGFR Slope as a Surrogate End Point for Clinical Kidney Events in a Nonglomerular Mechanism of Acute eGFR Change

Session Information

• CKD: Kidney Function and Extrarenal Complications
  October 25, 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, Camperdown, 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

Glomerular Filtration Rate (GFR) decline is a proposed surrogate kidney endpoint and attractive alternative to the lengthy, expensive, and large sample size requirements to reach “hard” clinical events in trials. Estimated (e)GFR decline has been successfully modelled using eGFR slope, where the correlation between total and chronic eGFR slopes and clinical endpoints was established. To date GFR slope has been tested on agents where acute GFR decline is driven by changes in glomerular haemodynamics. We tested the association of total and chronic eGFR slopes with clinical endpoints for fenofibrate, an agent with an acute eGFR decline mediated by non-glomerular actions.

Methods

The FIELD trial randomised adults to fenofibrate or placebo. Total eGFR slope was calculated using a repeated measures 2-slope linear mixed model for the entire intervention period. Sensitivity analyses were also performed limited to 3 years. Chronic eGFR slope was calculated from month 4. The clinical kidney endpoint was doubling of serum creatinine/eGFR<15ml/min/1.73m²,renal death or kidney replacement therapy. Frequency of clinical kidney endpoints based on baseline to 8-week washout eGFR was an exploratory subgroup analysis.

Results

9795 participants were followed for 5 years. A post-washout eGFR was ascertained in 94.3% of the washout sub-study participants. Fenofibrate was associated with a mean acute eGFR decline of -9.05 ml/min/1.73m²/annum. Fenofibrate slowed rate of chronic eGFR decline by 0.61 ml/min/1.73m²/annum (95% CI 0.50 to 0.71, P<0.0001), but worsened total eGFR slope (mean diff -1.54, 95% CI -1.65 to -1.44, P<0.0001). Fenofibrate use increased the clinical kidney endpoint 1 (HR 1.48, 95% CI 1.16 to 1.89, P=0.002) (Figure 1). There was no difference for clinical kidney outcomes in washout analyses.

Conclusion

Results generally support use of eGFR slope change as a surrogate for clinical kidney endpoints. Assessment post-wash out should be considered for agents with a large acute eGFR decline.