Kidney Week

Abstract: FR-PO315

Longitudinal Risk Assessment by kidneyintelX.dkdTM to Guide Adaptive Clinical Trials

Session Information

• Diabetic Kidney Disease: Clinical Modeling, Diagnosis, Education, and More
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 702 Diabetic Kidney Disease: Clinical

Authors

• Coca, Steven G., Icahn School of Medicine at Mount Sinai, New York, New York, United States

Steven G. Coca, DO, MS

• Stapleton, Sharon, Renalytix plc, London, London, United Kingdom

Sharon Stapleton, PhD

• Nadkarni, Girish N., Icahn School of Medicine at Mount Sinai, New York, New York, United States

Girish N. Nadkarni, MD, MPH

• Fleming, Fergus, Renalytix plc, London, London, United Kingdom

Fergus Fleming

• Heerspink, Hiddo Jan L., Rijksuniversiteit Groningen, Groningen, Groningen, Netherlands

Hiddo Jan L. Heerspink, PhD

Background

Albuminuria has been used as a biomarker to guide adaptive clinical trials in Diabetic Kidney Disease. Intra-individual coefficient of variation of albuminuria within an individual is high and 2024 KDIGO CKD guidelines state that increases in UACR less than a doubling, or reductions in albuminuria smaller than 50% are consistent with random fluctuations. The FDA De-novo marketing authozied kidneyintelX.dkd test incorporates biomarkers and clinical variables and categorizes patients at low, moderate, or high risk for progression of Diabetic Kidney Disease. Time-updated changes in future risk per kidneyintelX.dkd may help delineate response to DKD therapy, particularly in those with UACR changes in the ambiguous zone (i.e., -49% to +99%).

Methods

We measured tumor necrosis factor receptor 1 (TNFR-1), tumor necrosis factor receptor 2 (sTNFR-2), and kidney injury molecule (KIM-1) on banked plasma from CANVAS trial participants with baseline DKD (eGFR <60 ml/min/1.73 m² or UACR ≥30 mg/mg). We determined the kidneyintelX.dkd risk level at baseline and year 1 and assessed how changes in kidneyintelX.dkd were associated with subsequent DKD progression (composite outcome of ≥40% sustained decline in eGFR, or kidney failure) in those with ambiguous changes in UACR in the same period.

Results

933 participants with prevalent DKD had baseline and year 1 plasma samples, a median eGFR of 66 ml/min and median UACR of 55 mg/g. Post year 1, 78 (8.4%) participants experienced the outcome over the following median of 4.9 years. Of these, 31% experienced a 50% reduction and 13% experienced more than a doubling of uACR at year 1. In the ambiguous population (56%), 40% initially scored kidneyintelX.dkd moderate or high risk. Of these, at year 1, 27% moved to low risk with event rate was 3.3% (ref), 58% stayed at or moved to moderate risk with event rate 3.3-fold higher at 11%. In those that remained or moved to high risk (14%), the event rate was over 14-fold higher at 45%.

Conclusion

Re-assessment of risk via kidneyintelX.dkd at 1 year in those with ambiguous change in albuminuria robustly stratified patients for future progression of DKD. Adaptive clinical trials can consider kidneyintelX.dkd risk levels over time as a criterion to tailor interventions, particularly for those with moderate or high risk of progression after randomization.

Funding

• Commercial Support – Renalytix