Kidney Week

Abstract: TH-OR49

Advancing KidneyIntelX Precision Medicine Platform in CKD

Session Information

• Diabetic Kidney Disease - Clinical: Novel Insights into Precision Medicine
  October 24, 2024 | Location: Room 33, Convention Center
  Abstract Time: 05:00 PM - 05:10 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

• Edwards, Katherine Lucy, Renalytix plc, London, London, United Kingdom

Katherine Lucy Edwards, PhD

• Au, Emily Cho Kiu, Renalytix plc, London, London, United Kingdom

Emily Cho Kiu Au

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

Fergus Fleming

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

Girish N. Nadkarni, MD, MPH

Background

NBL1 and WFDC2 have been identified in experimental animals and omics-based platforms as markers of fibrosis in diabetic kidney disease and are associated with progression to kidney failure. The kidneyintelX.dkd test is an FDA De Novo marketing authorized test that currently incorporates measurement of three biomarkers via electrochemiluminescence Meso Scale platform with clinical variables and categorizes patients at low, moderate, or high risk for progression of DKD. We aimed to advance the translation of NBL1 and WFDC2 for inclusion in future versions of the KidneyIntelX platform through clinical assay development and independent validation of prognostic performance.

Methods

We established analytical characteristics using CLSI guidelines for two biomarkers of kidney disease progression (NBL1, WFDC2). We measured plasma concentrations at baseline in a replication cohort of 601 patients with DKD from the Penn Medicine Biobank (eGFR of 30-59 ml/min/1.73 m² or eGFR ≥60 ml/min/1.73 m² with UACR ≥30 mg/g). The associations of baseline levels with a composite outcome of ≥40% sustained decline in eGFR, or kidney failure (over 5 years) were evaluated using Cox proportional hazard models.

Results

Robust analytical parameters including repeatability were demonstrated (CV ≤5.5% for NBL1 and CV ≤5.2% for WFDC2) over clinically relevant ranges. Reference intervals at 95% confidence demonstrated discrimination between healthy populations (476 to 3366 pg/mL for NBL1 and 1342 to 5880 pg/mL for WFDC2) and those with diabetic kidney disease (807 to 20102 pg/mL for NBL1 and 2566 to 26538 pg/mL for WFDC2). The replication cohort had baseline median eGFR of 56 ml/min/1.73 m² and median UACR of 57 mg/g with 92 (15.3%) composite events. The adjusted hazard ratio per SD increment of log2 baseline concentration for NBL1 was 1.6 (p<0.001) and was 2.5 (p<0.001) for WFDC2 after adjustment for UACR, eGFR and HbA1c.

Conclusion

NBL1 and WFDC2 assays demonstrated robust analytical performance on transfer to the KidneyIntelX clinical laboratory platform. Both biomarkers were strongly associated with the kidney outcome and therefore merit further investigation for potential incorporation into the KidneyIntelX precision medicine platform.

Funding

• Commercial Support – Renalytix AI Inc.