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Abstract: TH-PO186

Distal Tubule Urinary Biomarkers in Diabetic Kidney Disease: Results from the VA NEPHRON-D Trial

Session Information

Category: Diabetic Kidney Disease

  • 702 Diabetic Kidney Disease: Clinical

Authors

  • Tamargo, Christina Lauren, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Hu, David, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Thiessen Philbrook, Heather, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Bonventre, Joseph V., Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Fried, Linda F., UPMC, Pittsburgh, Pennsylvania, United States
  • Coca, Steven G., Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Parikh, Chirag R., The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
Background

Urinary biomarkers of proximal renal tubule injury (KIM-1, NGAL, L-FABP) have demonstrated associations with DKD progression, but investigations of biomarkers of distal tubular health in DKD have been limited.

Methods

We evaluated associations between two distal tubular urinary biomarkers, epidermal growth factor (EGF) and uromodulin (UMOD), and DKD progression among 1135 participants in the Veterans Affairs Diabetes iN Nephropathy (VA NEPHRON-D) study. EGF and UMOD were measured by electrochemiluminescence assay in a single batch in urine samples collected at randomization.

Results

At baseline, the mean age was 64.9 years, the mean eGFR was 56.2 (18.9) ml/min/1.73 m2, and the median urine albumin-to-creatinine ratio was 840 (IQR 423-1761) mg/g. One hundred forty-eight patients (13.0%) had DKD progression over a median of 2.2 years of follow-up. Higher levels of EGF and UMOD were both independently associated with a lower risk of DKD progression in continuous models after adjustment for several covariates (adjusted HR 0.58 (0.34, 0.98) and 0.80 (0.66, 0.97); Figure 1). In categorical models, patients with the highest tertiles of both biomarkers had the lowest risk of DKD progression. However, associations were attenuated in models that adjusted for albuminuria, particularly for EGF (adjusted HR 0.70 (0.42, 1.15) and 0.55 (0.34, 0.89) for UMOD).

Conclusion

Among veterans with DKD, higher levels of distal tubular health markers were independently prognostic for a lower risk of DKD progression. Distal tubular health deserves further investigation in DKD cohorts and clinical trials.

Figure 1. Baseline Urinary EGF and UMOD associations with DKD progression

Funding

  • NIDDK Support