Abstract: FR-OR119

Longitudinal Changes in Plasma Biomarkers Strongly Associate with Risk for DKD Progression in the VA NEPHRON-D Trial

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 301 CKD: Risk Factors for Incidence and Progression

Authors

  • Coca, Steven G., Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Parikh, Chirag R., Yale University and VAMC, New Haven, Connecticut, United States
  • Huang, Yuan, VA Cooperative Studies Program, West Haven, Connecticut, United States
  • Moledina, Dennis G., Yale School of Medicine, New Haven, Connecticut, United States
  • Rao, Veena, Yale School of Medicine, New Haven, Connecticut, United States
  • Verghese, Divya Anna, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Obeid, Wassim, Yale School of Medicine, New Haven, Connecticut, United States
  • Nadkarni, Girish N., Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Ferket, Bart, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Fried, Linda F., VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, United States
Background

While baseline levels of plasma TNFR-1, TNFR-2, and KIM-1 are independently associated with risk for renal function decline in diabetic kidney disease (DKD), the prognostic value of longitudinal changes in these biomarkers is unknown.

Methods

In this ancillary study of the Veterans Affairs Nephropathy in Diabetes Trial (VA NEPHRON-D) that included 759 participants with plasma samples at both baseline and 1 year, we measured plasma TNFR1, TNFR2 and KIM-1 via MesoScale Discovery multiplex assay. We assessed the association between the change in plasma biomarker concentrations at 12 months from baseline with the renal endpoint (decline in eGFR or ESRD as defined in the trial) using Cox Proportional Hazards Models with adjustment for study arm, biomarker, eGFR and albuminuria at baseline and change in eGFR and albuminuria by 12 months.

Results

In the 123 (16%) participants who experienced the renal endpoint after 12 months, plasma TNFR1, TNFR2 and KIM-1 increased by 34%, 17%, and 6%, respectively by 12 months (TABLE). In the 636 participants that did not reach the renal endpoint, plasma TNFR1 and TNFR2 increased by 11% and 3%, respectively, whereas KIM-1 decreased by 6%. After multivariable adjustment, including baseline biomarker concentration eGFR, urine albumin at baseline and change in eGFR and albuminuria at 12 months, increases in TNFR1, TNFR2 and KIM-1 over time were associated with increased hazards of developing the renal end point (TABLE). There were no statistically significant differences in the change in the three biomarkers or interactions on the outcomes between the combination-therapy group vs. the monotherapy arms.

Conclusion

Longitudinal changes in plasma TNFR1, TNFR2 and KIM-1 add additional prognostic information to baseline concentrations of these markers, even after accounting for clinical variables, including changes in eGFR and albuminuria.

 Median ([Q1, Q3])Adjusted HR (95% CI)
 change (pg/ml) at 12 months from baseline
BiomakerNo renal event (n=636)Renal event (n=123)Baseline Biomarker (log2)Change in biomarker at 12 month (log2) from baseline (log2)Baseline eGFRChange in eGFR at 12 months from baselineBaseline UrAlb (log)Change in UrAlb at 12 months (log) from baseline (log)
TNFR144214233.92.41.030.932.41.9
[-371 ,1373][94 ,2916](2.5-6.4)(1.4-4.0)(1.01-1.04)(0.91-0.95)(1.8-3.0)(2.5-6.4)
TNFR227017972.33.51.010.932.52
[-969 ,1683][232 ,4056](1.4-3.7)(1.9-6.3)(0.99-1.03)(0.91-0.95)(1.9-3.2)(1.5-2.6)
KIM-1-25241.51.60.990.922.21.7
[-115 ,51][-142 ,292](1.2-1.8)(1.1-2.2)(0.98-1.01)(0.90-0.94)(1.6-2.8)(1.3-2.3)

Funding

  • NIDDK Support