Kidney Week

Abstract: PO0951

Longitudinal Changes in Plasma Biomarkers and Diabetic Kidney Disease Progression in VA NEPHRON-D

Session Information

• Diabetic Kidney Disease: Clinical - 1
  October 22, 2020 | Location: On-Demand
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 602 Diabetic Kidney Disease: Clinical

Authors

• Chen, Teresa K., Johns Hopkins University, Baltimore, Maryland, United States

Teresa K. Chen,

• Thiessen Philbrook, Heather, Johns Hopkins University, Baltimore, Maryland, United States

Heather Thiessen Philbrook,

• Obeid, Wassim, Johns Hopkins University, Baltimore, Maryland, United States

Wassim Obeid,

• Fried, Linda F., VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, United States

Linda F. Fried,

• L Heerspink, Hiddo Jan, UMCG, Groningen, Netherlands

Hiddo Jan L Heerspink,

• Parikh, Chirag R., Johns Hopkins University, Baltimore, Maryland, United States

Chirag R. Parikh,

• Coca, Steven G., Mount Sinai, New York, New York, United States

Steven G. Coca,

Group or Team Name

• CKD BioCon

Background

Pathways of inflammation are central to the pathogenesis of diabetic kidney disease (DKD). We previously reported in VA NEPHRON-D that higher baseline levels of soluble tumor necrosis factor receptors 1 and 2 [sTNFR1, sTNFR2] and kidney injury molecule-1 [KIM-1] were associated with DKD progression. Whether longitudinal changes in these and other promising biomarkers are also associated with subsequent kidney function decline is unclear.

Methods

We measured 6 plasma biomarkers (sTNFR1, sTNFR2, KIM-1, interleukin-18 [IL-18], monocyte chemoattractant protein-1 [MCP-1], chitinase-3-like protein-1 [YKL-40]) at baseline and 12 mths. Using Cox models, we studied associations of each biomarker (at baseline, at 12 mths, and relative change from baseline to 12 mths) with kidney function decline (first occurrence of eGFR decrease ≥30 ml/min/1.73 m² or >50% if randomization eGFR ≥60 and <60, respectively, or ESRD), adjusting for biomarker, sex, race, treatment arm, BMI, HgbA1c, eGFR, UACR at baseline and age, systolic BP, eGFR, UACR at 12 mths. We excluded events before 12 mths (n=5).

Results

Of 754 VA NEPHRON-D participants with baseline and 12-mth plasma samples, mean eGFR=57 ml/min/1.73 m² and median UACR=0.8 g/g. Over a median follow-up of 2.5 yrs, 118 (16%) had kidney function decline. Compared to quartiles 2&3, the highest quartile of delta sTNFR1, sTNFR2, KIM-1, and YKL-40 had 1.7 to 2.0-fold greater risks and the lowest quartile of delta MCP-1 had 52% lower risk of kidney function decline. Higher baseline and 12-mth biomarker levels were also associated with DKD progression [Figure].

Conclusion

Repeated measures of several plasma biomarkers in patients with DKD provided additional prognostic information even after adjusting for baseline biomarker levels, clinical variables, and time-updated eGFR and UACR.

Funding

• NIDDK Support