Abstract: PUB117
Modifying Effect of Albuminuria on the Association between Joslin Kidney Panel Biomarkers and Kidney Failure among Patients with Diabetes: Findings from the ACCORD/ACCORDION Trial
Session Information
Category: Diabetic Kidney Disease
- 702 Diabetic Kidney Disease: Clinical
Authors
- Tangiisuran, Balamurugan, Joslin Diabetes Center, Boston, Massachusetts, United States
- Shah, Hetal, Joslin Diabetes Center, Boston, Massachusetts, United States
- Galecki, Andrzej, University of Michigan, Department of Biostatistics, School of Public Health, Ann Arbour, Michigan, United States
- Lash, James P., University of Illinois Chicago College of Medicine, Chicago, Illinois, United States
- Krolewski, Andrzej S., Joslin Diabetes Center, Boston, Massachusetts, United States
- Doria, Alessandro, Joslin Diabetes Center, Boston, Massachusetts, United States
Background
The Joslin Kidney Panel (JKP) includes 21 serum proteins identified as predictors of risk of kidney failure (KF) in patients with diabetes. Our goal was to evaluate the association with KF and the predictive performance of JKP biomarkers in patients with type 2 diabetes with and without albuminuria at baseline.
Methods
A case-cohort analysis of the ACCORD/ ACCORDION cohort was carried out by selecting a 15% random sub-cohort plus all KF cases outside the sub-cohort. JKP biomarkers were measured in baseline serum samples using a custom multiplex Olink® assay. Weighted Cox models (adjusted by clinical KF predictors and trial treatment assignments) were used to assess the association between baseline JKP biomarkers and KF during follow-up by baseline albuminuria status.
Results
A total of 1,393 subjects were included in the study: 432 with albuminuria (urinary ACR >30 mg/g) and 961 with normoalbuminuria at baseline. There were 129 and 127 KF events in the albuminuric and normoalbuminuric strata, respectively, during a median follow-up of 6.1 years (IQR 4.0-9.4). Fifteen JKP markers showed a significant association with KF in the albuminuria stratum, with the axon-guidance protein EFNA4 showing the strongest effect (HR 3.96, 95% CI 2.05 – 7.67). By contrast, only six biomarkers were associated with KF in normoalbuminuric participants and with smaller HRs than in albuminuric participants. In an interaction analysis, 13 biomarkers showed significant differences in their effect on KF risk between albuminuria and normoalbuminuria strata. Addition of the JKP biomarkers to clinical predictors increased the C-index from 0.70 to 0.76 (p<0.0001) in the albuminuria stratum and from 0.58 to 0.67 (p<0.0001) in the normoalbuminuria stratum.
Conclusion
Currently available biomarkers of increased KF risk are more strongly associated with KF in albuminuric than in normoalbuminuric subjects with type 2 diabetes. While these proteins improve KF risk discrimination in both groups, the combined performance of clinical and biomarker predictors is lower among normoalbuminuric subjects. Studies are needed to identify novel biomarkers allowing better KF risk prediction in normoalbuminuria.
Funding
- NIDDK Support