MON-660 Association Between Joslin Kidney Panel Biomarkers And Cardiovascular Autonomic Neuropathy : Findings From Accord Trial

Abstract Disclosure: Y. Tang: None. A. Doria: None. R. Pop-Busui: None. Background: Cardiovascular autonomic neuropathy (CAN) predicts rapid kidney function decline among people with diabetes. The Joslin Kidney Panel (JKP) includes 21 serum proteins identified as predictors of kidney failure in diabetes. The goal of this study was to assess the association between JKP biomarkers and CAN in patients with type 2 diabetes (T2D). Methods: We randomly selected a 15% sample of all individuals with available serum samples who participated in the ACCORD clinical trial. CAN was defined based on previously validated cut-offs of heart rate variability (HRV) indices (standard deviations of all normal-to-normal R-R intervals [SDNN] < 17.13ms and root mean square of successive differences between normal-to-normal R-R intervals [RMSSD] < 24.94ms). JKP biomarkers were measured on baseline serum samples using a custom multiplex Olink® assay. A principal component analysis was conducted on scaled JKP biomarker concentrations. Logistic regression models with or without potential CAN confounders were applied to assess the association between baseline JKP biomarkers and baseline CAN. Results: A total of 925 ACCORD participants had available baseline serum JKP and CAN data. Of them, 623 (67.4%) had evidence of CAN at baseline. The top seven principal components accounted for 80% of the total variance of JKP biomarkers, which defined the statistical significance for further analyses as P < 0.007 after Bonferroni adjustment (0.05/7). Seven of the 21 JKP markers (KIM-1, IL-1RT1, CD27, TNFRSF10B, LRP11, EPHA2, LTBR) were significantly associated with increased prevalence of CAN at baseline (P<0.007) after adjusting for baseline eGFR. Three of these biomarkers (KIM-1, CD27, LTBR) remained significant after adjusting for potential confounders including ACEi/ARB use, beta-blocker use, age, sex, previous cardiovascular events, blood pressure, urine albumin creatinine ratio, and eGFR. KIM1 showed the most significant association (OR = 1.32 [1.10, 1.58], p= 0.002), followed by CD27 (OR = 1.56, [1.16, 2.11], p = 0.003), and LTBR (OR = 1.82 [1.21,2.72], P = 0.004). Conclusions: Several serum biomarkers of increased kidney failure risk, including neuronal proteins and TNF receptors, are associated with CAN among individuals with T2D. Further studies of the pathways tagged by these proteins may provide a better understanding of the links between CAN and diabetic kidney disease and may lead to the identification of novel pharmacological targets to simultaneously treat both conditions. Presentation: Monday, July 14, 2025