Biomarkers associated with early stages of kidney disease in adolescents with type 1 diabetes

Abstract

Objectives To identify biomarkers of renal disease in adolescents with type 1 diabetes (T1D) and to compare findings in adults with T1D. Methods: Twenty-five serum biomarkers were measured, using a Luminex platform, in 553 adolescents (median[interquartile range] age: 13.9[12.6, 15.2] years), recruited to the Adolescent Type 1 Diabetes Cardiorenal Intervention Trial. Association with baseline and final estimated glomerular filtration rate (eGFR), rapid decliner and rapid increaser phenotypes (eGFR slopes <-3 and >3ml/min/1.73m2/year, respectively) and albumin-creatinine ratio (ACR) were assessed. Results were also compared with those obtained in 859 adults (age: 55.5[46.1, 64.4) years) from the Scottish Diabetes Research Network Type 1 Bioresource. Results: In the adolescent cohort, baseline eGFR was negatively associated with trefoil factor-3 (TF-3), cystatin C and beta-2 microglobulin (B2M) (B coefficient[95%CI]: -0.19[-0.27, -0.12], p=7.0x10-7; -0.18[-0.26, -0.11], p=5.1x10-6; -0.12[-0.20, -0.05], p=1.6x10-3), in addition to clinical covariates. Final eGFR was negatively associated with osteopontin (-0.21[-0.28, -0.14], p=2.3x10-8) and cystatin C (-0.16[-0.22, -0.09], p=1.6x10-6). Rapid decliner phenotype was associated with osteopontin (OR: 1.83[1.42, 2.41], p=7.3x10-6), whereas rapid increaser phenotype was associated with fibroblast growth factor-23 (FGF-23) (1.59[1.23, 2.04], p=2.6x10-4). ACR was not associated with any of the biomarkers. In the adult cohort similar associations with eGFR were found; however, several additional biomarkers were associated with eGFR and ACR. Conclusions: In this young population with T1D and high rates of hyperfiltration, osteopontin was the most consistent biomarker associated with prospective changes in eGFR. FGF-23 was associated with eGFR increases, whereas TF-3, cystatin C and B2M were only associated with baseline eGFR.