Biomarkers associated with early stages of kidney disease in adolescents with type 1 diabetes
AuthorMarcovecchio, ML; Colombo, M; Dalton, RN; McKeigue, PM; Benitez-Aguirre, P; Cameron, FJ; Chiesa, ST; Couper, JJ; Craig, ME; Daneman, D; ...
Source TitlePediatric Diabetes
University of Melbourne Author/sCameron, Fergus
Document TypeJournal Article
CitationsMarcovecchio, M. L., Colombo, M., Dalton, R. N., McKeigue, P. M., Benitez-Aguirre, P., Cameron, F. J., Chiesa, S. T., Couper, J. J., Craig, M. E., Daneman, D., Davis, E. A., Deanfield, J. E., Donaghue, K. C., Jones, T. W., Mahmud, F. H., Marshall, S. M., Neil, A., Colhoun, H. M. & Dunger, D. B. (2020). Biomarkers associated with early stages of kidney disease in adolescents with type 1 diabetes. PEDIATRIC DIABETES, 21 (7), pp.1322-1332. https://doi.org/10.1111/pedi.13095.
Access StatusOpen Access
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 Cardio-Renal Intervention Trial. Associations with baseline and final estimated glomerular filtration rate (eGFR), rapid decliner and rapid increaser phenotypes (eGFR slopes <-3 and > 3 mL/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, cystatin C, and beta-2 microglobulin (B2M) (B coefficient[95%CI]: -0.19 [-0.27, -0.12], P = 7.0 × 10-7 ; -0.18 [-0.26, -0.11], P = 5.1 × 10-6 ; -0.12 [-0.20, -0.05], P = 1.6 × 10-3 ), in addition to clinical covariates. Final eGFR was negatively associated with osteopontin (-0.21 [-0.28, -0.14], P = 2.3 × 10-8 ) and cystatin C (-0.16 [-0.22, -0.09], P = 1.6 × 10-6 ). Rapid decliner phenotype was associated with osteopontin (OR: 1.83 [1.42, 2.41], P = 7.3 × 10-6 ), whereas rapid increaser phenotype was associated with fibroblast growth factor-23 (FGF-23) (1.59 [1.23, 2.04], P = 2.6 × 10-4 ). 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 trefoil factor-3, cystatin C, and B2M were associated with baseline eGFR.
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