Melissa J Johnson1, Kalie L Tommerdahl1,2,3, Carissa Vinovskis1, Sushrut Waikar4, Trenton Reinicke1, Chirag R Parikh5, Wassim Obeid5, Robert G Nelson6, Daniel H van Raalte7, Laura Pyle8, Kristen J Nadeau1,3, Petter Bjornstad9,10,11. 1. Department of Pediatrics, Section of Pediatric Endocrinology, Children's Hospital Colorado and University of Colorado Anschutz Medical Campus, Aurora, CO, USA. 2. Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO, USA. 3. Ludeman Center for Women's Health Research, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. 4. Section of Nephrology, Boston University School of Medicine and Boston Medical Center, Boston, MA, USA. 5. Division of Nephrology, Johns Hopkins School of Medicine, Baltimore, MD, USA. 6. Chronic Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, USA. 7. Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Centers, location VUMC, Amsterdam, The Netherlands. 8. Department of Biostatistics, Colorado School of Public Health, Aurora, CO, USA. 9. Department of Pediatrics, Section of Pediatric Endocrinology, Children's Hospital Colorado and University of Colorado Anschutz Medical Campus, Aurora, CO, USA. Petter.Bjornstad@childrenscolorado.org. 10. Ludeman Center for Women's Health Research, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. Petter.Bjornstad@childrenscolorado.org. 11. Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, 13123 E. 16th AveBox B265, Aurora, CO, USA. Petter.Bjornstad@childrenscolorado.org.
Abstract
BACKGROUND: Early identification of youth with type 1 diabetes (T1D) at risk for diabetic kidney disease may improve clinical outcomes. We examined the cross-sectional relationship between kidney biomarkers neutrophil gelatinase-associated lipocalin (NGAL), copeptin, interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), chitinase-3-like protein-1 (YKL-40), and monocyte chemoattractant protein-1 (MCP-1) and intrarenal hemodynamic function in adolescents with T1D. METHODS: Urine albumin-to-creatinine ratio (UACR), renal vascular resistance (RVR), glomerular filtration rate (GFR), intraglomerular pressure (PGLO), efferent arteriole resistance (RE), afferent arteriolar resistance (RA), and renal plasma flow (RPF), and the above indicated biomarkers were assessed in youth aged 12-21 years with and without T1D of < 10 years duration. RESULTS: Fifty adolescents with T1D (16.1 ± 3.0 years, HbA1c 8.6 ± 1.2%) and 20 adolescents of comparable BMI without T1D (16.1 ± 2.9 years, HbA1c 5.2 ± 0.2%) were enrolled. Adolescents with T1D demonstrated significantly higher GFR, RPF, RE, and PGLO than controls (39%, 33%, 74%, and 29%, respectively, all p < 0.0001). Adolescents with T1D also exhibited significantly lower RVR and RA than controls (25% and 155%, respectively, both p < 0.0001). YKL-40 and KIM-1 concentrations, respectively, were positively associated with GFR (r: 0.43, p = 0.002; r: 0.41, p = 0.003), RPF (r: 0.29, p = 0.08; r: 0.34, p = 0.04), UACR (r: 0.33, p = 0.02; r: 0.50, p = 0.0002), and PGLO (r: 0.45, p = 0.006; r: 0.52, p = 0.001) in adolescents with T1D. CONCLUSIONS: Higher concentrations of biomarkers YKL-40 and KIM-1 may help define the risk for intraglomerular hemodynamic dysfunction in youth with T1D. A higher resolution version of the Graphical abstract is available as Supplementary information.
BACKGROUND: Early identification of youth with type 1 diabetes (T1D) at risk for diabetic kidney disease may improve clinical outcomes. We examined the cross-sectional relationship between kidney biomarkers neutrophil gelatinase-associated lipocalin (NGAL), copeptin, interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), chitinase-3-like protein-1 (YKL-40), and monocyte chemoattractant protein-1 (MCP-1) and intrarenal hemodynamic function in adolescents with T1D. METHODS: Urine albumin-to-creatinine ratio (UACR), renal vascular resistance (RVR), glomerular filtration rate (GFR), intraglomerular pressure (PGLO), efferent arteriole resistance (RE), afferent arteriolar resistance (RA), and renal plasma flow (RPF), and the above indicated biomarkers were assessed in youth aged 12-21 years with and without T1D of < 10 years duration. RESULTS: Fifty adolescents with T1D (16.1 ± 3.0 years, HbA1c 8.6 ± 1.2%) and 20 adolescents of comparable BMI without T1D (16.1 ± 2.9 years, HbA1c 5.2 ± 0.2%) were enrolled. Adolescents with T1D demonstrated significantly higher GFR, RPF, RE, and PGLO than controls (39%, 33%, 74%, and 29%, respectively, all p < 0.0001). Adolescents with T1D also exhibited significantly lower RVR and RA than controls (25% and 155%, respectively, both p < 0.0001). YKL-40 and KIM-1 concentrations, respectively, were positively associated with GFR (r: 0.43, p = 0.002; r: 0.41, p = 0.003), RPF (r: 0.29, p = 0.08; r: 0.34, p = 0.04), UACR (r: 0.33, p = 0.02; r: 0.50, p = 0.0002), and PGLO (r: 0.45, p = 0.006; r: 0.52, p = 0.001) in adolescents with T1D. CONCLUSIONS: Higher concentrations of biomarkers YKL-40 and KIM-1 may help define the risk for intraglomerular hemodynamic dysfunction in youth with T1D. A higher resolution version of the Graphical abstract is available as Supplementary information.
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