TY - JOUR
T1 - Relationship between biomarkers of tubular injury and intrarenal hemodynamic dysfunction in youth with type 1 diabetes
AU - Johnson, Melissa J.
AU - Tommerdahl, Kalie L.
AU - Vinovskis, Carissa
AU - Waikar, Sushrut
AU - Reinicke, Trenton
AU - Parikh, Chirag R.
AU - Obeid, Wassim
AU - Nelson, Robert G.
AU - van Raalte, Daniel H.
AU - Pyle, Laura
AU - Nadeau, Kristen J.
AU - Bjornstad, Petter
N1 - Funding Information: K.L.T. receives salary and research support from the NIH/NHLBI (K23 HL159292), Children’s Hospital Colorado Research Scholar Award, University of Colorado Diabetes Research Center (P30 DK116073), Ludeman Family Center for Women’s Health Research at the University of Colorado, and the Department of Pediatrics, Section of Endocrinology at the University of Colorado School of Medicine. C.R.P. is supported by NIH/NHLBI (R01 HL085757) and NIH/NIDDK (UH3 DK114866, U01 DK106962, R01 DK093770). R.G.N. is supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. P.B. receives salary and research support from NIDDK (R01 DK129211, R21 DK129720, K23 DK116720, UC DK114886, and P30 DK116073), JDRF (3-SRA-2022–1097-M-B, 2-SRA-2019–845-S-B, 3-SRA-2017–424-M-B), Boettcher Foundation, American Heart Association (20IPA35260142), Ludeman Family Center for Women’s Health Research at the University of Colorado, the Department of Pediatrics, Section of Endocrinology, and Barbara Davis Center for Diabetes at University of Colorado School of Medicine. Funding Information: The CASPER and Renal-HEIR studies have been funded in whole or in part by NIH/NIDDK (K23-DK116720) and JDRF (2-SRA-2018–627-M-B). Funders had no role in the study design; collection, analysis, and interpretation of these data; writing the report; or the decision to submit the report. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as official policy or interpretation of the US government. Funding Information: The authors thank the staff and participants of the CASPER and Renal-HEIR studies for their important contributions. Publisher Copyright: © 2022, The Author(s), under exclusive licence to International Pediatric Nephrology Association.
PY - 2022/3
Y1 - 2022/3
N2 - 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 (P GLO), efferent arteriole resistance (R E), afferent arteriolar resistance (R A), 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, R E, and P GLO than controls (39%, 33%, 74%, and 29%, respectively, all p < 0.0001). Adolescents with T1D also exhibited significantly lower RVR and R A 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 P GLO (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. Graphical abstract: A higher resolution version of the Graphical abstract is available as Supplementary information. [Figure not available: see fulltext.]
AB - 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 (P GLO), efferent arteriole resistance (R E), afferent arteriolar resistance (R A), 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, R E, and P GLO than controls (39%, 33%, 74%, and 29%, respectively, all p < 0.0001). Adolescents with T1D also exhibited significantly lower RVR and R A 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 P GLO (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. Graphical abstract: A higher resolution version of the Graphical abstract is available as Supplementary information. [Figure not available: see fulltext.]
KW - Biomarkers
KW - Diabetic kidney disease
KW - KIM-1
KW - Pediatrics
KW - Tubular injury
KW - YKL-40
UR - http://www.scopus.com/inward/record.url?scp=85126238616&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s00467-022-05487-4
DO - https://doi.org/10.1007/s00467-022-05487-4
M3 - Article
C2 - 35286453
SN - 0931-041X
VL - 37
SP - 3085
EP - 3092
JO - Pediatric Nephrology
JF - Pediatric Nephrology
IS - 12
ER -