PMID- 35286453 OWN - NLM STAT- MEDLINE DCOM- 20221025 LR - 20231202 IS - 1432-198X (Electronic) IS - 0931-041X (Print) IS - 0931-041X (Linking) VI - 37 IP - 12 DP - 2022 Dec TI - Relationship between biomarkers of tubular injury and intrarenal hemodynamic dysfunction in youth with type 1 diabetes. PG - 3085-3092 LID - 10.1007/s00467-022-05487-4 [doi] 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. A higher resolution version of the Graphical abstract is available as Supplementary information. CI - (c) 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association. FAU - Johnson, Melissa J AU - Johnson MJ AD - Department of Pediatrics, Section of Pediatric Endocrinology, Children's Hospital Colorado and University of Colorado Anschutz Medical Campus, Aurora, CO, USA. FAU - Tommerdahl, Kalie L AU - Tommerdahl KL AD - Department of Pediatrics, Section of Pediatric Endocrinology, Children's Hospital Colorado and University of Colorado Anschutz Medical Campus, Aurora, CO, USA. AD - Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO, USA. AD - Ludeman Center for Women's Health Research, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. FAU - Vinovskis, Carissa AU - Vinovskis C AD - Department of Pediatrics, Section of Pediatric Endocrinology, Children's Hospital Colorado and University of Colorado Anschutz Medical Campus, Aurora, CO, USA. FAU - Waikar, Sushrut AU - Waikar S AD - Section of Nephrology, Boston University School of Medicine and Boston Medical Center, Boston, MA, USA. FAU - Reinicke, Trenton AU - Reinicke T AD - Department of Pediatrics, Section of Pediatric Endocrinology, Children's Hospital Colorado and University of Colorado Anschutz Medical Campus, Aurora, CO, USA. FAU - Parikh, Chirag R AU - Parikh CR AD - Division of Nephrology, Johns Hopkins School of Medicine, Baltimore, MD, USA. FAU - Obeid, Wassim AU - Obeid W AD - Division of Nephrology, Johns Hopkins School of Medicine, Baltimore, MD, USA. FAU - Nelson, Robert G AU - Nelson RG AD - Chronic Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, USA. FAU - van Raalte, Daniel H AU - van Raalte DH AD - Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Centers, location VUMC, Amsterdam, The Netherlands. FAU - Pyle, Laura AU - Pyle L AD - Department of Biostatistics, Colorado School of Public Health, Aurora, CO, USA. FAU - Nadeau, Kristen J AU - Nadeau KJ AD - Department of Pediatrics, Section of Pediatric Endocrinology, Children's Hospital Colorado and University of Colorado Anschutz Medical Campus, Aurora, CO, USA. AD - Ludeman Center for Women's Health Research, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. FAU - Bjornstad, Petter AU - Bjornstad P AD - 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. AD - Ludeman Center for Women's Health Research, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. Petter.Bjornstad@childrenscolorado.org. AD - 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. LA - eng GR - R01 HL085757/HL/NHLBI NIH HHS/United States GR - R01 DK093770/DK/NIDDK NIH HHS/United States GR - U01 DK106962/DK/NIDDK NIH HHS/United States GR - P30 DK116073/DK/NIDDK NIH HHS/United States GR - K23 DK116720/DK/NIDDK NIH HHS/United States GR - UH3 DK114866/DK/NIDDK NIH HHS/United States GR - R21 DK129720/DK/NIDDK NIH HHS/United States GR - U24 DK114886/DK/NIDDK NIH HHS/United States GR - K23 HL159292/HL/NHLBI NIH HHS/United States GR - L40 HL159798/HL/NHLBI NIH HHS/United States GR - R01 DK129211/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20220314 PL - Germany TA - Pediatr Nephrol JT - Pediatric nephrology (Berlin, Germany) JID - 8708728 RN - 0 (Lipocalin-2) RN - 0 (Interleukin-18) RN - 0 (Chitinase-3-Like Protein 1) RN - 0 (Chemokine CCL2) RN - AYI8EX34EU (Creatinine) RN - 0 (Glycated Hemoglobin A) RN - 0 (Biomarkers) RN - 0 (Albumins) SB - IM MH - Adolescent MH - Humans MH - Lipocalin-2 MH - *Diabetes Mellitus, Type 1/complications/diagnosis MH - Interleukin-18 MH - Chitinase-3-Like Protein 1 MH - Chemokine CCL2 MH - Creatinine MH - Glycated Hemoglobin MH - Biomarkers MH - Hemodynamics MH - Albumins PMC - PMC9470783 MID - NIHMS1800758 OTO - NOTNLM OT - Biomarkers OT - Diabetic kidney disease OT - KIM-1 OT - Pediatrics OT - Tubular injury OT - YKL-40 COIS- Conflicts of interest: M.J.J., K.L.T., C.V., S.W., T.R., W.O., R.G.N., L.P., and K.J.N. have no relationships relevant to the contents of this paper to disclose. C.R.P. reports serving as a member of the advisory board of and owning equity in RenalytixAI. He also serves as a consultant for Genfit and Novartis. D.H.vR. has served as a consultant and received honoraria from Boehringer Ingelheim and Eli Lilly, Merck, Novo Nordisk, and Sanofi and has received research operating funds from AstraZeneca, Boehringer Ingelheim-Eli Lilly Diabetes Alliance, MSD, and Novo Nordisk. P.B. reports serving as a consultant for AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Eli-Lilly, LG Chemistry, Sanofi, Novo Nordisk, and Horizon Pharma. P.B. also serves on the advisory boards of AstraZeneca, Bayer, Boehringer Ingelheim, Novo Nordisk, and XORTX. EDAT- 2022/03/15 06:00 MHDA- 2022/10/26 06:00 PMCR- 2023/12/01 CRDT- 2022/03/14 17:19 PHST- 2021/09/24 00:00 [received] PHST- 2022/01/31 00:00 [accepted] PHST- 2022/01/29 00:00 [revised] PHST- 2022/03/15 06:00 [pubmed] PHST- 2022/10/26 06:00 [medline] PHST- 2022/03/14 17:19 [entrez] PHST- 2023/12/01 00:00 [pmc-release] AID - 10.1007/s00467-022-05487-4 [pii] AID - 10.1007/s00467-022-05487-4 [doi] PST - ppublish SO - Pediatr Nephrol. 2022 Dec;37(12):3085-3092. doi: 10.1007/s00467-022-05487-4. Epub 2022 Mar 14.