TY - JOUR
T1 - Tubular injury in diabetic ketoacidosis
T2 - Results from the diabetic kidney alarm study
AU - Piani, Federica
AU - Melena, Isabella
AU - Severn, Cameron
AU - Chung, Linh T.
AU - Vinovskis, Carissa
AU - Cherney, David
AU - Pyle, Laura
AU - Roncal-Jimenez, Carlos A.
AU - Lanaspa, Miguel A.
AU - Rewers, Arleta
AU - van Raalte, Daniël H.
AU - Obeid, Wassim
AU - Parikh, Chirag
AU - Nelson, Robert G.
AU - Pavkov, Meda E.
AU - Nadeau, Kristen J.
AU - Johnson, Richard J.
AU - Bjornstad, Petter
N1 - Funding Information:
Financial support for this work provided by the Thrasher Research Foundation, ISPAD and JDRF, and NIH CTSA Grant UL1 TR002535. P.B. receives salary and research support from NIDDK (DK116720, DK114886), JDRF (2‐SRA‐2019‐845‐S‐B, 3‐SRA‐2017‐424‐M‐B), Boettcher Foundation, Center for Women's Health Research at University of Colorado, the Department of Pediatrics, Section of Endocrinology and Barbara Davis Center for Diabetes at University of Colorado School of Medicine. PB has acted as a consultant for AstraZeneca, Bayer, Bristol‐Myers Squibb, Boehringer Ingelheim, Eli‐Lilly, Sanofi, Novo Nordisk, and Horizon Pharma. PB serves on the advisory boards for AstraZeneca, Bayer, Boehringer Ingelheim, Novo Nordisk and XORTX. D.Z.I.C has received honoraria from Boehringer Ingelheim‐Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi‐Tanabe, Abbvie, Janssen, Bayer, Prometic, BMS, Maze and Novo‐Nordisk and has received operational funding for clinical trials from Boehringer Ingelheim‐Lilly, Merck, Janssen, Sanofi, AstraZeneca and Novo‐Nordisk. DvR has acted as a consultant and received honoraria from Boehringer Ingelheim and Lilly, Merck, Novo Nordisk, MSD, Sanofi and AstraZeneca and has received research operating funds from Boehringer Ingelheim‐Lilly Diabetes Alliance, AstraZeneca and MDS. All honoraria are paid to his employer (Amsterdam University Medical Center). CP is a member of the advisory board of RenalytixAI and owns equity in the same. He also serves on the DSMB board for Genfit, CP was supported by the grants: R01HL085757, P30DK079310. RJ has acted as a consultant for Horizon and AstraZeneca and has equity with XORTX Therapeutics and Colorado Research Partners LLC. FP, IM, CS, LTC, CV, LP, CRJ, MAL, AR, WO, RGN, MP, KJN have no disclosures.
Funding Information:
We acknowledge the work of the Children's Hospital Colorado Emergency Department Research team and Children's Hospital Colorado CTRC research nursing group.
Publisher Copyright:
© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
PY - 2021/11
Y1 - 2021/11
N2 - Objective: Glomerular injury is a recognized complication of diabetic ketoacidosis (DKA), yet the tubular lesions are poorly understood. The aim of this prospective study was to evaluate the presence and reversibility of tubular injury during DKA in children with type 1 diabetes (T1D). Research Design and Methods: Blood and urine samples were collected from 40 children with DKA (52% boys, mean age 11 ± 4 years, venous pH 7.2 ± 0.1, glucose 451 ± 163 mg/dL) at three timepoints: 0–8 and 12–24 h after starting insulin, and 3 months after discharge. Mixed-effects models evaluated the changes in tubular injury markers over time (neutrophil gelatinase-associated lipocalin [NGAL], kidney injury molecule 1 [KIM-1], and interleukin 18 [IL-18]). We also evaluated the relationships among the tubular injury biomarkers, copeptin, a vasopressin surrogate, and serum uric acid (SUA). Results: Serum NGAL, KIM-1, and IL-18 were highest at 0–8 h (306.5 ± 45.9 ng/mL, 128.9 ± 10.1 pg/mL, and 564.3 ± 39.2 pg/mL, respectively) and significantly decreased over 3 months (p = 0.03, p = 0.01, and p < 0.001, respectively). There were strong relationships among increases in copeptin and SUA and rises in tubular injury biomarkers. At 0–8 h, participants with acute kidney injury (AKI) [17%] showed significantly higher concentrations of tubular injury markers, copeptin, and SUA. Conclusions: DKA was characterized by tubular injury, and the degree of injury associated with elevated copeptin and SUA. Tubular injury biomarkers, copeptin and SUA may be able to predict AKI in DKA.
AB - Objective: Glomerular injury is a recognized complication of diabetic ketoacidosis (DKA), yet the tubular lesions are poorly understood. The aim of this prospective study was to evaluate the presence and reversibility of tubular injury during DKA in children with type 1 diabetes (T1D). Research Design and Methods: Blood and urine samples were collected from 40 children with DKA (52% boys, mean age 11 ± 4 years, venous pH 7.2 ± 0.1, glucose 451 ± 163 mg/dL) at three timepoints: 0–8 and 12–24 h after starting insulin, and 3 months after discharge. Mixed-effects models evaluated the changes in tubular injury markers over time (neutrophil gelatinase-associated lipocalin [NGAL], kidney injury molecule 1 [KIM-1], and interleukin 18 [IL-18]). We also evaluated the relationships among the tubular injury biomarkers, copeptin, a vasopressin surrogate, and serum uric acid (SUA). Results: Serum NGAL, KIM-1, and IL-18 were highest at 0–8 h (306.5 ± 45.9 ng/mL, 128.9 ± 10.1 pg/mL, and 564.3 ± 39.2 pg/mL, respectively) and significantly decreased over 3 months (p = 0.03, p = 0.01, and p < 0.001, respectively). There were strong relationships among increases in copeptin and SUA and rises in tubular injury biomarkers. At 0–8 h, participants with acute kidney injury (AKI) [17%] showed significantly higher concentrations of tubular injury markers, copeptin, and SUA. Conclusions: DKA was characterized by tubular injury, and the degree of injury associated with elevated copeptin and SUA. Tubular injury biomarkers, copeptin and SUA may be able to predict AKI in DKA.
KW - diabetic ketoacidosis
KW - kidney disease
KW - tubular injury
KW - uric acid
KW - vasopressin
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U2 - 10.1111/pedi.13259
DO - 10.1111/pedi.13259
M3 - Article
C2 - 34435718
AN - SCOPUS:85114377597
SN - 1399-543X
VL - 22
SP - 1031
EP - 1039
JO - Pediatric diabetes
JF - Pediatric diabetes
IS - 7
ER -