Tubular injury in diabetic ketoacidosis: Results from the diabetic kidney alarm study

Federica Piani, Isabella Melena, Cameron Severn, Linh T. Chung, Carissa Vinovskis, David Cherney, Laura Pyle, Carlos A. Roncal-Jimenez, Miguel A. Lanaspa, Arleta Rewers, Daniël H. van Raalte, Wassim Obeid, Chirag Parikh, Robert G. Nelson, Meda E. Pavkov, Kristen J. Nadeau, Richard J. Johnson, Petter Bjornstad

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)1031-1039
Number of pages9
JournalPediatric diabetes
Issue number7
StatePublished - Nov 2021


  • diabetic ketoacidosis
  • kidney disease
  • tubular injury
  • uric acid
  • vasopressin

ASJC Scopus subject areas

  • Internal Medicine
  • Pediatrics, Perinatology, and Child Health
  • Endocrinology, Diabetes and Metabolism


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