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

Abstract

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.

Determinants of acute kidney injury in children with new onset type 1 diabetes: A cohort study of children aged <15 years: Auckland, New Zealand (2006–2016)

“…This implies that these cases are likely to have also developed intrinsic tubular injury, a finding confirmed by several recent studies in children in DKA. 3,19,20 There are few if any studies in the paediatric literature to compare rates of AKI in common paediatric conditions, such as gastroenteritis. The 3 most common causes of hospital acquired AKI are renal perfusion insufficiency, nephrotoxic drugs and contrast agents, two of these are at least potentially avoidable and not seen…”

“…This implies that these cases are likely to have also developed intrinsic tubular injury, a finding confirmed by several recent studies in children in DKA. 3 , 19 , 20 …”

Acute and chronic kidney complications in children with type 1 diabetes mellitus

“…al reported that DKA is characterized by markers of reversible tubular injury and that the degree of injury is associated with elevated copeptin and serum uric acid (SUA) levels in children with T1DM [3]. In fact, during the onset of T1DM, high levels of copeptin and SUA are associated with the presence of tubular injury markers, such as neutrophil gelatin-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), chitinase 3-like 1 (YKL-40), interleukin 18 (IL-18), and monocyte chemoattractant protein-1 (MCP-1) [3]. Aminoaciduria can also be considered a marker of tubular dysfunction, since an increased excretion of amino acids has been reported during DKA [27][28][29].…”

“…A delayed therapeutic intervention may lead to the persistence of glomerular vasoconstriction, which may result in an acute tubular necrosis (described in about 30% of patients with T1DM onset [ 1 ]), thus shifting AKI from functional to intrinsic [ 15 , 16 ]. For this reason, there has been a recent focus on the investigation of early tubular AKI biomarkers, in order to diagnose functional AKI in a timely manner, and to hopefully prevent the evolution to intrinsic AKI [ 3 , 17 ].…”

“…Children with type 1 diabetes mellitus (T1DM) can present with kidney involvement both in the acute setting presenting with acute kidney injury (AKI), as well as tubular damage and in the chronic setting presenting with diabetic kidney disease (DKD) [1][2][3][4][5][6].…”