Serial urinary neutrophil gelatinase associated lipocalin in pediatric diabetic ketoacidosis with acute kidney injury

Abstract

Abstract Background Acute kidney injury (AKI) due to Diabetic Ketoacidosis (DKA) is rather common. Novel biomarkers to diagnose AKI are being increasingly used in different settings. The use of urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) in predicting persistent AKI in pediatric DKA cases is still not thoroughly investigated. Methods This was a secondary analysis of Saline versus Plasma-Lyte in Ketoacidosis (SPinK) trial data; 66 children (> 1 month-12 years) with DKA, defined by the International Society for Pediatric and Adolescent Diabetes (ISPAD), were analyzed. Children with cerebral edema, chronic kidney disease and those who received pre-referral fluids and/or insulin were excluded. uNGAL and urine NGAL-creatinine ratio (uNCR) at 0 and 24 h were measured in all. Persistent AKI was defined as a composite outcome of continuance of AKI defined by the Kidney Disease Improving Global Outcomes (KDIGO) stage 2 or 3 beyond 48 h from AKI onset, progression of AKI from either KDIGO stage 0 or 1 to a worse stage, need of renal replacement therapy or death. Main outcomes Thirty-five (53%) children had AKI at admission; 32 (91.4%) resolved within 48 h. uNGAL was significantly higher in the AKI group at admission [79.8 ± 27.2 vs 54.6 ± 22.0, p = 0.0002] and at 24 h [61.4 ± 28.3 vs 20.2 ± 14.5, p = 0.0003]. Similar trend was observed with uNCR at admission [6.7 ± 3.7 vs 4.1 ± 2.6, p = 0.002] and at 24 h [6.3 ± 2.5 vs 1.2 ± 1.0, p = 0.01]. Furthermore, uNGAL at admission showed a moderate positive linear correlation with serum creatinine. Additionally, elevated uNGAL at 0 and 24 h correlated with corresponding KDIGO stages. Admission uNGAL >88 ng/ml and uNCR of >11.3 ng/mg had a sensitivity of 66% and 67%, specificity of 76% and 95%, and Area under the receiver operating characteristic curve (AUC) of 0.78 and 0.89 respectively for predicting persistent AKI at 48 h. Conclusions Majority of AKI resolved with fluid therapy. While uNGAL and uNCR both correlated with serum creatinine and AKI stages, serial uNCR was a better predictor of persistent AKI than uNGAL alone. However, feasibility of routine uNGAL measurement to predict persistent AKI in DKA needs further elucidation. Trial registration This was a secondary analysis of the data of SPinK trial [CTRI/2018/05/014042 ( ctri.nic.in )].

Keywords

• Type1 diabetes
• Ketoacidosis
• Pediatric
• Acute kidney injury
• Lipocalin