Serum and urine FGF23 and IGFBP-7 for the prediction of acute kidney injury in critically ill children

Abstract

Background: Fibroblast growth factor 23 (FGF23) and insulin-like growth factor binding protein 7 (IGFBP-7) are suggested to be biomarkers for predicting acute kidney injury (AKI). We compared them with proposed AKI biomarker of cystatin C (CysC), and aimed (1) to examine whether concentrations of these biomarkers vary with age, body weight, illness severity assessed by pediatric risk of mortality III score, and kidney function assessed by estimated glomerular filtration rate (eGFR), (2) to determine the association between these biomarkers and AKI, and (3) to evaluate whether these biomarkers could serve as early independent predictors of AKI in critically ill children.

Methods: This prospective single center study included 144 critically ill patients admitted to the pediatric intensive care unit (PICU) regardless of diagnosis. Serum and spot urine samples were collected during the first 24 h after PICU admission. AKI was diagnosed based on the AKI network (AKIN) criteria.

Results: Twenty-one patients developed AKI within 120 h of sample collection, including 11 with severe AKI defined as AKIN stages 2 and 3. Serum FGF23 levels were independently associated with eGFR after adjustment in a multivariate linear analysis (P < 0.001). Urinary IGFBP-7 (Adjusted OR = 2.94 per 1000 ng/mg increase, P = 0.035), serum CysC (Adjusted OR = 5.28, P = 0.005), and urinary CysC (Adjusted OR = 1.13 per 1000 ng/mg increase, P = 0.022) remained significantly associated with severe AKI after adjustment for body weight and illness severity, respectively. Urinary IGFBP-7 level was predictive of severe AKI and achieved the AUC of 0.79 (P = 0.001), but was not better than serum (AUC = 0.89, P < 0.001) and urinary (AUC = 0.88, P < 0.001) CysC in predicting severe AKI.

Conclusions: Serum FGF23 levels were inversely related to measures of eGFR. In contrast to serum and urinary FGF23 which are not associated with AKI in a general and heterogeneous PICU population, an increased urinary IGFBP-7 level was independently associated with the increased risk of severe AKI diagnosed within the next 5 days after sampling, but not superior to serum or urinary CysC in predicting severe AKI in critically ill children.

Keywords: Acute kidney injury; Critically ill children; Cystatin C; Fibroblast growth factor 23; Insulin-like growth factor binding protein 7; Pediatric risk of mortality III score.

Fig. 1

Comparison of the levels of biomarkers among critically ill children with non-AKI, mild AKI, and severe AKI. a serum level of FGF23, b serum level of IGFBP-7; c serum level of CysC, d urinary level of FGF23, e urinary level of IGFBP-7, f urinary level of CysC. AKI network stage 1 was defined as mild AKI. AKI network stages 2 and 3 were defined as severe AKI. Each circle represents an individual patient; the horizontal lines indicate geometric means with 95% confidence interval. Probability values: the Mann-Whitney U test. The P value for comparison between non-AKI (n = 123) and severe AKI (n = 11), and for comparison between mild (n = 10) and severe (n = 11) AKI

Fig. 2

ROC curves for the ability of urinary IGFBP-7, serum and urinary cystatin C, and PRISM III score to predict severe AKI in critically ill children. AKI network stages 2 and 3 were defined as severe AKI. AKI, acute kidney injury; AUC, the area under the ROC curve; PRISM III, pediatric risk of mortality III; ROC, receiver operating characteristic. The P value for comparison between the AUCs of urinary IGFBP-7 and serum cystatin C was 0.103 and for comparison between the AUCs of urinary IGFBP-7 and urinary cystatin C was 0.225