Serum FGF23 and Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL) Correlation with Glomerular Filtration Rate, Measured with a Reference Technique in Children with CKD

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Background: Prognosis of chronic kidney disease (CKD) is closely related to early diagnosis and initiation of nephroprotective measures. Current kidney injury biomarkers are suboptimal for predicting kidney disease progression. Fibroblast Growth Factor 23 (FGF23) is well described as an early marker that increases proportionally to worsening CKD stages in adults. Neutrophil gelatinase-associated lipocalin (NGAL) is known to increase early after acute kidney injury, as a marker of AKI severity, however, it has not been validated as an early marker in CKD. The aim of this study is to investigate the association between FGF23, NGAL and glomerular filtration rate (GFR) in children and evaluate their role in ascertaining moderate to severe CKD. Methods: Children aged 5 to 20 years old requiring kidney function assessment following primary nephropathy, solid organ transplantation or secondary nephropathy were recruited prospectively in a tertiary hospital of Switzerland for a reference measure of their GFR, with simultaneous measurement of plasma FGF23 and urinary NGAL. Results: 123 clearances were analyzed, in children mostly post solid organ transplantation (46%) or with primary nephropathy (37%). 42% had stage I CKD, 40% had stage II CKD and 12% had stage III or IV CKD. FGF23 was significantly higher in stage III or IV CKD (mean: 282.02 UI/ml ± 174.71) compared to stage I (mean: 143.76 UI/ml ± 178.61 ; p<0.001) or stage II (mean: 104.61 UI/ml ± 63.52; p<0.001). The area under the ROC curve for FGF23 to discriminate CKD stages I-II versus III-IV was 0.864 (95% confidence interval (CI): 0.780-0.947). NGAL values were more elevated in stage III or IV CKD (mean: 103.65 UI/ml ± 129.43) compared to stage I (mean: 36.19 UI/ml ± 100.36 ; p=0.016) or stage II (mean: 44.86 UI/ml ± 104.66; p=0.082). The area under the ROC curve for NGAL to discriminate CKD stages I-II versus III-IV was 0.688 (95% CI: 0.512-0.864). Conclusions: FGF23 is significantly associated with decreasing GFR in children and discriminates for the presence of moderate to severe CKD in children. NGAL was not as strongly associated to decreasing GFR. Further studies are needed to evaluate FGF23 and NGAL as markers of CKD progression.

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