Urinary Nephrin as a Biomarker of Glomerular Maturation and Injury Is Associated with Acute Kidney Injury and Mortality in Critically Ill Neonates

Abstract

Background: Nephrin is a key component of the slit diaphragm of the glomerular podocyte, and increased urinary nephrin level may reflect glomerular injury. Objectives: To determine whether urinary nephrin is a useful biomarker of glomerular maturation and injury and whether it is associated with acute kidney injury (AKI) and neonatal intensive care unit (NICU) mortality in critically ill neonates. Methods: Urinary samples were serially collected in 234 neonates during NICU stay for measurements of nephrin, cystatin C (CysC), and albumin. AKI diagnosis was based on neonatal Kidney Disease: Improving Global Outcome (KDIGO) criteria. Results: Of the neonates, 26 developed AKI and 24 died during NICU stay. The independent contributors to the initial urinary nephrin level obtained on the first 24 h admitted to NICU were gestational age (p = 0.004) and initial urinary CysC level (p < 0.001). Both initial (p = 0.037) and peak (p = 0.039) urinary nephrin were significantly associated with AKI, even after controlling for significant covariates, and had an area under the receiver-operating characteristic curve (AUC) of 0.71 and 0.70, respectively, for predicting AKI. At the optimal cutoff value of 0.375 μg/mg urinary creatinine, the initial urinary nephrin displayed sensitivity of 61.5% and specificity of 76.9% for predicting AKI. The AUCs for initial and peak urinary nephrin to predict NICU mortality were 0.81 and 0.83, respectively. Conclusions: Urinary nephrin, which may decrease with increasing glomerular maturity, is significantly associated with increased risk for AKI and NICU mortality even after adjustment for potential confounders. A higher level of urinary nephrin may be independently predictive of AKI and NICU mortality in critically ill neonates.

Urinary nephrin—a potential marker of early glomerular injury: a systematic review and meta-analysis

“…The diagnostic accuracy of urinary nephrin for detecting PE and diabetic nephropathy could therefore be extrapolated into use as a potential predictor of early glomerular injury, particularly in the setting of AKI. Recently, studies have emerged investigating the value of urinary nephrin for predicting AKI, particularly in critically ill neonates [66,67]. These studies concluded that urinary nephrin may well provide a marker for predicting AKI, demonstrating a diagnostic sensitivity of 62.5%, 61.5%, and specificity of 82.1%, 76.9% respectively at a cut-off point of NCR = 0.375 µg/mg, suggesting that urinary nephrin may give an early indication of podocyte damage as an indicator of those infants at risk of developing AKI.…”

“…These studies concluded that urinary nephrin may well provide a marker for predicting AKI, demonstrating a diagnostic sensitivity of 62.5%, 61.5%, and specificity of 82.1%, 76.9% respectively at a cut-off point of NCR = 0.375 µg/mg, suggesting that urinary nephrin may give an early indication of podocyte damage as an indicator of those infants at risk of developing AKI. This is an area of intense interest in the literature [30,66,67], since a single biomarker may not suffice to define AKI given inherent renal heterogeneity and the disparate settings under which kidney injury occurs [68].…”

Use of non-conventional biomarkers in the early diagnosis of acute kidney injury in preterm newborns with sepsis

“…Reports have described nephrin as a biomarker of AKI in NICU settings. A study enrolling newborns concluded that initial urinary nephrin levels were higher in newborns with AKI than in newborns without AKI, indicating that increased nephrin levels might occur as a consequence of glomerular immaturity, particularly in preterm newborns 51 .…”

“…Nephrin may become an important biomarker of early glomerular injury 50 and AKI in NICU settings, particularly for preterm newborns 51 .…”

“…It is unknown whether glomerular injury is induced in the early stages of neonatal AKI. A study with neonates described urinary nephrin as a maturation and glomerular injury biomarker significantly associated with development of AKI and death in NICU settings 51 .…”