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

Neonatology. 2019;116(1):58-66. doi: 10.1159/000499083. Epub 2019 Apr 12.

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.

Keywords: Acute kidney injury; Critically ill neonates; Glomerular injury; Mortality; Urinary nephrin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / mortality*
  • Acute Kidney Injury / physiopathology*
  • Acute Kidney Injury / urine
  • Area Under Curve
  • Biomarkers / urine
  • Critical Illness / mortality
  • Cystatin C / urine
  • Female
  • Gestational Age
  • Humans
  • Infant, Newborn
  • Intensive Care Units, Neonatal
  • Length of Stay / statistics & numerical data
  • Logistic Models
  • Male
  • Membrane Proteins / urine*
  • Multivariate Analysis
  • Predictive Value of Tests
  • Prospective Studies
  • ROC Curve

Substances

  • Biomarkers
  • Cystatin C
  • Membrane Proteins
  • nephrin