# Fetal Urinary Cystatin C, NGAL and Beta-2-Microglobulin as Predictors of Postnatal Renal Function Impairment and Death in Fetuses with Lower Urinary Tract Obstruction

## TL;DR

This study shows that fetal urine markers like Cystatin C, NGAL, and Beta-2-Microglobulin can predict kidney problems and death in babies with urinary tract blockages before birth.

## Contribution

The study introduces fetal urinary biomarkers as potential predictors of postnatal renal dysfunction and mortality in fetuses with lower urinary tract obstruction.

## Key findings

- Cystatin C corrected for creatinine was the strongest predictor of decreased kidney function 30 days after birth.
- NGAL and Beta-2-Microglobulin also showed significant predictive value for postnatal outcomes.
- The biomarkers could help guide prenatal decisions and improve counseling for affected families.

## Abstract

Background/Objectives: Fetal lower urinary tract obstruction (LUTO) is a rare congenital anomaly that often leads to pulmonary hypoplasia and kidney dysfunction, which contribute to increased mortality. Prenatal estimation of the severity of LUTO is challenging due to the lack of specific diagnostic tools, which may guide clinical decisions. The aim of this analysis was to assess the role of fetal urinary concentrations of neutrophil gelatinase-associated lipocalin (NGAL), β2-microglobulin (B2M) and Cystatin C (CysC) in the prediction of unfavorable outcomes, such as postnatal renal dysfunction and death, among LUTO patients. Methods: A total of 38 women carrying fetuses with suspected LUTO (based on ultrasound features) were included in the study. Fetal urine was collected from the bladder of the fetus under ultrasound guidance, and measurements of NGAL, CysC and B2M were performed using an enzyme-linked immunosorbent assay. We analyzed the role of NGAL, CysC and B2M in the prediction of renal dysfunction or death within 30 days after birth. Results: Fetal urinary NGAL, CysC and B2M corrected for fetal urinary creatinine (FuCr) were significant predictors of impaired postnatal renal function or death within 30 days after birth. AUCs of ROC curves for NGAL/FuCr, CysC/FuCr and B2M/FuCr as predictors of renal dysfunction or death within 30 days after birth were: 0.793 (95% CI: 0.614–0.972, p = 0.001), 0.857 (95% CI: 0.7–1.0, p < 0.0001), 0.764 (95% CI: 0.562–0.966, p = 0.01), respectively. Among assessed biomarkers, only CysC/FuCr corrected for creatinine (p = 0.02) was associated with decreased eGFR on day 30 of postnatal life, whereas NGAL (p = 0.07) and B2M (p = 0.12) were not. AUCs of ROC curves for NGAL/FuCr, CysC/FuCr and B2M/FuCr as predictors of renal dysfunction on day 30 after birth were: 0.756 (95% CI: 0.535–0.976, p = 0.02), 0.833 (95% CI: 0.649–1.0, p = 0.0004), 0.722 (95% CI: 0.482–0.963, p = 0.07), respectively. Conclusions: Fetal urinary NGAL, CysC and B2M may constitute a promising tool in early prediction of impaired renal function and mortality in fetuses with LUTO. Accurate prediction of renal function decline after birth is crucial for proper pre- and postnatal counseling and may support prenatal intervention decision making. Further studies are required to establish the role of the studied biomarkers in the prediction of adverse outcomes.