Fetal biochemistry in CAKUT: Insights from 40 Years of reference center experience

Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) are a major cause of fetal and neonatal morbidity, often leading to postnatal renal impairment. Accurate prenatal assessment of renal prognosis remains challenging, and fetal biochemical evaluation has been developed to support prenatal counseling and clinical decision-making.

To synthesize 40 years of institutional experience in fetal biochemistry and to assess, in comparison with the existing literature, the prognostic value of biochemical markers in predicting postnatal renal function.

This narrative review integrates retrospective data from fetal serum and urine samples collected in a tertiary hospital expert department in fetal biochemistry with findings from the existing literature. The prognostic performance of fetal biochemical markers for predicting postnatal renal outcomes was evaluated.

β2-microglobulin in fetal serum and urine emerged as a key biomarker, demonstrating 96 % sensitivity and 85 % specificity in predicting poor renal prognosis. Sequential sampling increased accuracy, particularly in cases of lower urinary tract obstruction (LUTO). Combining β2-microglobulin, sodium, and calcium improved predictive models, offering better prognostic discrimination than ultrasound alone. Fetal urine analysis revealed that chloride levels below 110 mmol/L and sodium levels above 100 mmol/L were associated with a 93 % risk of postnatal renal failure. In cases of oligohydramnios, integrating β2-microglobulin levels (>5 mg/L) with amniotic fluid volume enhanced risk stratification. These markers influenced clinical decisions, supporting vesico-amniotic shunting (VAS), termination of pregnancy (TOP), or conservative management based on renal function prognosis.

Despite the invasiveness of fetal sampling and the need for specialized expertise, biochemical markers provide crucial insights for prenatal counseling and individualized management in CAKUT. Future research should focus on non-invasive alternatives, such as amniotic fluid proteomics and urinary biomarkers, to refine risk assessment and improve neonatal outcomes. Standardizing protocols and integrating biochemical testing into routine prenatal care could significantly enhance the early detection and management of CAKUT.