Prenatal body fluid analysis in the evaluation of CAKUT

Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of chronic kidney disease in children. Although prenatal ultrasound enables early detection, its ability to predict postnatal renal outcome, particularly in bilateral cases, remains limited due to substantial phenotypic variability and the inability of imaging to capture ongoing disease processes. Genetic testing improves etiological classification but shows weak genotype-phenotype correlations and limited prognostic value, reflecting the multifactorial nature of CAKUT and prompting investigation of molecular biomarkers in prenatal body fluids. This review summarizes current prenatal prognostic strategies in CAKUT, including imaging, genetics, and downstream molecular approaches such as transcriptomics, metabolomics, and proteomics, with particular emphasis on peptide-based profiling. Among these, prenatal peptide signatures derived from fetal urine or amniotic fluid have demonstrated strong prognostic performance for predicting postnatal renal outcome and may capture early molecular processes related to tissue remodeling and inflammation. However, translation into clinical practice remains challenging. Validation requires large prospective multicenter studies that are difficult to conduct in rare diseases and often lack sustained funding. In addition, implementation will likely rely on mass spectrometry-based assays in clinical laboratories. Despite these hurdles, integrating molecular peptide profiling with improved and standardized imaging approaches may enhance prenatal counselling and clinical decision-making in CAKUT.