Fetal urinary peptides to predict postnatal outcome of renal disease in fetuses with posterior urethral valves (PUV)

Bilateral congenital abnormalities of the kidney and urinary tract (CAKUT), although are individually rare diseases, remain the main cause of chronic kidney disease in infants worldwide. Bilateral CAKUT display a wide spectrum of pre- and postnatal outcomes ranging from death in utero to normal postnatal renal function. Methods to predict these outcomes in utero are controversial and, in several cases, lead to unjustified termination of pregnancy. Using capillary electrophoresis coupled with mass spectrometry, we have analyzed the urinary proteome of fetuses with posterior urethral valves (PUV), the prototypic bilateral CAKUT, for the presence of biomarkers predicting postnatal renal function. Among more than 4000 fetal urinary peptide candidates, 26 peptides were identified that were specifically associated with PUV in 13 patients with early end-stage renal disease (ESRD) compared to 15 patients with absence of ESRD before the age of 2. A classifier based on these peptides correctly predicted postnatal renal function with 88% sensitivity and 95% specificity in an independent blinded validation cohort of 38 PUV patients, outperforming classical methods, including fetal urine biochemistry and fetal ultrasound. This study demonstrates that fetal urine is an important pool of peptides that can predict postnatal renal function and thus be used to make clinical decisions regarding pregnancy.