USE OF AMNIOTIC FLUID PEPTIDES FOR PREDICTING POSTNATAL RENAL FUNCTION IN CONGENITAL ANOMALIES OF THE KIDNEY AND THE URINARY TRACT

摘要

Bilateral congenital anomalies of the kidney and urinary tract (CAKUT) are the main cause of childhood chronic kidney disease (CKD). Accurate and non-biased prenatal prediction of postnatal disease evolution is currently lacking, but is essential for prenatal counseling and disease management. Here the inventors aimed to develop an objective and quantifiable risk prediction method based on amniotic fluid (AF) peptides. 178 fetuses with bilateral CAKUT were included in a prospective multicenter study. The AF peptide content was studied using capillary electrophoresis coupled to mass spectrometry. The endpoint was early-onset renal failure (CKD stage 3-5) or death due to end-stage renal disease at two years of age. Among the ~7000 peptide candidates, 98 were associated with early severe renal failure. The most frequently found peptides associated with severe disease were fragments from extracellular matrix proteins and thymosin-P4. Combination of those 98 peptides in a classifier lead to the prediction of postnatal renal outcome in a blinded validation set of 51 patients with a 88% (95%CI: 64-98) sensitivity, 97% (95%CI: 85-100) specificity and an AUC of 0.96 (95%CI: 0.87-1.00), outperforming predictions based on currently used clinical methods. The classifier also predicted normal postnatal renal function in 75% of terminated pregnancies where fetopathology showed kidneys compatible with normal life. Analysis of AF peptides thus allows a precise and quantifiable prediction of postnatal renal function in bilateral CAKUT with potential major impact on pre- and postnatal disease management.