Improved prenatal assessment of kidney disease using multiple ultrasound features

Abstract

ABSTRACT Background Congenital anomalies of the kidney and urinary tract (CAKUT), often discovered in utero, cover a wide spectrum of outcomes ranging from normal postnatal kidney function to foetal death. The current ultrasound workup does not allow for an accurate assessment of the outcome. The present study aimed to significantly improve the ultrasound-based prediction of postnatal kidney survival in CAKUT. Methods Histological analysis of kidneys of 15 CAKUT foetuses was performed to better standardize the ultrasound interpretation of dysplasia and cysts. Ultrasound images of 140 CAKUT foetuses with 2-year postnatal follow-up were annotated for amniotic fluid volume and kidney number, size, dysplasia and/or cysts using a standardized ultrasound readout. Association of ultrasound features and clinical data (sex and age at diagnosis) with postnatal kidney function was studied using logistic regression. Amniotic fluid proteome related to kidney dysplasia or cysts was characterized by mass spectrometry. Results Histologically, poor ultrasound corticomedullary differentiation was associated with dysplastic lesions and ultrasound hyperechogenicity was associated with the presence of microcysts. Of all ultrasound and clinical parameters, reduced amniotic volume, dysplasia and cysts were the best predictors of poor outcome (odds ratio 57 [95% confidence interval (CI) 11–481], 20 [3–225] and 7 [1–100], respectively). Their combination into an algorithm improved prediction of postnatal kidney function compared with amniotic volume alone (area under the receiver operating characteristics curve 0.92 [95% CI 0.86–0.98] in a 10-fold cross-validation). Dysplasia and cysts were correlated (Cramer's V coefficient = 0.44, P < .0001), but amniotic fluid proteome analysis revealed that they had a distinct molecular origin (extracellular matrix and cell contacts versus cellular death, respectively), probably explaining the additivity of their predictive performances. Conclusion Antenatal clinical advice for CAKUT pregnancies can be improved by a more standardized and combined interpretation of ultrasound data.