Paediatric nephrology

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INTRODUCTION AND AIMS: Foetal bilateral obstructive nephropathies are associated with a wide spectrum of outcomes ranging from prenatal death with terminal renal failure, absence of amniotic fluid and pulmonary hypoplasia, to survival with normal renal function. Biomarkers that can discriminate between end stage renal disease (ESRD) at birth or ESRD at a later stage in life will be of great help in prenatal counselling. Reliable biomarkers are currently absent. Therefore, the goal of this study was to improve the use of foetal urine for post-natal renal function prediction by applying urinary proteome analysis to identify proteome biomarkers that can discriminate between early- or late-ESRD in bilateral obstructive nephropathies. METHODS: The foetal urinary proteome of 65 patients with posterior urethral valves (PUV) as a prototypic bilateral obstructive nephropathy was studied using capillary electrophoresis coupled to mass spectrometry (CE-MS). RESULTS: 28 of the 65 PUV patients were divided in two groups: early-ESRD (n=13 patients) and late-ESRD (n=15 patients). Analysis of the foetal urinary proteome identified 26 differentially expressed (corrected for multiple testing) peptides between these groups. Subsequently, thirteen of the 26 peptides were combined in a model (the 13PUV model) that allowed separating early-ESRD from late-ESRD in these 28 patients. In the next step the 13 peptide model was validated in a blinded manner using the remaining 38 samples of the PUV cohort that where not used for the discovery phase of the study. These foetal urines were analyzed by CE-MS and scored using the 13PUV model. This analysis predicted the postnatal renal function outcome (eg. early-ESRD versus late-ESRD) with a high sensitivity and specificity of 88 and 91%, respectively. The 13PUV panel was not correlated (r= -0.292, P=0,1663) with gestational age between the age of 23 and 37 weeks when taking into account only samples (n=24) with normal post-natal renal function at the age of 1 (defined as post-natal serum creatinine <50 μmol/L). CONCLUSIONS: We have identified and validated foetal urinary peptides that allow prediction of post-natal renal function in patients with posterior urethral valves that will be of great help in prenatal counselling.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.