Urinary peptidome analysis of kidney failure in children with obstructive uropathy

Children with congenital obstructive uropathy (OU) who survive infancy are at increased risk for progressive chronic kidney disease (CKD), but disease onset and severity vary widely, highlighting the need for improved risk stratification. The present study evaluated whether urinary peptidome analysis could predict progression to kidney failure (KF) in children with OU.

Urinary peptidome analysis was performed on 151 samples from children with OU enrolled in the Chronic Kidney Disease in Children (CKiD) Study. Progression to KF was defined as a ≥50% decline in estimated glomerular filtration rate or initiation of kidney replacement therapy. Peptides were incorporated into a random survival forest model developed in a training cohort and tested in an independent validation cohort. Performance was compared to the 5-year Kidney Failure Risk Equation (KFRE).

Over a median follow-up of 5.6 years, 33% (50/151) of children progressed to KF. Iterative cross-validation identified 47 urinary peptides predictive of KF within 5 years in the training set of 101 patients. The model achieved an area under the curve of 88.6% (95% CI: 75.2-97.8), with sensitivity of 66.7% and specificity of 88.0% in the validation cohort of 50 patients, demonstrating similar overall performance, but higher specificity and lower sensitivity, than the KFRE. Independent and external validation in 162 patients with CKD other than OU confirmed the performance of the peptide model.

Urinary peptidomics identifies children with mild to moderate OU-related CKD at risk for KF with high specificity and moderate sensitivity. Although overall performance was comparable to the KFRE, the peptide model's specificity may be particularly useful for stratifying patients at intermediate KFRE risk. A higher resolution version of the Graphical abstract is available as Supplementary information.