Association Between Newborn Metabolic Profiles and Pediatric Kidney Disease

Abstract

IntroductionMetabolomics offers considerable promise in early disease detection. We set out to test the hypothesis that routine newborn metabolic profiles at birth, obtained through screening for inborn errors of metabolism, would be associated with kidney disease and add incremental information to known clinical risk factors.MethodsWe conducted a population-level cohort study in Ontario, Canada, using metabolic profiles from 1,288,905 newborns from 2006 to 2015. The primary outcome was chronic kidney disease (CKD) or dialysis. Individual metabolites and their ratio combinations were examined by logistic regression after adjustment for established risk factors for kidney disease and incremental risk prediction measured.ResultsCKD occurred in 2086 (0.16%, median time 612 days) and dialysis in 641 (0.05%, median time 99 days) infants and children. Individual metabolites consisted of amino acids, acylcarnitines, markers of fatty acid oxidation, and others. Base models incorporating clinical risk factors only provided c-statistics of 0.61 for CKD and 0.70 for dialysis. The addition of identified metabolites to risk prediciton models resulted in significant incremental improvement in the performance of both models (CKD model: c-statistic 0.66 NRI 0.36 IDI 0.04, dialysis model: c-statistic 0.77 NRI 0.57 IDI 0.09). This was consistent after internal validation using bootstrapping and a sensitivity analysis excluding outcomes within the first 30 days.ConclusionRoutinely collected screening metabolites at birth are associated with CKD and the need for dialytic therapies in infants and children, and add incremental information to traditional clinical risk factors.

Metabolomic Patterns in Adolescents With Mild to Moderate CKD

“…This explains our observation of attenuated CKD-3b Tyr/Cr levels. This is consistent with previous findings in adults and infants with CKD 7, 15. Moreover, in advanced CKD, gut microbiota metabolize Tyr into protein-bound p-Cresol, a phenolic compound and uremic toxin creating a further decline in Tyr, while Cr continues to rise 9 …”

Association between newborn screening analyte profiles and infant mortality

“…Unlike a recent study of early neonatal mortality among very preterm infants [4], our model was only modestly predictive of 6-month infant mortality (optimism-corrected c-statistic: 0.61). Although we have previously demonstrated varying degree to which newborn screening analytes can be used to identify infants at risk for neonatal sepsis (optimism-corrected c-statistic among term infants: 0.85) or pediatric chronic kidney disease (optimismcorrected c-statistic: 0.66) [3,11], the models for both of these specific morbidities performed better than that for mortality observed here. This discordance in predictive ability of our mortality model and our previous studies of specific morbidities may be due to inherent physiological heterogeneity of all-cause infant mortality during the first 6 months of life.…”

Proteinuria and venous thromboembolism in pregnancy: a population-based cohort study

“…Demographic and vital statistics information was obtained from the Ontario Registered Persons Database. Pregnancy and maternal health data were captured in the MOMBABYdataset that links administrative records of all mothers with a delivery and their newborns across Ontario [ 14 ]. Diagnostic and procedural information from all hospitalizations was determined using the Canadian Institute for Health Information (CIHI) Discharge Abstract Database (DAD).…”