In response to PA-12-265, "Ancillary Studies to Major Ongoing Clinical Research Studies to Advance Areas of Scientific Interest within the Mission of the NIDDK," NYU School of Medicine and the New York State Department of Health propose to assess the effect of exposure to environmental oxidant stressors, bisphenol A (BPA) and phthalates, in pediatric patients with chronic kidney disease (CKD). CKD can be caused by congenital abnormalities of the genitourinary tract or acquired glomerular disorders. Regardless of the underlying etiology, current treatment for CKD yields progress to end stage kidney disease. It is important disappointing outcomes and many affected children to identify modifiable factors that impact on the clinical course of CKD to design interventions can be adjuncts to medical therapy for affected children. BPA is used to manufacture polycarbonate resin that coat food and beverage containers, and phthalate metabolites are commonly found in processed foods. Both molecules cause oxidant stress, are associated with obesity and hypertension in children, and have been linked to increased risk of cardiovascular disease in adults. Preliminary data suggest that exposure to BPA and phthalates is associated with an increase in low-grade albuminuria in healthy children. However, the implications for these exposures in children who are more vulnerable because of medical conditions such as CKD has not been studied. We propose to test the hypothesis that exposure to BPA and phthalates will have an adverse effect in children with CKD and be associated with an increased risk of worse renal outcomes. This Ancillary Study will utilize stored biosamples that have been obtained during the performance of the following four NIDDK-funded clinical studies - CKiD, NEPTUNE, FSGS Clinical Trial and FONT trial. It will compare two groups of children with CKD - one with focal segmental glomerulosclerosis (FSGS) and a second with non-glomerular disease. The project will focus on children because of their unique vulnerability to environmental chemicals and reduced confounding by other co-morbidities that are prevalent in adults. We will assess longitudinal changes in kidney function assessed by estimated glomerular filtration rate (eGFR), proteinuria, blood pressure (BP), and excretion of biomarkers of tubular injury (KIM-1 and NGAL) associated with BPA and phthalate exposures in children with CKD. Finally, we will evaluate whether the environmental chemicals increase oxidant stress in children with CKD. This is the first study to assess the unique vulnerability of children with CKD to environmental exposures that are modifiable through diet and may provide rationale for newer therapeutic approaches to this group of patients. It unites a recognized pediatric nephrologist (H. Trachtman) with an expert in children's environmental health (L. Trasande), and builds upon a productive track record of collaboration between the multiple PIs.
Current treatment regimens for pediatric patients with chronic kidney disease (CKD) produce disappointing outcomes, and the impact of these potentially modifiable environmental chemical exposures on CKD progression has not been studied systematically. We therefore propose an an ancillary study to four ongoing clinical trials of CKD to assess the unique vulnerability of children with CKD to environmental exposures that are modifiable through diet. The proposed work may suggest that dietary and other modifications to reduce BPA, phthalate and other environmental exposures that produce oxidative stress may be useful as adjuncts to medical interventions for children with CKD.