The Central Biochemistry Laboratory for the Chronic Kidney Disease in Children Cohort (CKiD)

PROJECT SUMMARY/ABSTRACT In this proposal, we will leverage our laboratory’s extensive expertise and experience in National Institutes of Health (NIH) observational studies and provide kit management, specimen management, study management, routine diagnostic testing, and specialty renal biomarker testing for the Chronic Kidney Disease in Children (CKiD) study. The University of Minnesota’s Advanced Research and Diagnostic Laboratory (ARDL) has become a trusted resource for clinical trial testing. Here we emphasize our ability to perform accurate and precise iohexol measurements using liquid chromatography tandem mass spectrometry (LC-MS/MS) to allow for gold standard measured glomerular filtration rate (mGFR) determinations in CKiD subjects. This and routine diagnostic testing is instrumental in understanding the relationships of chronic kidney disease (CKD) to neurocognitive development, behavior development, social development, and cardiovascular disease risk. CKiD investigators previously developed the CKiD under 25 (U25) equation to estimate GFR (eGFR) since adult eGFR equations do not perform well in this young demographic. Our specific aims are (Aim 1) to analyze specimens undergoing the CKiD iohexol mGFR protocol for adolescents in the 14-17 years of age via new recruitment to better validate and possibly improve upon the U25 eGFR equation accuracy. We are approaching this with the hypothesis that when incorporating a larger pediatric population with mGFR results into the U25 eGFR equation, specifically in the emerging adult population where data is sparse, the accuracy of the U25 eGFR equation will be tested, validated, and potentially improved should the U25 equation model need adjustment. Aim 2 involves acquiring mGFR results and specimens from a healthy young adult kidney donor population at M Health Fairview to evaluate the U25 equation. Our hypothesis is since the current U25 equation was primarily generated from a CKD pediatric population, by evaluating young healthy patients with this equation, the study will examine U25 equation continuity in all patients or it will assist in formulating a new model that provides a better estimate of GFR in healthy and diseased pediatric populations. Lastly, Aim 3 sets out to analyze routine and novel biomarkers to assess clinical interpretation and their relation to eGFR, cardiovascular risk, social/behavioral development, and CKD progression. Our hypothesis is that biomarkers such as creatinine and cystatin C will be input into the U25 equation and the results will allow for following CKD progression. Biomarkers T50 and FGF23 will assist investigators in evaluating cardiovascular health in subjects ≥14 years old with CKD at stages 4-5