When children have kidney dysfunction, their decline is more rapid than adults, and they develop many other complicating medical conditions that threaten their life expectancy. The majority of young adults with a history of kidney failure in childhood suffer significant comorbidities, with as much as a 10- to 100-fold increased risk of cardiovascular disease and 30- to 150-fold higher mortality compared to their age matched peers. The ability of physicians to identify when kidney function decline accelerates or the early onset of cardiovascular disease is currently limited. Recent advances in the laboratory techniques available to study the nature and variety of urine proteins (urine proteomics) have led to the discovery of highly discriminant biomarkers of varied diseases, and also suggested new potential targets for therapy. However, these techniques have not been applied to study progression of chronic kidney disease (CKD) in children. Analysis of urine has several advantages over blood serum or plasma: urine can be obtained easily and in much larger volumes. Also, urine sampling can be frequent and repeated. As urine is a filtrate of serum, it has a comparatively simpler composition. This proposal, in response to RFA-DK-14-011 for the Chronic Kidney Disease Biomarkers Consortium (CKD BioCon) (U01), proposes to utilize recent advances in state-of-the-art urine proteomic profiling as well as the comprehensive careful characterization of and collection of biosamples from children with CKD in the Chronic Kidney Disease in Children (CKiD) cohort over the last decade, to perform the first large-scale discovery and validation of novel urinary biomarkers of CKD progression in children.
Advanced kidney disease in childhood threatens normal growth and development and is associated with early cardiovascular disease and death. Clinically applicable biologic markers of declining kidney function are lacking. Combining in-depth analysis of urine proteins (urine proteomics) with nearly 10 years of data and urine samples from the Chronic Kidney Disease in Children (CKiD) cohort, this study seeks to identify novel markers for progression of kidney disease and targets for treatment.