Research Project Core 2

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PROJECT 2 ABSTRACT “DERIVATION AND VALIDATION OF IMAGING BIOMARKERS FOR CKD PROGRESSION” There is a need for biomarkers that can identify children with Congenital Anomalies of the Kidneys and Urinary Tract (CAKUT) early in life at high risk of future CKD progression. Early identification of children who are at highest risk of CKD progression would help guide trials of therapies for those most likely to benefit from early treatment and spare those patients at low risk of progression potential treatment-associated harms. Two potential biomarkers of CKD progression that are available immediately after birth are renal parenchymal area (RPA) and kidney echogenicity. RPA is the gross area of the kidney in maximal longitudinal length minus the area of the collecting system. RPA “corrects” for a dilated collecting system, which is present in many children with CAKUT, and thus better estimates the functional area of the kidney than the currently used measurement of kidney length. RPA may measure the functional reserve of the kidneys, with smaller areas associated with lower nephron mass and greater probability of CKD progression. Kidney echogenicity is easily assessed on ultrasound and may predict CKD progression independent of RPA. If RPA estimates the quantity of the kidney parenchyma, echogenicity measures the quality of the remaining nephron mass. However, because kidney echogenicity is currently subjectively assessed and ways to measure kidney echogenicity have not been developed, its present utility as a clinical biomarker of CKD progression is limited. This proposed research will develop a method to objectively measure kidney echogenicity and then, using the Chronic Kidney Disease in Children (CKiD) study, will validate RPA and kidney echogenicity as two novel anatomic biomarkers of CKD progression among children with CAKUT. The advantages of these biomarkers are that they may predict CKD progression prior to the appearance of later serum or urine biomarkers, such as nadir creatinine or proteinuria, and can be measured non-invasively immediately after birth on routine clinical imaging. We will evaluate the use of RPA as a predictor of kidney function decline, and will develop an automated method to reliably and accurately measure kidney echogenicity among a cohort of 100 children without and with CKD at CHOP, and then will use ROC analysis to validate these imaging biomarkers of CKD progression among children with CAKUT enrolled in CKiD.