Progression of chronic kidney disease (CKD) in children leads to end stage renal disease (ESRD), which is associated with mortality rates 30-150 times higher than the general pediatric population. The traditional biomarkers, serum creatinine and proteinuria, are used to predict progression of CKD in clinical trials even though both correlate poorly with the progression of CKD and the response to interventions. There are numerous candidate therapies for CKD, but with a continued reliance on serum creatinine and proteinuria, clinical trials will likely continue to fail.
The field of CKD biomarkers in children is a very promising area of research with a small amount of resources invested to date. Predicting progression of CKD will allow clinicians to better time follow-up, referral for transplant, and provide better guidance to families. More importantly, an optimal panel of biomarkers and risk prediction model can replace proteinuria and serum creatinine in biomarker guided clinical trials. We plan to measure urine and serum biomarkers of kidney injury, inflammation, repair, and fibrosis from the samples of the children enrolled in the CKD in Children (CKiD) cohort and Assessment, Serial Evaluation, and Subsequent Sequelae in AKI (ASSESS-AKI) cohort. Our ultimate goal is to facilitate clinical trials for children with CKD in order to identify new treatments.
Susan L. Furth, MD, PhD
The University of Pennsylvania
- de Fontnouvelle CA, Greenberg JH, Thiessen-Philbrook HR, Zappitelli M, Roth J, Kerr KF, Devarajan P, Shlipak M, Coca S, Parikh CR, TRIBE-AKI Consortium.: Interleukin-8 and Tumor Necrosis Factor Predict Acute Kidney Injury After Pediatric Cardiac Surgery. Ann Thorac Surg. 2017 Dec; 2017 Aug 16. PMID: 28821332
- Greenberg JH, Parikh CR: Biomarkers for Diagnosis and Prognosis of AKI in Children: One Size Does Not Fit All. Clin J Am Soc Nephrol. 2017 Sep 7; 2017 Jun 30. PMID: 28667085
- Greenberg JH, Zappitelli M, Devarajan P, Thiessen-Philbrook HR, Krawczeski C, Li S, Garg AX, Coca S, Parikh CR, TRIBE-AKI Consortium.: Kidney Outcomes 5 Years After Pediatric Cardiac Surgery: The TRIBE-AKI Study. JAMA Pediatr. 2016 Nov 1. PMID: 27618162
- Greenberg JH, Whitlock R, Zhang WR, Thiessen-Philbrook HR, Zappitelli M, Devarajan P, Eikelboom J, Kavsak PA, Devereaux PJ, Shortt C, Garg AX, Parikh CR, TRIBE-AKI Consortium.: Interleukin-6 and interleukin-10 as acute kidney injury biomarkers in pediatric cardiac surgery. Pediatr Nephrol. 2015 Sep; 2015 Apr 15. PMID: 25877915
- Zappitelli M, Greenberg JH, Coca SG, Krawczeski CD, Li S, Thiessen-Philbrook HR, Bennett MR, Devarajan P, Parikh CR, Translational Research Investigating Biomarker Endpoints in Acute Kidney Injury (TRIBE-AKI) Consortium.: Association of definition of acute kidney injury by cystatin C rise with biomarkers and clinical outcomes in children undergoing cardiac surgery. JAMA Pediatr. 2015 Jun. PMID: 25844892
- Greenberg JH, Coca S, Parikh CR: Long-term risk of chronic kidney disease and mortality in children after acute kidney injury: a systematic review. BMC Nephrol. 2014 Nov 21; 2014 Nov 21. PMID: 25416588