Pediatric Chronic Kidney Disease Research

The incidence of chronic kidney disease (CKD) in the pediatric population has increased over the past two decades, disproportionately affecting poor and ethnic minority children. According to the National Institute of Diabetes and Digestive and Kidney Diseases, the primary causes of pediatric kidney failure vary by age:

  • birth to age 4: birth defects and hereditary diseases
  • ages 5 to 14: hereditary diseases, nephrotic syndrome, and systemic diseases
  • ages 15 to 19: diseases that affect the glomeruli (the filtering unit of the kidney)

CKD is characterized by an irreversible deterioration of renal function that gradually progresses to end-stage renal disease (ESRD). CPCE’s research in this area focuses on the early identification of those at high risk for pediatric chronic kidney disease. 


Renal Parenchymal Area Biomarkers

Congenital anomalies of the kidney and urinary tract (CAKUT), including posterior urethral valves and kidney dysplasia, account for 50 to 60 percent of CKD in children and are the most common cause of ESRD in this age group. However, our ability to predict which children with CAKUT will develop ESRD and their timing of progression is poor.

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.

Because we currently have limited understanding of the patients who would benefit from aggressive management to delay CKD progression to prevent the comorbidities of ESRD, this study aims to develop and validate novel biomarkers of CKD progression for children with CAKUT for kidney echogenicity and renal parenchymal area. We are working with computer engineers in the Center for Biomedical Imaging Computing and Analytics at The University of Pennsylvania to develop automated methods using pattern recognition and imaging segmentation to objectively measure kidney echogenicity relative to the liver on ultrasound, which is associated with glomerular and non-glomerular kidney disease.

To date, we have successfully developed a method to objectively measure renal parenchymal area using a semi-automated process. We have also developed normalized renal parenchymal growth curves from birth to 10 months. These will allow detection of children with smaller than normal functional kidney areas, who may be at risk for chronic kidney disease. Additionally, we have identified an association between renal parenchymal area <3rd percentile area and an increased risk of ESKD among infant boys with posterior urethral valves.


RPA measurement of: (a) kidney with mild hydronephrosis using semi-automated and manual segmentation; the semi-automated process includes (b) initialization of the segmentation process after which the algorithm automatically (c) segments the kidney into the (e) functional kidney parenchyma (white) and the collecting system (dark central area); (d) manual segmentation of the same kidney and the resultant (f) RPA are shown for comparison.

 

What’s Next: We will validate kidney echogenicity and renal parenchymal area, for which we have developed an automated method of measurement, as biomarkers for the progression of CKD among children with congenital urologic disease.

Funding:  Center for Pediatric Clinical Effectiveness, Satellite Healthcare

Please contact Gregory Tasian, MD, MSc, MSCE, attending urologist at CHOP, for more information about this line of research.


Pediatric Chronic Kidney Disease Published Research

Pulido JE, Furth SL, Zderic SA, Canning DA, Tasian GE.  Renal Parenchymal Area and Risk of End Stage Renal Disease in Boys with Posterior Urethral Valves. Clin J Am Soc Nephrol. 2014 March;9(3):499-505.

Wang H, Pulido JE, Song Y, Furth SL, Tu C, Zhang C, Li C, Tasian GE. Segmentation of Renal Parenchymal Area from Ultrasound Images Using Level Set Evolution. Conf Proc IEEE Eng Med Biol Soc. 2014 Aug; 4703-6.

Fischer K, Li C, Wang H, Song Y, Furth SL, Tasian GE. Renal Parenchymal Area Growth Curves for Children aged 0 to 10 months. Journal of Urology. In press.