New Biorepository Will Spur Research Into Neurogenic Bladder, Renal Function Biomarkers, Urinary Tract Infections, and the Urinary Microbiome in Children With Spina Bifida

A multidisciplinary team of researchers from the Divisions of Pediatric Urology, Pediatric Hospital Medicine, and Pediatric Nephrology at UPMC Children's Hospital of Pittsburgh has created a new biorepository to collect and analyze urine samples from children with spina bifida who also have neurogenic bladders.

The biorepository will gather urine samples from participants longitudinally for five years for analysis. Children with spina bifida who are under the age of 18 are eligible to participate in the study. 

The study's lead investigator is Catherine Forster, MD, MS, FAAP, from the Division of Pediatric Hospital Medicine. Co-investigators include Janelle Fox, MD, MS FACS, from the Division of Pediatric Urology, and Dana Y. Fuhrman, DO, MS, from the Division of Pediatric Nephrology. 

Study Aims

Historically, chronic kidney disease and renal failure have been a leading cause of mortality in patients with spina bifida, though since the 1970s, significant progress has been made to improve patients' renal health and long-term outcomes. However, renal injury and progression to chronic kidney disease and end-stage renal failure are still a cause of great concern for individuals with spina bifida. 

One of the main goals for the new urinary biorepository is to search for potential biomarkers that can be studied and ultimately used as longitudinal predictors of renal function in the spina bifida patient population. The ability to predict which spina bifida patients may be most at risk for developing chronic kidney disease and its downstream effects would allow clinicians to better manage and treat patients in an ongoing manner through surveillance tactics and recognition of when clearly defined markers of health have changed. While not currently feasible with existing diagnostic tools, this approach is ultimately what the research team hopes to develop with their data.

"There has never been a prospective, longitudinal study of this kind conducted before, so we have the potential to make important findings that could reshape what we know about neurogenic bladder and its complications in individuals with spina bifida,” says Fox.

One aspect the study team has a particular interest in is the urinary microbiome. At baseline, individuals with spina bifida and neurogenic bladder have a perturbed bladder urothelium and a urinary microbiome that can vary widely across individuals. Urine samples collected throughout the study will be analyzed in an attempt to better characterize the general nature of the urinary microbiome and also how the microbiome varies across etiologies of neurogenic bladder, whether or not the microbiome changes significantly over time, and whether acute changes in individuals can potentially be used as biomarkers or predictors of renal fitness and for more accurately diagnosing urinary tract infections.

Because children with spina bifida typically all have some form or degree of neurogenic or neuropathic bladders, this patient population exhibits the highest risk for repetitive urinary tract infections and infections of increased severity. Distinguishing between urinary tract infection and asymptomatic bacteriuria in this patient population has always been difficult as current testing methods lack the sensitivity and specificity needed to deal with a patient population who have a baseline disturbed bladder environment. This no doubt has and continues to lead to many instances of inappropriate antibiotic use and its concomitant effects, such as multi-drug resistant infections. 

Establishing a definitive approach to distinguishing actual urinary tract infections (UTI) from asymptomatic bacteriuria (ABU) that results from commensal colonization is a high priority for this and other vulnerable patient populations.

"A main aim of our study is to see if we can devise a better strategy for accurately and promptly diagnosing UTI in these patients by using individualized or etiology-specific microbiome marker panels that can show changes over time in comparison to baseline metrics,” says Dr. Fox.

Learnings from this research may also potentially help other patient populations for whom neurogenic bladder is of significant concern and can lead to some of the same downstream morbidities, for example, in individuals with spinal cord injuries.

“The data we collect may indicate useful biomarker profiles that we can use to predict the likelihood of renal injury and progression to chronic kidney disease, and how we treat urinary tract infections in these patients, how the microbiome influences or signifies the presence of UTI in individuals, and a step forward in the more judicious use of antibiotic therapies," says Dr. Fox.

Study Team Members

Catherine Forster, MD, MS, FAAP – Lead Investigator
Janelle Fox, MD, MS, FACS – Co-Investigator
Dana Y. Fuhrman, DO, MS – Co-Investigator
Megan Cuda
Santhosh Donepudi
Jennifer Fantuzzo
Elizabeth Hartigan
Nina Kowalewski
Alyssa Messina, CRNP
Rachel Sada