Pilot Study To Explore KGF Use To Mitigate Injury in Neuropathic Bladders

A new pilot grant will allow UPMC Children’s Hospital of Pittsburgh researchers to explore whether keratinocyte growth factor (KGF) can aid in reducing bladder injury and urinary tract infections in patients with neuropathic or neurogenic bladders.

Catherine Forster, MD, MS, FAAP, assistant professor in the Paul C. Gaffney Division of Pediatric Hospital Medicine, and Carlton M. Bates, MD, professor and chief of the Division of Pediatric Nephrology, are co-investigators of the new study funded by the Institute for Infection, Inflammation & Immunity in Children (i4Kids) at the University of Pittsburgh.

The title of their study is “KGF to Reduce Bladder Injury and Susceptibility to Urinary Tract Infection in Neuropathic Bladders.”

“What we know about children with spina bifida is that as a consequence of their condition and resultant bladder dysfunction, they are at very high risk for recurrent urinary tract infection (UTI) and more severe infections when they occur. These repetitive UTIs carry with them the potential for significant long-term renal morbidities and disruption in quality-of-life,” says Dr. Forster. "At baseline, we know that our spina bifida patients have injured bladder urothelial cells. These perturbations of the urothelium, we hypothesize, are what ultimately lead to an increased rate of UTIs in some children with spina bifida.”

The main aim of Dr. Forster and Bates’ study is to examine how KGF affects urothelial injury in a model of neuropathic bladder and whether KGF therapy decreases susceptibility to urinary tract infection.

Drs. Forster and Bates will first examine whether KGF mitigates urothelial injury in a mouse model of spina bifida. They will then examine how KGF-driven urothelial repair affects the response to induction of urinary tract infection in the same mouse model. They will examine the urothelium, bladder, and urine at various time points to look for signs of improvement in bladder histology, decreases in bladder bacterial counts, and a better immunologic response of the urothelium to the presence of bacteria in the KGF-treated mice.

"We hypothesize that the urothelium will show improvement after KGF therapy and that we will see fewer bacteria over time, signifying a more normal response of the urothelial tissues to the presence of bacterial invaders,” says Dr. Forster. "If we can normalize the urothelium in these patients, we think we can prevent or potentially reduce susceptibility to UTI and many of the downstream effects associated with neuropathic bladder, the worst of which is repeated renal injury and chronic kidney disease."

Learn more about Dr. Forster and her research and Dr. Bates and the research at the Bates Laboratory.