New Research Finding: KGF Protective in Cyclophosphamide Bladder Injury

April 29, 2020

Carlton Bates MDUPMC Children’s Hospital of Pittsburgh Division of Pediatric Nephrology researchers studying the mechanisms that lead to cyclophosphamide bladder injury (CBI) showed in a paper1 published in January in the American Journal of Pathology that Keratinocyte Growth Factor (KGF) plays a role in mitigating and recovering from CBI. Division Chief Carlton M. Bates, MD, is the senior author on the paper and Director of the Bates Laboratory and the team that worked on the research.

Cyclophosphamide (CP) is a chemotherapeutic agent used to treat various forms of cancer. CP also is used to treat nephrotic syndrome and rheumatological diseases, including systemic lupus erythematosus, because of its suppressive effects on the immune system.

However, CP has, among other toxicities, the potential to injure the bladder urothelium causing acute and possibly life-threatening hemorrhagic cystitis and bladder cancer years after treatment.

Dr. Bates’ CBI research is funded by a National Institutes of Health (NIH) R01 grant2 that he was awarded in 2019 to study the “Role of FGFR2 Signaling in Bladder Injury and Regeneration.”

Dr. Bates’ study in a mouse model, showed that KGF, given prior to CP, blocked CP-driven apoptosis and accelerated regeneration of urothelial cells in the bladder. KGF also led to higher fidelity repair of bladder urothelium after CP when compared with vehicle treatment. 

This initial study points in the direction of KGF being a potential therapeutic agent that could be given in tandem with cyclophosphamide to mitigate its potential toxicities and bladder damage. More studies will need to be conducted to better understand the mechanisms by which KGF can act against cyclophosphamide-induced bladder injury, and Dr. Bates and colleagues are currently working on  additional research as part of their NIH R01 study. 

Learn more about Dr. Bates and the Division of Pediatric Nephrology at UPMC Children's Hospital of Pittsburgh. 

Further Reading

1. Narla ST, Bushnell DS, Schaefer CM, Nouraie M, Bates CM. Keratinocyte Growth Factor Reduces Injury and Leads to Early Recovery From Cyclophosphamide Bladder Injury. Am J Pathology. 2020; 190(1): 108-124.

2. Role of FGFR2 Signaling in Bladder Injury and Regeneration. Project number: R01DK121493. Principal investigator: Carlton M. Bates, MD.