Here are examples of recent publications that arose from collaborative projects between NURAG investigators:
Predicting Outcomes for Children with Congenital Obstructive Uropathy
- McLeod DJ, Ching CB, Sebastião YV, Greenberg JH, Furth SL, McHugh KM, Becknell B. (2019) Common clinical markers predict end-stage renal disease in children with obstructive uropathy. Pediatr Nephrol. 34(3):443-448. PMID: 30317433.
- Sebastião YV, Cooper JN, Becknell B, Ching CB, McLeod DJ. (2020) Prediction of kidney failure in children with chronic kidney disease and obstructive uropathy. Pediatr Nephrol. [Online ahead of print.] PMID: 32583045.
- McLeod DJ, Sebastião YV, Ching CB, Greenberg JH, Furth SL, Becknell B. (2020) Longitudinal kidney injury biomarker trajectories in children with obstructive uropathy. Pediatr Nephrol. [Online ahead of print.] PMID: 32444926.
In this series of publications, Drs. Daryl McLeod (Urology) and Brian Becknell (Nephrology) investigated whether biomarkers of kidney dysfunction or tubular injury can identify children with obstructive uropathy who are most likely to progress to end stage kidney disease. Both biomarkers have predictive value, and kidney failure risk equations that rely solely on biomarkers of kidney dysfunction lack sufficient sensitivity and specificity. These findings motivate these investigators to integrate their findings into the Urology-Nephrology Combined Clinic and to build upon their discoveries to develop better models of chronic kidney disease progression.
Protective Roles for Urothelium During Urinary Tract Obstruction
Long-standing collaborations between Drs. Ashley Jackson (AWRI), Christina Ching (Urology), Brian Becknell (Nephrology), and Kirk McHugh (OSU Division of Anatomy) identified renal urothelial remodeling as a key physiologic adaptation during urinary tract obstruction. Depletion of the urothelial plaque impairs this adaptation and accelerates the development of obstructive uropathy. The latest studies from this group have identified the temporally limited progenitor properties of Krt5+ cells within the developing and obstructed renal urothelium, as well as the potential for urothelial peptides to serve as biomarkers of clinically significant urinary tract obstruction.
- Jackson AR, Li B, Cohen SH, Ching CB, McHugh KM, Becknell B. (2018) The uroplakin plaque promotes renal structural integrity during congenital and acquired urinary tract obstruction. Am J Physiol Renal Physiol. 315(4):F1019-F1031. PMID: 29897287.
- Gupta S, Jackson AR, DaJusta DG, McLeod DJ, Alpert SA, Jayanthi VR, McHugh K, Schwaderer AR, Becknell B, Ching CB. (2018) Urinary antimicrobial peptides: Potential novel biomarkers of obstructive uropathy. J Pediatr Urol. 14(3):238.e1-238.e6. PMID: 29706289.
- Jackson AR, Hoff ML, Li B, Ching CB, McHugh KM, Becknell B. (2019) Krt5+ urothelial cells are developmental and tissue repair progenitors in the kidney. Am J Physiol Renal Physiol. 317(3):F757-F766. PMID: 31322419.
Molecular Circuits that Protect the Urinary Tract from Bacterial Infection
In this series of publications, NURAG investigators have collaborated to elucidate the signal transduction networks that regulate antimicrobial peptide production by the bladder’s urothelium and the kidney’s intercalated cells. Studies by Dr. Christina Ching (Urology) and Brian Becknell (Nephrology) identified roles for the cytokine, Interleukin-6, and its downstream transcription factor, Stat3, in promoting antimicrobial peptide production and limiting bacterial invasion of the urothelium. Studies by Dr. John David Spencer, supported by Drs. Ching and Becknell, implicated Ribonuclease 7 as an antimicrobial peptide that shields the urinary tract from bacterial invasion and implicated the insulin as a key driver of the kidney’s antimicrobial defenses against UTI.
- Ching CB, Gupta S, Li B, Cortado H, Mayne N, Jackson AR, McHugh KM, Becknell B. (2018) Interleukin-6/Stat3 signaling has an essential role in the host antimicrobial response to urinary tract infection. Kidney Int. 93(6):1320-1329. PMID: 29475562.
- Murtha MJ, Eichler T, Bender K, Metheny J, Li B, Schwaderer AL, Mosquera C, James C, Schwartz L, Becknell B, Spencer JD. (2018) Insulin receptor signaling regulates renal collecting duct and intercalated cell antibacterial defenses. J Clin Invest. 128(12):5634-5646. PMID: 30418175.
- Eicher T, Bender B, Murtha MJ, Schwartz L, Metheny J, Solen L, Jaggers RM, Bailey MT, Gupta S, Mosquera C, Ching C, La Perle K, Li B, Becknell B, Spencer JD. (2019) Ribonuclease 7 Shields the Kidney and Bladder from Invasive Uropathogenic Escherichia coli Infection. J Am Soc Nephrol. 30(8):1385-1397.