Joo-Seop Park, PhD

Dysfunction of the proximal tubule segment in the nephron of the kidney causes Faconi renotubular syndrome (FRTS). Due to defective reabsorption function in their proximal tubule cells, FRTS patients show polyuria, polydipsia, glycosuria, and phosphaturia. A mutation in HNF4a shows an association with FRTS in humans. However, there is not much known about how Hnf4a regulates nephron development. The Park lab found that Hnf4a expressed in both immature and mature proximal tubule cells in the developing mouse kidney. Their genetic analysis showed the requirement of Hnf4a for immature proximal tubules to develop into mature proximal tubules. Consistent with this, the Hnf4a mutant mice had considerably fewer proximal tubules in their kidneys, recapitulating FRTS symptoms. Furthermore, these mice developed kidney stones, suggesting that improper proximal tubule function can lead to the formation of kidney stones. This study, published in JCI Insight, demonstrated the critical role of Hnf4a in proximal tubule development and provided novel insights into the etiology of FRTS.

Andrew C. Strine, MD; Pramod P. Reddy, MD; and Brian A. VanderBrink, MD

Andrew Strine, MD; Pramod Reddy, MD; and Brian VanderBrink, MD, are the lead site investigators for a multi-center study for Enhanced Recovery After Surgery (ERAS). ERAS is a multidisciplinary program that requires on-the-ground changes to how all members of the patient care team deliver care. It involves care principles developed to maximize peri-operative metabolic stress and optimize fluid balance. Principles in enhanced recovery protocols include: reduced pre-operative fasting, goal-directed fluid therapy guidelines, avoidance of bowel preparation, minimizing opioid analgesia, early post-operative mobilization, and enteral feeding. The aim is to determine if these care principles will maximize recovery from surgery while minimizing morbidity. This is a prospective study enrolling patients undergoing urologic reconstruction procedures. Enrollment is ongoing with a total of 17 participants to date.

Pramod P. Reddy, MD; Brian A. VanderBrink, MD; and W. Robert DeFoor, Jr., MD, MPH

Posterior urethral valves (PUV) is a cause of bladder outlet obstruction in boys. Patients with PUV account for between 15 to 18% of all pediatric kidney transplantations each year. Being born with PUV has a significant impact on the health and quality of life of not only the pediatric patient but also their parents with health and societal repercussions. The lack of biomarkers for urinary tract injury resulting from PUV has prevented the accurate clinical phenotyping and risk stratification of these patients. Urine is an ideal source of biomarkers for urinary tract injury in patients with PUV as it serves as a liquid biopsy of the urinary tract. We aim to develop and validate a novel biomarker panel for identifying patients with PUV at risk for increased urinary tract injury and for monitoring response to therapy. Future characterization of the biological significance of the miRNAs identified as biomarkers may lead to discovery of novel pathological mechanisms and potential therapeutic targets. The cost of care and burden of the disease are significant for this patient population and collectively this patient population will benefit from standardization of clinical care to reduce harm and cost of care. Enrollment is ongoing with a total of 49 participants to date.