Joo-Seop Park, PhD

Defective Notch signaling can cause Alagille syndrome in humans. This affects multiple organs including the kidneys in these patients. It is not fully understood how Notch signaling regulates kidney development. The Park lab found that Notch signaling primes nephron progenitors for differentiation without promoting the formation of a specific segment of the nephron. This study, published in Development, presents a novel model of mammalian nephrogenesis.

Pramod P. Reddy, MD, and Andrew C. Strine, MD

Drs. Pramrod Reddy, MD, and Andrew Strine, MD, are lead site investigators for a multi-center study on testicular tissue cryopreservation (TTC). Many regimens of chemotherapy and / or radiation for cancer and other diseases are gonadotoxic with the potential for permanent azoospermia. With an improving survival due to the advent of more effective multimodal therapies, the late effects on fertility have become increasingly important. Limited options for fertility preservation exist in prepubertal patients due to a lack of mature sperm and in those who cannot provide a semen sample. The multi-center study offers TTC to patients who are undergoing gonadotoxic therapies and cannot provide a semen sample. TTC is currently an investigational protocol, as it is contingent on the development of experimental therapies for the maturation of spermatogonial stem cells into sperm. The specific aims are to cryopreserve testicular tissue as a resource to use for fertility preservation by participants in the future and to develop a biobank of testicular tissue to use for research on optimization of these experimental techniques. Enrollment is ongoing with a total of 20 participants to date.

Brian A. VanderBrink, MD, and Andrew C. Strine, MD

Drs. Brian VanderBrink, MD, and Strine are the lead site investigators for a multi-center study on long-term outcomes in patients with bladder exstrophy. Developed to objectively study a variety of clinical outcomes in pediatric urology on a large scale, the Pediatric Urology Midwest Alliance (PUMA) consists of five major centers in the midwest. In a cohort of over 200 patients with bladder exstrophy over a 36-year period, the risk of bladder augmentation or urinary diversion, and need for clean intermittent catheterization (CIC), was significant after primary closure of the bladder and increased over time. The risk of bladder augmentation or urinary diversion was 52.0% by 10 years of age and increased to 72.1% by 18 years of age. A majority of patients also required CIC, including 65.7% of the entire cohort and 86.0% of adults at last follow-up. The study demonstrates the feasibility of such a collaborative model for clinical research and will allow for better counseling of patients and families on long-term outcomes with bladder exstrophy in the future. At the 2017 Pediatric Urology Fall Congress in Montreal, Canada, presentation of the study resulted in an award for the best clinical abstract.

Pramod P. Reddy, MD, and Brian A. VanderBrink, MD

Drs. Reddy and VanderBrink are the lead site investigators for another P.U.M.A. study on long-term outcomes for renal replacement therapy (RRT) and CIC in patients with posterior urethral valves. In a cohort of 274 patients with posterior urethral valves over a 20-year period, the risk of RRT was significant with 25% requiring dialysis or transplantation by 13 years of age. Serum nadir creatinine before 1 year of age was strongly predictive of RRT with a risk of 0% for <0.4, 2% for 0.4-0.69, 27% for 0.7-0.99, and 100% for ≥1.0. CIC was also recommended in many patients, including 50.0% by 14 years of age. The study will allow for better counseling of patients and families on long-term outcomes with posterior urethral valves as well as the identification of those at risk and interventions to preserve their renal function in the future. The study was presented at the 66th Annual Meeting of the Societies for Pediatric Urology in San Francisco, California and was recognized as a finalist for the best clinical abstract.

W. Robert DeFoor, MD, MPH, and Eugene Minevich, MD

Urolithiasis is becoming more prevalent in children in the United States. There is a report of an increased risk of recurrent stones and a high rate of urinary metabolic abnormalities in children who form stones. A multi-disciplinary Stone Center, initiated at our institution in June 2014, addresses this growing patient population. Assignment of a full-time nurse coordinates care among the Divisions of Urology, Nephrology and Hypertension, Nutrition Therapy, and Human Genetics providers. We assessed clinical outcomes for 208 children, with the average age of 14, evaluated in the Stone Center. The mean follow-up was 1.4 years. About half of the patients had a urinary metabolic abnormality increasing their risk of recurrent stone formation. The number of patients undergoing surgical procedures decreased from 40% to 18% during the one year before and at any time after the first visit. The average number of emergency department visits per year decreased from 1.5 to 0.5 before and after the first visit. Given the rising prevalence and impact of stone disease in children, a multi-disciplinary stone center can be a feasible option to coordinate care and improve clinical outcomes. In short-term follow-up, the number of surgical procedures and emergency department visits required by our patients appeared to decrease after going to the Stone Center. Further analysis is necessary to determine if aggressive medical management will decrease kidney stone recurrence rates.