Pediatric KIDney Stone (PKIDS) Care Improvement Network Multi-Center Study

This prospective cohort study compares stone clearance, and the lived experiences for pediatric patients after ureteroscopy, extracorporeal shockwave lithotripsy, and percutaneous nephrolithotomy while also measuring the longitudinal impact of kidney stone disease. Clinical status (stone size, stone location), and patient characteristics (age and sex), determine the effect of the heterogeneity of treatment. The results will provide information that helps patients make individualized decisions about the best surgical approach. The study will also identify surgical techniques specific to URS, SWL, and PCNL that improve stone clearance and patients’ experiences for each procedure. This study will generate knowledge about alternative surgical treatments to remove kidney stones in patients 8 to 21 years of age (at enrollment) at the 22 sites in the PKIDS Care Improvement Network.

Grant Awarded to Study Renal Interstitium

The renal interstitial cells show extensive heterogeneity and patterning along the cortical / medullary axis of a newborn mouse kidney. The patterned domains of the renal interstitium precisely map to the different anatomical domains within the kidney. It is unknown how the different interstitial cell types arise and what role they play in kidney development. A research team led by Joo-Seop Park, PhD, focused on a sub-population of interstitial cells called the proximal tubule (PT) interstitium. They found that Notch/Rbpj and Yap/Taz transcription factors were active within PT interstitium and that blocking either pathway using Foxd1Cre caused developmental arrest of adjacent PTs. These data suggest that PT interstitium plays critical roles in PT formation. They hypothesized that the Notch/Rbpj and Yap/Taz transcription factors regulate the PT interstitium produces signals that promote the differentiation / maturation of the PTs. Such crosstalk may allow the co-maturation and integration of the PTs and other cortical cell types. The team received a multi-PI R01 grant from the NIH to further pursue this important area of research. Their work will open up an entirely new field of kidney interstitial biology that will have a long and lasting impact on multiple fields including kidney development, kidney disease, tissue engineering and kidney injury/regeneration.

Urinary Exosome Analysis to Identify Biomarkers of Bladder Injury in Patients with Posterior Urethral Valves (PUV)

Almost all patients with PUV develop some form of bladder dysfunction with lower urinary tract symptoms. In the more severely affected cases, the ongoing injury can result in progression to chronic kidney disease and end-stage renal disease. Our group undertook a non-invasive study of urine from these patients with the goal of improving outcomes by identifying biomarkers associated with exosomes, nano-sized membranous extracellular vesicles (EVs). EVs release from cells lining the urinary tract into urine contain RNA, protein, and other metabolites that reflect the status of the cells of origin. We utilize a transcriptome approach to profile the RNA composition of EVs from patients with PUV and from controls. Our preliminary data identifies differential expression of about 20 RNAs in patients with PUV. Regulation of pathological pathways implicate several of these RNSas, such as fibrosis. We are currently investigating the expression of these candidate RNAs in a larger patient cohort. Successful completion of the study will provide diagnostic and prognostic biomarkers for PUV-related bladder and kidney disease.

Enhanced Recovery After Surgery (ERAS) Multi-Center Study

The hypothesis is that enhanced recovery after surgery (ERAS) peri-operative care principles are implementable at free-standing pediatric hospitals with ≥ 75% adherence to protocol items. We aim to determine if the proposed protocol is optimal to maximize recovery from surgery while minimizing morbidity, characterize protocol deviations by providers and study sites, and define short and long-term outcomes from surgery after application of the ERAS protocol. We aim to broaden exposure of the pediatric urology community to ERAS and demonstrate its application at other medical centers. As ERAS is a multidisciplinary program that requires on-the-ground changes to care delivery by all patient care team members, this study contains a built-in pilot portion to demonstrate that ERAS can be effectively implemented at other centers to attain similar or even better outcomes. Following this will be an exploratory phase where centers enroll patients, and we follow their outcomes over the course of at least one year after surgery. We are currently in the pilot phase at Cincinnati Children’s.

Outcomes of Open and Robotic Assisted Laparoscopic Ureteral Reimplantation Multi-Center Study

As part of a multi-site study, we are evaluating our Cincinnati Children's pediatric urology experience, the associated outcomes, and morbidity of the robotic-assisted laparoscopic (RAL) approach to correct vesicoureteral reflux in children compared to the open approach. The hypotheses to test include: 1) The efficacy of the RAL approach will be comparable to the open approach to correct vesicoureteral reflux; and 2) The length of hospital stay, narcotic drug requirements, and length of post-operative catheterization will decrease compared to the open approach.

This study seeks to compare these two procedures for outcomes. Primary outcomes will be success of the procedure, measured by a four-month post-operative voiding cystourethrogram (VCUG) and secondary outcomes-length of hospital stay, narcotic requirements, and length of post-operative catheterization, both retrospectively and prospectively. This study follows patients enrolled in this study for 10 years.

Outcomes in Patients with Posterior Urethral Valves

The Division of Urology is currently determining those at increased risk for urinary tract injury by identifying of putative miRNA biomarkers in the urine to determine if they correlate with currently accepted measures of the severity of urinary tract injury. We are also prospectively collecting and reviewing clinical data points for this patient population to follow their clinical outcomes and predict their prognosis. We will compare outcomes to reduce variability and standardize the diagnosis, treatment and management of patients with PUV.

Long-Term Outcomes in Patients with Bladder Exstrophy Multi-Center Study (Pediatric Urology Midwest Alliance - PUMA)

In a cohort of over 200 patients with bladder exstrophy over 36 years, 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. Additionally, a majority of patients require 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 allows for better counseling of patients and families on long-term outcomes with bladder exstrophy in the future.

Long-Term Outcomes for Renal Replacement Therapy (RRT) and Clean Intermittent Catheterization (CIC) in Patients with Posterior Urethral Valves Multi-Center Study (PUMA)

In a cohort of 274 patients with posterior urethral valves over a 20 years, 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 is something to recommend 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.