Prasad Devarajan, MD

Dr. Devarajan has continued with a wide spectrum of approaches to kidney health and disease processes; spanning from molecular, genomic and proteomic approaches, to human observational and clinical trials. Dr. Devarajan is the director of the NIH-funded P50 Center of Excellence in Nephrology, a unique multi-disciplinary research program designed to support basic, translational, and clinical research on critical pediatric kidney diseases that have major unmet needs. The proposal includes several research projects in the areas of acute kidney injury, proteinuric kidney disease, and lupus nephritis, with participation from recognized teams of investigators from multiple disciplines. Also included are high-resource Gene Expression, Proteomics and Biomarker Cores with core leaders of international repute. Dr. Devarajan is also the nephrology lead investigator for several NIH-funded prospective clinical studies. He has also established a Kidney Biomarker Laboratory which now performs more than 50 distinct assays for acute and chronic kidney disease biomarkers. Dr. Devarajan is also the director and principal investigator (PI) of the NIH T32-funded Fellowship in Nephrology. Dr. Devarajan’s research on biomarkers and new therapeutic targets in kidney diseases has yielded over 25 publications and new patent applications during the last fiscal year. He is currently the PI or Co-PI on 8 NIH grants.

Stuart L. Goldstein, MD

Dr. Goldstein is the director of the Center for Acute Care Nephrology (CACN), and has had a very productive research year, with achievements that spanned the scope of the center’s research missions. The nephrotoxic medication acute kidney injury (AKI) reduction project, NINJA, which resulted in a four year sustained reduction in AKI, preventing AKI in more than 400 children, has spread to 13 US pediatric centers. This collaborative has already observed decreases in nephrotoxic medication exposure and associated AKI. The CACN also coordinated and completed the largest prospective pediatric AKI study ever undertaken: “Assessment of Worldwide AKI, Renal angina and Epidemiology in Children (AWARE)”. In addition, the CACN coordinated the DIRECT study, which is a genome wide association study for nephrotoxic medication associated AKI; and the NICHD sponsored Pediatric Opportunistic Pharmacokinetic Study arm of the Pediatric Trials Network. The CACN has pioneered applications of specialized techniques such as aquapheresis and the Molecular Adsorbent Recirculating System for liver support The CACN also launched an LDL-apheresis program to treat patients with refractory FSGS. We are the only single center in the US to offer all of these specialized novel extracorporeal techniques. In addition, the CACN demonstrated unparalleled commitment to education via the CRRT University simulation course, that the center offered to more than 200 RNs and MDs from all over the world during the past two years. In addition, the CACN received a 3rd year of extramural funding this year. Finally, the CACN hosted the 2nd International Symposium on AKI in Children in Cincinnati; with attendees drawn from 20 countries and 26 US states.

Elizabeth C. Jackson, MD

Dr. Jackson is the director of the Healthy Bladder Clinic, and continues her active research program in optimizing the management of nocturnal enuresis. She has completed a randomized prospective trial comparing the effectiveness of the voice recordable alarm with the buzzer alarm for nocturnal enuresis. Dr. Jackson presented the results at the International Children’s Continence Society Meetings. She is submitting another alarm study to evaluate different teaching methods. She has also completed an evaluation of the two-day versus the one day metabolic stone profile in children. Preliminary findings suggest that more than half the children with a 48 hour urine collection have a significant abnormality that would have been missed if only 24 hours of urine had been tested. Her results were pooled with a multicenter consortium, and the paper is ready for submission. She is actively supervising Catherine Forster, fellow in hospital medicine, as she researches urinary tract infections in children on clean intermittent catheterization. The Journal of the Pediatric Infectious Disease Society accepted her article, "Frequency of Multi-Drug Resistant Organisms Cultured from Urine in Children on Clean Intermittent Catheterization".

Mark Mitsnefes, MD

Dr. Mitsnefes’ research interest has been to define biologic targets for interventions to prevent progression of cardiovascular disease in children with chronic kidney disease, through epidemiological and translational studies. Dr. Mitsnefes is a co-investigator and co-chair of the Cardiovascular Subcommittee in the multicenter NIH funded study of chronic kidney disease in children, the CKiD study. In one published study, CKiD investigators examined if masked ambulatory hypertension is predictable from casual blood pressure. Masked hypertension, even during sleep, was especially uncommon in subjects with low normal casual blood pressure (BP) (≤25th percentile). These data suggest that at least in clinical settings with limited access to ambulatory blood pressure monitoring (ABPM), an estimation of BP outside the medical office could be made based on a BP obtained during a clinic visit; if the casual BP is in the low normal range, ABPM could be omitted from the patient’s evaluation. In another published study, he showed that in young kidney transplant recipients, elevated ambulatory blood pressure is frequently unrecognized, undertreated, and associated with left ventricular hypertrophy (LVH). The high prevalence of abnormal ABP, including masked hypertension, and its association with LVH supports the case for routine ABPM and cardiac structure evaluation as the standard of care in these patients

Edward Nehus, MD

Dr. Nehus has ongoing research efforts in comparative effectiveness research in kidney transplantation, novel biomarkers of early kidney injury and chronic kidney disease in children with obesity. Dr. Nehus is currently collaborating with the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) consortium to evaluate early kidney injury in children undergoing bariatric surgery. In a recent publication, Teen-LABS investigators examined kidney outcomes in severely obese adolescents up to three years following bariatric surgery. This study indicated that early kidney injury improved following bariatric surgery in adolescents with evidence of preoperative kidney disease. Dr. Nehus is also a co-investigator of a Patient-Centered Outcomes Research Institute (PCORI) award that will investigate novel applications of propensity score-based methods to improve research validity in studies using secondary data. Dr. Nehus is applying this research methodology to national registry data of pediatric kidney transplant recipients to evaluate the long-term outcomes of steroid-avoidance immunosuppression protocols in this patient population.

Michael Bennett, PhD

Dr. Bennett is the director of the Biomarker Laboratory and do-director of the Center of Excellence in Pediatric Nephrology Proteomics Core. His primary research interests include biomarkers and mechanisms of nephrotic syndrome and lupus nephritis. This year, Dr. Bennett discovered and validated an investigational panel of biomarkers that can distinguish steroid sensitive from steroid resistant nephrotic syndrome. This panel has the potential to assist physicians in the early diagnosis of steroid resistance and help them to tailor more appropriate treatment plans for patients with this serious and progressive disease. Dr. Bennett also worked this year, in collaboration with Hermine Brunner, MD, to develop an adult and pediatric Renal Activity Index for Lupus Nephritis (RAIL) biomarker panel. The RAIL is a robust and highly accurate noninvasive measure of lupus nephritis activity. Dr. Bennett’s work has resulted in 10 peer reviewed publications this year, and one patent application.

David Hooper, MD

Dr. Hooper’s research interests lie in improving clinical outcomes for children with a kidney transplant through the design of reliable healthcare systems both locally and nationally. The multidisciplinary kidney transplant innovation team he leads has established a true learning health system to provide comprehensive chronic disease management for children with a kidney transplant and to continuously measure care and improve outcomes of these patients at Cincinnati Children’s. Their data system has automated tracking of more than 30 outcome and process metrics enabling the identification of gaps in care, and the ability to use structured quality improvement methods together with clinical outcomes research to systematically improve health. This year, his team has developed and implemented a comprehensive system to identify barriers to patients taking their immunosuppressive medications, coupled with patient-centered shared decision making tools to help patients overcome those barriers. As a result, the rate of acute rejection episodes has improved, sparing patients from kidney injury and costly therapies. Nationally, his team launched the Improving Renal Outcomes Collaborative, a network based learning health system focused on improving health, longevity, and quality of life for children with a kidney transplant. Dr. Hooper is leading over 120 physicians, researchers, nurses, other staff and patients and caregivers from 16 centers nationally to specifically improve blood pressure control, decrease acute rejection and improve quality of life for nearly 2,000 children with a kidney transplant nationwide.

Donna Claes, MD, MS

By creating a highly reliable, clinical care delivery system, Dr. Claes’ academic interest is to significantly slow the rate of decline in kidney function over time in pediatric chronic kidney disease (CKD) patients at Cincinnati Children's by focusing on the improved treatment of common associated comorbidities – such as hypertension and proteinuria. Dr. Claes has lead a team to first define the overall quality of care we wish to achieve in this patient population, and then build the necessary framework and decision support tools to process and assimilate relevant outcome data over time. As there are no national benchmarks to compare the rate of pediatric CKD progression across the US by center, especially in regards to the management of these common comorbidities associated with CKD progression, Dr. Claes’ vision is for Cincinnati Children's to become the leader in pediatric CKD care delivery. Dr. Claes is also the site PI for multi-center clinical and pharmacologic studies, such as the NIH funded Chronic Kidney Disease in Children (CKiD) and Cure Glomerulonephritis (CureGN) studies.

Elif Erkan, MD, MS

Dr. Erkan’s research focus is to understand the detrimental effects of proteinuria in glomerular diseases and to examine the protein-protein interactions involved in albumin endocytosis in the proximal tubule epithelial cells. Dr. Erkan is particularly interested in investigating the multiple facets of molecular pathways that lead to progression in focal segmental glomerulosclerosis (FSGS). Dr. Erkan investigates the mechanism of albumin endocytosis in proximal tubule epithelial cells, and determines how albumin overload may contribute to tubular apoptosis/autophagy in glomerular diseases. The goal of this project is to dissect the molecular pathways, and cell signaling events, involved in the cross-talk between apoptosis and autophagy in glomerular disease particularly in FSGS. She recently showed that children with FSGS display derangement of urinary lipid metabolites. This novel finding led to approval of an ancillary study enrolling patients with nephrotic syndrome from a national cohort, NEPTUNE. The goal of this study is to understand how lipid metabolites contribute to progression in FSGS.

Brian Siroky, PhD

The focus on Dr. Siroky’s laboratory is on the mechanisms of renal cyst and tumor formation that occur in the inherited disease Tuberous Sclerosis Complex (TSC), and the identification of targeted therapies for these lesions. He is also interested in the structural and functional relationship between renal epithelial primary cilia, specialized cellular organelles whose dysfunction linked to cystogenesis, and mTOR signaling, the pathway dysregulated in TSC. He is currently developing a patient urine-derived epithelial cell culture system coupled with cutting edge 3-dimensional culture methodology to both characterize structure/function and evaluate response to potential therapies in a patient-specific fashion. In collaboration with clinicians in the Cincinnati Children's TSC Clinic, Dr. Siroky is the PI of a retrospective clinical study aimed at determining the clinical benefit of early mTOR inhibitor treatment on renal cystic disease in patients with TSC. Dr. Siroky also collaborates with researchers at Cincinnati Children's and the UC College of Medicine on a funded project studying the mechanisms by which renal epithelial cells sense and adapt to a hyperosmolal microenvironment, specifically the role of the primary cilium and transient receptor potential channels in this process. In collaboration with researchers at the University of Alabama at Birmingham, Dr. Siroky contributed to a published study that found hyperglycemia, in the absence of cilia, results in renal structural and functional damage and accelerates renal cystogenesis, suggesting that diabetes is a risk factor in the progression of polycystic kidney disease.