Elif Erkan, MD, MS
Erkan's primary research focus is to investigate how proteinuria contributes to the progression of glomerular diseases particularly focal segmental glomerulosclerosis (FSGS). Erkan proposed that urinary lipid signature in children is a valuable tool to predict prognosis and diagnosis in FSGS. Erkan is the PI for NIH funded RO3 grant entitled "Urinary Lipidomic profile in FSGS: A novel biomarker". Erkan has an ongoing funded research project investigating the role of LDL pheresis in removal of lipid metabolites and cytokines, and development of early atherosclerosis in FSGS. Furthermore, Erkan studies the role of cPLA2 in progression of FSGS in adriamycin induced mouse model, funded by the NIH O'Brien Core Center, University of Alabama. Erkan serves as site PI for CureGN, a national cohort for glomerular disease. Erkan investigates the predictive and prognostic value of amniotic biomarkers in babies found to have oligo/anhydramnios with moderate to severe CAKUT in collaboration with the Fetal Care Center at Cincinnati Children's.
As a physician-scientist and an educator, Erkan is involved in mentoring, generating educational curriculum, and coordinating educational activities of undergraduate students, residents, fellows and post-doctoral candidates. She serves as the fellowship program director in pediatric nephrology. She is the co-PI for a global health project with our sister institution Kerala, India, with funding from the International Society of Nephrology.
Francisco Flores, MD
Flores is the medical director of clinical services and the Molecular Adsorbent Recirculating System (Mars TM) Program in the Division of Nephrology and Hypertension. In the past year, his clinical efforts focused on providing renal support to patients with liver disease. These included the development of novel outpatient clinics for patients with nonalcoholic fatty liver disease with renal involvement, consensus to initial MARS TM at Cincinnati Children's, guideline to provide intraoperative continuous renal replacement therapy during liver transplantation and guideline to provide extracorporeal liver support to patients with acute liver failure / acute on chronic liver failure. In addition, his ongoing collaboration with Children's Hospital of Montefiore, supports the Pediatric MARS TM Program at that institution.
Flores' interest in the provision of continuous renal replacement therapy in pediatric patients led him to develop in collaboration with the Center for Acute Care Nephrology's leadership, the order set to prescribed CRRT with CARPEDIEM in children 2.5 to 10kg and the guideline for the use of citrate regional anticoagulation with CARPEDIEM. In the last year, Flores presented at 12 international conferences on the use of CRRT in pediatric AKI and has co-authored one manuscript.
Flores' other areas of clinical endeavors in the past year included the care of patients with chronic kidney disease/ESRD. He is the principal investigator for the EMERALD study to examine the safety and tolerability of patiromer for managing hyperkalemia in chronic kidney disease. He is the principal investigator for the Rockwell RMFPC-22 trial, a study testing the use of ferric pyrophosphate citrate to maintain hemoglobin levels in pediatric ESRD patients. He is the principal investigator for the study evaluating the safety and tolerability of ferric citrate in the management of hyperphosphatemia related to CKD and he is also the principal investigator for the trial of daprodustat for the treatment of anemia associated to CKD in pediatric patients.
Stuart L. Goldstein, MD
Goldstein, MD, FAAP, FASN, FNKF, is the director of the Center for Acute Care Nephrology (CACN). He had a very productive research year, with achievements spanning the scope of the CACN’s research missions. Goldstein chaired the first-ever Acute Disease Quality Initiative (ADQI; www.adqi.net) devoted to pediatric nephrology (pADQI) in Napa, CA. In addition to Goldstein, four current CACN faculty (Prasad Devarajan, MD, Katja Gist, DO, MSc, Jolyn Morgan, MSN, APRN, CNP, CDN, and Natalja Stanski, MD) as well as three previous CACN members (Rajit Basu, MD, Shina Menon, MD, and Theresa Mottes, APRN-NP, CPNP-AC, CDN) served as pADQI faculty. Eight manuscripts planned from this endeavor will set the research agenda for pediatric critical care nephrology for the next decade.
The nephrotoxic medication acute kidney injury (AKI) reduction project, NINJA, is now in 13 US pediatric centers and continues to show significant harm reduction across the collaborative. Goldstein and other NINJA collaborative hospitals receive funding from the Agency for Healthcare Research and Quality to accelerate dissemination of NINJA to even more hospitals using cutting-edge implementation techniques.
The CACN successfully integrated its real-time AKI risk stratification system, the renal angina index (RAI), to guide novel AKI biomarker NGAL testing in critically ill patients in the PICU. The CACN received funding from the NIH P50 Center of Excellence grant to use the RAI/NGAL data in real-time to drive clinical decision support. We have improved the prediction of AKI significantly with this approach. Kidney International Reports published the first-year results of this TAKING FOCUS 2 effort.
The CACN also continues to serve as the lead pediatric site for numerous innovative extracorporeal device studies and including the Selective Cytopheretic Device™ (SCD, SeaStar Medical; publications in Kidney International Reports and Pediatric Nephrology), the HF20™ CRRT filter (Baxter Healthcare, publication in Pediatric Nephrology), the Seraph 100 Microbind™ filter (Exthera Medical; first pediatric patient treated). In addition, the CACN served as the lead and coordinating site for the multicenter EARNEST and GUIDANCE studies to develop and validate thresholds for urine of neutrophil gelatinase associated lipocalin (The NGAL Test™; BioPorto Diagnostics) to aid in the risk assessment for AKI in children admitted to the PICU. These data will form the clinical research necessary for FDA marketing approval for NGAL in the United States.
David K. Hooper, MD, MS
As medical director of the Kidney Transplant Program, Hooper dedicates his work to developing and implementing learning healthcare systems to improve care and health outcomes for children who require kidney transplantation. Under his leadership and in collaboration with transplant surgery, the Kidney Transplant Program at Cincinnati Children's is making kidney transplantation possible for children who otherwise might not receive it. In the calendar year 2021, Cincinnati Children's performed more kidney transplants in children than any other program in the country. Among them was a child requiring amniotic infusions while a fetus and was anuric at birth requiring several modalities of dialysis and complex coordination of care to get her ready for transplant. The team received referrals of several children from outside centers because the local centers either lack the expertise or deem them too small or medically complex for transplantation. Hooper and colleagues published the results of their work to reduce rejection episodes by supporting improved adherence in The American Journal of Kidney Disease. They also demonstrated and published that their approach not only improves the lives of their patients, it also saves money for the healthcare system.
The Improving Renal Outcomes Collaborative that Hooper leads expanded to include 42 kidney transplant programs, now accounting for approximately 60% of all children to receive a kidney transplant in the United States last year. This year, IROC published the effects of COVID-19 in the world's largest cohort of COVID-tested pediatric kidney transplant recipients. IROC also continued its work to reduce rejection episodes in kidney transplant recipients. Hooper is the principal investigator of a multi-center study of donor derived cell-free DNA monitoring in kidney transplant recipients. He also serves as the site principal investigator on NIH and other funded research changing the field of pediatric kidney transplant including the Validating Injury to the Renal Transplant Using Urinary Signatures in Children (VIRTUUS) study to evaluate urinary biomarkers of rejection, the Preemptive Rituximab to Prevent Recurrent Focal Segmental Glomerulosclerosis Post-Transplant (PRI-VENT) study of interventions to prevent recurrent FSGS.
Mark Mitsnefes, MD, MS
Mitsnefes' research interest is to define biologic targets for interventions to prevent the progression of cardiovascular disease in children with chronic kidney disease (CKD) through epidemiological and translational studies. 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.
During the past year, he published 16 articles. One of the highlights is a Hypertension (Mitsnefes et al.) publication titled "Pediatric ambulatory blood pressure monitoring classification: the case for a change" promoting a new classification of ambulatory blood pressure in children. This article discusses the limitations of current classification and the justification of new classification based on prior publications by Mitsnefes team. Based on this article, the American Heart Association adapted and published in Hypertension (July 2022) the new ABPM classification.
Mitsnefes was a leading author of another article in Hypertension looking at diastolic function in children enrolled in the CKiD study. In this study, Mitsnefes et al. found a high prevalence (> 30%) of abnormal diastolic function determined by high E/e'. This is important since diastolic dysfunction is one of the earliest manifestations of cardiac dysfunction and associates with the development of heart failure, one of the leading causes of mortality in children with ESKD. The key novel observation in this study is that sustained ambulatory hypertension is associated with abnormal diastolic function independent of casual systolic blood pressure and LVH. These data indicate that ABPM might better identify children with CKD at risk for subclinical cardiac dysfunction than casual blood pressure alone and justify a more aggressive therapeutic approach to blood pressure control in these children.
Mitsnefes continues as program director for the Schubert Research Clinic at Cincinnati Children's Hospital Medical Center. In this capacity, he leads the Participant and Clinical Interactions (PCI) core of the Center for Clinical and Translational Science and Training (CCTST) at the University of Cincinnati.
Meredith Posner Schuh, MD
Schuh's clinical and research focus is on neonatal nephrology. Schuh's lab focuses on how prematurity impacts nephron endowment and risk for chronic kidney disease later in life. To address this problem, her lab uses a non-human primate model to identify the mechanism of late gestation human nephrogenesis. The Journal of American Society of Nephrology recently published Schuh's recent work using this model. She is the awardee of the American Society of Nephrology KidneyCure 2021 Norman Siegel Research Scholar Grant to address this important problem. In addition to her research on prematurity and kidney development, her lab studies the genetics of severe CAKUT supported by the CCTST Mentored Translational Research Grant.Hillarey Stone, DO, MS
Stone’s clinical and research interests involve improving the care of children with genetic kidney diseases. Her research specifically focuses on uncovering the genetic mechanisms underlying glomerular disorders, including nephrotic syndrome, IgA nephropathy, and IgA vasculitis with nephritis. Through collaborations with the Center for Autoimmune Genomics and Etiology (CAGE), she studies the role of transcriptional regulation in the development of these diseases.
In addition to her research efforts, Stone is establishing a multi-disciplinary renal genetics clinic that will allow a patient to see a nephrologist, medical geneticist and genetic counselor. This will allow for collaboration among these specialists and provide a streamlined approach to the screening, diagnosis, counseling, and initial management of children with known or suspected genetic kidney disease. In addition to its clinical aspects, this clinic will also facilitate research, with the goal to identify novel Mendelian causes of various kidney diseases.
Charles Varnell, Jr., MD, MS
Varnell currently serves as the associate medical director of the Kidney Transplant Program at Cincinnati Children's. His research interest focuses on developing learning health systems to support children and young adults with a kidney transplant. In the last year, he published several peer-reviewed papers – most notably the quality improvement experience of a "Medication Adherence Promotion System to Reduce Late Kidney Allograft Rejection" published in the American Journal of Kidney Diseases; the follow-up study of COVID-19 in Pediatric Kidney Transplant – a study through the Improving Renal Outcomes Collaborative (IROC) published in Pediatric Nephrology; "A Review of The Learning Health System for Pediatric Nephrology" published in Pediatric Nephrology; and a "Cost-Effectiveness Analysis of Adherence Promotion Strategies to Improve Rejection Rates in Adolescent Kidney Transplant Recipients" published in the American Journal of Kidney Diseases. Varnell is active in IROC, working with centers to understand and improve immunosuppression medication adherence and acute rejection in kidney transplant patients. He serves on the IT committee for NAPRTCS and the Epic Pediatric Nephrology Steering Board.Stefanie Benoit, MD, MPH, MA
Benoit has a clinical and research focus in pediatric onco-nephrology. As treatment regimens, immunotherapy strategies and radiotherapy technology rapidly evolve, there is a critical need for investigators who can balance the competing demands of the complex oncology patient population both in the acute setting and throughout their survivorship journey. Benoit's two ongoing studies receive funding from the University of Cincinnati Cancer Institute. In the first study, she is forming a survivorship cohort of children who underwent bone marrow transplantation. She is evaluating how the management of transplant-associated thrombotic microangiopathy affects long-term outcomes, and she is using innovative cardiovascular and biomarker data to identify chronic kidney disease earlier. In the second project, Benoit is embarking on an innovative research project using a mouse model to evaluate the long-term renal effects of proton beam radiation therapy. In addition, Benoit is a contributing member in several quality improvement projects in the Cancer and Blood Diseases Institute and the Late Effects Working Group of the Center for International Blood & Marrow Transplant Research.
Benoit is director of the Nephrology Clinical Laboratory. The lab performs a wide range of high-complexity clinical tests for both clinical and research clientele, with a special emphasis on interrogating the complement system. Benoit and her team are adept at developing and validating novel assays for clinical use. In addition to CAP and CLIA licensing, all laboratory practices are GLP compliant.
Kyle McCracken, MD, PhD
McCracken’s research interests include kidney development and tissue engineering. His lab primarily focuses on applying embryologic principles to deriving human kidney tissues from pluripotent stem cells. He recently authored a study submitted for publication to Nature Biotechnology, describing the generation of 3D branching ureteric bud organoids that can be applied to a variety of investigations of kidney disease and physiology. McCracken recently completed his clinical and research nephrology training at Boston Children’s Hospital and Brigham and Women’s Hospital, respectively, where he received support from the American Society of Nephrology KidneyCure Ben J. Lipps Fellowship. He came to Cincinnati Children’s Hospital Medical Center to start his laboratory and establish collaborations between the Division of Nephrology and Hypertension and the Center for Stem Cell and Organoid Medicine (CuSTOM).Prasad Devarajan, MD
Devarajan's research includes a wide spectrum of approaches to kidney health and disease processes, spanning from molecular, genomic and proteomic approaches to human observational and clinical trials. Devarajan is the director of the National Institutes of Health (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. Devarajan is also the nephrology lead investigator for several NIH-funded prospective clinical studies. He is currently the principal investigator (PI) or Co-PI on three additional basic science NIH grants. He established a unique kidney biomarker laboratory that now performs more than 50 distinct assays for acute and chronic kidney disease biomarkers. Devarajan is also the PI of the NIH T32-funded Nephrology / Hypertension Fellowship.
Devarajan's innovative research on biomarkers and new therapeutic targets in kidney diseases yielded over 15 publications during the last year. Thomson-Reuters lists Devarajan in the "World's Most Influential Scientific Minds," an honor bestowed in recognition of ranking among the top 1% of researchers for most cited publications in the field of medicine. During the past year, BioPorto, a medical diagnostics company that closely partnered with Cincinnati Children's to advance and commercialize the concepts of acute kidney injury biomarkers in children, elected Devarajan to serve as the senior medical director.
Donna Claes, MD, MS, BS-Pharmacy
Claes' primary academic focus is on quality improvement (QI) and leadership efforts for the chronic kidney disease (CKD)/end-stage kidney disease (ESKD) populations within Cincinnati Children's Hospital. Claes leads the focused efforts to institute various processes, tools and practices within the pediatric dialysis unit to eliminate dialysis-related infections. In addition, Claes continues to serve as the medical director for the chronic kidney disease program where she continues to supervise many of the processes and efforts her team developed to provide reliable health care delivery to all CKD patients seen by the Cincinnati Children's nephrology team. Peers recognized Claes for her excellence in clinical care and leadership efforts by being awarded the Cincinnati Children's Clinical Faculty – Clinical Care Achievement Award in Spring 2022.
Finally, Claes continues to provide leadership within the Cincinnati Children's Fetal Care Center for nephrology-related care needs, such as developing care algorithms and pathways for infants born with severe kidney disease or kidney failure.
