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 with major unmet needs. The proposal includes several research projects in the areas of acute kidney injury, cardio-renal syndromes, and kidney fibrosis, with participation from recognized teams of investigators from multiple disciplines. Also included are high-resource gene expression, proteomics, biomarker, enhancement, and training cores with core leaders of international repute. Devarajan is the nephrology lead investigator for several NIH-funded prospective clinical studies. He is currently the principal investigator or co-principal investigator on eight NIH grants. He established a unique kidney biomarker laboratory which now performs more than 50 distinct assays for acute and chronic kidney disease biomarkers. Devarajan is the director and principal investigator (PI) of the NIH T32-funded Nephrology / Hypertension Fellowship.
Devarajan’s research on biomarkers and new therapeutic targets in kidney diseases has yielded over 15 publications during the last year. Thomson-Reuters listed 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. The prestigious Association of American Physicians elected him as a member during the past year.
Elif Erkan, MD
Erkan’s primary research focus is to investigate how proteinuria contributes to progression of glomerular diseases particularly focal segmental glomerulosclerosis (FSGS). Erkan demonstrated that the urinary lipid biomarker signature in children is a valuable tool to predict prognosis and diagnosis. Erkan receives ongoing funding for a 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 FSGS, funded by the NIH O’Brien Core Center, University of Alabama Lipidomics Center.
A second project is to understand the role of protein kinase B (Akt) in albumin handling by proximal tubule epithelial cells. Erkan demonstrated that urinary shedding of albumin receptor cubilin predicts progression and proteinuria in type I diabetes mellitus.
As a physician-scientist and educator, Erkan is active in mentoring and coordinating activities of undergraduate students, residents, fellows and post-doctoral candidates.
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 at Cincinnati Children's. 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 initiate MARS TM at Cincinnati Children's, and guidelines to provide intraoperative continuous renal replacement therapy during liver transplantation.
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 at Cincinnati Children's for the EMERALD study, examining the safety and tolerability of Patiromer for the management of hyperkalemia in chronic kidney disease. He is also 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. Lastly, he developed algorithms and guidelines which serve to reduce the risk of hemodialysis and peritoneal dialysis catheters exit site infections.
Since March of this year, Flores led the division in Cincinnati Children's efforts to address the COVID-19 pandemic. At the institutional level, he collaborated with other divisions in the development of institutional guidelines to treat COVID-19 patients and in the diagnosis and management of children with multisystem inflammatory syndrome. At the divisional level, he leads the development of guidelines to reduce the risk of exposure for patients and providers in both the outpatient and inpatient care settings. During the recovery phase, Flores coordinated the restructuring of the nephrology clinics, aiming to reduce potential COVID-19 exposure and maximize the benefit of patient-provider interactions.
Stuart L. Goldstein, MD, FAAP, FNKF
Goldstein 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. The nephrotoxic medication acute kidney injury (AKI) reduction project, NINJA, resulted in a seven-year sustained reduction in AKI, preventing AKI in more than 800 children. It is now in 13 U.S. pediatric centers, with two publications resulting from this work in Kidney International and The American Journal of Health System Pharmacy. This collaborative observed a 23% sustained decrease in nephrotoxic medication exposure and associated AKI. Based on these results, implementation began in the 140 pediatric hospital Solutions for Patient Safety Collaborative. The CACN collaborated with the Division of Oncology and Stem Cell Transplant programs to reduce nephrotoxic medication associated AKI, with data published in Biology of Blood and Bone Marrow Transplantation and Pediatric Blood and Cancer.
The CACN successfully integrated its real-time AKI risk stratification system, the renal angina index (RAI), to guide novel AKI biomarker testing in critically ill patients in the PICU. The CACN received funding from a Nephrology P50 Center of Excellence grant to use the RAI / NGAL data in real-time to drive clinical decision support. We improved prediction of AKI significantly with this approach. The CACN pioneered applications of specialized techniques such as aquapheresis and the Molecular Adsorbent Recirculating System for liver support. The CACN participated in a three-center retrospective study detailing pediatric application of the Aquadex device, published in the Clinical Journal of the American Society of Nephrology. The CACN launched an LDL-apheresis program to treat patients with refractory FSGS and offered this therapy for the first time for adults with lipoprotein-A elevations, which increases risk for atherosclerotic heart disease. The CACN remains the only single center in the U.S. to offer all of these specialized novel extracorporeal techniques. The CACN and Cincinnati Children's is the first U.S center selected to treat critically ill neonates and infants with the CARPEDIEM™ CRRT machine, the first such device specifically designed for patients 2.5 to 10 kg in weight.
David K. Hooper, MD, MS
Hooper is the 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 this record year, Cincinnati Children’s performed the highest number of living donor transplants of any program in the country and performed a record of 32 transplants (living and deceased donor) transplants in this fiscal year. Among them were two heart / kidney transplants, one liver / kidney transplant, two highly sensitized patients, one child with complex congenital heart disease, a young child who was anuric and required dialysis from birth, and 15 children referred in from outside centers because the local centers either lacked the expertise or deemed them too small or medically complex for transplantation. The transplant program continued to build on chronic disease management programs to reduce rejection episodes by supporting improved adherence and enhance safe and effective transitions.
The Improving Renal Outcomes Collaborative that Hooper leads expanded to include 34 kidney transplant programs, now accounting for more than half of all children to receive a kidney transplant in the United States last year. The publication of the first research study from this platform was in the journal Pediatrics demonstrating the rapid standardization and improvement of blood pressure measurement across 17 centers. IROC shifted focus to spreading techniques and strategies to improve medication adherence to reduce rejection episodes network-wide. In addition to Hooper’s academic work with IROC, he partnered with Edward Holland, MD, of the Cincinnati Eye Institute, to develop and grow a unique program for ocular surface stem cell transplantation children with aniridia. They published the findings from their first 13 patients in the journal Cornea. Hooper 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 and the North American Pediatric Renal Trials and Collaborative Studies.
Mark Mitsnefes, MD, MS
Mitsnefes’ research interest is to define biologic targets for interventions to prevent progression of cardiovascular disease in children with 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 an important study in CJASN assessing the role of blood pressure (BP) load from ambulatory blood pressure monitoring (ABPM) in predicting progression to ESRD and LVH in children with CKD. In this study, BP load does not provide additive value in discriminating outcomes when used independently or in conjunction with mean systolic BP in children with CKD. Another high-impact study published in AJKD showed that in children with CKD, adiposity is independently of BP associated with left ventricular hypertrophy (LVH) indicating that obesity may therefore have a substantial impact on cardiovascular risk among these children.
Mitsnefes also serves as a co-investigator and training program director of the AHA-funded Ship Ahoy study (Study of High BP in Pediatrics; Adult Hypertension Onset in Youth). One of the important publications last year includes a study examining cardiac function published in Hypertension. The study determined that subclinical changes in left ventricular systolic and diastolic function is detectable even at BP levels below the hypertensive range as currently defined.
In the past year, Mitsnefes completed the second educational course on pediatric hypertension for primary care physicians through the ECHO program led by the Center for Telemedicine.
Mitsnefes continues as program director for the Schubert Research Clinic at Cincinnati Children's. 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.
Edward Nehus, MD, MS
Nehus’ primary research investigated early kidney disease in childhood obesity and obesity-related type 2 diabetes mellitus. During the last year, Nehus continued this line of research by investigating the effects of bariatric surgery on early kidney disease in adolescents with these conditions. Nehus published a study last year in Kidney International showing bariatric surgery may have more beneficial effects on kidney outcomes when performed in adolescence, as compared to adulthood. In another study published in Diabetes Care, Nehus demonstrated that bariatric surgery improves early kidney injury in severely obese adolescents with type 2 diabetes. The American Society of Pediatric Nephrology webinar entitled “Using TOD2AY to improve tomorrow’s renal outcomes in childhood diabetes” presented this research. Nehus has ongoing research efforts to identify early markers of kidney injury in children with type 2 diabetes to improve the long-term outcomes of children with this condition.
Nehus received a promotion to program director of the Pediatric Nephrology Fellowship Training Program in July of 2020. Nehus' active involvement in the American Society of Pediatric Nephrology Program Directors Committee, seeks to facilitate training and certification of future pediatric nephrologists. Through collaboration with Nephrology Program Directors across the country, Nehus continues to promote the advancement of the training program at Cincinnati Children's and foster the next generation of clinical scientists.
Meredith Posner Schuh, MD
Schuh’s research focuses on how prematurity can lead to low nephron endowment and increased risk for chronic kidney disease later in life. We lack a molecular understanding of how nephrons form during the third trimester and why there is an interruption of this process in preterm birth. During the past year, Schuh received the K12 Child Health Career Development Award from Cincinnati Children’s and the P50 Pilot & Feasibility Award from NIH to study this important problem. The long-term goal is to restore or enhance nephron endowment in premature, low birth weight infants to decrease their chronic kidney disease risk.
Charles Varnell, Jr., MD
Varnell is in the second year of a KL2/CT2 career development award. His primary training objective is to become a learning health systems researcher, mentored by Peter Margolis, MD, PhD, and David Hooper, MD, MS. Additionally, as a PEDSNet Scholar, he is working with the Improving Renal Outcomes Collaborative (IROC) – a multicenter learning health system that focuses on improving the health, longevity, and quality of life for children with a kidney transplant – to study immunosuppression medication adherence and acute rejection in kidney transplant patients.
In the last year, Varnell graduated from the Quality Scholars Program at Cincinnati Children’s. He continued to further his informatics skills as a certified Epic Physician Builder and joined the national Epic Pediatric Nephrology Steering Board.
Stefanie Benoit, MD, MPH
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 capable of balancing 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, 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, 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 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 received a promotion to director of the Nephrology and Hepatology Clinical Lab in July of 2020. She led the laboratory team in developing clinical serology testing for COVID-19 at Cincinnati Children's. She provides critical laboratory services to multiple cross-institutional COVID-19 research projects.
Donna Claes, MD
Claes’ primary academic focus is on quality improvement (QI) efforts for the chronic kidney disease (CKD) / end-stage kidney disease (ESKD) populations within Cincinnati Children’s. Claes serves as the medical director for the chronic kidney disease program and is the medical director for the Dialysis Unit at Cincinnati Children's. Claes led efforts to provide reliable health care delivery to all CKD patients seen by the Cincinnati Children's nephrology team by using a CKD patient registry with the electronic health record patient registry, associated CKD specific decision support tools. Pre-visit planning ensures meeting and providing all anticipated CKD related care needs (such as necessary laboratory tests to screen for common CKD related complications, ambulatory blood pressure monitoring, and immunizations) during the upcoming scheduled visit. The 2019 American Society of Nephrology Annual Meeting highlighted her work in a presentation. In addition, this past year, Claes created similar care tools that automate patient-level and population-level reports for the Cincinnati Children's dialysis population to drive care improvement. In addition to improving local care outcomes, these registries and reporting tools allow Claes to easily collaborate with other researchers across the U.S. for any potential CKD / ESKD related research studies.
Claes provides 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. Claes worked as the lead investigator along with other pediatric nephrologists to understand the survival hospital discharge and health care utilization needs for neonates born with kidney failure in the United States. The 2020 Annual Dialysis Conference presented her work. Finally, Claes continues involvement with the Standardized Care for Improved Outcomes in Pediatric ESKD (SCOPE) learning network, with the goal to eliminate dialysis-related infections in the pediatric dialysis population, using many of the SCOPE tools and learnings to reduce dialysis-related infections within the Cincinnati Children's dialysis population.
