Study Team

Isidro Salusky, Principal Investigator, Executive Committee

As a clinical-translational research scientist, I have focused my research efforts on the abnormalities of bone and mineral metabolism that are associated with chronic kidney disease (CKD) in children. I have also worked withexperimentalmodels of CKD. Over the years, I have aimed to advance our understanding of the mechanisms of disordered mineral metabolism in patients with CKD, including the role of parathyroid hormone, vitamin D, and more recently fibroblast growth factor 23 (FGF23). Through continuousNIH funding, my research group has described the features of bone diseases across the stages of CKD, and after renal transplantation. My group has also provided significant groundwork for elucidating the relationship between abnormalitiesof bone and mineral metabolism and vascular calcifications in children and young adults treated with dialysis. In addition, we have demonstrated that the recommended doses of aluminum-containing binders were associated plasma and tissue aluminum accumulation. We have defined the effects of therapy with active vitamin D sterols and binders on the skeletal lesion of secondary hyperparathyroidism. My current efforts are focused on studying the role of FGF23 in the pathogenesis of CKD-Mineral and Bone Disorder, with the aim of understanding the relationship between bone and FGF23 across the spectrum of CKD. In this line of research, we have characterized for the first time the expression of FGF23 in bone in CKD patients as early as stage 2. More recently, we have characterizedthe role of iron and erythropoietin on FGF23 production in CKD in experimental models and humans. Such studies led to the UO1 application on the assessment of an iron-based binder on FGF23 levels in children with CKD (funding to start in 7/19).

Tamara Isakova, Executive Committee (Northwestern University)

I am an established clinical investigator with a strong record of independent funding from the NIH and experience in epidemiologic and patient-oriented research and in multi-center clinical trials. I investigate novel mechanisms underlying the development of cardiovascular disease in patients with chronic kidney disease (CKD). My research activities have included work on the Chronic Renal Insufficiency Cohort (CRIC) Studyand the conduct of a series of physiologic and interventional studies of mineral metabolism in health and in CKD. I am on the Steering Committeesfor the NIDDK-funded U01 Consortium on Pilot Studies in CKDandthe UG3/UH3 funded pragmatic trial of higher vs. lower serum phosphate targets in patients undergoing hemodialysis (HiLo). The COMBINE (CKD Optimal Management with Binders and Nicotinamide) Study is the parent study for my R01-supported ancillary study, which investigatedthe impact of phosphate and fibroblast growth factor 23 (FGF23) reduction strategies on bone and mineral metabolism and on intermediate cardiovascular and renal end points in patients with CKD. My second R01 builds on these research efforts and leverages my ongoing work in the CRIC Study to test hypotheses that will advance the vascular calcificationfield by evaluating the novel T50 assay as a candidate biomarker and elevated levels of deoxycholic acid as a possible modifiable disease mechanism with the ultimate goal of ameliorating adverse outcomes in patients with CKD. I have experience and expertise in clinical trials targeting patients with CKD and disordered mineral metabolism. I am well-positioned to serve on the Executive and Steering Committees for the, FIT4KID trial, the U01-funded multi-center clinical trial of ferric citrate in children with CKD.

David Elashoff, Executive Committee

Dr. David Elashoff is a Professor of Medicine and Biostatistics at UCLA and Director of the Department of Medicine Statistics Core. He serves as Leader for the Biostatistics, Study Design and Clinical Data Management Program (BSD-CDM) for the UCLA CTSI. His main areas of statistical research are in developing statistical methods for the analysis of high throughput genomic and proteomic data. He has extensive collaborative experience on a variety of basic science, clinical research and clinical trials projects, including those with members of the School of Dentistry, Department of Medicine, Jonsson Comprehensive Cancer Center (JCCC), School of Nursing, and investigators at their partner institutions. As an investigator on the BSD-CDM, he collaborates with program leaders to implement the CTSI-wide network of biostatistics consulting services and develop joint research in genomics, proteomics, bioinformatics and clinical correlates. His collaborations with the Boston University CTSA have led to new funding this year from the NCI Early Detection Research Network Biomarker Discovery Laboratory Grant, identifying and validating early detection lung cancer biomarkers. He will continue to collaborate with CTSI investigators in both general statistics and in microarray and other genomic analysis. His membership on the Cancer Biomarkers Study Section of the NCI will continue and provide valuable insight to biomarkers and clinical relationships.

Frederick Kaskel, Principal Investigator

I am a translational investigator with expertise in basic renal physiology and research in glomerular disease and chronic kidney failure in children. I have considerable experience in leading national and international scientific activities and was a PI on the NIDDK Focal Segmental Glomerulosclerosis Clinical Trial, President of the 15thScientific Congress of the International Pediatric Nephrology Association and former President of the American Societyof Pediatric Nephrology. I served on the FDA Cardiovascular Renal Advisory Panel and currently on the Pediatric Advisory Panel, the Scientific Steering Committee of Nephcure and the Standing Renal Committee of the National Qualify Forum. I was Chair of the Clinical Translational Science Awards Consortium Child Health Oversight Committee and PI on a R13 application entitled: “Advancing Opportunities for Pediatric Research and the Role of CC-CHOC within NCATS.” Of importance to this application, I have been the PI on a T32 Training Grant on Developmental Nephrology for the past ten years and Chief of the Division of Pediatric Nephrology for eighteen years. Currently as Director of Life Course Research Program at Einstein’s Institute for Clinical and Translational Research, and the Co-Director for the Thesis Committee for its Clinical Research Training Program, I am fully aware of the importance of strict adherence to the principals of human investigation. I have considerable experience in administering projects, leading multidisciplinary teams of investigators, training high school, university and medical undergraduates, and residents/fellows, and implementing effectivecommunication regarding time-lines for research development, data analyses, submission of new scientific information for presentation and publication, and maintaining budgetary adherence.As PI at the Albert Einstein College of Medicine, I will lend my expertise to the Phosphate Binding Therapy and Chronic Kidney Disease in Children study.

Sabina Kennedy

...

Michelle Denburg, Principal Investigator

Michelle Denburg, MD, MSCE, is board certified in pediatric nephrology and is director of Research for the Division of Nephrology at CHOP. She is an associate professor of Pediatrics and Epidemiology and Senior Scholar in the Center for Clinical Epidemiology and Biostatistics at the University of Pennsylvania Perelman School of Medicine. She is a faculty member of the Clinical Futures, a CHOP Research Institute Center of Emphasis. She is an Attending Physician in the Cancer Survivorship Program and the CHOP-Penn Glomerular Clinic. Dr. Denburg leads a multidisciplinary research program focused on complications of childhood kidney diseases, including chronic kidney disease (CKD), glomerular disease, and kidney stone disease, with a particular interest in bone health and altered mineral metabolism. Her research includes analyses of large electronic health record databases, and observational, translational, and interventional patient-oriented studies. Dr. Denburg is the co-director of the Penn-CHOP Kidney Innovation Center. She is the associate director for the Pediatric Center of Excellence in Nephrology supported by funding from the National Institute of Diabetes and Digestive and Kidney Disease. She also served as co-PI in the NIDDK CKD Biomarkers Consortium to identify novel biomarkers for CKD progression in children. She initiated and leads GLEAN (Glomerular Learning Network), a multi-institutional collaborative focused on outcomes improvement in children with glomerular disease and is co-PI of the PRESERVE study (Preserving Kidney Function in Children with Chronic Kidney Disease) that is leveraging the health data resources of 16 centers to address evidence gaps in blood pressure management for children with CKD. Dr. Denburg is committed to mentoring trainees and junior investigators engaged in clinical research. Mentees have included clinical fellows and junior faculty members in multiple subspecialties, medical students, residents, and biostatistics graduate students.

Farzana Perwad, Principal Investigator

Dr. Farzana Perwad is a specialist who cares for children with kidney disease, including those requiring dialysis and kidney transplant. Her expertise includes evaluating and treating chronic kidney disease in children, nephrotic syndrome (a disorder that causes excessive excretion of protein in the urine), kidney stones, urinary tract infections, and kidney or urinary tract abnormalities that were present at birth. Her research focus is to understand the molecular mechanisms of regulation of phosphorus and vitamin D metabolism in the setting of chronic kidney disease.

Anthony Portale, Principal Investigator

I am a Professor of Pediatrics, former Chief of the Division of Pediatric Nephrology, and former Medical Director of the Pediatric Kidney Transplant Program at UCSF. I have been a principal investigator on NIH and other grants with a special interest in vitamin D, phosphorus, and FGF23. I was the principal investigator on the cloning of the 25-hydrdoxyvitamin D- α-hydroxylase gene and subsequent studies of its molecular regulation by phosphorus and FGF23in the kidney.

Mark Mitsnefes, Principal Investigator

I am an established clinical investigator with expertise in the area of understanding the development of risk factors for cardiovascular disease in children with chronic kidney disease (CKD). My long-term career goal is to define biologic targets for interventions to prevent and slow progression of CVD in children with CKD through advancing Patient-Oriented Research (POR). Since2003, I have been a co-investigator and co-chair of cardiovascular committee for the CKiD study, NIH-funded the multicenter study of children with CKD. In our analysis of the CKD data we showed that children with CKD stage 2-3a, FGF23 was an independent predictor of left ventricular hypertrophy.  My role within the CKiD and extensive experience in studying CKD outcomes in children has prepared me to be a co-investigator for the current grant.

Thomas Blydt-Hansen, Principal Investigator

The goal of the proposed research is to investigate the intervention of phosphate binding usingsevelamer in children with chronic kidney disease (CKD) to mitigate progression of CKD and CKD-associated mineral bone disease. The impact of this intervention is mediated via regulation of FGF23, which is also increasingly recognized as arisk factor for poor outcomes like cardiovascular disease. Specifically, we plan to conduct a randomized controlled trial of the intervention over a 5-year period. I have the expertise, leadership and motivation necessary to successfully carry out the proposed work. I have a broad background in pediatric, with specific training and expertise in key research areas for this application. As a nephrology fellow at McGill, I conducted research on the pathophysiology of X-linked hypophosphatemia. As a clinician investigator at the University of Manitoba, I have been a longstanding site investigator for two pivotal prospective studies: the CKiD study investigating disease progression in pediatric CKD; and the STOPP study investigating the impact of steroid treatment on bone health in pediatric chronic disease, including nephrotic syndrome. We have been highly successful at recruitment and retention to these studies, and have been recognized by the CKiD study for our contribution. I am an active contributor to the progression core of the CKiD study, which has already produced a number of important publications. During 2006-2007 my research career was disrupted due requirements for clinical coverage resulting from several maternity leaves by my clinical colleagues. Since then, my principal current area of research is in the identification and characterization of biomarkers of kidney disease, which is directly applicable to the focus of this project on early detection of disease risk markers and intervention. I am the principal investigator for an ongoing Canadian multicenter study to identify urine biomarkers of rejection using metabolomic and proteomic platforms, andco-investigator on local and national studies to identify biomarkers for chemotherapy related kidney injury and diabetic kidney disease. As PI or co-Investigator on several university-, NIH-and CIHR-funded grants, I have a proven track record as a collaborative researcher. Thecurrent application builds logically on my prior involvement with the CKiD study, with co-investigators who themselves are leaders in the field of pediatric CKD and mineral-bone disease. In summary, I have a demonstratedrecord of accomplished and productive research projects in an area of high relevance for our young CKDpopulation, and my expertise and experience have prepared me to lead the proposed project.

Bradley Warady, Principal Investigator

I have been actively involved in the study of pediatric CKD/ESRD for more than 30years. My experience includes membership on the Board of Directors of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) since 2002 and my coordination of a number of multicenter research initiatives. I have also served as theCo-Principal Investigator of the NIH U01 Chronic Kidney Disease in Children (CKiD) study since its inception in 2003. My interest/expertise in the area of CKD and ESRD management include dialysis, transplantation, growth, anemiaand progression of chronic kidney disease.

Raymond Quigley, Principal Investigator

After completing my fellowship in 1991, I joined the faculty of the Pediatric Department at the University of Texas Southwestern Medical Center at Dallas. I initially was performing bench research inrenal physiologyas evidenced by my publications. In January of 2006,I was appointed the medical director for the dialysis unit at Children's Medical Center of Dallas. At that time, I spent most my effort in the dialysis unit and thenephrology clinic at Children's Medical Center. I now have over10 years of experience in working with patients with varying degrees of chronic kidney disease as well as end-stage renal disease. I think my previous work in renal physiology has also helped by abilities to work in research as well as understand the basic pathophysiology underlying the problems with chronic kidney disease.

Poyyapakkam R.Srivaths, Prinicpal Investigator

My research focus in elucidating cardiovascular morbidity ties well intothe current project which is to look at the efficacy of phosphatebinders with Dr. Salusky. Cardiovascular mortality is 1000 times more common in children with ESRD than age matched controls. Elucidating the risk factors for this unusually high cardiovascular risk has been the focus of my research. I have been interested in elucidating the mechanism of cardiac calcifications in children with end stage renal disease and have been working on such projects for the past 3 years. Our previous work on prevalenceand progression of cardiac calcifications in children receiving hemodialysis has resulted in 3 separate abstracts and presented at National scientific meetings and three publications thus far.

Jorge Ramirez, Principal Investigator

I am the director of Pediatric Nephrology at Hewell Kids Kidney Center atArnold Palmer Hospital for Children and Associate Professor of Pediatrics at the University of Central Florida. During my Fellowship at UCLA I participated in an RO1 clinical trial characterizing the effects PTH in children on dialysis. It was during thistime that I perfected my skills for iliac crest bone biopsies under the mentorship of Isidro Salusky, MD. Over the last decade I have focused my career in addressing the many issues compounding the medical care of children with kidney disease. In the past I have acted as PI and participated in industries sponsored studiesincluding; Paracalcitrol, Vitamin-D receptor, andDarbopoetin. However today, many of the solutions for these children rest at the forefront of pediatric kidney research. It will be through the efforts of this multi-center prospective clinical trial in the pediatric population with CKD stages 3-4 to control FGF23 levelsthat we can effect a change in toprevent the development of secondary hyperparathyroidism and improve outcomes such as CKD progression, cardiovascular disease and bone disease. Thus creating a new paradigm for treatment for CKD-MBD.

Shoba Narayan, Principal Investigator

Dr. Shoba Narayan is board certified in pediatrics and pediatric nephrology with over 10 years of experience. Dr. Narayan received her medical degree from the UCLA David Geffen School of Medicine, where she also completed her pediatric residency and fellowship training in pediatric nephrology. She has extensive knowledge in all aspects of pediatric kidney diseases and volunteers her time to further help children with renal conditions.

Christine Sethna, Principal Investigator

Christine Sethna, MD, EdM, is the division director of pediatric nephrology in the Department of Pediatrics at Cohen Children’s Medical Center CCMC

Abby Basalely, Principal Investigator

Joyce Samuel, Principal Investigator

Dr. Joyce Samuel is an associate professor of pediatrics at McGovern Medical School at UTHealth Houston. Dr. Samuel treats children with all forms of kidney disease (both inherited and acquired). She also treats children with high blood pressure from infancy through early adulthood. Dr. Samuel believes in building a strong connection with the family as well as the patient to provide the best possible care for the child. She has developed innovative approaches to provide personalized medical care to her patients. She acknowledges that she cannot expect all children to respond the same way to treatment, so she is devoted to providing individualized care by using the best scientific evidence available.

Amira Al-Uzri, Principal Investigator

Khalid Myda, Principal Investigator

Keith A. Hruska, Principal Investigator

John Mahan, Principal Investigator

Michael Zappitelli, Principal Investigator