2023 Department of Pediatrics Academic Annual Report

Dr. Webb also collaborates with investigators in the Cardiac Intensive Care Unit to better understand the alterations in perfusion, cytokines and inflammation that lead to acute kidney injury in infants undergoing cardiac surgery. The goal of this study, funded by the Kaul Pediatric Research Institute, is to reduce complications, hospital time and morbidity, and improve survival in these critically ill children. CHILDHOOD HYPERTENSION PROGRAM Daniel Feig, M.D., leads the Childhood Hypertension Program, which has identified critical mechanisms involved in the development of adolescent onset essential hypertension as well as the risk factors associated with hypertensive target organ damage. Previous clinical trials have demonstrated that elevated serum uric acid causes vascular damage and activation of the renin angiotensin system, resulting in high blood pressure that can be mitigated by uric acid–lowering therapy. The ESTABLISH (impact of Early Life STressors on the BLood Pressure and Vascular Function in AdoleScents and CHildren) is a recent clinical trial that evaluated the impact of adverse childhood experiences (ACE), including neglect, malnutrition, poverty and violence, on the function of blood vessels and regulation of blood pressure. The study found that such exposures lead to impaired vasodilation of regulatory vessels long before changes in blood pressure. While previous studies indicated that adults exposed to ACEs have increased risk for cardiovascular disease, our study is the first to show demonstrable physiologic changes as early as adolescence. Ongoing investigations, including those funded by a new UO1 Grant, are aimed at elucidating the mechanisms of these changes and prevention of later cardiovascular disease. We have launched several initiatives aimed at identification and reduction of organ injury secondary to hypertension. We now perform annual 24-hour ambulatory BP monitoring (ABPM) studies in all of our dialysis and transplant patients. In these populations, hypertension is exceedingly common, as is severe cardiovascular injury secondary to hypertension. ABPM is the gold standard for detecting hypertension and risk for target organ damage. We have begun working with investigators at Zucker School of Medicine at Hofstra on the Kids: Nocturnal Investigation into Glomerular Disease, Hypertension and Transcriptomics (KNIGHT) to investigate the impact of chronobiology on hypertension and hypertensive target organ damage. RESEARCH AND EDUCATION IN GLOBAL HEALTH Erica Bjornstad, M.D., Ph.D., MPH, continues her research and educational initiatives to improve kidney health worldwide, collaborating with UAB partners in Zambia and Malawi. She strives to understand the epidemiology and risk factors of acute kidney injury in low resourced areas. Her early work in Malawi validated a bedside dipstick to triage trauma patients at risk for kidney injury. She is also evaluating the impact of fluid resuscitation strategies on the incidence and severity of acute kidney injury following accidental trauma. These endeavors will dramatically reduce morbidity in trauma victims. Dr. Bjornstad has launched an online educational case conference between UAB Pediatric Nephrology and several groups in Zambia and Malawi to provide collaboration, education and scholarship in the international nephrology community. The short-term goals of this program include supporting training for pediatric nephrology practitioners in Malawi and Zambia, countries with fewer than one practitioner per 10 million people. With the support of the International Pediatric Hypertension Association (IPNA), we have developed a sister program with Levy Mwanawasa University Teaching Hospital in Lusaka, Zambia. Paul Mashanga, the only practicing Pediatric Nephrologist in Zambia, came to Children’s of Alabama for four weeks in 2023 for cultural and scientific exchange, and we plan to increase the bilateral exchange in 2024. RESEARCH IN RENAL DIALYSIS UNIT The Renal Dialysis Unit (RDU) is one of the largest pediatric dialysis units in the nation. In addition to providing state-of-the-art care, it is a leader in national studies aimed to improve the outcomes of children with chronic kidney disease and those requiring dialysis. Led by Dr. Sahar Fathallah, these include investigational new drug studies aimed at control of elevated serum potassium levels, control of serum phosphate and bone mineral dysregulation of chronic kidney disease. We are also very active in critical longitudinal observational trials, including CKiD (the study of Chronic KIDney Disease in Children) and the North American Pediatric Renal Transplant and Chronic Kidney Study (NAPRTCS). During the pandemic, Dr. Bjornstad became a leader in national and international registries to understand the impact of COVID-19 on kidney injury in children and adults. She has developed a registry that monitors isolated renal injury as well as thrombocytopenia and multi-organ system failure (TAMOF) in children with COVID-19 infection. PROGRAM IN PEDIATRIC KIDNEY TRANSPLANTATION Michael Seifert, M.D., MSCI, investigates ways to improve long-term outcomes in children who receive kidney transplants. In a seminal study, he has demonstrated that early immunologic activation, seen on surveillance kidney transplant biopsies, predicts long term complications even before changes in laboratory values. These findings have altered how many programs monitor children with kidney transplants. His current NIH-funded studies are aimed at identifying biomarkers of kidney transplant dysfunction and new therapeutic targets to mitigate late transplant failure. These studies include STAMPEDE (Spatial Transcriptomics to Discover Mechanisms of PEDiatric Kidney Transplant Endothelial Injury), BuMPER-CAR (Integrating Biomarkers from Multiple Platforms to Enhance Diagnosis of Rejection in Children and Young Adults after Renal Transplantation) and the RO1 funded study, Clinical and Molecular biomarkers of endpoints in Children. Dr. Seifert is also investigating use of biomarkers and cell-free DNA in the non-invasive diagnosis of renal allograft rejection. He is also the lead investigator for mechanistic studies on a recently funded multi-center trial, Advancing Transplant Outcomes in Children (ATOC), and a site principal investigator for a multi-national study aimed at reducing risk of recurrence of inflammatory kidney disease after transplantation and management of post-transplant vesicoureteral reflux, and understanding the role of high risk APOL1 genotypes in long-term renal allograft survival.

2023 Academic Annual Report

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