Acute kidney injury (AKI) and chronic kidney disease (CKD) are strongly associated with morbidity and mortality across multiple patient populations. Given that there is currently no specific therapy for AKI or CKD once either has occurred, having a means to predict a patient at risk for renal injury in order to prevent or attenuate damage is invaluable. The overarching goal of this proposal is to predict AKI and AKI to CKD transition in high risk patients. As an assistant professor at the University of Pittsburgh in both pediatric nephrology and intensive care medicine, Dr. Fuhrman has a firm commitment to the study of measures to predict and ultimately prevent the AKI to CKD transition. The main goal of this study is to establish an objective method to quantify renal fitness in young adult congenital heart disease (CHD) patients, a growing population that is at risk for numerous kidney insults across a lifetime. A lack of renal fitness, defined by reduced glomerular reserve and increased susceptibility to tubular injury, may indicate a poor ability of the kidney to respond to external stressors. There currently is no readily available means to quantify renal fitness clinically. Dr. Fuhrman plans to quantify glomerular reserve in CHD patients ages 18-28 by measuring estimated glomerular filtrate rate (eGFR) values using cystatin C before and after a protein load, an easily replicated method that she piloted as a T32 Training Grant recipient along with her mentor, Dr. George Schwartz, during her nephrology fellowship years. When these patients are subsequently admitted to the hospital for coronary bypass (CBP) exposure, she plans to determine the association of glomerular reserve and AKI risk. In addition, prior to a CPB exposure, Dr. Fuhrman will assess the expression of tubular biomarkers, which have been previously shown to be early markers of kidney damage. The association of these biomarkers with AKI similarly will be determined at the time of hospital admission for CBP exposure. Patients will be followed for 1 and 2 years in order to determine if preoperative glomerular reserve and tubular biomarkers estimate the risk of eGFR decline and/or the development of proteinuria. No prior studies have examined the long-term effects of glomerular reserve or preoperative tubular biomarker values in any patient group. Dr. Fuhrman has assembled a mentoring team of internationally recognized researchers led by Dr. John Kellum, her current mentor and an internationally renowned researcher who has done extensive work on predicting AKI and the use of biomarkers. The strong institutional support along with the guidance of a multidisciplinary mentorship team that Dr. Fuhrman will receive under this award will provide her with the necessary foundation to become an independent investigator with expertise in methods to predict and prevent adverse kidney outcomes in numerous patient groups. !
There are growing numbers of young adults with heart birth defects and they all have high risks of developing short term and long term kidney injury. This research will allow us to develop personalized approaches to the care of these patients in order to prevent the known significant problems with kidney disease. Through this career development award I will obtain the knowledge and skills to predict kidney stress that I will apply to future studies in other pediatric and adult patient populations. !
