This proposal is for a Mentored Clinical Training Award (K23) for Dr. Joshua Samuels. The goal of this research is to provide career development and experience necessary to become a competitive independent clinical investigator, and to gain important knowledge regarding the development and outcome of acute kidney failure (AKF). The research will include patients admitted to the intensive care unit at MD Anderson Cancer Center (MDACC). Having already completed an MPH concentrating in Epidemiology, his didactic development plan includes Ph.D. level coursework at the UT-Houston School of Public Health, a period of laboratory training to gain facility with molecular epidemiology, and structured mentoring from two highly successful investigators. The protocol for the research is designed to facilitate his growth as a clinician-scientist and to evaluate clinical and genetic factors associated with AKF in critically ill patients with cancer. Cancer has become a leading cause of morbidity and mortality,with increasing hospitalization. AKF affects over 50,000 hospitalized Americans each year, and the mortality of patients with AKF in intensive care units has been reported as high as 86%. Current predictive models are inadequate to provide individualized prognostication. This study aims to refine predisposing clinical exposures and evaluate genetic markers that predict the onset and prognosis of AKF in critically ill cancer patients. The first phase uses a retrospective case-control design. Logistic and Cox regression modeling will be used to evaluate demographic and environmental exposure factors independently and in multivariate fashion to produce a final prediction model. Mortality and length of stay information will also be collected to evaluate associations between exposures and outcome. The second phase will prospectively validate the new clinical models and go further by evaluating multiple genetic polymorphisms as factors associated with AKF. The innovative addition of genetic analysis may provide enough improvement to allow patient specific prognostication. Overall, this study will allow for better prediction of AKF in ICU patients and better prognostication of their outcome. A better understanding of the risk factors and genetic susceptibility will allow quicker recognition of AKF and aid future research to develop more effective prevention or treatment options. The projects will launch the candidate into a career as an independent clinical investigator in Nephrology.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Mentored Patient-Oriented Research Career Development Award (K23)
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Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
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Rankin, Tracy L
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University of Texas Health Science Center Houston
Internal Medicine/Medicine
Schools of Medicine
United States
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Samuels, Joshua (2012) The increasing burden of pediatric hypertension. Hypertension 60:276-7
Samuels, Joshua; Ng, Derek; Flynn, Joseph T et al. (2012) Ambulatory blood pressure patterns in children with chronic kidney disease. Hypertension 60:43-50
Samuels, Joshua; Ng, Chaan S; Nates, Joseph et al. (2011) Small increases in serum creatinine are associated with prolonged ICU stay and increased hospital mortality in critically ill patients with cancer. Support Care Cancer 19:1527-32