Impact of Acute Kidney Injury on Kidney Disease Progression

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DESCRIPTION (provided by applicant): This particular grant application is submitted in response to the funding opportunity announcement that seeks to establish an Acute Kidney Injury (AKI) Natural History Consortium with the primary objective of following the natural history of patients with AKI after they finish the acute phase of their illness for comparison with concurrent relevant control patients. AKI is a common and serious complication in hospitalized patients. The incidence of AKI has increased dramatically over the past several decades based on information from large Medicare databases suggesting an increase in the number of cases by 11% per year. Whereas in-hospital complications of AKI have been extensively studied, the long-term sequelae of AKI, specifically its contribution to the development and progression of CKD leading to end-stage renal disease, have not been thoroughly evaluated. The specific aims of this proposal are as follows: SPECIFIC AIM #1: To examine the independent risk of prior history of AKI on chronic kidney disease (CKD) progression in a long-term prospective cohort study of critically ill patients. We hypothesize that the diagnosis of AKI is associated with a higher rate of progression of CKD (after the recovery of the acute illness) compared to no diagnosis of AKI in subjects admitted to intensive care unit (ICU). SPECIFIC AIM #2: To examine the independent risk of a prior history of AKI on the development of increased oxidative stress, chronic inflammation and progressive cardiovascular disease in a long-term prospective cohort study of critically ill patients. We hypothesize that AKI causes an increased oxidative stress burden and contributes to the chronic inflammatory response and worsened cardiovascular risk profiles of affected patients in the ICU compared to those without the diagnosis of AKI in the ICU. SPECIFIC AIM #3: a) To compare the relative and combined predictive capacities of a biomarker panel in the early diagnosis of AKI in high-risk critically ill patients; b) To determine if the same biomarker panel predicts the severity of AKI (need for renal replacement therapy, dialysis-free survival) and other clinically-relevant outcomes (mortality and ICU/hospital length of stay). We hypothesize that: 1) a biomarker panel that includes kidney specific markers of injury, such as urine IL-18, NGAL, F2- isoprostanes, and serum/urine cystatin C obtained at the time of enrollment will be superior to a single marker in diagnosing AKI based on AKIN criteria in a susceptible population of patients in the ICU; ii) Same biomarker panel will be superior to a single marker in predicting severity of AKI and other clinically-relevant outcomes. In order to achieve the proposed aims, we will recruit 500 subjects from a unique and novel resource, the Validation of biomarkers in Acute Lung Injury Diagnosis (VALID) study, a large (2550 subject) prospective observational cohort of a heterogeneous critically ill population followed throughout their ICU and remaining hospital stay.