Early detection strategies and determination of chronification risk in acute kidney injury

Abstract

Acute Kidney Injury (AKI) increases patient's morbidity and mortality, and it is highly manifested in intensive care patients. When AKI is not rapidly reversible and complications cannot be clinically managed, renal replacement therapy (RRT) may be an option. However, in spite of advances in critical care, nephrology, and RRT, mortality for patients requiring dialysis is still near 50%. Thus, once treatment is still limited, prevention and early detection of AKI are fundamental to improve patient outcomes. The best AKI care process should probably include integrated data of all possible patient information, including use of old and new biomarkers, clinical risk assessment scores, functional tests, and early detection by eAlert systems. The objective of this project are: 1. to test an eAlert system that deflagrates when patients that will undergo elective cardiac surgery with cardiopulmonary bypass (CPB) are admitted with a low glomerular filtration rate (GFR) or Renal Reserve (RR), being prone to AKI, 2. to determine if senescence-related urinary markers (p21, p16, Klotho and TGFbeta, G1/S and G2/M proportions) may be good early AKI biomarkers, 3. To determine if biomarkers and RR may be good to distinguish who will develop CKD in a long-term analysis, presuming development of pro-fibrotic cell phenotype, 4. To determine if biomarkers levels correlate with loss of RR after CPB, 5. To determine if renal biomarkers behave differently in patients with or without pre-existing CKD.To study this, we will enroll adult patients with or without pre-existing chronic kidney disease that will undergo elective cardiac surgery with CPB at the Prince of Wales Hospital, Sydney, Australia. All patients will have a Glomerular Filtration Rate measured by 51Cr-EDTA Clearance (51Cr-EDTA), RR and estimaetd GFR (eGFR) before the CPB. When GFR is < 60 mL/min/1.73 m2 or RR is < 15 mL/min/1.73 m2, and eAlert will be automatically generated, directed to the team responsible for care of the patients. After the cardiac procedure, we will collect urine samples to determine the levels of the following proposed biomarkers: TIMP2 x IGFBP7, p21, p16, Klotho, TGFbeta, in addition to a 6h-urine sample collection to isolate cells harvested from urinary sediment to determine G1/S and G2/M proportions. One, three and six months after the CPB, patients will be evaluated regarding eGFR and renal reserve. (AU)