Marco Fiorentino1,2, Giuseppe Castellano2, John A Kellum1. 1. Department of Critical Care Medicine, Center for Critical Care Nephrology, CRISMA (Clinical Research, Investigation, and Systems Modeling of Acute Illness) Center, University of Pittsburgh School of Medicine, Pittsburgh, USA. 2. Department of Emergency and Organ Transplantation, Nephrology, Dialysis and Transplantation Unit, University of Bari, Bari, Italy.
Abstract
BACKGROUND: Acute kidney injury (AKI) is a common clinical condition directly associated with adverse outcomes. Several AKI biomarkers have been discovered, but their use in clinical and preclinical studies has not been well examined. This study aims to investigate the differences between clinical and preclinical studies on AKI biomarkers. METHODS: We performed a systematic review of clinical and preclinical interventional studies that considered AKI biomarkers in enrollment criteria and/or outcome assessment and described the main differences according to their setting, the inclusion of biomarkers in the definition of AKI and the use of biomarkers as primary or secondary end points. RESULTS: In the 151 included studies (76 clinical, 75 preclinical), clinical studies have prevalently focused on cardiac surgery (38.1%) and contrast-associated AKI (17.1%), while the majority of preclinical studies have focused on ether ischemia-reperfusion injury or drug-induced AKI (42.6% each). A total of 57.8% of clinical studies defined AKI using the standard criteria and only 19.7% of these studies used AKI biomarkers in the definition of renal injury. Conversely, the majority of preclinical studies defined AKI according to the increase in serum creatinine and blood urea nitrogen, and 32% included biomarkers in that definition. The percentage of both clinical and preclinical studies with biomarkers as a primary end point has not significantly increased in the last 10 years; however, preclinical studies are more likely to use AKI biomarkers as a primary end point compared with clinical studies [odds ratio 2.31 (95% confidence interval 1.17-4.59); P = 0.016]. CONCLUSION: Differences between clinical and preclinical studies are evident and may affect the translation of preclinical findings in the clinical setting.
BACKGROUND: Acute kidney injury (AKI) is a common clinical condition directly associated with adverse outcomes. Several AKI biomarkers have been discovered, but their use in clinical and preclinical studies has not been well examined. This study aims to investigate the differences between clinical and preclinical studies on AKI biomarkers. METHODS: We performed a systematic review of clinical and preclinical interventional studies that considered AKI biomarkers in enrollment criteria and/or outcome assessment and described the main differences according to their setting, the inclusion of biomarkers in the definition of AKI and the use of biomarkers as primary or secondary end points. RESULTS: In the 151 included studies (76 clinical, 75 preclinical), clinical studies have prevalently focused on cardiac surgery (38.1%) and contrast-associated AKI (17.1%), while the majority of preclinical studies have focused on ether ischemia-reperfusion injury or drug-induced AKI (42.6% each). A total of 57.8% of clinical studies defined AKI using the standard criteria and only 19.7% of these studies used AKI biomarkers in the definition of renal injury. Conversely, the majority of preclinical studies defined AKI according to the increase in serum creatinine and blood urea nitrogen, and 32% included biomarkers in that definition. The percentage of both clinical and preclinical studies with biomarkers as a primary end point has not significantly increased in the last 10 years; however, preclinical studies are more likely to use AKI biomarkers as a primary end point compared with clinical studies [odds ratio 2.31 (95% confidence interval 1.17-4.59); P = 0.016]. CONCLUSION: Differences between clinical and preclinical studies are evident and may affect the translation of preclinical findings in the clinical setting.
Authors: Mehdi Jafari-Oori; Marco Fiorentino; Giuseppe Castellano; Abbas Ebadi; Farshid Rahimi-Bashar; Paul C Guest; Amir Vahedian-Azimi; Amirhossein Sahebkar Journal: Adv Exp Med Biol Date: 2021 Impact factor: 2.622
Authors: Stephen J McWilliam; Rachael D Wright; Gavin I Welsh; Jack Tuffin; Kelly L Budge; Laura Swan; Thomas Wilm; Ioana-Roxana Martinas; James Littlewood; Louise Oni Journal: Clin Kidney J Date: 2020-10-21