AKI-Sapere- a novel prognostic of Acute Kidney Injury due to cardiac surgery

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ABSTRACT Acute kidney injury (AKI) is common, expensive to treat, and associated with >50% mortality. Each year, millions of patients undergo cardiovascular surgery, medical imaging, or cytotoxic chemotherapy, all of which place them at significant risk for AKI. Around 30% of cardiac surgery patients develop AKI, with even mild AKI significantly increasing the risk of negative outcomes such as progression to chronic kidney disease and 30-day mortality. Although recent research on renal biomarkers has shown promise in diagnosing AKI progression, as yet no tests or models can effectively identify prior to surgery patients at risk for AKI initiation. If patients at risk for developing AKI can be accurately identified before surgery, preoperative and perioperative procedures could be modified to minimize the risk of AKI. Such risk minimization is particularly important since there are no pharmacologic therapies available for the effective prevention or treatment of AKI. Therefore, a clinical tool to predict AKI prior to its initiation remains a critical unmet need. Only through early prediction can clinicians make informed decisions to improve the care of patients at risk of AKI and to limit the burden of this catastrophic complication of surgery and critical illness. By utilizing our novel and robust assay for measuring a patient’s “molecular age”, HealthSpan Dx has developed AKI-Sapere, a multivariate assay that can successfully identify patients at risk for AKI initiation prior to coronary artery bypass graft (CABG) surgery. AKI-Sapere combines measurement of our innovative marker of molecular age along with a DNA marker of genetic predisposition for cardiovascular disease, and a baseline measurement of renal function. In a pilot study of 96 patients undergoing CABG procedures, AKI-Sapere predicted risk of AKI and was superior to AKI risk models composed of clinical variables, such as the Cleveland Clinic Thakar score, or a panel of ten renal biomarkers known to predict AKI progression. In this Fast Track proposal, we propose to conduct multi-center clinical trials to refine the risk score and validate the clinical utility of AKI-Sapere to identify patients at risk for AKI prior to CABG. Completion of these aims will demonstrate the clinical utility of AKI-Sapere in CABG patients and will allow us to bring this test to market, first as a lab developed test (LDT) and ultimately as an FDA-approved device. Prediction of AKI initiation by AKI- Sapere has the potential to dramatically change clinical practice by providing a significantly greater opportunity to intervene, to alter the ensuing renal insult, to council patients and clinicians, and to ultimately diminish the impact of AKI and the associated morbidity on patients and healthcare. Furthermore, use of AKI-Sapere for patient stratification in multiple settings would catalyze the clinical development of novel preventative and treatment strategies for AKI, including potentially AKI caused by sources other than CABG (high-risk surgery, organ transplantation, radiographic imaging and chemotherapy).