Prediction of Major Adverse Kidney Events and Recovery (Pred-MAKER) in COVID-19 Patients

PROJECT SUMMARY Major adverse kidney events (MAKE) are common in individuals hospitalized with COVID-19, particularly inthe United States. Our data from Mount Sinai show that ~40% of hospitalized patients develop acute kidneyinjury (AKI); 20% of those need renal replacement therapy, and the mortality rate in patients that experienceCOVID-19 associated AKI is several-fold greater than patients without AKI. Furthermore, we have seen thatthe rate of non-recovery is also significantly higher compared to those observed in non-COVID AKI,highlighting the potential long-term effects of SARS-CoV-2-associated kidney damage. We propose to utilizethe highly coordinated tissue and biospecimen collection machinery that has been initiated at the Mount SinaiHealth System. As the largest hospital system at the epicenter of the crisis, Mount Sinai treated anddischarged nearly 10,000 COVID-19 patients and created a central IRB approval and data coordination systemunder the auspices of the newly formed Mount Sinai COVID Informatics Center. As part of biospecimen andclinical data collation efforts, we have consented and obtained blood, urine or clinically indicated kidney biopsysamples from over 700 patients at the time of admission. Using these samples, we propose (1) to use a multipronged approach to determine the biomarkers that areassociated with MAKE; (2) to develop a machine learning-based predictive algorithm using a combination ofmultiplexed biomarker expression levels and clinical metrics; and, (3) to determine cellular pathways that areresponsible for COVID-associated AKI by combining multiomics interrogation of SARS-CoV-2 positive patienturine and kidney biopsies as well as the time-dependent transcriptomic signatures of in vitro primary proximaltubule cells. First, our results will have an immediate translational outcome, which will help focus clinical efforts on highrisk patients and triage low risk patients quicker. In addition, our proposal will lead to improved understandingof the complex disease mechanisms that cause the unique kidney injury signatures in COVID-19 and may leadto development of novel biomarkers and therapeutics that may prove beneficial during post-COVID clinicalcare. Our rigorous approach is innovative, and it is supported by established complementary assays. We haveassembled an experienced multidisciplinary team encompassing bioengineers, nephrologists, basic scientists,informaticians and virologists that will help improve the understanding of the landscape of kidney outcomesduring COVID-19 hospitalizations.