NEW YORK – Startup RenalytixAI has partnered with Mount Sinai Health System to launch a clinical study to analyze biomarkers that may predict major adverse kidney events in patients hospitalized with COVID-19.
London-based RenalytixAI believes the multi-part stratification study will help advance commercialization of its KidneyIntelX blood-based assay for acute and chronic kidney disease (CKD) detection.
Renalytix was launched as a partnership between EKF Diagnostics and Mount Sinai Health System in order to commercialize artificial intelligence-enabled clinical diagnostic tools for the early detection of kidney disease and transplant management. RenalytixAI currently has a CLIA-certified laboratory in New York and an additional lab in Salt Lake City, Utah.
"When [COVID-19] was spreading in late March and early April, we saw that this was not only a respiratory disease, but affecting the kidneys as well," explained Steven Coca, RenalytixAI cofounder and associate nephrology professor at the Icahn School of Medicine at Mount Sinai. "After we got our initial footing with patient care, however, we began to realize just how much acute kidney injury was occurring in these COVID-19 patients."
According to Coca, the researchers will attempt to understand the molecular relationship between COVID-19 and kidney disease. John Cijang He, chief of nephrology at the Icahn School of Medicine at Mount Sinai and study co-investigator, noted that about 40 percent of the COVID-19 patients that Mount Sinai's health system has treated so far have developed acute kidney injury (AKI).
In the project, Mount Sinai researchers will use RenalytixAI's KidneyIntelX AI platform to launch detailed machine-learning prediction models that analyze more than 25 clinical features and biomarkers — incorporating RNA and protein biomarkers found in plasma and urine— to stratify COVID-19 patients in Mount Sinai's health system into low-, medium-, and high-risk groups for adverse kidney disease stages.
Coca explained that the multi-phase study, called "Prediction of Major Adverse Kidney Events and Recovery" (Pred-MAKER), will collect both blood and urine samples from at least 500 COVID-19 patients at Mount Sinai. Coca and his team will analyze the epidemiology of COVID-19 patients exhibiting AKI; specificallly examining the incidence and severity of AKI, the risk factors associated with AKI, the proportion of patients requiring dialysis, associated patient mortality, as well as the propensity to recover kidney function in patients who survive.
While human angiotensin-converting enzyme 2 (ACE2) acts a transmembrane enzyme for SARS-CoV-2, Coca noted that there are several hypotheses attempting to explain the disease's destructive behavior within kidney tissue in the enzyme's presence.
"The present virus [may] bind with ACE2, which is well expressed in the kidneys, (particularly in podocytes and proximal tubular epithelial cells)… and could serve as a binding site and potential injury mechanisms," Coca explained. "Or … pre-existing AKI induced by severe sepsis may be exacerbated by SARS-CoV-2, as once the initial kidney injury occurs and alters the integrity of cell-to-cell-junctions, the virus might then gain access to ACE2 on the luminal surface."
"We're taking biomarker work [that] we've been doing for years in AKI and CKD and measuring, at least in a subset of these several thousands of patients, blood and urine biomarkers along inflammation and kidney injury pathways," Coca added. "We have experience from multiple studies that you get additional prognostic information when you're interrogating these biomarkers."
Coca therefore believes that the KidneyIntelX platform, which incorporates clinical variables and kidney disease biomarkers, will allow the team to predict onset, severity, and recovery from AKI in COVID-19 patients.
Because kidneys are a target of injury for COVID-19, certain liquid biopsy biomarkers that Coca's team will analyze may also affect viral activity, which means the researchers' work may also aid in the overall prognosis of COVID-19 patients.
Coca also noted that kidney tubular dysfunction in early-stage COVID-19 patients can also cause proteinuria. He therefore aims to use proteinuria as a predictive biomarker because it may lead to other indicators marking a drop in kidney function (such as fluctuating levels of potassium and electrolytes).
"The hypercatabolic state this virus is causing, along with the kidney disease injury, is causing a major taxing of the [clinical] system, as we're trying to keep up with the disease and treatment," Coca said. "Given the amount of people that need [dialysis] and the amount of resources it needs, we've been chasing the tail to keep up the monitoring of these substances."
In the long-term, Coca expects patients to receive a significant burden of unresolved kidney injury or underlying kidney fibrosis from severe tubular damage.
In addition to having identified that COVID-19 patients with multiple organ failure eventually develop AKI, the researchers have also found that some patients instead develop AKI before respiratory failure and ahead of several long-term CKD consequences.
"[SARS-CoV-2-triggered kidney disease] is in the acute phase right now, but chronic conditions are also very important," He explained. "Assuming the patients will recover in the future, they will eventually develop CKD, and we know the biomarkers will also predict the chronic phase."
Therefore, the group is also establishing plans for longitudinal studies that will use KidneyIntelX to predict long-term CKD patient outcomes. Besides aiding in the diagnosis and treatment of COVID-19-induced kidney injury in the near-term, RenalytixAI CEO James McCullough said the collaboration with Mount Sinai will help the firm further demonstrate KidneyIntelX's clinical utility for assessing kidney inflammation and disease progression ultimately leading to commercial translation of the assay later this year.
"The clinical, IT, and other teams at Mount Sinai are working very closely with RenalytixAI," McCullough noted. "We now have the resources, and the coordination with key constituents on the clinical side, to make as much headway for what's going to be a burgeoning population."
McCullough said that RenalytixAI has also established plans for a US regulatory pathway and a reimbursement framework but declined to provide further details.
"The assay will help determine who is progressing, who is not, who has kidney disease ultimately coming out of this pandemic, who will be able to live with it in the long term, and how we can apply a limited amount of clinical resources to this patient population," McCullough said.