After obtaining promising initial results in a smaller trial launched earlier this year, a biotech startup has begun a new multi-center trial with Mount Sinai, and medical schools at Yale, the University of Michigan Medical School, Johns Hopkins, and Rutgers to predict long-term kidney disease risk in recovering COVID-19 patients.
RenalytixAI, a London-based diagnostics firm runs a blood-based assay for predicting the risk of progressive decline in patients' kidney function. The firm's researchers run a sample on a multiplex electrochemiluminescence assay to identify three biomarkers, then combine data derived from a patient's electronic medical record to generate a risk score of the patient's progressive kidney decline.
As part of the new trial, the team will monitor recovered patients who developed acute kidney injury while in the hospital or may potentially suffer from chronic kidney disease in the future.
In the smaller study, the researchers collected both blood and urine samples from patients hospitalized with COVID-19. The team analyzed the incidence and severity of acute kidney injury, certain risk factors associated with the condition, the proportion of patients needing dialysis, patient mortality, and how often surviving patients recovered kidney function.
Coca's team initially published a preprint regarding the results and expects to publish a finalized version of the study examining a total of 3,993 COVID-19 patients in the Journals of American Society of Nephrology later this year.
"While 46% (1,835) of the population acquired AKI, 17% of those [patients] required dialysis, and the mortality [of the AKI population] was about 50%," Steven Coca, RenalytixAI cofounder and associate nephrology professor at the Icahn School of Medicine at Mount Sinai, explained. "We found that about a third of patients with AKI that survived did not recover kidney function by the time of discharge."
Despite patients in the trial having a median hospital stay length of about 10 days, Coca and his colleagues realized they needed to track patients' recovery time and observe long-term kidney function post-discharge to better gauge their risk of CKD.
Coca explained that in the new trial, his team will collect blood and urine samples of COVID-19 survivors with AKI before they are released from the hospital.
"Severity and duration of AKI in the setting of COVID appears to more severe than 'standard AKI,'" Coca noted in an email. "Thus, we believe the risk for CKD after surviving COVID-AKI will be higher than routine AKI, and risk stratification will be needed to determine who will need to be seen by nephrologists and who needs more aggressive post-AKI care."
RenalytixAI's academic collaborators will collect blood and urine samples from their health systems and send them to Mount Sinai, where Coca's team will analyze the samples. The group aims to process samples from as many as 4,000 patients over the course of the multi-year longitudinal study.
"Now that patients have recovered from COVID-19, you can see them in person and measure markers including their IGG antibodies as part of the longitudinal assessment." Coca said. "Obviously, you'd overwhelm nephrologists since you can't follow up with every COVID-19 patient, so we want to do a re-stratification of these samples."
Coca and his colleagues will examine blood and urine biomarkers after three months to determine if they help predict which patients progress with CKD. The biomarkers Coca's team will examine are broadly associated with either inflammation, AKI, or CKD progression
The group will then create a risk score based on the samples to establish a prediction for long-term outcome. Coca said that the team will watch for changes in biomarkers found by the assay in patients who return for longitudinal visits.
The group will passively examine a patient's kidney behavior over time by accessing their electronic medical records following the initial sample collection.
Coca argued that a patient's one- to three-month follow up sample — even when adjusted for EGFR, kidney function, urine albumin, and other clinical variables — contains blood markers that add additional prognostic value "above and beyond" what the clinical variables can provide. He therefore anticipates spotting critical clinical findings from the MASKeD-COVID trial.
"Because we were in a surge phase in the past few months, we did not assay a large proportion of samples from patients … and thus the first collection will be in the post-discharge phase," Coca explained. "Ironically, the post-discharge sample is the most valuable sample for predicting [CKD] progression."
Noting that there have been "some rumblings" from pharmaceutical companies about COVID-19 drug development, Coca said that the last aim of the study will be to research how distinct phenotypes occur for COVID-related kidney disease. By collecting kidney biopsies from a patient subset with persistent evidence of kidney disease, the team will perform transcriptomic and proteomic analysis using single-cell sequencing to further understand the condition.
Matthias Kretzler, a nephrology, computational medicine, and bioinformatics professor who leads the team at University of Michigan will also research how COVID-19 can cause lasting damage to a surviving patient's organs in addition to the kidneys, including the heart, lungs, and the endocrine system.
"We are also looking at kidney and immune cell single-cell sequencing [data] of patients with COVID-19 to learn what molecular mechanisms it is using while damaging cells, and conversely, if we identify such mechanisms, how we can modify them with existing treatment," Kretzler added.
This story first appeared in our sister publication, 360Dx, which provides in-depth coverage of in vitro diagnostics and the clinical lab market.