There is great value, both for clinical trials and clinical practice, in biomarkers that identify patients at greatest risk of developing chronic kidney disease (CKD) after acute kidney injury, explained Steven Coca, DO, MS, Icahn School of Medicine at Mount Sinai.
Biomarkers that can help identify the patients with acute kidney injury (AKI) who are most likely to progress to chronic kidney disease (CKD), even years later, will be valuable for both clinical trials and clinical practice, explained Steven G. Coca, DO, MS, professor of medicine, associate chair for clinical and translation research for the Department of Internal Medicine, and director of clinical research for the Division of Nephrology, Icahn School of Medicine at Mount Sinai.
How can biomarkers be used to identify patients at risk of complications after acute kidney injury?
That's a great question. My research initially focused largely on biomarkers in acute kidney injury, and we were focused really in the acute timeframe of onset of injury, the first few days during the depths of the AKI episode. Part of the problem with use of those biomarkers acutely in AKI is we don't have a great therapy for standard AKI. Although, we are seeing scenarios where markers such as serum NGAL [neutrophil gelatinase-associated lipocalin] in the setting of hepatorenal syndrome, or should I say liver disease with AKI, can help differentiate hepatorenal vs ATN [acute tubular necrosis].
There's urinary biomarkers that Chirag Parikh, MBBS, PhD, and Dennis Medina, MD, PhD, have been investigating that help determine acute interstitial nephritis as an etiology of AKI vs other types. There can be kidney biomarkers used in kidney donors to determine their potential for strong graft function and longevity in the kidney recipient.
And lastly, we are showing decent associations of some of the biomarkers I mentioned prior—whether it be the TNF [tumor necrosi factor] receptors, urinary MCP [monocyte chemoattractant protein]-1, urinary EGF [epidermal growth factor], urinary YKL-40 is another biomarker—after AKI that then stratify patients into the risk for chronic kidney disease and cardiovascular events, including heart failure. I should also mention some of the plasma that's blood based, the angiopoietin 1 and 2 are other biomarkers, too, that have been investigated. A lot of that work is done by the ASSESS-AKI consortium, a group of investigators that have sequential samples collected during and after AKI.
And it's really that AKI to CKD transition, I think, that lends the most drive to use these biomarkers. Because if we're going to have therapies work for AKI—while it's complicated in the hospital, especially for generic ATN—I think targeting that AKI to CKD transition phase, you have more time to dissect things out, and we could have therapies, whether they are repurposed or brought over from our standard CKD models or whether there's novel therapies that target the maladaptive repair that occurs after AKI.
I think therapies there will be potentially efficacious if we can employ them. And these biomarkers I mentioned can help, at least at the clinical trial phase—if we're not ready to use it clinically yet, because we need that validation—can help enrich the trials for having a higher level of those that will develop the adverse events, including CKD progression and cardiovascular events, and it allows you to do a more efficient clinical trial, save time, shorten the duration of the trial, and really maximize the chances for finding a signal for a therapy in that AKI to CKD window.
So, that's really where I see the biomarkers coming in: post discharge, perhaps up to 3 months after discharge. Since only probably 15% to 20% of those AKIs will be progressive in the next few years for CKD, if you can identify a group that will be at 30%, 40%, 50%, or 60% risk of progression with those biomarkers plus clinical variables, again, that will be the most valuable to the field in terms of clinical trials, and ultimately clinical care.