A few years ago, when I was conducting thesis research, I happened upon an article authored by an EPA researcher that stated that cats could be considered “canaries” for environment-related thyroid problems arising in humans (Dye et al., 2007). Many years later, my beloved cat Noodle B. developed thyroid problems. While being medicated, the poor thing also went on to develop kidney problems.
While I made a mental note to keep tabs on my thyroid, I wondered, could cats also be considered canaries for kidney problems that we might face in the future? It’s possible—a clear link exists between the state of the thyroid and kidney health (Mariani & Berns, 2012)—but rather than wait for a cat model, a more direct path is now available. Our own proteomes are perhaps the best sentinel to tell us what might be happening with our kidneys, particularly when they suddenly begin to fail.
According to the Mayo Clinic, acute kidney injury (AKI) can happen suddenly and happens surprisingly often in hospitalized patients. The symptoms can be non-existent or non-obvious and if the injury is severe enough, dialysis or even kidney replacement may be needed.
With AKI requiring dialysis (AKI-D), the prognosis can be grim. Based on statistics from the Veteran’s Affairs/National Institutes of Health Acute Renal Failure Trial Network (ATN) study, the hyperacute phase, which lasts about the first eight days, has a 49% mortality (Yu et al., 2018). Past the 8-day mark or the acute phase, the survival chances improve to 77.6% during the 28-day time point used in the study.
In a recent article, a team of researchers looked to better understand the pathogenesis of AKI-D and discover a way to better predict survival early (Yu et al., 2018). Analyzing samples from the ATN study with the SOMAscan® Assay they found 33 proteins with elevated levels in patients who perished within eight days of the first blood sample being taken. These elevated proteins point to increased activity in processes involving inflammation, coagulation and endothelial cell injury. There were also several protein changes that hinted at a longer survival rate, but only by a few weeks.
This article is also the first one to implicate several proteins, such as tissue plasminogen activator, matrix metalloproteinase-8 and soluble urokinase plasminogen activator receptor in the increase risk of death in AKI-D. Is this a first step to a deeper understanding about the molecular underpinnings of AKI-D and to potential new therapies? It would be nice if changes in the proteome provide not only a dire warning of imminent danger but also a silver lining of effective treatment.
Dye, J. A., Venier, M., Zhu, L., Ward, C. R., Hites, R. A., & Birnbaum, L. S. (2007). Elevated PBDE levels in pet cats: sentinels for humans? Environ Sci Technol, 41(18), 6350-6356.
Mariani, L. H., & Berns, J. S. (2012). The renal manifestations of thyroid disease. J Am Soc Nephrol, 23(1), 22-26. doi:10.1681/ASN.2010070766
Yu, L. R., Sun, J., Daniels, J. R., Cao, Z., Schnackenberg, L., Choudhury, D., . . . Portilla, D. (2018). Aptamer-Based Proteomics Identifies Mortality-Associated Serum Biomarkers in Dialysis-Dependent AKI Patients. Kidney Int Rep, 3(5), 1202-1213. doi:10.1016/j.ekir.2018.04.012