Serbia
Serbia (Србија)
Biomarkers of Uremic Cardiotoxicity
The Serbs enter the 2022 NephroWorldCup looking for the holy grail of dialysis: the one single biomarker that predicts cardiovascular disease. For decades researchers have searched for this one single marker. Until now, we've relied on regression models to predict cardiovascular mortality; models whose components are often commonly tested markers, such as albumin, hemoglobin, ESA use, etc. etc (Figure 1).
The continued interest in finding this marker has now led researchers to microRNAs (miRNA).
Figure 1: The AROii model for predicting mortality on hemodialysis | Presented at the 2019 European Renal Association meeting | Courtesy of Dr. Jyoti Baharani
Video 1: MicroRNAs (miRNA)
MicroRNAs (miRNA) are being studied for ADPKD, kidney allograft rejection, and as the holy grail in cardiac disease for end-stage kidney patients. miRNAs are non-coding fragments of RNA that prevent other messenger RNAs from producing their protein product (i.e., prevent translation of an mRNA to its encoded protein) (Video 1). Research in miRNAs is popping up everywhere in the CVRM sciences (Carousel 1).
Carousel 1: The many areas of microRNA (miRNA) study (zoom in for details)
There are many miRNAs and more being found regularly. Databases have been developed to keep track of the miRNAs being discovered (Link 1). A few miRNAs (I use that term loosely) have been implicated in cardiovascular disease and one in particular has been the focus of the Serbian squad.(Figure 2).
Link 1: MicroRNA databases | Courtesy of Dr. Francisco J. Enguita
Figure 2: miRNAs implicated in congestive heart failure | Presented at 2019 American Heart Association meeting | Courtesy of Dr. Tomasz Guzik (zoom in for details)
For this year's competition the Serbian research team looked at miRNA-133 and its diagnostic role, if any, in cardiovascular disease in hemodialysis patients. This 18-month prospective study analyzed blood biomarkers in 87 CKD and ESKD patients (63 non-dialysis CKD and 24 dialysis patients). Patients were followed for cardiovascular events, which included:
myocardial infarction
stable or unstable angina pectoris
peripheral arterial disease
heart failure
cardiac death
Figure 3: miRNA-133 levels based on CV events
As expected, traditional biomarkers such as albumin and hemoglobin had predictive power in determining cardiac disease, but alone were non-diagnostic. MicroRNA-133 was not statistically different in either group (Figure 3).
And so it seems that we're back to where we started. A single biomarker remains elusive; notwithstanding a valiant effort by the Serbian team. The Serbian squad may be years ahead of the prevailing currents in CVRM science. miRNAs will continue to be studied and research into these interesting molecules is in its infancy.
"We all have our favorite microRNA's" -- Dr. Laura Denby | 2018 Scottish Renal Association meeting -- Courtesy of Dr. Joanna Prentice