Additionally, one study investigated whether mitochondria and cytosolic ROS are produced in the heart of CKD mice using a novel method for induction of renal failure through dietary delivery of adenine. After 11 weeks of follow-up, mice developed only mild cardiac phenotype followed by increased plasma creatinine levels, an increase in systolic blood pressure, early cardiac volumetric parameter impairment and increased mitochondrial oxidation [10, 4].
Uremic toxins as mediators of cardiac failure
Uremic toxins may also play an important role in the progression of CV disease in the setting of CKD. The highly protein-bound uremic toxin indoxyl sulfate has emerged as a potent toxin adversely affecting both the kidney and heart. Direct cardiac effects of this and other uremic toxins have been recently demonstrated in in vitro and in vivo studies. Potent fibrogenic and prohypertrophic effects, as well as oxidative stress-inducing effects, appear to play a central role in uremic-toxin driven renal and cardiac pathology .
In one of the experiments, redox sensors were used to screen whether different uremic toxins can be involved in cardiac failure. Researchers stably expressed H2O2 biosensors in both the cytosol and mitochondria of the cardiomyocytes. The sensors proved to be very responsive to H2O2 levels. In mitochondria, H2O2 concentration of 5 μM already led to mitochondria response, whereas in the cytosol, the response was observed when the concentrations of H2O2 were 20 μM or higher. Sensors were saturated when the levels of H2O2 were between 50 and 100 μM. Results of this analysis confirmed increased cytosolic and mitochondrial H2O2 levels with fractions from the dialysate, and increased cell death in the hydrophilic fraction partially protected by protein SS-31 .