Mitochondria: a new therapeutic target in chronic kidney disease

Abstract

Cellular metabolic changes during chronic kidney disease (CKD) may induce higher production of oxygen radicals that play a significant role in the progression of renal damage and in the onset of important comorbidities. This condition seems to be in part related to dysfunctional mitochondria that cause an increased electron “leakage” from the respiratory chain during oxidative phosphorylation with a consequent generation of reactive oxygen species (ROS).ROS are highly active molecules that may oxidize proteins, lipids and nucleic acids with a consequent damage of cells and tissues.To mitigate this mitochondria-related functional impairment, a variety of agents (including endogenous and food derived antioxidants, natural plants extracts, mitochondria-targeted molecules) combined with conventional therapies could be employed.However, although the anti-oxidant properties of these substances are well known, their use in clinical practice has been only partially investigated. Additionally, for their correct utilization is extremely important to understand their effects, to identify the correct target of intervention and to minimize adverse effects.Therefore, in this manuscript, we reviewed the characteristics of the available mitochondria-targeted anti-oxidant compounds that could be employed routinely in our nephrology, internal medicine and renal transplant centers. Nevertheless, large clinical trials are needed to provide more definitive information about their use and to assess their overall efficacy or toxicity.

The Unexpected Effects of L-Carnitine Supplementation on Lipid Metabolism in Hemodialysis Patients

“…This results in mitochondria-derived oxidative stress and leads to persistent tissue damage. As L-carnitine is an essential enzyme co-factor in energy metabolism it could be one of the so called mitochondria-targeted molecules which could modulate the specific signal transduction cascade and lead to significant improvement of cellular defense against chronic inflammation and oxidative stress [15]. Moreover, after performing multivariate regression analysis we were able to show a link between the FTI increase and a lesser number of IDH episodes which could suggest that positive energy balance (with an increase in prealbumin and FTI) and a reduction of MIS eventually led to better hemodynamic stability.…”

Upregulation of Oxidative Stress Related Genes in a Chronic Kidney Disease Attributed to Specific Geographical Locations of Sri Lanka

“…The mitochondria are the largest producer of the ROS within cells due to the electron leak from the electron transport chain [40]. The increased oxidative stress in chronic kidney disease is in part attributed to the dysfunctional mitochondria which cause an increased electron leakage from the respiratory chain during oxidative phosphorylation with a consequent generation of ROS [16]. We observed an upregulation of the NLRP3 gene in both the CKDu and CKD patients with fold changes of 6.55 and 11.30, respectively ( p < 0.01).…”

“…ROS is however generated in CKD by several internal processes including hyperactivation of NADPH oxidase, increased production of oxidative stress markers, and the release of uremic toxins [16]. We therefore analyzed the expression pattern of genes reacting to internal sources of oxidative stress production to better understand the environmental versus physiological sources of oxidative stress in the study groups.…”

“…The increased oxidative stress in chronic kidney disease is in part attributed to the dysfunctional mitochondria which cause an increased electron leakage from the respiratory chain during oxidative phosphorylation with a consequent generation of ROS [16]. NLR family pyrin domain containing 3 (NLRP3) is known to be activated by mitochondrial ROS [16] and therefore it was selected to study the influence of mitochondrial oxidative stress.…”

“…NLR family pyrin domain containing 3 (NLRP3) is known to be activated by mitochondrial ROS [16] and therefore it was selected to study the influence of mitochondrial oxidative stress. Fibroblast growth factor-23 (FGF23), a bone-derived hormone, although not directly linked to oxidative stress, is believed to influence systemic phosphate homeostasis, vitamin D metabolism, and alpha klotho expression [18], all factors which play roles in the oxidative stress balance.…”