Mitochondrial Dysfunction in Kidney Disease and Uremic Sarcopenia

Abstract

Recently, there has been an increased focus on the influences of mitochondrial dysfunction on various pathologies. Mitochondria are major intracellular organelles with a variety of critical roles, such as adenosine triphosphate production, metabolic modulation, generation of reactive oxygen species, maintenance of intracellular calcium homeostasis, and the regulation of apoptosis. Moreover, mitochondria are attracting attention as a therapeutic target in several diseases. Additionally, a lot of existing agents have been found to have pharmacological effects on mitochondria. This review provides an overview of the mitochondrial change in the kidney and skeletal muscle, which is often complicated with sarcopenia and chronic kidney disease (CKD). Furthermore, the pharmacological effects of therapeutics for CKD on mitochondria are explored.

Keywords: CKD - chronic kidney disease; kidney; mitochondria; sarcopenia; skeletal muscle.

FIGURE 1

Mitochondrial damage in CKD and uremic sarcopenia. (A) Stressors like sepsis, ischemia and toxins induce acute mitochondrial damage. Pathogenesis such as hypertension, diabetes, and obesity induce chronic mitochondrial damage. Uremic toxins accumulated in AKI and CKD also induce mitochondrial damage. On the other hand, mitochondrial damage itself exacerbates kidney damage, forming a vicious cycle in CKD progression. (B) In CKD, mitochondrial damage mediates uremic sarcopenia. AKI, acute kidney injury; CKD, chronic kidney disease; ROS, reactive oxygen species; ATP, adenosine triphosphate.

FIGURE 2

Mitochondrial dysfunction in the kidney and the skeletal muscle. Both kidney failure and sarcopenia are associated with mitochondrial damage, and there are several common findings or processes in the kidney and the skeletal muscle. Mitochondrial damage, usually accompanied with morphological change for altered dynamics and decreased biogenesis, results in ROS accumulation or deficiency in ATP production. ROS production, which can induce mitochondrial damage, promote inflammation or cytochrome C release leading to apoptosis. Low efficiency in ATP production also leads to cell injury. CKD progression or uremic sarcopenia can result from combination of these phenomena. Therapeutics for CKD have various effects on some or all of these processes. At the same time, these processes can still be a novel therapeutic target. CKD, chronic kidney disease; ROS, reactive oxygen species; ATP, adenosine triphosphate.