Mitochondrial Dysfunction in Chronic Kidney Disease

Chronic kidney disease (CKD) is a prevalent condition and a global public health challenge, associated with all-cause mortality. CKD can progress toward end-stage renal disease (ESRD), requiring renal replacement therapy with dialysis or kidney transplantation. Understanding the mechanisms responsible for the initial development of CKD may alleviate its progression to ESRD. The kidney has a high demand for energy to fuel renal tubular transport, which is primarily provided by its high numbers of mitochondria. These organelles also modulate many important factors that regulate cellular function, including cell proliferation, apoptosis, oxidative stress, and calcium signaling. In recent years, compelling experimental evidence implicates mitochondrial injury in the development and progression of several forms of CKD. This in turn promoted development of novel compounds to protect mitochondrial function, some of which have shown promising efficacy and safety in clinical trials. This chapter discusses distinct forms of mitochondrial injury in the context of CKD, with particular focus on hypertension, which occurs in 70–90% of patients with CKD, and polycystic kidney disease (PKD), an inherited disorder that represents the fourth leading cause of kidney failure worldwide. Lastly, we discuss the primary mechanisms of action and potential renoprotective effects of emerging therapies targeting mitochondria in CKD.