Chronic kidney disease (CKD) is a serious public health problem. Current therapies are designed to slow down progression of
the disease and avoid the necessity of dialysis or kidney transplantation. CKD is characterized by chronic inflammation and progressive
cell death resulting in fibrotic rebuilding of renal tissue. Melatonin, the primary product of the pineal gland, has been shown to have
pluripotent protective effects in many organs and tissues. It exerts anti-hypertensive, anti-inflammatory, anti-apoptotic, and antiremodelling
actions. A principal mechanism of these numerous melatonin benefits resides in its extraordinary high efficacy as an antioxidant
and scavenger protecting cells both extracellularly and in all subcellular structures. In addition to these receptor-independent actions,
the effects of melatonin via specific MT-receptors may be beneficial. In several animal models of CKD, involving experimental hypertension,
diabetes mellitus and various models of nephrotoxicity, melatonin reduced the oxidative burden, attenuated the chronic inflammation
and limited apoptosis. These effects were associated with the reduction of proteinuria, damage of parenchymal cells and fibrosis.
In humans, melatonin’s chronobiological action attenuates sleep disturbances in hemodialyzed patients suffering from a relative melatonin
deficiency. Moreover, melatonin reduces the oxidative burden and improves iron metabolism in hemodialyzed patients. In conclusion,
the pleiotropic physiological actions of melatonin induce beneficial effects at numerous pathophysiological levels related to CKD
both under experimental and clinical conditions. It is hoped that this review will prompt a large clinical trial to determine the efficacy of
this nontoxic indoleamine as a potential treatment for this debilitating disease.