The smell of renal protection against chronic kidney disease: Hydrogen sulfide offers a potential stinky remedy

Chronic kidney disease (CKD) is a common global health challenge characterized by irreversible pathological processes that reduce kidney function and culminates in development of end-stage renal disease. It is associated with increased morbidity and mortality in addition to increased caregiver burden and higher financial cost. A central player in CKD pathogenesis and progression is renal hypoxia. Renal hypoxia stimulates induction of oxidative and endoplasmic reticulum stress, inflammation and tubulointerstitial fibrosis, which in turn, promote cellular susceptibility and further aggravate hypoxia, thus forming a pathological vicious cycle in CKD progression. Although the importance of CKD is widely appreciated, including improvements in the quality of existing therapies such as dialysis and transplantation, new therapeutic options are limited, as there is still increased morbidity, mortality and poor quality of life among CKD patients. Growing evidence indicates that hydrogen sulfide (H2S), a small gaseous signaling molecule with an obnoxious smell, accumulates in the renal medulla under hypoxic conditions, and functions as an oxygen sensor that restores oxygen balance and increases medullary flow. Moreover, plasma H2S level has been recently reported to be markedly reduced in CKD patients and animal models. Also, H2S has been established to possess potent antioxidant, anti-inflammatory, and anti-fibrotic properties in several experimental models of kidney diseases, suggesting that its supplementation could protect against CKD and retard its progression. The purpose of this review is to discuss current clinical and experimental developments regarding CKD, its pathophysiology, and potential cellular and molecular mechanisms of protection by H2S in experimental models of CKD.