Renoprotection by 5-Methoxytryptophan in Kidney Disease

Kidney disease, be it acute or chronic, has a complex pathology and is a significant human health problem. Increasing interest has been focused on exploring therapeutic targets that can be used to safeguard kidney function under a variety of detrimental conditions. In this article, we review the protective effects of 5-methoxytryptophan (5-MTP), a tryptophan metabolite, on kidney injury. Published studies indicate that serum 5-MTP is increased in patients with chronic kidney disease (CKD), suggesting that 5-MTP is a biomarker for CKD and has therapeutic values. Indeed, rodent models of kidney injury induced by folic acid, lipopolysaccharide (LPS), unilateral ureteral obstruction (UUO), and ischemia/reperfusion all demonstrate that exogenous 5-MTP exhibits nephroprotective effects. The underlying mechanisms involve anti-oxidative damage via activating antioxidant systems such as Nrf2/heme oxygenase-1, anti-inflammation, anti-fibrosis, and enhanced mitophagy. To further explore the underlying mechanisms and the potential of 5-MTP as a kidney therapeutic compound, future studies need to include more rodent models of kidney injury induced by a variety of insults. Moreover, how to boost endogenous 5-MTP content and its potential synergistic effects with other therapeutic approaches aiming to combat kidney diseases also remain to be explored.