Abstract
Kidney diseases have become one of the most common health care problems. Due to a growing number of advanced aged patients with concomitant disorders the prevalence of these diseases will increase over the coming decades. Despite available laboratory tests, accurate and rapid diagnosis of renal dysfunction has yet to be realized, and prognosis is uncertain. Moreover, data on diagnostic and prognostic markers in kidney diseases are lacking. The kynurenine (KYN) pathway is one of the routes of tryptophan (Trp) degradation, with biologically active substances presenting ambiguous properties. The KYN pathway is known to be highly dependent on immunological system activity. As the kidneys are one of the main organs involved in the formation, degradation and excretion of Trp end products, pathologies involving the kidneys result in KYN pathway activity disturbances. This review aims to summarize changes in the KYN pathway observed in the most common kidney disease, chronic kidney disease (CKD), with a special focus on diabetic kidney disease, acute kidney injury (AKI), glomerulonephritis and kidney graft function monitoring. Additionally, the importance of KYN pathway activity in kidney cancer pathogenesis is discussed, as are available pharmacological agents affecting KYN pathway activity in the kidney. Despite limited clinical data, the KYN pathway appears to be a promising target in the diagnosis and prognosis of kidney diseases. Modulation of KYN pathway activity by pharmacological agents should be considered in the treatment of kidney diseases.
Highlights
Kidney diseases represent various medical conditions, affecting more than 850 million people worldwide [1]
KYN pathway metabolite accumulation has been shown in many reports concerning acute kidney injury (AKI) or chronic kidney disease (CKD) [10], and appropriate and clear conclusions indicating whether KYN metabolites have a direct effect on kidney damage are difficult to draw, because kidney filtration decreases in most nephrological disorders
We thoroughly review the relationship between KYN pathway activity and the most common kidney disorder, CKD, with special attention given to diabetic kidney disease, AKI, glomerulonephritis and monitoring kidney graft function
Summary
Kidney diseases represent various medical conditions, affecting more than 850 million people worldwide [1]. Limited data are available, a role for the glutamatergic system in physiological and pathological conditions in kidneys has been reported [7]. The kynurenine (KYN) pathway is the major route of tryptophan (Trp) metabolism, leading to the formation of many biologically active agents (Fig. 1) [8]. KYN pathway metabolite accumulation has been shown in many reports concerning acute kidney injury (AKI) or CKD [10], and appropriate and clear conclusions indicating whether KYN metabolites have a direct effect on kidney damage are difficult to draw, because kidney filtration decreases in most nephrological disorders. Data establishing a role for the KYN pathway in physiological conditions are lacking. We aimed to analyse changes in KYN pathway activity reported in animal models of kidney diseases and in humans. Potential implications for kidney disease treatment are highlighted based on recently published studies
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