Kynurenine/Tryptophan Ratio Predicts Angiotensin Receptor Blocker Responsiveness in Patients with Diabetic Kidney Disease

Wu, Ming‐Hsien; Lin, Chieh‐Mo; Chiu, Daniel T.; Chen, Szu-Tah

doi:10.3390/diagnostics10040207

Cited by 13 publications

(10 citation statements)

References 45 publications

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“…Two cross-sectional studies showed that plasma KYN, KYNA, QUIN [61], and KYN/TRP [62] were increased in patients with diabetic kidney disease (DKD) and correlated with eGFR. Four other observational studies found that KYN levels were positively associated with proteinuria [63, 64] and could distinguish between DKD patients with macroalbuminuria and diabetic patients without albuminuria [65, 66]. A small longitudinal study showed that urinary KYNA could differentiate between progressive albuminuria and non-progressive albuminuria in patients with type 1 diabetes [67].…”

Section: Kp In Ckdmentioning

confidence: 99%

The Kynurenine Pathway in Acute Kidney Injury and Chronic Kidney Disease

et al. 2021

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Background: The kynurenine pathway (KP) is the major catabolic pathway for tryptophan degradation. The KP plays an important role as the sole de novo nicotinamide adenine dinucleotide (NAD+) biosynthetic pathway in normal human physiology and functions as a counter-regulatory mechanism to mitigate immune responses during inflammation. Although the KP has been implicated in a variety of disorders including Huntington’s disease, seizures, cardiovascular disease, and osteoporosis, its role in renal diseases is seldom discussed. Summary: This review summarizes the roles of the KP and its metabolites in acute kidney injury (AKI) and chronic kidney disease (CKD) based on current literature evidence. Metabolomics studies demonstrated that the KP metabolites were significantly altered in patients and animal models with AKI or CKD. The diagnostic and prognostic values of the KP metabolites in AKI and CKD were highlighted in cross-sectional and longitudinal human observational studies. The biological impact of the KP on the pathophysiology of AKI and CKD has been studied in experimental models of different etiologies. In particular, the activation of the KP was found to confer protection in animal models of glomerulonephritis, and its immunomodulatory mechanism may involve the regulation of T cell subsets such as Th17 and regulatory T cells. Manipulation of the KP to increase NAD+ production or diversion toward specific KP metabolites was also found to be beneficial in animal models of AKI. Key Messages: KP metabolites are reported to be dysregulated in human observational and animal experimental studies of AKI and CKD. In AKI, the magnitude and direction of changes in the KP depend on the etiology of the damage. In CKD, KP metabolites are altered with the onset and progression of CKD all the way to advanced stages of the disease, including uremia and its related vascular complications. The activation of the KP and diversion to specific sub-branches are currently being explored as therapeutic strategies in these diseases, especially with regards to the immunomodulatory effects of certain KP metabolites. Further elucidation of the KP may hold promise for the development of biomarkers and targeted therapies for these kidney diseases.

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Section: Kp In Ckdmentioning

confidence: 99%

The Kynurenine Pathway in Acute Kidney Injury and Chronic Kidney Disease

et al. 2021

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“…Neither TNF-α nor IL-6 are related to the KYN/Trp ratio, but TNF-α is associated with the KYN level, indicating inflammatory system activation in diabetic nephropathy. Although Trp and the KYN/Trp ratio were shown to be associated with albuminuria, only the KYN/Trp ratio has been proven to predict response to drugs lowering albuminuria levels in diabetic kidney disease [ 45 ].…”

Section: Kidney Diseasesmentioning

confidence: 99%

“…Additionally, the relationship between KYN and albuminuria, proteinuria and GFR diminished in patients taking these drugs, suggesting their beneficial role in kidney function preservation. The plasma KYN/Trp ratio is also reported to be significantly associated with albuminuria and ARB responsiveness in diabetic kidney disease patients [ 45 ].…”

Section: Kidney Diseasesmentioning

confidence: 99%

Kynurenine pathway in kidney diseases

Zakrocka

Załuska

2021

Pharmacol. Rep

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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.

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“…Tryptophan metabolites are uremic solutes and are AHR ligands, which promote CKD progression ( Table 1 ). In a small study of CKD patients, an increased ratio of the tryptophan metabolite, kynurenine, to tryptophan was associated with macroalbuminuria and responsiveness to AT 1 R blockers (ARBs) ( Wu et al, 2020 ). This study suggests upregulation of the ACE/Ang II/AT 1 R pathway in these individuals.…”

Section: Raas and Ahrmentioning

confidence: 99%

Aryl Hydrocarbon Receptor Mechanisms Affecting Chronic Kidney Disease

Curran

Kopp

2022

Front. Pharmacol.

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The aryl hydrocarbon receptor (AHR) is a basic helix-loop-helix transcription factor that binds diverse endogenous and xenobiotic ligands, which regulate AHR stability, transcriptional activity, and cell signaling. AHR activity is strongly implicated throughout the course of chronic kidney disease (CKD). Many diverse organic molecules bind and activate AHR and these ligands are reported to either promote glomerular and tubular damage or protect against kidney injury. AHR crosstalk with estrogen, peroxisome proliferator-activated receptor-γ, and NF-κB pathways may contribute to the diversity of AHR responses during the various forms and stages of CKD. The roles of AHR in kidney fibrosis, metabolism and the renin angiotensin system are described to offer insight into CKD pathogenesis and therapies.

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Kynurenine/Tryptophan Ratio Predicts Angiotensin Receptor Blocker Responsiveness in Patients with Diabetic Kidney Disease

Cited by 13 publications

References 45 publications

The Kynurenine Pathway in Acute Kidney Injury and Chronic Kidney Disease

The Kynurenine Pathway in Acute Kidney Injury and Chronic Kidney Disease

Kynurenine pathway in kidney diseases

Aryl Hydrocarbon Receptor Mechanisms Affecting Chronic Kidney Disease

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