Tryptophan levels associate with incident cardiovascular disease in chronic kidney disease
Vetalise C Konje1, Thekkelnaycke M Rajendiran2, Keith Bellovich3
1Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI, USA.
Insights
Low tryptophan levels are linked to a higher risk of developing cardiovascular disease (CVD) in chronic kidney disease (CKD) patients. This finding may help identify individuals at increased risk for CVD.
Area of Science:
- Biochemistry
- Nephrology
- Cardiology
Background:
- Cardiovascular disease (CVD) risk is elevated in chronic kidney disease (CKD) due to factors like inflammation and oxidative stress.
- The kynurenine pathway (KP), involved in tryptophan metabolism, is linked to inflammation and CVD in general and dialysis populations.
- The specific association between KP and incident CVD in CKD patients remains unclear.
Purpose of the Study:
- To investigate the relationship between tryptophan metabolites and incident cardiovascular disease (CVD) in patients with chronic kidney disease (CKD).
- To determine if tryptophan catabolites can serve as predictive biomarkers for CVD in the CKD population.
Main Methods:
- Tryptophan metabolites were quantified using targeted mass spectrometry in three patient groups: established CVD, no CVD with incident CVD, and no CVD.
- Patient groups were matched for key demographics and CKD stage, with differences noted in cholesterol and proteinuria.
- Follow-up was conducted for a median of 2 years to identify incident CVD events.
Main Results:
- Tryptophan and kynurenine levels were significantly lower in patients who developed incident CVD compared to those without CVD or with prior CVD.
- Elevated kynurenic acid, 3-hydroxykynurenine, and kynurenine correlated with worsening CKD stage.
- Higher baseline tryptophan levels were associated with substantially lower odds of developing incident CVD, even after adjusting for traditional risk factors.
- Including tryptophan and kynurenine levels improved the prediction of incident CVD by 8% (AUC from 0.76 to 0.82).
Conclusions:
- This study demonstrates a significant association between low tryptophan levels and the incidence of cardiovascular disease (CVD) in patients with chronic kidney disease (CKD).
- Tryptophan and kynurenine metabolites show potential as biomarkers for predicting CVD risk in the CKD population.
- Further research is warranted to explore the therapeutic implications of modulating the kynurenine pathway in CKD patients to mitigate CVD risk.
Background:
Non-traditional risk factors like inflammation and oxidative stress play an essential role in the increased cardiovascular disease (CVD) risk prevalent in chronic kidney disease (CKD). Tryptophan catabolism by the kynurenine pathway (KP) is linked to systemic inflammation and CVD in the general and dialysis population. However, the relationship of KP to incident CVD in the CKD population is unknown.
Methods:
We measured tryptophan metabolites using targeted mass spectrometry in 92 patients with a history of CVD (old CVD); 46 patients with no history of CVD and new CVD during follow-up (no CVD); and 46 patients with no CVD history who developed CVD in the median follow-up period of 2 years (incident CVD).
Results:
The three groups are well-matched in age, gender, race, diabetes status and CKD stage, and only differed in total cholesterol and proteinuria. Tryptophan and kynurenine levels significantly decreased in patients with 'Incident CVD' compared with the no CVD or old CVD groups (P = 5.2E-7; P = 0.003 respectively). Kynurenic acid, 3-hydroxykynurenine and kynurenine are all increased with worsening CKD stage (P < 0.05). An increase in tryptophan levels at baseline was associated with 0.32-fold lower odds of incident CVD (P = 0.000014) compared with the no CVD group even after adjustment for classic CVD risk factors. Addition of tryptophan and kynurenine levels to the receiver operating curve constructed from discriminant analysis predicting incident CVD using baseline clinical variables increased the area under the curve from 0.76 to 0.82 (P = 0.04).
Conclusions:
In summary, our study demonstrates that low tryptophan levels are associated with incident CVD in CKD.
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