scholarly journals Tryptophan Metabolism in Patients With Chronic Kidney Disease Secondary to Type 2 Diabetes: Relationship to Inflammatory Markers

2017 ◽  
Vol 10 ◽  
pp. 117864691769460 ◽  
Author(s):  
Subrata Debnath ◽  
Chakradhar Velagapudi ◽  
Laney Redus ◽  
Farook Thameem ◽  
Balakuntalam Kasinath ◽  
...  

Objective: Type 2 diabetes (T2D) is the primary case of chronic kidney disease (CKD). Inflammation is associated with metabolic dysregulation in patients with T2D and CKD. Tryptophan (TRP) metabolism may have relevance to the CKD outcomes and associated symptoms. We investigated the relationships of TRP metabolism with inflammatory markers in patients with T2D and CKD. Methods: Data were collected from a well-characterized cohort of type 2 diabetic individuals with all stages of CKD, including patients on hemodialysis. Key TRP metabolites (kynurenine [KYN], kynurenic acid [KYNA], and quinolinic acid [QA]), proinflammatory cytokines (tumor necrosis factor-α [TNF-α] and interleukin-6 [IL-6]), and C-reactive protein were measured in plasma. The KYN/TRP ratio was utilized as a surrogate marker for indoleamine 2,3-dioxygenase 1 (IDO1) enzyme activity. Results: There was a significant inverse association between circulating TRP level and stages of CKD ( P < 0.0001). Downstream bioactive TRP metabolites KYN, KYNA, and QA were positively and robustly correlated with the severity of kidney disease ( P < 0.0001). In multiple linear regression, neither TNF-α nor IL-6 was independently related to KYN/TRP ratio after adjusting for estimated glomerular filtration rate (eGFR). Only TNF-α was independently related to KYN after taking into account the effect of eGFR. Conclusions: Chronic kidney disease secondary to T2D may be associated with accumulation of toxic TRP metabolites due to both inflammation and impaired kidney function. Future longitudinal studies to determine whether the accumulation of KYN directly contributes to CKD progression and associated symptoms in patients with T2D are warranted.

Author(s):  
T. Mazur ◽  
N. Demikhova ◽  
T. Rudenko ◽  
A. Yurchenko ◽  
O. Yezhova ◽  
...  

Chronic inflammation, atherosclerosis, tubulointerstitial fibrosis, and vascular damage play a crucial role in the progression of chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (DM). However, specific biomarkers that can determine the progression of diabetic kidney disease, including patients with minimal albuminuria, remain undefined. The present study aimed to determine markers of chronic inflammation as indicators of CKD progression in patients with type 2 DM. Methods. 45 patients with type 2 DM and stage 1-3 CKD were involved in this cross-sectional observational study. Analysis of cellular mechanisms of CKD progression was performed on the concentrations of endothelin-1 (ET-1), fibronectin (FN), tumor necrosis factor-alpha (TNF-α), transforming growth factor beta-1 (TGF-β1), and monocyte chemoattractant protein (MCP) -1) in the serum. Results. In patients with type 2 DM, an increasing trend in the majority of endothelial and proinflammatory mediators was found according to the CKD stages despite normal albuminuria. Conclusions. Concentrations of TNF-α, ET, TGF-β1 and MCP-1 can be used to assess the progression of CKD in patients with type 2 DM with normal albuminuria. Further researches are needed to determine early indicators of diabetic kidney disease progression.


2016 ◽  
Vol 252 ◽  
pp. e143-e144
Author(s):  
O. Vikulova ◽  
N. Lebedeva ◽  
A. Zheleznyakova ◽  
A. Nikitin ◽  
M. Shamkhalova ◽  
...  

Author(s):  
Jiwoon Kim ◽  
Ji Sun Nam ◽  
Heejung Kim ◽  
Hye Sun Lee ◽  
Jung Eun Lee

Abstract. Background/Aims: Trials on the effects of cholecalciferol supplementation in type 2 diabetes with chronic kidney disease patients were underexplored. Therefore, the aim of this study was to investigate the effects of two different doses of vitamin D supplementation on serum 25-hydroxyvitamin D [25(OH)D] concentrations and metabolic parameters in vitamin D-deficient Korean diabetes patients with chronic kidney disease. Methods: 92 patients completed this study: the placebo group (A, n = 33), the oral cholecalciferol 1,000 IU/day group (B, n = 34), or the single 200,000 IU injection group (C, n = 25, equivalent to 2,000 IU/day). 52% of the patients had less than 60 mL/min/1.73m2 of glomerular filtration rates. Laboratory test and pulse wave velocity were performed before and after supplementation. Results: After 12 weeks, serum 25(OH)D concentrations of the patients who received vitamin D supplementation were significantly increased (A, -2.4 ± 1.2 ng/mL vs. B, 10.7 ± 1.2 ng/mL vs. C, 14.6 ± 1.7 ng/mL; p < 0.001). In addition, the lipid profiles in the vitamin D injection group (C) showed a significant decrease in triglyceride and a rise in HDL cholesterol. However, the other parameters showed no differences. Conclusions: Our data indicated that two different doses and routes of vitamin D administration significantly and safely increased serum 25(OH)D concentrations in vitamin D-deficient diabetes patients with comorbid chronic kidney disease. In the group that received the higher vitamin D dose, the lipid profiles showed significant improvement, but there were no beneficial effects on other metabolic parameters.


Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1066-P ◽  
Author(s):  
KATHERINE R. TUTTLE ◽  
MARK LAKSHMANAN ◽  
BRIAN L. RAYNER ◽  
ROBERT S. BUSCH ◽  
ALAN G. ZIMMERMANN ◽  
...  

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 536-P
Author(s):  
MICHAEL BLANKENBURG ◽  
CSABA P. KOVESDY ◽  
SELINE EISENRING ◽  
ANNE FETT ◽  
EMILE W. SCHOKKER ◽  
...  

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 233-OR
Author(s):  
KATHERINE R. TUTTLE ◽  
BRIAN L. RAYNER ◽  
MARK LAKSHMANAN ◽  
BRAD WOODWARD ◽  
ANITA KWAN ◽  
...  

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