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. 2018 Sep 23;10(10):384.
doi: 10.3390/toxins10100384.

The Impact of Uremic Toxicity Induced Inflammatory Response on the Cardiovascular Burden in Chronic Kidney Disease

Ligia Maria Claro  1 , Andrea N Moreno-Amaral  2 , Ana Carolina Gadotti  3 , Carla J Dolenga  4 , Lia S Nakao  5 , Marina L V Azevedo  6 , Lucia de Noronha  7 , Marcia Olandoski  8 , Thyago P de Moraes  9 , Andréa E M Stinghen  10 , Roberto Pécoits-Filho  11
Affiliations

The Impact of Uremic Toxicity Induced Inflammatory Response on the Cardiovascular Burden in Chronic Kidney Disease

Ligia Maria Claro et al. Toxins (Basel). .

Abstract

Uremic toxin (UT) retention in chronic kidney disease (CKD) affects biological systems. We aimed to identify the associations between UT, inflammatory biomarkers and biomarkers of the uremic cardiovascular response (BUCVR) and their impact on cardiovascular status as well as their roles as predictors of outcome in CKD patients. CKD patients stages 3, 4 and 5 (n = 67) were recruited and UT (indoxyl sulfate/IS, p-cresil sulfate/pCS and indole-3-acetic acid/IAA); inflammatory biomarkers [Interleukin-6 (IL-6), high sensitivity C reactive protein (hsCRP), monocyte chemoattractant protein-1 (MCP-1), soluble vascular adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble Fas (sFas)] and BUCVRs [soluble CD36 (sCD36), soluble receptor for advanced glycation end products (sRAGE), fractalkine] was measured. Patients were followed for 5.2 years and all causes of death was used as the primary outcome. Artery segments collected at the moment of transplantation were used for the immunohistochemistry analysis in a separate cohort. Estimated glomerular filtration rate (eGFR), circulating UT, plasma biomarkers of systemic and vascular inflammation and BUCVR were strongly interrelated. Patients with plaque presented higher signs of UT-induced inflammation and arteries from CKD patients presented higher fractalkine receptor (CX3CR1) tissue expression. Circulating IS (p = 0.03), pCS (p = 0.007), IL-6 (p = 0.026), sFas (p = 0.001), sCD36 (p = 0.01) and fractalkine (p = 0.02) were independent predictors of total mortality risk in CKD patients. Our results reinforce the important role of uremic toxicity in the pathogenesis of cardiovascular disease (CVD) in CKD patients through an inflammatory pathway.

Keywords: fractalkine (CX3CL1); fractalkine receptor (CX3CR1); inflammatory biomarkers; sCD36; sRAGE; uremic toxins.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The scatter plots (a–c) show the relationship between the concentrations of UTs and glomerular filtration rate (GFR) in CKD patients in pre-dialysis. Similarly, the scatter plots (d–f) show the correlation with biomarkers of the uremic cardiovascular response and GFR.
Figure 2
Figure 2
(A) Graph with the total percentage (%) of tissue expression of fractalkine receptor (CX3CR1) by immunohistochemistry (IHC). * p = 0.002, significant difference between donor and CKD receptor tissue expression of CX3CR1; t Student (p < 0.05). Demonstrative images showing the negative (B) and immunopositivity (C) (red arrow) tissue expression of CX3CR1 for medium power field (200×), in the renal arteries.
Figure 3
Figure 3
Cox regression univariate analysis for evaluating the relationship between independent co-variables and clinical outcomes in CKD patients of the study.
Figure 4
Figure 4
Flow chart of the study.
See this image and copyright information in PMC

References

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