Endothelial dysfunction and low-grade inflammation in the transition to renal replacement therapy

Gennip, April C.E. van; Broers, Natascha J. H.; Meulen, Karlien J. ter; Canaud, Bernard; Christiaans, Maarten H. L.; Cornelis, T.; Gelens, M.; Hermans, Marc; Konings, Constantijn; Net, Jeroen B. van der; Sande, Frank M. van der; Schalkwijk, Casper G.; Stifft, Frank; Wirtz, Joris J. J. M.; Kooman, Jeroen P.; Martens, Remy J H

doi:10.1371/journal.pone.0222547

Cited by 19 publications

(16 citation statements)

References 43 publications

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“…Vorm et al showed increased von Willebrand factor levels, another indicator of endothelium impairment in CKD and ESRD patients [ 52 ]. The gathered observation remains in line with the inference made by Gennip et al, who reported increased serum levels of endothelial dysfunction biomarkers in ESRD as compared with controls [ 53 ]. Altogether, these reports lead one to the conclusion that changes occurring in CKD are responsible for worsening the vascular condition and can lead to atherosclerosis development.…”

Section: Oxidative Stress (Os) and Reactive Oxygen Species (Ros) Isupporting

confidence: 91%

Oxidative Storm Induced by Tryptophan Metabolites: Missing Link between Atherosclerosis and Chronic Kidney Disease

Kwiatkowska

Hermanowicz

Myśliwiec

et al. 2020

Oxidative Medicine and Cellular Longevity

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Chronic kidney disease (CKD) occurrence is rising all over the world. Its presence is associated with an increased risk of premature death from cardiovascular disease (CVD). Several explanations of this link have been put forward. It is known that in renal failure, an array of metabolites cannot be excreted, and they accumulate in the organism. Among them, some are metabolites of tryptophan (TRP), such as indoxyl sulfate and kynurenine. Scientists have become interested in them in the context of inducing vascular damage in the course of chronic kidney impairment. Experimental evidence suggests the involvement of TRP metabolites in the progression of chronic kidney disease and atherosclerosis separately and point to oxidative stress generation as one of the main mechanisms that is responsible for worsening those states. Since it is known that blood levels of those metabolites increase significantly in renal failure and that they generate reactive oxygen species (ROS), which lead to endothelial injury, it is reasonable to suspect that products of TRP metabolism are the missing link in frequently occurring atherosclerosis in CKD patients. This review focuses on reports that shed a light on TRP metabolites as contributing factors to vascular damage in the progression of impaired kidney function.

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Section: Oxidative Stress (Os) and Reactive Oxygen Species (Ros) Isupporting

confidence: 91%

Oxidative Storm Induced by Tryptophan Metabolites: Missing Link between Atherosclerosis and Chronic Kidney Disease

Kwiatkowska

Hermanowicz

Myśliwiec

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…It should be taken into account that while kidney transplantation aims to restore kidney function, it incompletely abrogates mechanisms of disease. Moreover, an aggregate of factors specific to the transplant milieu such as a chronic low-grade immunologic response to the kidney allograft, long-term toxicity of maintenance immunosuppressive, as well as various degrees of progressive uremia, contribute to perpetuate chronic inflammation, redox imbalance, and deregulated mineral and bone metabolism, which have to be proposed as major independent and evolving pathophysiological mechanisms, whose mitigation may counterbalance-at least to a considerable extent-the excess risk of cardiovascular disease and graft failure post-kidney transplantation [30,32,101,103,104]. Below, we provide several examples of where opportunities may lie.…”

Section: Inflammation and Oxidative Stress And Vascular Calcificationmentioning

confidence: 99%

Lifestyle, Inflammation, and Vascular Calcification in Kidney Transplant Recipients: Perspectives on Long-Term Outcomes

Sotomayor

Velde-Keyzer

Borst

et al. 2020

JCM

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After decades of pioneering and improvement, kidney transplantation is now the renal replacement therapy of choice for most patients with end-stage kidney disease (ESKD). Where focus has traditionally been on surgical techniques and immunosuppressive treatment with prevention of rejection and infection in relation to short-term outcomes, nowadays, so many people are long-living with a transplanted kidney that lifestyle, including diet and exposure to toxic contaminants, also becomes of importance for the kidney transplantation field. Beyond hazards of immunological nature, a systematic assessment of potentially modifiable—yet rather overlooked—risk factors for late graft failure and excess cardiovascular risk may reveal novel targets for clinical intervention to optimize long-term health and downturn current rates of premature death of kidney transplant recipients (KTR). It should also be realized that while kidney transplantation aims to restore kidney function, it incompletely mitigates mechanisms of disease such as chronic low-grade inflammation with persistent redox imbalance and deregulated mineral and bone metabolism. While the vicious circle between inflammation and oxidative stress as common final pathway of a multitude of insults plays an established pathological role in native chronic kidney disease, its characterization post-kidney transplant remains less than satisfactory. Next to chronic inflammatory status, markedly accelerated vascular calcification persists after kidney transplantation and is likewise suggested a major independent mechanism, whose mitigation may counterbalance the excess risk of cardiovascular disease post-kidney transplant. Hereby, we first discuss modifiable dietary elements and toxic environmental contaminants that may explain increased risk of cardiovascular mortality and late graft failure in KTR. Next, we specify laboratory and clinical readouts, with a postulated role within persisting mechanisms of disease post-kidney transplantation (i.e., inflammation and redox imbalance and vascular calcification), as potential non-traditional risk factors for adverse long-term outcomes in KTR. Reflection on these current research opportunities is warranted among the research and clinical kidney transplantation community.

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“…Levels of VCAM-1 and ICAM-1 increase in parallel with the progression to CKD to ESKD [123]. Therefore, patients undergoing hemodialysis have elevated levels of VCAM-1 that are not affected by the dialysis procedure; patients undergoing peritoneal dialysis have also higher levels of VCAM-1 and ICAM-1 compared to controls and hemodialysis subjects [124, 125].…”

Section: Assessment Of Endothelial Dysfunction In Ckd: Biochemical Mamentioning

confidence: 99%

Assessment of Endothelial and Microvascular Function in CKD: Older and Newer Techniques, Associated Risk Factors, and Relations with Outcomes

Theodorakopoulou

Schoina

Sarafidis³

2020

Am J Nephrol

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Background: Endothelium is the inner cellular lining of the vessels that modulates multiple biological processes including vasomotor tone, permeability, inflammatory responses, hemostasis, and angiogenesis. Endothelial dysfunction, the basis of atherosclerosis, is characterized by an imbalance between endothelium-derived relaxing factors and endothelium-derived contracting factors. Summary: Starting from the semi-invasive venous occlusion plethysmography, several functional techniques have been developed to evaluate microvascular function and subsequently used in patients with CKD. Flow-mediated dilatation of the forearm is considered to be the “gold standard,” while in the last years, novel, noninvasive methods such as laser speckle contrast imaging and near-infrared spectroscopy are scarcely used. Moreover, several circulating biomarkers of endothelial function have been used in studies in CKD patients. This review summarizes available functional methods and biochemical markers for the assessment of endothelial and microvascular function in CKD and discusses existing evidence on their associations with comorbid conditions and outcomes in this population. Key Messages: Accumulated evidence suggests that endothelial dysfunction occurs early in CKD and is associated with target organ damage, progression of renal injury, cardiovascular events, and mortality. Novel methods evaluating microvascular function can offer a detailed, real-time assessment of underlying phenomena and should be increasingly used to shed more light on the role of endothelial dysfunction on cardiovascular and renal disease progression in CKD.

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Endothelial dysfunction and low-grade inflammation in the transition to renal replacement therapy

Cited by 19 publications

References 43 publications

Oxidative Storm Induced by Tryptophan Metabolites: Missing Link between Atherosclerosis and Chronic Kidney Disease

Oxidative Storm Induced by Tryptophan Metabolites: Missing Link between Atherosclerosis and Chronic Kidney Disease

Lifestyle, Inflammation, and Vascular Calcification in Kidney Transplant Recipients: Perspectives on Long-Term Outcomes

Assessment of Endothelial and Microvascular Function in CKD: Older and Newer Techniques, Associated Risk Factors, and Relations with Outcomes

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