Indoxyl sulfate, a uremic trigger for platelets

Díaz‐Ricart, Maribel

doi:10.1182/blood-2017-03-773218

Cited by 3 publications

(4 citation statements)

References 7 publications

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“…This hyperactivity is caused by uremic toxins and inflammatory reactions that have activating effects on platelets, placing CKD patients at a higher risk of thrombosis than people with normal kidney function. 4 , 5 Thus, for these patients, EPO therapy with its effect on platelet activation might not be a good choice.…”

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confidence: 99%

Roxadustat Does Not Affect Platelet Production, Activation, and Thrombosis Formation

Zhao

Xie

et al. 2021

ATVB

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Objective: Roxadustat is a new medication for the treatment of renal anemia. EPO (erythropoietin)—the current treatment standard—has been reported to enhance platelet activation and production. However, to date, the effect of roxadustat on platelets is unclear. To address this deficiency, herein, we have evaluated the effect of roxadustat on platelet production and function. Approach and Results: We performed several mouse platelet functional assays in the presence/absence of in vitro and in vivo roxadustat treatment. Both healthy and 5/6 nephrectomized mice were utilized. The effect of roxadustat on platelet function of healthy volunteers and chronic kidney disease patients was also evaluated. For platelet production, megakaryocyte maturation and proplatelet formation were assayed in vitro. Peripheral platelet and bone marrow megakaryocyte counts were also determined. We found that roxadustat could not stimulate washed platelets directly, and platelet aggregation, spreading, clot retraction, and P-selectin/JON/A exposure were similar with or without in vitro or in vivo roxadustat treatment among both healthy and 5/6 nephrectomized mice. In vivo mouse thrombosis models were additionally performed, and no differences were detected between the vehicle and roxadustat treatment groups. EPO, which was considered a positive control in the present study, promoted platelet function and production as reported previously. Megakaryocyte maturation and proplatelet formation were also not significantly different between control mice and those treated with roxadustat. After receiving roxadustat for 14 days, no difference in the peripheral platelet count was observed in the mice. Conclusions: Administration of roxadustat has no significant impact on platelet production and function.

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confidence: 99%

Roxadustat Does Not Affect Platelet Production, Activation, and Thrombosis Formation

Zhao

Xie

et al. 2021

ATVB

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“…Indoxyl sulfate is a protein-bound uremic toxin derived from the amino acid tryptophan and is produced by intestinal bacteria. 16 Indoxyl sulfate has been shown to promote platelet hyper-reactivity as demonstrated by an enhanced response to platelet agonists thrombin and collagen, increased P-selectin expression and release of platelet microparticles. 16 The platelet hyper-reactivity induced by indoxyl sulfate has been shown to induce thrombosis in a mouse model.…”

Section: Discussionmentioning

confidence: 99%

“…16 Indoxyl sulfate has been shown to promote platelet hyper-reactivity as demonstrated by an enhanced response to platelet agonists thrombin and collagen, increased P-selectin expression and release of platelet microparticles. 16 The platelet hyper-reactivity induced by indoxyl sulfate has been shown to induce thrombosis in a mouse model. 17 Thromboembolism itself has a two-fold greater risk in patients with advanced kidney disease and is a common complication for patients on dialysis.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of platelet function in cats with and without kidney disease: a pilot study

Benson

Quimby

Shropshire

et al. 2020

Journal of Feline Medicine and Surgery

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Objectives The aims of this study were to determine if stable chronic kidney disease (CKD) cats and uremic crisis cats have altered platelet function, and to determine the prevalence of positive fecal occult blood in CKD cats. Methods Platelet function in normal cats, clinically stable International Renal Interest Society (IRIS) stage 2–4 CKD cats and CKD cats experiencing a uremic crisis were evaluated using impedance aggregometry. Area under the curve (AUC) at 6 mins was calculated for saline, adenosine diphosphate (AUCADP) and arachidonic acid (AUCASPI). The AUC in addition to hematocrit, platelet count and mean platelet volume (MPV) were compared between groups using the Kruskal–Wallis test followed by Dunn’s post-hoc analysis. Guaiac fecal occult blood tests were performed on fecal samples and results were compared between groups using a χ2 for trend test. Results AUCADP ( P = 0.04) and AUCASPI ( P = 0.05) were significantly higher in uremic crisis cats compared with normal cats at 6 mins. Hematocrit was significantly higher in normal cats when compared with IRIS stage 3 and 4 ( P = 0.002) and uremic crisis ( P = 0.0008) cats, with no difference among groups for platelet count or MPV. The proportion of cats with positive fecal occult blood samples was significantly different between groups ( P = 0.0017); 50% uremic crisis cats, 33% IRIS stage 3 and 4 cats, and 10% IRIS stage 2 cats were positive, while no normal cats were positive. The proportion of cats with platelet clumping was significantly different between groups ( P = 0.03). Conclusions and relevance Platelet hyper-reactivity may be occurring in CKD cats experiencing a uremic crisis. The etiology of positive fecal occult blood samples in CKD cats is unclear and did not appear to be related to decreased platelet function as measured in this study and requires further investigation.

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“…If they are not detected and treated in a timely manner, it will inevitably lead to death. Indoxyl sulfate (IS), as a typical protein binding uremic toxin in serum, is considered an important marker for predicting CKD. , Therefore, reliable and early detection of IS is an effective strategy to reduce the incidence of CKD. Long-term use of metformin in diabetes patients will affect the absorption of vitamin B12, which plays a role in protecting the nervous system.…”

Section: Introductionmentioning

confidence: 99%

Portable, Intelligent Fluorescence Sensing Platform for Dense Convolutional Network-Capable Detection of Indophenol Sulfate and Methylmalonic Acid Using a Luminescent Eu@HOF Film

Hu,

Yan

2023

ACS Sens.

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Indophenol sulfate (IS) and methylmalonic acid (MMA) are biomarkers of chronic kidney disease (CKD) and diabetes polyneuropathy (DPN), respectively. Portable and accurate monitoring of IS and MMA is very important to ensuring human health. The dense convolutional network (DenseNet) with image recognition has great potential in fluorescence sensing, but developing a platform with high precision and portability to diagnose the disease still faces huge challenges. Herein, we developed a high-sensitivity platform with a fluorescence material, a smartphone, and the DenseNet to monitor IS and MMA. A redemitting Eu@PFC-13 (1) is prepared, and 1 shows high selectivity and low detection limits (DLs) to detect IS and MMA. The sensing mechanism of 1 toward IS and MMA is investigated by experiments and theoretical calculation. For detecting IS and MMA in serum and urine, 1 is fabricated into an Eu@PFC-13/AG (2) film with DLs of 1.4 and 1.6 μM, respectively. In addition, a portable smartphone platform is designed to monitor IS and MMA with high precision. Moreover, the DenseNet is constructed by Python, which can output the concentration of analytes by identifying fluorescence images and judge whether any is in a dangerous range. This work not only proposes a novel method that integrates a fluorescence material, a smartphone, and deep learning to detect analytes but also opens a new way for the diagnosis of CKD and DPN.

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Indoxyl sulfate, a uremic trigger for platelets

Cited by 3 publications

References 7 publications

Roxadustat Does Not Affect Platelet Production, Activation, and Thrombosis Formation

Roxadustat Does Not Affect Platelet Production, Activation, and Thrombosis Formation

Evaluation of platelet function in cats with and without kidney disease: a pilot study

Portable, Intelligent Fluorescence Sensing Platform for Dense Convolutional Network-Capable Detection of Indophenol Sulfate and Methylmalonic Acid Using a Luminescent Eu@HOF Film

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