p-Cresol sulfate and indoxyl sulfate induce similar cellular inflammatory gene expressions in cultured proximal renal tubular cells

Sun, Chaomin; Hsu, Hsiang Hao; Wu, Mai-Szu

doi:10.1093/ndt/gfs133

Cited by 154 publications

(131 citation statements)

References 35 publications

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“…The following cell and organ systems were investigated (n of each study is in parentheses) ( Table 2): renal tubules (9), 34,[36][37][38][39]43,45,47,50 endothelium (6), [26][27][28][29][30]33 leukocytes (2), 30,31 whole vessels (2), 40,41 whole kidney (2), 40,42 cardiac cells (2), 35,49 smooth muscle cells (2), 46,51 hepatocytes (2), 32,51 intestinal cells (1), 48 and adipocytes (1). 44 A few studies concentrated on more than one target system: one study was on both the whole vessel and kidney 40 and one study was on leukocyte-endothelial interaction.…”

Section: Resultsmentioning

confidence: 99%

The Uremic Toxicity of Indoxyl Sulfate and p-Cresyl Sulfate

Vanholder

Schepers

Pletinck

et al. 2014

Journal of the American Society of Nephrology

577

463

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A growing number of publications supports a biologic effect of the protein-bound uremic retention solutes indoxyl sulfate and p-cresyl sulfate. However, the use of unrealistically high free concentrations of these compounds and/or inappropriately low albumin concentrations may blur the interpretation of these results. Here, we performed a systematic review, selecting only studies in which, depending on the albumin concentration, real or extrapolated free concentrations of indoxyl sulfate and p-cresyl sulfate remained in the uremic range. The 27 studies retrieved comprised in vitro and animal studies. A quality score was developed, giving 1 point for each of the following criteria: six or more experiments, confirmation by more than one experimental approach, neutralization of the biologic effect by counteractive reagents or antibodies, use of a real-life model, and use of dose-response analyses in vitro and/or animal studies. The overall average score was 3 of 5 points, with five studies scoring 5 of 5 points and six studies scoring 4 of 5 points, highlighting the superior quality of a substantial number of the retrieved studies. In the 11 highest scoring studies, most functional deteriorations were related to uremic cardiovascular disease and kidney damage. We conclude that our systematic approach allowed the retrieval of methodologically correct studies unbiased by erroneous conditions related to albumin binding. Our data seem to confirm the toxicity of indoxyl sulfate and p-cresyl sulfate and support their roles in vascular and renal disease progression.

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Section: Resultsmentioning

confidence: 99%

The Uremic Toxicity of Indoxyl Sulfate and p-Cresyl Sulfate

Vanholder

Schepers

Pletinck

et al. 2014

Journal of the American Society of Nephrology

577

463

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“…Impaired function of the intestinal mucosal barrier and fluid overload in the early stages of kidney disease are thought to be directly responsible for the translocation of both intact bacteria and their fragments or bacterial bioproducts across the intestinal mucosal barrier into the circulation. The bacteria and their products affect the activation of the innate immune system which explains the persistence of systemic inflammation in the course of CKD [13,14,17,[27][28][29][30][31].…”

Section: Uremic Compounds and Function Of The Intestinal Mucosal Barriermentioning

confidence: 99%

Role of Uremic Compounds in Organ Injury

Falaschi¹,

Fenoglio²,

Dellagiovanna³

et al. 2014

J Nephrol Ther

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“…When renal function is impaired, waste Cardiac fibrosis in vivo 147,148 Increased cardiac oxidative stress 148 Functional impairment 116,133,134 Renal inflammation with increased proinflammatory cytokine gene expression 135,137 Glomerulosclerosis and renal interstitial fibrosis with activation of profibrotic gene and protein expression 116,133,134,136,170 Enhancing renal oxidative stress, both in vitro and in vivo 64 including 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid, 2-methoxyresorcinol, p-OHhippuric acid, other indoles (kinurenine, kynurenic acid, quinolinic acid, and melatonin), advanced glycation end products (3-deoxyglucosone, fructoselysine, glyoxal, methylglyoxal, N ε -(carboxymethyl)lysine, and pentosidine), polyamines (putrescine, spermidine, and spermine), and peptides (leptin and retinol-binding protein).…”

Section: Uremic Toxinsmentioning

confidence: 99%

“…A recent study has supported this pathway by showing that IS can activate genes regulating inflammatory and profibrotic processes, such as IL-6 and TGF-β1, in renal proximal tubular cells. 137 IS may be implicated in the renal imbalance of NO and ROS in CKD. The net effect is in favor of ROS predominance that is linked to renal vasoconstriction, abnormal sodium and water handling, abnormal glomerular filtration and tubular function, and systemic hypertension.…”

Section: Kidneymentioning

confidence: 99%

Cardiorenal Syndrome

Lekawanvijit

Kompa

Wang

et al. 2012

Circulation Research

152

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Cardiorenal syndrome is a condition in which a complex interrelationship between cardiac dysfunction and renal dysfunction exists. Despite advances in treatment of both cardiovascular and kidney disease, cardiorenal syndrome remains a major global health problem. Characteristic of the pathophysiology of cardiorenal syndrome is bidirectional cross-talk; mediators/substances activated by the disease state of 1 organ can play a role in worsening dysfunction of the other by exerting their biologically harmful effects, leading to the progression of the syndrome. Accumulation of uremic toxins is a hallmark of renal excretory dysfunction. Removal of some toxins by conventional dialysis is particularly problematic because of their high protein binding. In this review, we demonstrate that protein-bound uremic toxins may play an important role in progression of cardiovascular disease in the setting of chronic kidney disease. The highly protein-bound uremic toxin indoxyl sulfate has emerged as a potent toxin adversely affecting both the kidney and heart. Direct cardiac effects of this toxin have been recently demonstrated both in vitro and in vivo. Specifically, potent fibrogenic and prohypertrophic effects, as well as oxidative stress-inducing effects, appear to play a central role in both renal and cardiac pathology. Many of these adverse effects can be suppressed by use of a gut adsorbent, AST-120. Potential mechanisms underlying indoxyl sulfate−induced cardiorenal fibrosis are discussed. Future research and clinical implications conclude this review.

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p-Cresol sulfate and indoxyl sulfate induce similar cellular inflammatory gene expressions in cultured proximal renal tubular cells

Abstract: PCS and IS stimulate significant cellular inflammation. Similar immune and cellular inflammatory responses were induced by PCS or IS on cultured proximal renal tubular cells.

Cited by 154 publications

References 35 publications

The Uremic Toxicity of Indoxyl Sulfate and p-Cresyl Sulfate

The Uremic Toxicity of Indoxyl Sulfate and p-Cresyl Sulfate

Role of Uremic Compounds in Organ Injury

Cardiorenal Syndrome

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