P-Cresyl Sulfate Is a Valuable Predictor of Clinical Outcomes in Pre-ESRD Patients

Lin, Cheng‐Jui; Pan, Chi-Feng; Chen, Chuang; Sun, Fang‐Ju; Wang, Duen-Jen; Chen, Han‐Hsiang; Liu, Hsuan‐Liang; Wu, Chih‐Jen

doi:10.1155/2014/526932

Cited by 31 publications

(31 citation statements)

References 26 publications

(36 reference statements)

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“…Other non-RCTs also reported that probiotics could change urinary p-cresol excretion and fecal p-cresol composition to some extent [28,29]. A 3-year longitudinal study indicated that a 5μmol/L increase of PCS might be associated with a 17% increased risk of rapid progression to dialysis in pre-dialysis CKD patients [30]. Another study with a larger sample size also supported the positive relationship of PCS and independent cardiovascular events [31].…”

Section: Discussionmentioning

confidence: 89%

Efficacy of Probiotics Supplementation On Chronic Kidney Disease: a Systematic Review and Meta-Analysis

Jia

Yang

et al. 2018

Kidney Blood Press Res

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Background/Aims: Dysbiosis of the intestinal microbiota may accelerate the progression of chronic kidney disease (CKD) by increasing the levels of urea toxins. In recent years, probiotics have been recognized to maintain the physiological balance of the intestinal microbiota. In this study, we aim to assess the therapeutic effects of probiotics on CKD patients with and without dialysis via meta-analysis. Methods: We conducted a meta-analysis of randomized controlled trials (RCTs) by searching the databases of Pubmed, EMBASE and Cochrane Library (No. CRD42018093080). Studies on probiotics for treatment of CKD adults lasting for at least 4 weeks were selected. The primary outcomes were the levels of urea toxins, and the second outcomes were the levels of interleukin (IL)-6, C-reactive protein (CRP) and hemoglobin (Hb). The risk of bias was assessed by Cochrane Collaboration’ tool, and the quality of evidence was appraised with the Grading of Recommendation Assessment. Means and standard deviations were analyzed by random effects analysis. Stratified analysis was done and sensitivity analysis was performed when appropriate. Results: Totally, eight studies with 261 patients at CKD stage 3 to 5 with and without dialysis were included. We found a decrease of p-cresyl sulfate (PCS) of 3 studies with 125 subjects (P = 0.01, SMD -0.57, 95% CI, -0.99 to -0.14, I² = 25%) and an increase of IL-6 in 3 studies with 134 subjects (P = 0.03, 95% CI, SMD 0.37, 0.03 to 0.72, I² = 0%) in the probiotics groups. Analysis of serum creatinine (P = 0.47), blood urine nitrogen (P = 0.73), CRP (P = 0.55) and Hb (P = 0.49) yielded insignificant difference. Conclusion: Limited number of studies and small sample size are limitations of our study. Probiotics supplementation may reduce the levels of PCS and elevate the levels of IL-6 whereby protecting the intestinal epithelial barrier of patients with CKD.

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Section: Discussionmentioning

confidence: 89%

Efficacy of Probiotics Supplementation On Chronic Kidney Disease: a Systematic Review and Meta-Analysis

Jia

Yang

et al. 2018

Kidney Blood Press Res

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“…Although causal relationships between PCS and clinical outcomes are yet to be established, a 3-year longitudinal study in 74 predialysis patients showed that each 5-mmol/L increase in serum PCS was associated with a 12% (95% CI, 1% to 21%) increased risk of a cardiovascular event and a 17% (95% CI, 5% to 30%) increased risk of progressing to dialysis after controlling for eGFR and age (21). These results were supported in a larger cohort (n=499), which showed that free serum PCS was associated with cardiovascular events independent of both eGFR and Framingham risk factors (hazard ratio, 1.39; 95% CI, 1.02 to 1.89) (22).…”

Section: Discussionmentioning

confidence: 99%

Synbiotics Easing Renal Failure by Improving Gut Microbiology (SYNERGY)

Rossi

Johnson

Morrison

et al. 2016

Clinical Journal of the American Society of Nephrology

293

262

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Background and objectives The generation of key uremic nephrovascular toxins, indoxyl sulfate (IS), and p-cresyl sulfate (PCS), is attributed to the dysbiotic gut microbiota in CKD. The aim of our study was to evaluate whether synbiotic (pre-and probiotic) therapy alters the gut microbiota and reduces serum concentrations of microbiome-generated uremic toxins, IS and PCS, in patients with CKD.Design, setting, participants, & measurements Predialysis adult participants with CKD (eGFR=10-30 ml/min per 1.73 m 2 ) were recruited between January 5, 2013 and November 12, 2013 to a randomized, double-blind, placebo-controlled, crossover trial of synbiotic therapy over 6 weeks (4-week washout). The primary outcome was serum IS. Secondary outcomes included serum PCS, stool microbiota profile, eGFR, proteinuria-albuminuria, urinary kidney injury molecule-1, serum inflammatory biomarkers (IL-1b, IL-6, IL-10, and TNF-a), serum oxidative stress biomarkers (F 2 -isoprostanes and glutathione peroxidase), serum LPS, patient-reported health, Gastrointestinal Symptom Score, and dietary intake. A prespecified subgroup analysis explored the effect of antibiotic use on treatment effect.Results Of 37 individuals randomized (age =69610 years old; 57% men; eGFR=2468 ml/min per 1.73 m 2 ), 31 completed the study. Synbiotic therapy did not significantly reduce serum IS (22 mmol/L; 95% confidence interval [95% CI], 25 to 1 mmol/L) but did significantly reduce serum PCS (214 mmol/L; 95% CI, 227 to 22 mmol/L). Decreases in both PCS and IS concentrations were more pronounced in patients who did not receive antibiotics during the study (n=21; serum PCS, 225 mmol/L; 95% CI, 238 to 212 mmol/L; serum IS, 25 mmol/L; 95% CI, 28 to 21 mmol/L). Synbiotics also altered the stool microbiome, particularly with enrichment of Bifidobacterium and depletion of Ruminococcaceae. Except for an increase in albuminuria of 38 mg/24 h (P=0.03) in the synbiotic arm, no changes were observed in the other secondary outcomes. ConclusionIn patients with CKD, synbiotics did not significantly reduce serum IS but did decrease serum PCS and favorably modified the stool microbiome. Large-scale clinical trials are justified.

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“…PCS is a newly identified uremic toxin which has been associated with CKD progression and with cardiovascular disease and mortality risk (Wu et al, ; Lin et al, ; Lin et al, ; Lin et al, ). In the vasculature, PCS has been demonstrated to induce an inflammatory process, mainly by increasing ROS production in endothelial cells and leukocytes (Schepers et al, ; Itoh et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…All available clinical studies on PCS, whether in hemodialysis or in CKD patients not yet on dialysis therapy, reported a strong association with cardiovascular mortality as well as with vascular disease (Wu et al, ; Lin et al, ; Lin et al, ; Lin et al, ).…”

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confidence: 99%

Para‐cresyl sulfate acutely impairs vascular reactivity and induces vascular remodeling

Gross

Massy

Hénaut

et al. 2015

Journal Cellular Physiology

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Chronic kidney disease (CKD) is characterized by vascular remodeling and the retention of uremic toxins, several of which are independently associated with the high cardiovascular mortality rate in CKD patients. Whether the association between these uremic toxins and cardiovascular mortality is due to induction of vascular dysfunction and resulting vascular remodeling remains to be determined. This study evaluates the effects of para-cresyl sulfate (PCS), a newly identified uremic toxin, on vascular function and remodeling. PCS acutely induced oxidative stress in both endothelial and vascular smooth muscle cells, with a maximal effect at 0.15 mM, corresponding to the mean "uremic" concentration found in dialysis patients. PCS significantly increased within 30 min phenylephrine-induced contraction of mouse thoracic aorta, through direct activation of rho-kinase, independently of oxidative stress induction, as demonstrated by the capacity of rho-kinase inhibitor Y-27632 to abolish this effect. After exposure of the aorta to PCS for 48 h, we observed inward eutrophic remodeling, a hallmark of uremic vasculopathy characterized by a reduction of the area of both lumen and media, with unchanged media/lumen ratio. In conclusion, elevated PCS concentrations such as those observed in CKD patients, by promoting both vascular dysfunction and vascular remodeling, may contribute to the development of hypertension and to cardiovascular mortality in CKD.

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P-Cresyl Sulfate Is a Valuable Predictor of Clinical Outcomes in Pre-ESRD Patients

Cited by 31 publications

References 26 publications

Efficacy of Probiotics Supplementation On Chronic Kidney Disease: a Systematic Review and Meta-Analysis

Efficacy of Probiotics Supplementation On Chronic Kidney Disease: a Systematic Review and Meta-Analysis

Synbiotics Easing Renal Failure by Improving Gut Microbiology (SYNERGY)

Para‐cresyl sulfate acutely impairs vascular reactivity and induces vascular remodeling

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