Indoxyl sulfate and high-density lipoprotein cholesterol in early stages of chronic kidney disease

Wang, Li; Fei, Xiang; Ji, Jun; Ding, Xiaoqiang; Shen, Bo; Chen, Jing; Chen, Yunqin; Xue, Ning; Zhang, Lin; Jiang, Xiaotian; Cao, Xuesen

doi:10.1080/0886022x.2020.1845731

Cited by 5 publications

(5 citation statements)

References 45 publications

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“…Consistent with previous reports, the study found that PD patients with higher serum tIS concentrations exhibited a higher prevalence of conditions typically associated with cardiovascular risk, such as older age, diabetes, elevated diastolic blood pressure, and low HDL cholesterol [6, 10,33,34]. These patients also encountered well-recognized complications in PD, which have the potential to contribute to technique failure.…”

Section: Discussionsupporting

confidence: 89%

Association between serum total indoxyl sulfate, intraperitoneal inflammation, and peritoneal dialysis technique failure: a 3-year prospective cohort study

Stepanova,

Driianska,

Korol

et al. 2024

Preprint

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Background The impact of protein-bound uremic toxins, specifically indoxyl sulfate (IS) on peritoneal dialysis (PD) complications remains controversial. This study aimed to explore the link between serum total IS (tIS) levels, proinflammatory cytokines in serum and peritoneal dialysate effluent (PDE), and PD techniques survival. Methods In this prospective cohort study, 84 patients were followed up for three years and analyzed. Stratification into Low tIS (< 22.6 µmol/L) and High tIS (≥ 22.6 µmol/L) groups was based on the median serum tIS concentration. Logistic regression, Kaplan-Meier, receiving operation characteristic, and Cox regression analyses assessed associations between tIS levels, cytokine concentrations (IL-6, MCP-1, TNF-α), and PD technique failure. Results The High tIS group exhibited poor clinical characteristics compared with the Low-tIS group. Elevated tIS levels significantly correlated with higher PDE cytokine levels, without a corresponding rise in serum cytokine levels. Serum tIS levels ≥ 50 µmol/L predicted PD technique failure with 70.4% sensitivity and 87.9% specificity (p < 0.0001). The association between high tIS levels and PD technique failure persisted after adjusting for relevant factors (HR 3.14, 95% CI 1.13; 8.72), but the inclusion of PDE cytokines in the model diminished this association (HR 2.18, 95% CI 0.93; 5.14). Conclusion Our findings underscore the link between elevated tIS levels, peritoneal inflammation, and an increased risk of PD technique failure. Monitoring tIS levels in PD patients may be clinically relevant for risk assessment and personalized management, potentially enhancing long-term PD outcomes. Future research could explore interventions targeting tIS reduction to alleviate peritoneal inflammation and improve PD prognosis.

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Section: Discussionsupporting

confidence: 89%

Association between serum total indoxyl sulfate, intraperitoneal inflammation, and peritoneal dialysis technique failure: a 3-year prospective cohort study

Stepanova,

Driianska,

Korol

et al. 2024

Preprint

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“…Furthermore, our results revealed a significant inverse association between total fecal ODA and tIS levels. tIS is a gut-derived uremic toxin that accumulates in patients with kidney failure due to impaired renal clearance [44,45]. Elevated tIS levels have been associated with adverse cardiovascular outcomes, including increased risk of CVD and mortality in patients with kidney failure [46,47].…”

Section: Discussionmentioning

confidence: 99%

Gut Microbiota’s Oxalate-Degrading Activity and Its Implications on Cardiovascular Health in Patients with Kidney Failure: A Pilot Prospective Study

Stepanova,

Tolstanova,

Aleksandrova

et al. 2023

Medicina

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Background and Objectives: The present study aims to investigate the association between gut microbiota’s oxalate-degrading activity (ODA) and the risk of developing cardiovascular disease (CVD) over a three-year follow-up period in a cohort of patients undergoing kidney replacement therapy (KRT). Additionally, various factors were examined to gain insight into the potential mechanisms underlying the ODA–CVD link. Materials and Methods: A cohort of 32 KRT patients and 18 healthy volunteers was enrolled in this prospective observational pilot study. Total fecal ODA, routine clinical data, plasma oxalic acid (POx), serum indoxyl sulfate, lipid profile, oxidative stress, and proinflammatory markers were measured, and the patients were followed up for three years to assess CVD events. Results: The results revealed that patients with kidney failure exhibited significantly lower total fecal ODA levels compared to the healthy control group (p = 0.017), with a higher proportion showing negative ODA status (≤−1% per 0.01 g) (p = 0.01). Negative total fecal ODA status was associated with a significantly higher risk of CVD events during the three-year follow-up period (HR = 4.1, 95% CI 1.4–16.3, p = 0.003), even after adjusting for potential confounders. Negative total fecal ODA status was significantly associated with elevated POx and indoxyl sulfate levels and linked to dyslipidemia, increased oxidative stress, and inflammation, which are critical contributors to CVD. Conclusions: The findings contribute novel insights into the relationship between gut microbiota’s ODA and cardiovascular health in patients undergoing KRT, emphasizing the need for further research to elucidate underlying mechanisms and explore potential therapeutic implications of targeting gut microbiota’s ODA in this vulnerable population.

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“…Reduced renal function is known to be associated with modification of lipoprotein structure and lipoprotein metabolism disorders [33][34][35]. According to some studies, the progressive loss of renal function is associated with increased concentration of IS and a decreased level of HDL-c [36] and a study by Li Wang et al showed that there is an association between IS and HDL-c levels regardless of renal impairment, i.e., that IS is an independent risk factor for low HDL-c concentrations [37]. A correlating analysis of our results revealed that IS and KYN did not show a significant association with HDL-c values in the participants included in the study.…”

Section: Discussionmentioning

confidence: 99%

Status of tryptophan metabolites in different stages of chronic kidney disease of non-diabetc etiology

et al. 2022

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Introduction. Modification of tryptophan metabolism during the progression of chronic kidney disease may have significant pathophysiological consequences. The aim of this study was to investigate the status of metabolic products of tryptophan, indoxyl sulfate and kynurenine in different stages of chronic kidney disease. Material and Methods. In all participants included in the cross-sectional study (n = 66) with previously diagnosed chronic kidney disease, the parameters of renal function were measured: glomerular filtration rate using radionuclide plasma clearance with 99mTc-labelled diethylene triamine penta-acetate and effective renal plasma flow using 131Ilabeled orthoiodohippuric acid. Plasma concentrations of indoxyl sulfate and kynurenine were measured by high-performance liquid chromatography. Results. A significant difference was observed in the concentrations of both metabolites between the observed groups (Group II - measured glomerular filtration rate - 15 - 60 ml/min/1.73 m?; n = 36 vs. Group I measured glomerular filtration rate > 60 l/ min/1.73 m?; n = 26): indoxyl sulfate 1.07 ? 0.89 vs. 2.44 ? 4.05 ?g/ ml, p < 0.001; kynurenine 3.15 ? 0.22 vs. 3.21 ? 0.17 ?g/ml, p < 0.05. The correlation was statistically significant between glomerular filtration rate and kynurenine - r = -0.38, p = 0.001 and indoxyl sulfate - r = 0.56, p ? 0.001; effective plasma renal flow and kynurenine - r = -0.33, p < 0.05 and indoxyl sulfate - r = 0.46, p ? 0.001. Conclusion. There is a significant difference in the plasma concentrations of indoxyl sulfate and kynurenine in the group of patients with glomerular filtration rate of 15 - 60 ml/min/1.73 m? compared to patients with glomerular filtration rate > 60 ml/min/1.73 m?. In patients with chronic kidney disease, plasma concentrations of both metabolites of tryptophan are inversely correlated with the glomerular filtration rate and effective plasma renal flow.

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Indoxyl sulfate and high-density lipoprotein cholesterol in early stages of chronic kidney disease

Cited by 5 publications

References 45 publications

Association between serum total indoxyl sulfate, intraperitoneal inflammation, and peritoneal dialysis technique failure: a 3-year prospective cohort study

Association between serum total indoxyl sulfate, intraperitoneal inflammation, and peritoneal dialysis technique failure: a 3-year prospective cohort study

Gut Microbiota’s Oxalate-Degrading Activity and Its Implications on Cardiovascular Health in Patients with Kidney Failure: A Pilot Prospective Study

Status of tryptophan metabolites in different stages of chronic kidney disease of non-diabetc etiology

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