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The Association between Serum Indoxyl Sulfate, P-Cresyl Sulfate and Cardiovascular Risk Factors in Peritoneal Dialysis Patients

Abstract

Aschalew Fikru Hiruy1, Qianqian Xiong1, Xiaolei Guo1, Li Li1, Qiman Jin1, Jing Zhao1, Xuechun Lin1, Shuiqing He1, Chenjiang Ying1,3, and Xuezhi Zuo2*

Background: Indoxyl Sulfate (IS) and p-Cresol Sulfate (pCS) are two important gut-derived uremic toxins accumulated in patients with Chronic Kidney Disease (CKD). They have been reported contributing greatly to Cardiovascular Disease (CVD) both in epidemiological studies and animal models. The present study was conducted to explore whether IS and pCS contribute to CVD by accelerating cardiovascular risk factors in Peritoneal Dialysis (PD) patients.

Methods: A cross-sectional study was conducted on 119 PD patients. Serum IS and pCS were measured by Ultra-High-Performance LC–tandem MS (UPLCMS/ MS), and metabolic parameters involved in cardiovascular risk were measured by auto-biochemistry analyzer machine. Univariate and multivariate linear regression models were performed to determine the association between the independent variables (IS and pCS) and clinical indexes. Multivariable-adjusted logistic regression models were used to estimate the odds ratios (ORs, 95% confidence intervals (CIs)).

Results: The median BMI of PD patients was 20.10 (18.95, 22.90) kg/m2. The median serum IS and pCS concentrations were 22.46 (13.45, 29.92) mg/L and 12.41 (5.29, 24.45) mg/L, respectively. Positive significant associations were observed between serum IS concentration and PD duration, creatinine, prealbumin, phosphorus, magnesium and β2-microglobulin (β2-m) with the corresponding correlation coefficient r and p value of 0.22 (P=0.020), 0.48 (P<0.001), 0.32 (P<0.001), 0.34 (P<0.001), 0.28 (P=0.002), 0.50 (P<0.001). Also, statistically negative significant associations were observed between IS and estimated Glomerular Filtration Rate (eGFR)-0.46 (P<0.001). Besides, a significant positive association between pCS and albumin 0.32 (P<0.001) was indicated.

Conclusions: Serum clinical indexes were dependent cardiovascular risk factors for increasing IS and pCS levels, which contribute to CVD in peritoneal dialysis patients. Mechanism research should be conducted in the future to explore causality.

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