| Objective Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are belong to protein-bound uremic toxins which are related to progression of CKD and complications of ESRD. The present study aims to (1) establish analytical methods for plasma IS and PCS and (2) identify related factors for plasma IS and PCS in maintenance hemodialysis (MHD) patients. The relationships between IS, PCS and complications in MHD as well as factors which have potential impact on plasma IS and PCS are demonstrated.Methods Patients who had been on hemodialysis treatment for at least 6 months and aged≥18 years were enrolled. The clinical data were collected. Plasma was sampled just before and end of hemodialysis treatment. Plasma IS and PCS were detected using high-performance liquid chromatography electrospray tandem mass spectrometry (HPLC-ESI-MS/MS). The biochemical parameters were also detected in the same time by the laboratory in Zhongshan Hospital Fudan University. Then logistic regression was performed with IS and PCS as dependent variable, respectively.Results Two hundred and fifty eight (male 145, female 113) MHD patients were enrolled in the study. The plasma concentrations of IS and PCS in MHD patients were 35.0±17.9μg/ml and 19.4(8.4-31.7)μg/ml, respectively; while those in healthy control were 1.15±0.72μg/ml and 0.67±0.41μg/ml, respectively. Mutivariate logistic regression with IS as dependent variable and BMI, takingβ-blocker, albumin, pre-albumin, BUN, Cr, Apo-A, Hcy,β2M, PCS as covariates was performed. We found that BMI was inversely correlated with IS (β=-10.18, P=0.001), while Cr (β=8.005, P<0.001) and PCS(β=13.39, P<0.001) were independently correlated with IS. Then, another multivariate logistic model was performed with PCS as dependent variable and smoking history, diabetes, taking ARB, taking active vitamin D, BUN, Cr, P, Ca*P, iPTH, IS as covariates. The results showed that BUN(β=1.091, P=0.005), Cr(β=1.002, P=0.022), P (β=9.405, P=0.004) and IS(β=9.52, P< 0.001) were significantly related to PCS. There was an inverse relationship between taking ARB (β=-7.64, P=0.023), taking active vitamin D (β=-8.62, P=0.006) and PCS. Whereas, the relationship between Ca*P and PCS became borderline (β=4.052, P=0.053).Conclusions The plasma concentrations of IS and PCS in maintenance hemodialysis patients were significantly higher than those in healthy control. BMI, Cr and PCS were significantly correlated with IS, while the related factors of PCS were BUN, Cr, P, IS, taking ARB and active vitamin D. Objective Cardiovascular disease is the leading cause of death in hemodialysis patients, while left ventricular hypertrophy (LVH) and valve calcification are the main complications in this population. The present study aims to:(1) Analyze the risk factors for LVH; (2) Identify risk factors for aortic valve calcification (AVC) and mitral valve calcification (MVC); (3) Demonstrate the relationship between indoxyl sulfate (IS), p-cresyl sulfate (PCS) and mortality as well as cardiovascular events in maintenance hemodialysis patients.Methods Clinical data were collected, biochemical parameters were determined by our laboratory using standard methods, and IS, PCS were detected using HPCL-ESI-MS/MS. For all patients participated in the study, echocardiography was examined. Then the cohort was followed to record cardiovascular events (including arrhythmia, angina pectoris, myocardial infarction and congestive heart failure) and mortality (including cardiovascular mortality and death resulted from other causes). Logistic regression was employed to identify risk factors for AVC, MVC and LVH. The relationships between IS, PCS and mortality as well as cardiovascular events were determined by proportional hazards model.Results Exactly two hundred and fifty eight hemodialysis patients (male 145, female 113) were enrolled. In the following process (mean follow-up time:18.5±4.4 months),34 patients had experienced cardiovascular events attack (8 arrhythmia,7 angina pectoris,3 myocardial infarction,16 congestive heart failure) and 23 patients died(10 patients died from cardiovascular complications). The prevalence of LVH was very high with a rate of 64.3% in MHD patients. Logistic regression showed that BMI (β=7.227, P=0.005), SBP (β=9.035, P=0.012), IS (β=6.452, P=0.033) and NT-proBNP (β=7.708, P=0.001) were significantly correlated to LVH, and that spKt/V(β=-8.437, P=0.046) was inversely correlated to LVH. Age (β=7.42, P= 0.049), dialysis duration (β= 6.663, P=0.006), history of primary hypertension(β= 4.019. P=0.048) and PCS(β=7.62, P=0.023) were significantly correlated to AVC, while pre-albumin (β=-7.671, P=0.017) was inversely correlated to AVC. Likewise, dialysis duration (β=12.076, P<0.001) and history of primary hypertension(β= 7.328, P=0.001) were significantly related to MVC. In addition, there was a significant positive relationship betweenβ2M and MVC (β= 7.63, P=0.016) and a negative relationship between MVC and albumin (β=-10.275, P=0.014) as well as Cr (β=-0.004, P=0.018). The incidence of congestive heart failure in the group with high plasma IS (> 32.35μg/ml) was significantly higher than that in the group with low plasma IS (<32.35μg/ml) (Log-Rank P=0.021). High plasma IS predicted the high risk in congestive heart failure attack after corrected for other risk factors (P= 0.035, RR[95%CI]:1.015[1.002,1.046]). Multivariate Cox regression showed that old age (P=0.033, RR[95%CI]:1.073[1.006,1.145]), MVC (P=0.007, RR[95%]: 10.326[1.915,55.694]), high value of LVMI (P=0.009, RR[95%CI]:1.056[1.014, 1.112]) and low serum pre-albumin (P<0.001, RR[95%CI]:0.538[0.364,0.721]) were the significant predictor for all-cause mortality. The cardiovascular mortality in the group with high plasma PCS (> 19.35μg/ml) was higher than that in the group with low plasma PCS (< 19.35μg/ml) (Log-Rank P=0.025). Furthermore, high plasma PCS significantly predicted high cardiovascular mortality risk in MHD patients (P=0.041, RR[95%]:[1.065,1.304]).Conclusions In MHD patients:(1) IS is the significant risk factor for LVH and high plasma IS can predict congestive heart failure attack in the future. (2) PCS is significantly correlated with AVC and high plasma PCS is parallel with increased cardiovascular mortality risk. (3) The risk factors for LVH are BMI, SBP, spKt/V, IS and NT-proBNP. (4) Valve calcification is prevalent with a rate of 51.6%, and the prevalence of AVC (48.8%) is higher than MVC (17.1%). Age, dialysis duration, history of primary hypertension, pre-albumin and PCS are the significant risk factors for AVC, while the significant risk factors for MVC include dialysis duration, history of primary hypertension, albumin, P2M and Cr. |
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