Chi-Feng Pan

Serum protein-bound uraemic toxins and clinical outcomes in haemodialysis patients

BACKGROUND The protein-bound uraemic toxin p-cresol is associated with immunodeficiency in haemodialysis (HD) patients. We investigated the effect of serum p-cresol, indoxyl sulphate and other variables on clinical outcomes in HD patients during a 20-month follow-up. METHODS We enrolled 100 stable HD patients from a single medical centre. The primary outcomes were infection-related hospitalization, cardiovascular events and all-cause mortality. Serum total and free p-cresol and indoxyl sulphate levels were measured using ultra-performance liquid chromatography. Biochemical data were collected concurrently. RESULTS Multivariate logistic regression analysis revealed that infection-related hospitalization correlated with free p-cresol (adjusted odds ratio: 1.70, P = 0.01) and highly sensitive C-reactive protein (hsCRP) (adjusted odds ratio: 2.07, P = 0.01); cardiovascular event was associated with free p-cresol (adjusted odds ratio: 1.78, P = 0.01) and nPCR (adjusted odds ratio: 0.01, P = 0.02); and all-cause mortality was related to albumin (adjusted odds ratio: 0.04, P = 0.01). The Kaplan-Meier method showed that free and total p-cresol were significantly associated with cardiovascular events (log-rank P < 0.01 and log-rank P < 0.01, respectively). Serum free p-cresol seemed to have a trend to correlate with infection-related hospitalization during a 20-month follow-up (log-rank P = 0.05). CONCLUSIONS Serum free and total p-cresol levels were significantly related to cardiovascular events. In addition, serum free p-cresol and hsCRP levels were also found to be associated with infection-related hospitalization.

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

Background/Aims. Previous studies have reported p-cresyl sulfate (PCS) was related to endothelial dysfunction and adverse clinical effect. We investigate the adverse effects of PCS on clinical outcomes in a chronic kidney disease (CKD) cohort study. Methods. 72 predialysis patients were enrolled from a single medical center. Serum biochemistry data and PCS were measured. The clinical outcomes including cardiovascular event, all-cause mortality, and dialysis event were recorded during a 3-year follow-up. Results. After adjusting other independent variables, multivariate Cox regression analysis showed age (HR: 1.12, P = 0.01), cardiovascular disease history (HR: 6.28, P = 0.02), and PCS (HR: 1.12, P = 0.02) were independently associated with cardiovascular event; age (HR: 0.91, P < 0.01), serum albumin (HR: 0.03, P < 0.01), and PCS level (HR: 1.17, P < 0.01) reached significant correlation with dialysis event. Kaplan-Meier analysis revealed that patients with higher serum p-cresyl sulfate (>6 mg/L) were significantly associated with cardiovascular and dialysis event (log rank P = 0.03, log rank P < 0.01, resp.). Conclusion. Our study shows serum PCS could be a valuable marker in predicting cardiovascular event and renal function progression in CKD patients without dialysis.

Serum p-cresyl sulfate predicts cardiovascular disease and mortality in elderly hemodialysis patients

Introduction Previous studies have shown that serum p-cresyl sulfate (PCS) and indoxyl sulfate (IS) were significantly related to clinical outcomes in patients on hemodialysis (HD). However, evidence for the relationship in elderly HD patients remains scarce. We explore whether the two toxins can predict clinical outcomes in elderly HD patients. Material and methods Fifty stable HD patients more than 65 years old were enrolled from a single medical center. Serum total and free PCS, IS levels and biochemistry were measured concurrently. The clinical outcomes including cardiovascular events and all-cause mortality were analyzed after 38-month follow-up. Results Univariate Cox proportional hazard ratio analysis revealed that cardiovascular events were associated with gender (p = 0.02), diabetes (p < 0.01), calcium (p = 0.01), total PCS (p < 0.01), free PCS (p < 0.01) and total IS (p = 0.05). Multivariate analysis showed that diabetes (p = 0.01), total PCS (p = 0.01) and free PCS (p = 0.04) were related to cardiovascular events. For all-cause mortality, only total PCS (p = 0.01) reached significance after adjusting other confounding factors. However, Kaplan-Meier analysis indicated that free PCS (p = 0.02) and total PCS (p < 0.01) were significantly associated with cardiovascular events and total PCS (p = 0.048) was related to all-cause mortality during 38-month follow-up. Conclusions Our results indicate that total PCS is a valuable marker in predicting cardiovascular event and all-cause mortality in elderly HD patients.

Indoxyl Sulfate Impairs Endothelial Progenitor Cells and Might Contribute to Vascular Dysfunction in Patients with Chronic Kidney Disease

Background/Aims: Indoxyl sulfate (IS) is a protein-bound uremic toxin that accumulates in patients with chronic kidney disease (CKD). We explored the effect of IS on human early endothelial progenitor cells (EPCs) and analyzed the correlation between serum IS levels and parameters of vascular function, including endothelial function in a CKD-based cohort. Methods: A cross-sectional study with 128 stable CKD patients was conducted. Flow-mediated dilation (FMD), pulse wave velocity (PWV), ankle brachial index, serum IS and other biochemical parameters were measured and analyzed. In parallel, the activity of early EPCs was also evaluated after exposure to IS. Results: In human EPCs, a concentration-dependent inhibitory effect of IS on chemotactic motility and colony formation was observed. Additionally, serum IS levels were significantly correlated with CKD stages. The total IS (T-IS) and free IS (F-IS) were strongly associated with age, hypertension, cardiovascular disease, blood pressure, PWV, blood urea nitrogen, creatine and phosphate but negatively correlated with FMD, the estimated glomerular filtration rate (eGFR), hemoglobin, hematocrit, and calcium. A multivariate linear regression analysis also showed that FMD was significantly associated with IS after adjusting for other confounding factors. Conclusions: In humans, IS impairs early EPCs and was strongly correlated with vascular dysfunction. Thus, we speculate that this adverse effect of IS may partly result from the inhibition of early EPCs.

Indoxyl Sulfate, Not P-Cresyl Sulfate, is Associated with Advanced Glycation end Products in Patients on Long-Term Hemodialysis

Background/Aims: Advanced glycation end products (AGEs) are pro-inflammatory and pro-oxidative compounds that play a critical role in endothelial dysfunction and atherosclerosis. Protein-bound uremic toxins, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), inhibit endothelial function. We explored the association of IS and PCS with AGEs in a hemodialysis (HD) cohort. Methods: This study was a cross-sectional study that recruited 129 stable patients on maintenance HD in a single medical center from July 1 to July 15, 2011. Serum levels of total and free IS, PCS and AGEs were measured concurrently. General laboratory results and patient background were also investigated. Results: Serum levels of AGEs were associated with total IS (r = 2.7, p < 0.01) but not total PCS (r = 0.01, NS), free IS (r = 0.11, NS) or free PCS (r = 0.04, NS) using Pearsons analysis. Multiple linear regression analysis showed that total IS was significantly related to AGEs (β = 0.296, p < 0.01), free IS (β = 0.502, p < 0.01) and creatinine (β = 0.294, p < 0.01). Serum AGEs levels were also independently correlated with diabetes status (β = 0.250, p = 0.01) and total IS (β = 0.341, p < 0.01) concentrations after adjusting for other confounding variables. Moreover, patients with diabetes had higher serum AGEs levels than patients without diabetes (p < 0.01). Conclusions: These findings suggest that serum levels of total IS were associated with AGEs levels, which may participate in the process of atherosclerosis.

Pentoxifylline Decreases Dialysis Risk in Patients With Advanced Chronic Kidney Disease

Few studies evaluated the effects of pentoxifylline on hard endpoints in patients with predialysis stage 5 chronic kidney disease (CKD). Thus, we tried to explore the effects of pentoxifylline and its interaction with renin‐angiotensin‐aldosterone system (RAAS) blockade on the development of endstage renal disease (ESRD) and mortality. This nationwide cohort study retrospectively included patients who had a serum creatinine level of >6 mg/dL and received erythropoiesis‐stimulating agents (ESAs) between 2000 and 2010. We analyzed 7,366 pentoxifylline users and 7,366 propensity score‐matched nonusers. Using Cox proportional hazard models, pentoxifylline reduced the risks of ESRD and the composite renal outcome but not that of mortality. In terms of the risks of developing ESRD, pentoxifylline alone exerted a comparable beneficial effect to combined therapy with an RAAS inhibitor and greater renoprotection than RAAS inhibitor monotherapy. This study suggests pentoxifylline is efficacious in slowing progression to ESRD in patients with predialysis stage 5 CKD.

Association of Indoxyl Sulfate With Fibroblast Growth Factor 23 in Patients With Advanced Chronic Kidney Disease

Background:Protein-bound uremic toxins—indoxyl sulfate (IS) and p-cresyl sulfate (PCS)—can not only predict clinical outcomes but also may relate to bone-mineral disorders in patients with chronic kidney disease (CKD). However, the relationship between protein-bound uremic toxins and fibroblast growth factor 23 (FGF23) has not been studied before. The objective of this study was to explore the association of IS and PCS with FGF23 in a CKD-based cohort. Methods:This is a cross-sectional study that enrolled 80 stable CKD stage 3 to 5 patients who met the inclusion criteria in a single medical center. Serum levels of IS, PCS and FGF23 were measured concurrently. General biochemistry and patient background were also investigated. Results:Serum FGF23 and IS concentrations were elevated commensurately with deteriorating renal function. Pearsons analysis showed that FGF23 levels were significantly associated with blood urea nitrogen (r = 0.381, P < 0.05), creatinine (r = 0.632, P < 0.01), estimated glomerular filtration rate (r = −0.447, P < 0.05), phosphate (r = 0.543, P < 0.01), intact parathyroid hormone (r = 0.543, P < 0.01), IS (r = 0.432, P < 0.01) and PCS (r = 0.318, P < 0.05). After adjusting other confounding factors by stepwise multiple linear regression analysis, only creatinine (&bgr; = 0.82, P < 0.01), phosphate (&bgr; = 0.28, P = 0.02) and IS (&bgr; = 0.39, P = 0.04) retained statistically significant associations with FGF23. Moreover, serum levels of IS were higher in patients with high FGF23 concentration (>90 pg/mL, median value) than those with lower FGF23 (P < 0.01). Conclusions:Results indicated that only IS but not PCS correlated independently with FGF23 in worsening CKD. IS may be an independent factor involved in regulation of bone-mineral metabolism.

Absolute interdialytic weight gain is more important than percent weight gain for intradialytic hypotension in heavy patients

Aim:  Few published reports have mentioned the difference between absolute interdialytic weight gain (IDWG) and IDWG/DW (IDWG%), and subsequent effects on daily dialysis. The aim of present study was to evaluate the difference between absolute IDWG and IDWG% in new haemodialysis patients.

Interdialytic weight gain does not influence the nutrition of new hemodialysis patients.

OBJECTIVE The aim of the present study was to assess the relationship between interdialytic weight gain (IDWG) and nutrition markers in hemodialysis (HD) patients, by means of repeated measures analysis. METHODS The records of 255 patients, who had recently received conventional HD for a minimum of 1 year, were retrospectively reviewed. Nutrition markers, including serum albumin, serum phosphate, blood urea nitrogen, and creatinine, were recorded at monthly intervals and subjected to repeated measures analysis. RESULTS Patients with higher IDWG/dry weight (IDWG%) (>5%) had significantly lower body mass index throughout the study. Repeated measures analysis of variance indicated no significant difference in these nutrition markers for patients with different IDWG%. At the end of the study, neither IDWG nor IDWG% were found to be associated with albumin or phosphate, on linear regression analysis. CONCLUSIONS There was no evidence of better nutrition in new HD patients with higher IDWG%. Although increased intake is promoted as critical for improving nutritional status in HD patients, it may be inappropriate to focus solely on the benefits of higher IDWG%, which can also lead to the development of hypertension, left ventricular hypertrophy, and intradialytic hypotension.

Gastrointestinal-related Uremic Toxins in Peritoneal Dialysis: A Pilot Study with a 5-year Follow-up

BACKGROUND AND AIMS P-cresyl sulfate (PCS) and indoxyl sulfate (IS) were not only novel but essential factors associated with cardiovascular disease and mortality in patients with chronic kidney disease and hemodialysis. However, little evidence exams the effect in peritoneal dialysis (PD) patients. METHODS This pilot study recruited 46 stable PD patients in a single medical center. Serum levels of IS, PCS and biochemistry were measured concurrently. Clinical outcomes including cardiovascular, all-cause mortality and PD failure event were recorded during a 5-year follow-up. RESULTS Serum levels of free and total PCS were lower in patients with residual renal function (11.67 ± 6.92, p = 0.014, 0.77 ± 0.48, p = 0.046, respectively). Multivariate Cox regression analysis showed age (HR: 1.07, p = 0.01), serum CO2 (HR: 0.67, p = 0.02) and total PCS (HR: 1.05, p <0.01) were independently associated with cardiovascular events; only free PCS (HR: 1.42, p <0.01) reached significant correlation with all-cause mortality. Total IS (HR: 1.27, p = 0.03) significantly correlated with PD failure event after adjusting other confounding factors. Kaplan-Meier analysis revealed that patients with higher total and free PCS levels had higher cardiovascular events (log rank p <0.01, log rank p = 0.05, respectively) and mortality event (log rank p = 0.02, log rank p = 0.03, respectively) than those with lower levels. In addition, total IS (log rank p = 0.04), total PCS (log rank p = 0.01) and free PCS (log rank p <0.01) could independently predict PD failure event during the study period. CONCLUSIONS Our findings suggest PCS and IS may be a valuable surrogate in predicting poor clinical outcomes in PD patients.