Cheng-Jui Lin

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-cresylsulfate and indoxyl sulfate level at different stages of chronic kidney disease

Indoxyl sulfate and p‐cresylsulfate was associated with poor clinical outcome of uremia. We explored the relationship between the two toxins and renal function in chronic kidney disease (CKD) patients. This study enrolled 103 stable CKD patients (stage 3–5 and hemodialysis (HD) patients). Serum levels of indoxyl sulfate and p‐cresylsulfate were measured using ultra performance liquid chromatography. General laboratory results and patient background were also checked. Patients with advanced CKD had higher serum indoxyl sulfate, p‐cresylsulfate based on ANOVA test. There were significant correlation between indoxyl sulfate and p‐cresylsulfate and serum creatinine after multivariate regression analysis (B=3.59, P<0.01; B=0.93, P=0.04, respectively). In addition, there was a positive correlation between indoxyl sulfate and p‐cresylsulfate level (r=0.61, P<0.01). Indoxyl sulfate and p‐cresylsulfate level increased gradually while renal function declined and reached the peak at the stage of HD. Serum indoxyl sulfate level was closely associated with p‐cresylsulfate level in CKD patients. J. Clin. Lab. Anal. 25:191–197, 2011.

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.

Comparison of extracellular volume and blood pressure in hemodialysis and peritoneal dialysis patients.

Background: Extracellular volume (ECV) assessment by bioimpedance analysis is a reliable technique for determining post dialysis target weight. Overhydration and dehydration are two points of dialysis patients’ fluid status and both affect blood pressure. We compared ECV and blood pressure between hemodialysis and peritoneal dialysis patients. Methods: We studied ECV of 74 (38 females and 36 males) normal subjects, 121 (63 females and 58 males) stable chronic hemodialysis and 84 (57 females and 27 males) stable chronic peritoneal dialysis patients. ECV as a percentage of body weight was designated ECV%. An ECV% over 28% in male patients and over 25% in females was defined as overhydration according to the 100th percentile of normal subjects. An ECV% below 21% in male patients and below 18% in females was defined as dehydration. Hypertension was defined as systolic blood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg. Results: In male and female hypertension and normotension, the ECV% of peritoneal dialysis patients was significantly higher than that of hemodialysis patients (all p < 0.0001). The overhydration frequency of peritoneal dialysis patients was significantly higher than that of hemodialysis patients (p < 0.0001). The dehydration frequency of peritoneal dialysis patients was significantly less than that of hemodialysis patients (p < 0.01). The proportion of hypertension in peritoneal dialysis patients was higher than that in hemodialysis patients, but with no significant difference (p = 0.085). All male and female patients with overhydration had hypertension in either the hemodialysis or peritoneal dialysis group. Patients with dehydration usually had normotension, but some of them had hypertension. Conclusions: (1) Overhydration and hypertension are more common in peritoneal dialysis patients than in hemodialysis patients. (2) Dehydration is noticed in hemodialysis patients, but not in peritoneal dialysis patients.

Tetrandrine down-regulates ERK/NF-κB signaling and inhibits activation of mesangial cells

OBJECTIVES Tetrandrine (TET), a bisbenzylisoquinoline alkaloid isolated from Stephania tetrandra S. Moore of the Menispermaceae, possesses anti-inflammatory activity. We examined the effect of tetrandrine on interleukin-1β (IL-1β)-provoked inflammatory response in mesangial cells. MATERIALS AND METHODS Primary rat mesangial cells (PRMCs) were treated with IL-1β to induce inflammation to resemble glomerulonephritis. Cell viability, morphology and NO production were evaluated. Western blotting was applied for expression of matrix metalloproteinase-9 (MMP-9), inducible NO synthase (iNOS), extracellular signal-regulated kinase (ERK) and NF-κB-related molecules. Electrophoretic mobility shift assay was performed to examine the DNA-binding activity of NF-κB. RESULTS TET, at concentrations up to 10 μg/ml, had no significant effect on viability of PRMCs. At non-toxic concentrations, TET inhibited expression of phosphorylated ERK as well as phosphorylated IKK, enhanced degradation of IκBα and reduced the DNA-binding activity of NF-κB in IL-1β-primed PRMCs, suggesting an inhibitory effect on ERK/NF-κB signaling. TET attenuated the IL-1β-provoked expression of iNOS and release of NO. Moreover, both the protein expression and gelatinase activity of MMP-9, but not MMP-2, were markedly suppressed by TET. SIGNIFICANCE TET down-regulated ERK/NF-κB signaling and inhibited the expression of inflammatory mediators NO and MMP-9. Since these mediators appear to activate mesangial cells, TET may play an important role in prevention of glomerulonephritis.

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.

Acute tumor lysis syndrome in a hemodialysis patient with diffuse large B cell lymphoma

Acute tumor lysis syndrome (TLS) is a life-threatening complication of cancer therapy requiring prompt recognition and aggressive management. It occurs particularly in patients with lymphoproliferative disease during potent myelosuppressive therapy. To our knowledge, acute TLS in end-stage renal disease (ESRD) patients with malignancy is extremely rare and has never been reported in English literature. We report the first case of acute TLS in an ESRD woman with diffuse large B cell lymphoma after chemotherapy. Aggressive treatments with daily hemodialysis and allopurinol rather than hydration benefit the patient. There is neither optimal therapy in treating ESRD patients with TLS nor adequate guidelines for how to adjust the chemotherapy drug in hemodialysis patients. This case provides our experience to clinician how to treat acute TLS in ESRD patients.

Rituximab in the treatment of primary bilateral adrenal lymphoma with adrenal crisis

Primary adrenal lymphoma (PAL) is a rare extranodal non-Hodgkin’s lymphoma. The majority of the patients are elderly men with bilateral adrenal involvements. The optimal treatment of PAL has not been well established currently. We herein report on a patient with primary bilateral adrenal lymphoma and adrenal crisis that treated with rituximab. Our case does demonstrate that rituximab could be administered without significant toxicities, and resulted in clinical improvement with disease stabilization in this critically ill patient.

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.