Ya-Fei Yang

The effect of probiotics on serum levels of cytokine and endotoxin in peritoneal dialysis patients: a randomised, double-blind, placebo-controlled trial.

Inflammatory markers such as interleukin (IL)-6 and tumour necrosis factor-alpha (TNF-α) are elevated in dialysis patients and can predict cardiovascular events and all-cause mortality. Endotoxin is an important source and also another marker of inflammation in patients with chronic kidney disease. The aim of this study was to evaluate the impact of oral probiotics on serum levels of endotoxemia and cytokines in peritoneal dialysis (PD) patients. The decline of residual renal function, peritonitis episodes, and cardiovascular events were also recorded. From July 2011 to June 2012, a randomised, double-blind, placebo-controlled trial was conducted in PD patients. The intervention group received one capsule of probiotics containing 10(9) cfu Bifobacterium bifidum A218, 10(9) cfu Bifidobacterium catenulatum A302, 10(9) cfu Bifidobacterium longum A101, and 10(9) cfu Lactobacillus plantarum A87 daily for six months, while the placebo group received similar capsules containing maltodextrin for the same duration. Levels of serum TNF-α, interferon gamma, IL-5, IL-6, IL-10, IL-17, and endotoxin were measured before and six months after intervention. 39 patients completed the study (21 in the probiotics group and 18 in the placebo group). In patients receiving probiotics, levels of serum TNF-α, IL-5, IL-6, and endotoxin significantly decreased after six months of treatment, while levels of serum IL-10 significantly increased. In contrast, there were no significant changes in levels of serum cytokines and endotoxin in the placebo group after six months. In addition, the residual renal function was preserved in patients receiving probiotics. In conclusion, probiotics could significantly reduce the serum levels of endotoxin, pro-inflammatory cytokines (TNF-α and IL-6), IL-5, increase the serum levels of anti-inflammatory cytokine (IL-10), and preserve residual renal function in PD patients.

EARLY INITIATION OF CONTINUOUS AMBULATORY PERITONEAL DIALYSIS IN PATIENTS UNDERGOING SURGICAL IMPLANTATION OF TENCKHOFF CATHETERS

♦ Background: Nephrologists commonly recommend continuous ambulatory peritoneal dialysis (CAPD) with break-in periods of at least 2 weeks. We investigated the safety and feasibility of shorter break-in periods following surgical implantation of Tenckhoff catheters. ♦ Methods: We retrospectively examined 310 patients that underwent Tenckhoff catheter implantation for the first time. The early group comprised 226 patients that started CAPD ≤ 14 days after implantation; the late group comprised 84 patients that started CAPD > 14 days after implantation. Catheter-related complications within 6 months were analyzed. ♦ Results: A total of 310 patients were enrolled. Time to CAPD initiation was shorter in the early group (2.0 ± 2.7 days) than in the late group (40.6 ± 42.8 days) (p < 0.001). The bridge hemodialysis rate was higher in the late group (57.1%) than in the early group (31.4%) (p < 0.001). Overall, 33 early-group (14.6%) and 11 late-group patients (13.1%) developed catheter-related complications within 6 months. The early-group complications were leakage (n = 5), diminished outflow volume (n = 7), migration (n = 7), pericatheter hernia (n = 1), hemoperitoneum (n = 1), pericatheter infection (n = 3), and peritonitis (n = 9). The late-group complications were leakage (n = 2), diminished outflow volume (n = 5), migration (n = 2), and peritonitis (n = 2). Actuarial freedom from catheter-related complications was similar in both groups (log rank, p = 0.76). ♦ Conclusion: Early initiation of CAPD with surgically implanted Tenckhoff catheters is feasible and safe. Shorter break-in periods are not associated with more catheter-related complications. The data from our peritoneal dialysis population suggest that early initiation is not associated with an increased number of complications. This needs to be confirmed in a randomized trial.

Outpatient versus inpatient renal biopsy: a retrospective study.

OBJECTIVE AND METHODS There is a growing interest in the safety and efficacy of percutaneous kidney biopsy for outpatients in Taiwan. We conducted a retrospective study for patients receiving the biopsy in 2002 and 2003. Complication and mortality associated with the biopsy were compared between 147 inpatients and 183 outpatients who had been judged to need no hospitalization. All biopsies were performed using the ultrasound guidance and an automated spring-loaded biopsy device. RESULTS There were no death and no significant difference in complication rates between the two groups. No delayed gross hematuria, delayed pain, fever or biopsy site bleeding developed in outpatients, who were followed-up by telephone contacts for 1 - 5 days after they had been discharged. Both outpatients and inpatients with hematoma were younger than those without (p < 0.05). Template bleeding time was longer for inpatients with hematuria compared with inpatients without (12.0 vs. 5.8 minutes in average, p = 0.036), but not for outpatients (4.5 vs. 6.0 minutes in average, p = 0.282). There were moderate differences in platelet count between outpatients with hematuria and those without (p = 0.057), and in serum creatinine between inpatients with hematuria and those without (p = 0.069). CONCLUSION The outpatient renal biopsy appears to be equally as safe and efficient as the inpatient biopsy. However, we suggest checking template bleeding time and platelet count before biopsy for patients with clinical bleeding tendency, such as patients with a serum creatinine level over 4 mg/dl (approaching CKD stages IV, V) due to a higher risk of prolonged bleeding time. Outpatient biopsy with a 6-hour inpatient observation can be considered as a medically adequate procedure.

Real-Time PCR Analysis of the Intestinal Microbiotas in Peritoneal Dialysis Patients

ABSTRACT Bifidobacterium and Lactobacillus can beneficially affect the host by producing acetic acid and lactic acid, which lower pH and thereby inhibit the growth of pathogens or allow the probiotic bacteria to compete with pathogens for epithelial adhesion sites and nutrients. The transmural migration of enteric organisms into the peritoneal cavity can cause peritonitis in peritoneal dialysis (PD) patients. We hypothesized that the composition of the intestinal microbiota with regard to Lactobacillus species and Bifidobacterium species differed between PD patients and healthy controls. The aim of the study was to investigate these differences by real-time PCR analysis of fecal samples. From 1 August 2009 to 31 March 2010, a total of 29 nondiabetic PD patients and 41 healthy controls from China Medical University Hospital were recruited after giving their informed consent. Fecal samples were collected from the PD patients and their age-matched counterparts in the morning using a standardized procedure. DNA extracted from these samples was analyzed by real-time PCR. All bifidobacteria, Bifidobacterium catenulatum, B. longum, B. bifidum, Lactobacillus plantarum, L. paracasei, and Klebsiella pneumoniae were less frequently detected in the patient samples. Dysbiosis (microbial imbalance) may impair intestinal barrier function and increase host vulnerability to pathogen invasion. Further studies are necessary to confirm our findings before clinical trials with probiotic supplementation in PD patients.

Uremic Pruritus, Cytokines, and Polymethylmethacrylate Artificial Kidney

Uremic pruritus is one of the common complications in long-term dialysis patients. Recently, researchers reported that immunohypothesis with high serum level of cytokines could be the cause of uremic pruritus. Polymethylmethacrylate (PMMA) artificial kidney (AK) has been reported to adsorb more serum cytokines than other high-flux AKs. In July 2006, 30 patients with severe uremic pruritus from 300 chronic hemodialysis (HD) patients in a single center entered this prospective study. Their dialyzers were changed to PMMA AK for 4 weeks. The severity of pruritus was evaluated every week using the results of a questionnaire (pruritus score). Laboratory assays including predialysis serum blood urea nitrogen (BUN), creatinine, beta2-microglobulin (beta2M), calcium, phosphate, intact parathyroid hormone (iPTH), total CO(2), ferritin, hematocrit, high-sensitivity C-reactive protein (hsCRP), IL-1beta, IL-2, IL-6, IL-18, tumor necrosis factor-alpha (TNF-alpha), Kt/V, and beta2M clearance were measured before and at the end of 4 weeks of PMMA AK use. PMMA AK was effective in reducing the pruritus score from 23.46 +/- 11.94 to 7.38 +/- 6.42 (P < 0.001). The effect of uremic pruritus relief appeared after 1 week of PMMA AK use. There were no significant differences in the laboratory assay results including predialysis serum BUN, Cr, beta2M, calcium, phosphate, calcium-phosphate product, iPTH, total CO(2), ferritin, hematocrit, hsCRP, IL-1beta, IL-2, IL-6, IL-18, TNF-alpha, Kt/V, and beta2M clearance. The mechanism for the beneficial effect of PMMA AK on uremic pruritus remains to be determined. PMMA AK may be a useful adjuvant therapy in chronic HD patients with severe uremic pruritus.

A Comparison of Sevelamer Hydrochloride with Calcium Acetate on Biomarkers of Bone Turnover in Hemodialysis Patients

Objective. To evaluate the influence of sevelamer hydrochloride and calcium acetate on biomarkers of bone turnover in patients with hyperphosphatemia receiving hemodialysis. Methods. In this prospective, open-label, randomized, active-controlled study, 70 patients (38 men and 32 women) with hyperphosphatemia (serum phosphorus level >6.0 mg/dL) underwent a two-week washout period and were randomly selected to receive sevelamer hydrochloride (n = 37) or calcium acetate (n = 33) for eight weeks. Changes in serum levels of intact parathyroid hormone (iPTH), alkaline phosphatase (Alk-P), phosphorus, and calcium were measured and compared. Results. After eight weeks of treatment, calcium acetate lowered iPTH levels significantly more than sevelamer hydrochloride did (−178.0 vs. −69.0 pg/mL, p = 0.0019). Levels of Alk-P were significantly elevated in patients given sevelamer hydrochloride compared with levels in those given calcium acetate treatment (24.09 vs. 7.45 U/L, p = 0.0014). Changes in serum phosphorus levels did not differ between sevelamer hydrochloride (−1.93 mg/dL) and calcium acetate (−2.5 mg/dL) at the end of the study (p = 0.0514). Changes in the calcium and phosphorous product did not significantly differ between the sevelamer-hydrochloride group (−18.06 mg2/dL2) and the calcium-acetate group (−19.05 mg2/dL2, p = 0.6764). Fifteen patients (45.5%) treated with calcium acetate had hypercalcemia (serum-adjusted calcium level >10.5 mg/dL); the rate was significantly higher than that of patients treated with sevelamer (five [13.5%] of 37, p = 0.0039). Conclusion. Treatment with sevelamer hydrochloride had the advantage of maintaining stable iPTH levels and elevating Alk-P levels while lowering serum phosphorus levels and calcium-phosphorous product.

Intravenous iron attenuates postvaccination anti‐HBsAg titres after quadruple hepatitis B vaccination in dialysis patients with erythropoietin therapy

Background:  Anaemia in patients with end‐stage renal disease (ESRD) is commonly treated with recombinant human erythropoietin (rHuEPO), often in combination with an adjuvant iron supplement. There is much evidence that rHuEPO can influence the immune response by its effect on lymphocytes. Also, iron catalyses the formation of radicals and increases the risk of major infections by negatively affecting the immune system. The relationship between antibodies to hepatitis B surface antigen (anti‐HBsAg) responsiveness after hepatitis B vaccination and rHuEPO/adjuvant iron supplementation has not been reported before.

Reduction of Pro-Inflammatory Cytokines through Hemodiafiltration

Background. Hemodialysis (HD) prolongs the life of the patients with end stage renal disease (ESRD), but the survival rates are still lower than the general population. More than half of ESRD patients died from cardiovascular disease (CVD). Recent studies have revealed that CVD is a consequence of vascular inflammation, and that there are active inflammatory processes in ESRD patients. Reports have indicated that ESRD patients have fewer CVD events and better survival with hemodiafiltration (HDF), but the reasons for this remain unclear. This study attempts to prove that HDF reduces the CVD-related cytokines. Methods. Seventeen adult HD outpatients were put on HDF in our hospital from September 2004 to June 2006. We collected plasma samples before and six months after initiation of HDF. The target pro-inflammatory cytokines selected were interleukin-6 (IL-6), interleukin-18 (IL-18), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP). Results. After six months of HDF, most of the biochemical parameters did not changed. Plasma IL-18 and TNF-α are decreased significantly (p < 0.05) but IL-6 and CRP are not. Conclusions. IL-18 and INF-α decreased significantly after six months of HDF. These cytokines are key factors in atherosclerotic plaque formation and rupture, and a reduction of these inflammatory cytokines in HDF may reduce the CVD incidence and prolong life.

Comparing Risk of New Onset Diabetes Mellitus in Chronic Kidney Disease Patients Receiving Peritoneal Dialysis and Hemodialysis Using Propensity Score Matching

Chronic kidney disease (CKD) patients are at risk for developing new-onset diabetes mellitus (NODM) even after hemodialysis (HD) and peritoneal dialysis (PD) treatment. It is not clear if the incidence for NODM is different in CKD patients receiving HD and PD. This study compared the risk of NODM in PD patients and HD patients. Methods All HD and PD patients in Taiwan Renal Registry Database from 1997 to 2005 were included and all patients were followed to December 31, 2008. The risk of NODM was analyzed in PD patients and propensity score matched HD patients using logistic regression for early type NODM (< = 6 months after dialysis) and Cox regression for late type NODM (>6 months after dialysis). Results A total of 2548 PD patients and 10192 HD patients who had no diabetes on the initiation of dialysis were analyzed. The incidence for NODM was 3.7 per 100 patient/year for HD and 2.4 for PD patients. HD patients are more at risk for developing early type NODM (p<0.001) with an adjusted odds ratio of 1.41 [95% confidence interval (CI) 1.12–1.78)]. HD patients are more at risk for late type NODM (p<0.001) with an adjusted hazard ratio of 2.01 (95% CI: 1.77–2.29). Patient’s age was negatively associated with risk of early type of NODM (p<0.001) but positively associated with risk of late type NODM (p<0.001). Conclusions Chronic kidney disease patients receiving hemodialysis are more at risk for developing new-onset diabetes mellitus compared to those receiving peritoneal dialysis.

Renal hypouricemia is an ominous sign in patients with severe acute respiratory syndrome

Background: The purpose of this study is to determine the incidence and significance of hypouricemia in patients with severe acute respiratory syndrome (SARS). Pulmonary lesions in patients with SARS are thought to result from proinflammatory cytokine dysregulation. Acute renal failure has been reported in patients with SARS, but whether cytokines can injure renal tubules is unknown. Methods: Sixty patients diagnosed with SARS in Taiwan in April 2003 were studied. Patients were identified as hypouricemic when their serum uric acid (UA) level was less than 2.5 mg/dL (<149 μmol/L) within 15 days after fever onset. Urine UA and creatinine levels were available for 43 patients; the serum cytokines interleukin-6 (IL-6), IL-8, and tumor necrosis factor-α (TNF-α) were measured in 16 patients. Results: Sixteen patients (26.7%) had hypouricemia (UA, 1.68 ± 0.52 mg/dL [100 ± 31 μmol/L]). No differences in age, sex, symptoms, vital signs, hemogram, or other biochemistry data existed between the hypouricemic and normouricemic groups. Fractional excretion (FE) of UA (FEUA) in 12 hypouricemic patients was 39.6% ± 23.4%, significantly greater than that of 31 normouricemic patients (16.4% ± 11.4%; P < 0.0001). After adjustments for age and sex, high FEUA was significantly associated with the lowest blood oxygenation (P = 0.001; r = −0.624). The number of catastrophic outcomes (endotracheal intubation and/or death) adjusted for older age and sex showed that hypouremic patients had an odds ratio of 10.57 (confidence interval, 2.33 to 47.98; P = 0.002). Kaplan-Meier curves for catastrophic outcome–free results showed significant differences between patients with normouricemia or hypouricemia (P = 0.01). Serum IL-8 levels correlated significantly with FEUA (P < 0.001; r = 0.785) and inversely with serum UA level (P = 0.044; r = −0.509); neither IL-6 nor TNF-α level showed such correlations. Conclusion: One fourth of patients with SARS developed hypouricemia, which might result from a defect in renal UA handling and was associated with a high serum IL-8 level. Renal hypouricemia is an ominous sign in patients with SARS.