Extremely Low Dose of Erythropoiesis-Stimulating Agent May Be Associated with Increased Mortality in Hemodialysis Patients.

INTRODUCTION: Although high-dose erythropoiesis-stimulating agent (ESA) has been shown to increase mortality risk and adverse cardiovascular events in hemodialysis patients, the safety of extremely low-dose ESA is unclear. METHODS: We retrospectively analyzed the association between ESA dose and mortality in the monthly dosing range of 0-43,000 U of equivalent epoetin alfa in 304 Taiwan hemodialysis patients by using Cox proportional hazard model and cubic spline model. RESULTS: Compared with mean monthly ESA dose of 15,000-25,000 U (mean ± standard deviation 20,609 ± 2,662 U), monthly ESA dose of less than 15,000 U (mean ± standard deviation 7,413 ± 4,510 U) is associated with increased mortality. Monthly ESA dose of 25,001-43,000 U (mean ± standard deviation 31,160 ± 4,304 U) is not associated with higher mortality risk than monthly ESA dose of 15,000-25,000 U. The results were consistent in Cox proportional hazard models and cubic spline models. Subgroup analyses showed no significant heterogeneities among prespecified subgroups. CONCLUSIONS: Extremely low dose of ESA in hemodialysis patients may be associated with increased mortality risk. Future studies are warranted to prove this association.

Altered Monocytic Phenotypes are Associated with Uraemic Pruritus in Patients Receiving Haemodialysis.

Uraemic pruritus is one of the most bothersome symptoms in patients receiving haemodialysis. A total of 175 patients receiving maintenance haemodialysis, with 74 patients experiencing uraemic pruritus, were prospectively recruited to assess the influence of the phenotype of blood monocytes and various cytokines on uraemic pruritus. The phenotype of blood monocytes was determined by flow cytometry as classical (CD14++CD16-) monocytes, non-classical (CD14+CD16++) monocytes, and intermediate (CD14++CD16+) monocytes. Eight cyto-kines, including interleukin (IL)-2, interferon-γ, IL-12p70, IL-4, IL-5, IL-6, tumour necrosis factor-α, and IL-10, were simultaneously detected with a multi-plex bead-based immunoassay. Multivariate linear regression analysis showed that a higher percentage of intermediate monocytes (effect estimate 0.08; 95% confidence interval 0.01-0.16) were independent predictors of a higher visual analogue scale score for pruritus intensity. No differences were noted for all 8 cytokines between patients with and without uraemic pruritus. The results of this study indicate that altered monocytic phenotypes could play a role in uraemic pruritus.

Is dialysis vintage a perioperative risk for end-stage renal disease patients receiving total knee and hip arthroplasty.

BACKGROUND: End-stage renal disease is an independent risk factor for postoperative mortality and cardiovascular events, but dialysis vintage and its relationship with perioperative complication is not well studied. We did a population-based study to investigate this issue. MATERIALS AND METHODS: We identified patients who had total knee arthroplasty (TKA) or total hip arthroplasty (THA) surgeries during 1999-2010 from the National Health Insurance Research Database of Taiwan. Patients who had regular dialysis before surgery were recruited in our analysis. The outcome of interest was mortality, morbidities, intensive care unit admission rate, hospitalization duration, readmission rate, and medical costs. We did multivariate regression to adjust for age, sex, and Charlson comorbidity index (CCI) and to analyze the relationship of dialysis vintage and clinical outcomes. RESULTS: A total of 518 patients were enrolled for analysis. A total of 286 patients had TKA surgeries and 232 patients had THA surgeries. Patients who had TKA surgery were older and had more medical comorbidities than patients who had THA. After adjustment for age, sex, and CCI, TKA patients who had dialysis vintage <3 years had significantly higher medical costs ( p < 0.05). For THA patients, dialysis vintage is not an independent risk factor for outcomes of interest. CONCLUSION: Perioperative complication is associated with age and medical comorbidities. Longer dialysis vintage is not related to perioperative morbidities and mortalities or higher medical costs in either TKA or THA patients.

Icodextrin Is Associated with a Lower Mortality Rate in Peritoneal Dialysis Patients.

Background:Icodextrin (ICO) improves fluid removal in peritoneal dialysis (PD) patients. However, whether physiological benefits of ICO translate into patient survival remains unclear. We examine the association of ICO and clinical outcomes.Methods:We identified patients who initiated long-term PD from the National Health Insurance Research Database of Taiwan. We matched ICO users with non-users according to propensity score and survival status when ICO was prescribed. We utilized time-dependent analyses to avoid immortal time bias. Additional competing risk models were utilized for the outcomes except for death. The outcomes of interest were time to death, technique failure, peritonitis, major adverse cardiovascular events (MACE), and hospitalization.Results:A total of 4,914 PD patients were enrolled and 2,836 PD patients (57.7%) were identified as ICO users. The ICO users had significantly better overall survival (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.63 - 0.86), especially among early ICO users (HR 0.64; 95% CI 0.54 - 0.77, p value for interaction: 0.007). The ICO users were associated with higher risk of peritonitis (subdistribution HR 1.22, 95% CI 1.06 - 1.14) and hospitalization (subdistribution HR 1.14, 95% CI 1.05 - 1.24), considering competing risk of death. However, when considering ICO use as a time-varying covariate, ICO users shared similar risks for technique failure, peritonitis, MACE, and hospitalization as non-users. The effect of ICO on mortality was especially prominent among those early users.Conclusions:After adjustments for immortal time biases, ICO users were significantly associated with approximately 20% reduction in mortality, especially among early users.

Factors associated with poor outcomes of continuous renal replacement therapy.

Continuous renal replacement therapy (CRRT) is one of the dialysis modalities for critically ill patients. Despite intensive dialysis care, a high mortality rate is found in these patients. Our objective was to investigate the factors associated with poor outcomes in these patients. We conducted a retrospective cohort study using the National Health Insurance Research Database. Records of critically ill patients who received CRRT between 2007 and 2011 were retrieved, and the patients were categorized into two groups: those with acute kidney injury (AKI) and those with history of end-stage renal disease (ESRD). Our primary and secondary outcomes were in-hospital mortality and long-term survival and non-renal recovery (long-term dialysis dependence), respectively, in the AKI group. We enrolled 15,453 patients, with 13,204 and 2249 in the AKI and ESRD groups, respectively. Overall, 66.5% patients died during hospitalization. In-hospital mortality did not differ significantly between groups (adjusted odds ratio, 0.93; 95% CI, 0.84-1.02). Age, chronic liver disease, and cancer history were identified as independent risk factors for in-hospital mortality in both groups. Hypertension was associated with higher risk of in-hospital mortality in patients with AKI. Age, coronary artery disease, and admission to the medical intensive care unit (MICU) were risk factors for long-term dialysis dependence in patients with AKI. Patients with AKI and ESRD have similarly poor outcomes after CRRT. Older age and presence of chronic liver disease and cancer were associated with higher mortality. Older age, presence of coronary artery disease, and admission to MICU were associated with lower renal recovery rate in patients with AKI.

Additional benefit of dietitian involvement in dialysis staffs-led diet education on uncontrolled hyperphosphatemia in hemodialysis patients.

BACKGROUND: Sustained adherence to dietary phosphorus (P) restriction recommendations among hemodialysis patients is questionable. The aim of this study was to evaluate the effectiveness of additional diet education delivered by a dietitian on the control of hyperphosphatemia. METHODS: We conducted an 8-month prospective observational study in hemodialysis patients who had uncontrolled hyperphosphatemia. In the first half of the study (experimental) period, the dialysis nurses and physicians provided the routine dietetic education with the control group (n = 31), while the experimental group (n = 30) received the routine dietetic education plus an additional diet education delivered by dietitians. Both groups received the routine dietetic education in the rest of the study period to test whether the improvement of serum P level was sustained. The primary outcomes were changes in serum P level. RESULTS: At baseline, there was no significant difference in serum P levels between groups (P = 0.27). In the experimental period, monthly serum P levels decreased significantly in both groups (P < 0.001) and the magnitudes of reduction were 1.81 ± 1.46 and 0.94 ± 1.33 mg/dL in the experimental and control groups, respectively (P = 0.02), at the end. The experimental group maintained such improvement for one more month (P = 0.02), but faded out over time. CONCLUSION: Renal diet education guided either by dietitians plus dialysis staffs or dialysis staffs alone reduces serum P level and dietitian-guided diet education provides an additional benefit on controlling hyperphosphatemia in hemodialysis patients.

Decreased high-density lipoprotein cholesterol is associated with inflammation and insulin resistance in non-diabetic haemodialysis patients.

AIM: Lower serum high-density lipoprotein cholesterol (HDL-C) is associated with inflammation, insulin resistance and poor cardiovascular outcomes in the general population. However, in a large-scale study, the association between HDL and survival in haemodialysis patients was not present. The exact cause of lack of HDL-C protection in the dialysis population is still obscure. METHODS: A total of 89 stable non-diabetic haemodialysis patients were recruited. Fasting serum biochemical parameters, complete blood counts and inflammatory markers were obtained before the mid-week dialysis. Insulin resistance was assessed by the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). RESULTS: The mean age was 58.2±13.1 years, 37 (41.6%) patients were male. The mean HDL-C level was 56.3±17.1 mg/dL. By bivariate correlation analysis, a lower serum HDL-C level was related to higher body mass index (r=-0.425; P<0.001), higher triglyceride (r=-0.479; P<0.001) and higher HOMA-IR (r=-0.211; P<0.05) levels. The serum HDL-C level was also inversely related to high-sensitivity C-reactive protein (hsCRP) (r=-0.297; P=0.005) and tumour necrosis factor-α (TNF-α) (r=-0.295; P=0.005) and directly correlated with adiponectin (r=0.560; P<0.001). In multivariate linear regression analysis, HDL-C was found to be directly correlated with adiponectin (ß-coefficient=0.569; P<0.001) and inversely correlated with TNF-α (ß-coefficient=-0.292; P=0.001). CONCLUSION: A strong association between HDL-C, inflammatory surrogates, and insulin resistance in this non-diabetic, non-obese haemodialysis patient group is demonstrated. The HDL-C level is still a good parameter to screen high-risk patients.

Peritoneal thickening is not inevitable in long-term peritoneal dialysis and is associated with peritoneal transport characteristics: a two-centre sonographic study.

BACKGROUND: The peritoneum is subject to alterations in the life-long course of peritoneal dialysis (PD). Studies of the parietal peritoneum by non-invasive ultrasonography in PD patients are limited. We hypothesize that a prolonged PD duration is associated with a thicker peritoneum on ultrasonography and alterations in Doppler indexes of mesenteric vessels. METHODS: We recruited two groups of patients, 18 who had >7 years of PD and 18 who had <12 months of PD. We excluded patients with active peritonitis, history of major abdominal surgery, cirrhosis or malignancy. We measured the sonographic thickness of the parietal peritoneum and Doppler indexes of mesenteric vessels by trans-abdominal ultrasonography at two PD units in Taiwan. RESULTS: We found no significant difference between two groups of PD patients in peritoneal thickness and in Doppler indexes. However, our univariate and multivariate analysis indicated that peritoneal thickness is associated with peritoneal transport characteristics (dialysate/plasma creatinine) but not with age, duration of dialysis, body height, body weight or Doppler index. The peritoneum is significantly thicker in rapid transporters than in slow transporters (RUQ: 0.59 +/- 0.40 mm versus 0.27 +/- 0.29 mm, P = 0.01; LUQ: 0.60 +/- 0.40 mm versus 0.27 +/- 0.32 mm, P = 0.016; LQ: 1.07 +/- 0.85 mm versus 0.48 +/- 0.53 mm, P = 0.026). In addition, rapid transporters have a marginally lower Doppler resistive index of the superior mesenteric artery (0.87 +/- 0.08 versus 0.90 +/- 0.10, P = 0.028). CONCLUSIONS: Our data showed that peritoneal thickening is not inevitable in long-term PD patients. Sonographic thickness in the parietal peritoneum is associated with transport characteristics. Rapid transporters have a significantly thicker peritoneum. The Doppler index of mesenteric vessels had no association with PD duration or transport characteristics. Trans-abdominal ultrasonography is non-invasive and useful in evaluating peritoneal characteristics of PD patients.

Age is not a discriminating factor for outcomes of therapeutic upper gastrointestinal endoscopy.

BACKGROUND/AIMS: To compare the efficacy and complications of therapeutic endoscopy for acute nonvariceal upper gastrointestinal bleeding between the geriatric (aged 65 and older) and non-geriatric patients. METHODOLOGY: A total of 134 out of 259 hospitalized patients in the year 2005 had high-risk endoscopic lesions in UGI endoscopy and received therapeutic endoscopy. Seventy-six out of 134 patients were aged 65 and older (44 men), while 58 patients were aged 64 and younger (51 men). We compared clinical presentations, co-morbidities, endoscopic therapeutic procedures, endoscopic treatment failure, hospitalization days, blood transfusion, post-endoscopy complications (fever, acute coronary syndrome, aspiration pneumonia), and in-hospital mortality after therapeutic endoscopy. RESULTS: Geriatric patients had lower hemoglobin on arrival (9.19 +/- 2.7 vs. 10.64 +/- 2.46 g/dL, p = 0.002) and larger gastric ulcers (7.3 +/- 6.9 vs. 4.0 +/- 3.6 mm, p = 0.008). Failure of therapeutic endoscopy, defined as salvage endoscopy or surgery within 48 hours after first endoscopy, showed no difference (14% vs. 14%, p = 0.98). Hospitalization stay (mean 7.47 vs. 5.97 days, p = 0.2), blood transfusion more than 4 units (47% vs. 34%, p = 0.13), post-endoscopic complications, in-hospital mortality were all comparable between geriatrics and non-geriatrics. CONCLUSIONS: Our results serve a scientific basis that age is not a discriminating factor for outcomes in current therapeutic endoscopy.

Diltiazem suppresses collagen synthesis and IL-1beta-induced TGF-beta1 production on human peritoneal mesothelial cells.

BACKGROUND: After long-term treatment with continuous ambulatory peritoneal dialysis (CAPD), some patients may develop peritoneal fibrosis. Peritoneal mesothelial cells (PMCs) participate in the inflammatory reactions in the peritoneal cavity, and transforming growth factor-beta1 (TGF-beta1) and interleukin-1beta (IL-1beta) are involved in peritoneal fibrosis. Diltiazem is used frequently in patients with CAPD to treat hypertension. The objectives of this study were to examine the effects of diltiazem on collagen- and IL-1beta-induced TGF-beta1 production on human PMCs and the signalling pathway of diltiazem in this induction. METHODS: Human PMCs were cultured from the enzymatic disaggregation of human omentum. Collagen synthesis was measured by [3H]proline incorporation into pepsin-resistant, salt-precipitated collagen. The expression of collagen I and III, and TGF-beta1 mRNA was evaluated by northern blotting. The production of TGF-beta1 by human PMCs was measured by immunoassay. The changes of intracellular calcium level after adding Fura-2-AM were measured by fluorescence spectrophotometry. Western blotting was used to assess mitogen-activated protein kinase (MAPK) signalling proteins. RESULTS: We found that diltiazem (<0.2 mM) inhibited collagen I and III mRNA expression and collagen syntheses on a dose-dependent basis. Diltiazem (0.2 mM) suppressed IL-1beta- (5 ng/ml) induced TGF-beta1 production on human PMCs at both the protein and mRNA levels. Diltiazem (0.2 mM) also inhibited IL-1beta- (5 ng/ml) induced collagen I and III mRNA expression. Intracellular calcium levels did not change after the treatment with diltiazem, IL-1beta or both. The IL-1beta-treated human PMCs increased phospho-JNK (stress-activated c-Jun N-terminal kinase) and phospho-p38 MAPK expression, while diltiazem could suppress this phenomenon. CONCLUSIONS: Diltiazem suppressed collagen synthesis of human PMCs and inhibited IL-1beta-induced TGF-beta1 production on human PMCs. This signalling transduction may be through p38 MAPK and JNK pathways instead of intracellular calcium. These results suggest diltiazem to be a potential therapeutic regimen in preventing peritoneal fibrosis and support further in vivo studies.