Hyperphosphatemia as an independent risk factor for coronary artery calcification progression in peritoneal dialysis patients.

BACKGROUND: Coronary artery calcification (CAC) is associated with cardiovascular mortality in end-stage renal disease (ESRD) patients. The present study aimed to identify modifiable risk factors for CAC progression in peritoneal dialysis (PD) patients. METHODS: Adult patients who received regular PD for more than 6 months and underwent a series of coronary artery calcification score (CaCS) measurements by multislice spiral computed tomography (MSCT) with an interval of ≥ 6 months were included in this observational cohort study. The demographic characteristics and clinical data, including laboratory data and adequacy of PD, were collected. Curve estimation was used to fit the straight line and obtain the slope. Binary logistic regression was performed to identify the independent risk factors for CAC progression in the PD patients, and multivariate linear regression was conducted to identify factors associated with hyperphosphatemia. RESULTS: A total of 207 adult patients on PD (116 men, 56.0 %) with a mean age of 59.8 ± 15.9 years were recruited to this study, and 157 of them (75.8 %) received three or more CaCS assessments. The patients were divided into a slow group (n = 137) and a rapid group (n = 70) according to the linear regression slope or the average speed of development. The follow-up time was 33.0 ± 18.8 months. Multivariate logistic regression revealed that age and serum phosphate level were independent risk factors for CAC progression after adjustments. Multivariate linear regression revealed that hyperphosphatemia was associated with elevations in the transferrin and serum albumin levels and normalized protein catabolic rate (nPCR) and reductions in the hemoglobin level, residual Ccr, and PD Ccr. CONCLUSIONS: Hyperphosphatemia is an independent risk factor for CAC progression, and the serum phosphate level may be associated with protein intake and PD adequacy. These results provide important information for the clinical management of ESRD patients.

Suppressed expression of long non-coding RNA HOTAIR inhibits proliferation and tumourigenicity of renal carcinoma cells.

Although long non-coding RNAs (lncRNAs) are known to play an important role in cell regulation in several cancers, the regulatory mechanisms in renal carcinoma cells remain unclear. HOX transcript antisense RNA (HOTAIR), an lncRNA, coordinates with chromatin-modifying enzymes to regulate gene silencing. HOTAIR is over-expressed in several types of carcinoma cells. Thus, we hypothesised that lncRNA HOTAIR is crucial for cell proliferation and invasion and that its knockdown induces apoptosis in renal carcinoma cells. lncRNA HOTAIR expression was found to be elevated in renal carcinoma cells. Additionally, lncRNA HOTAIR knockdown by RNA interference with siRNA was found to significantly affect the cell cycle in the G0/G1 phase and weaken the abilities of cell proliferation and invasion in vitro. Xenograft experiments confirmed that the growth of xenograft tumours formed by renal carcinoma cells was suppressed after silencing lncRNA HOTAIR expression. Moreover, chromatin immunoprecipitation (ChIP) and RNA-binding protein immunoprecipitation (RIP) assays revealed that knockdown of lncRNA HOTAIR led to the weakening of the recruitment and binding abilities of EZH2 and H3K27me3 locus with lncRNA HOTAIR. Furthermore, the cell cycle-related gene locus was in an active transcriptional state by the silencing of lncRNA HOTAIR expression and modulation of covalent histones.

Nitrotyrosine level was associated with mortality in patients with acute kidney injury.

BACKGROUND: To examine the characteristics of oxidative stress in patients with acute kidney injury (AKI) and investigate the association between plasma nitrotyrosine levels and 90-day mortality in patients with AKI. METHODOLOGY/PRINCIPAL FINDINGS: 158 patients with hospital-acquired AKI were recruited to this prospective cohort study according to RIFLE (Risk, Injury, Failure, Lost or End Stage Kidney) criteria. Twelve critically ill patients without AKI and 15 age and gender-matched healthy subjects served as control. Plasma 3-nitrotyrosine was analyzed in relation to 90-day all cause mortality of patients with AKI. The patients with AKI were followed up for 90 days and grouped according to median plasma 3-nitrotyrosine concentrations. Highest 3-NT/Tyr was detected in patients with AKI compared with healthy subjects, and critically ill patients without AKI (ANOVA p<0.001). The 90-day survival curves of patients with high 3-NT/Tyr showed significant differences compared with the curves of individuals with low 3-NT/Tyr (p = 0.001 by log rank test). Multivariate analysis (Cox regression) revealed that 3-NT/Tyr (p = 0.025) was independently associated with mortality after adjustment for age, gender, sepsis and Acute Physiology and Chronic Health Evaluation (APACHE) II score. CONCLUSIONS/SIGNIFICANCE: There is excess plasma protein oxidation in patients with AKI, as evidenced by increased nitrotyrosine content. 3-NT/Tyr level was associated with mortality of AKI patients independent of the severity of illness.

Prevalence and risk factors associated with peripheral artery disease in elderly patients undergoing peritoneal dialysis.

BACKGROUND: Rapid growth of the elderly peritoneal dialysis (PD) population is posing a special challenge for renal teams. Peripheral artery disease (PAD) has been reported to be an independent predictor of cardiovascular and all-cause mortality in hemodialysis patients. However, the prevalence and associated risk factors for PAD in elderly PD patients have not yet been fully investigated. METHODS: A total of 69 elderly PD patients were included in the present study. PAD was defined as either an ankle-brachial index < 0.9 or a history of intermittent claudication, lower-limb amputation, foot ulcers, or gangrene. On enrollment, clinical and biochemical characteristics were collected. RESULTS: The overall prevalence of PAD was 31.9%. Compared with non-PAD patients, PAD patients were significantly older and more likely to be female and have longer PD duration and lower diastolic blood pressure (P < 0.001, = 0.002, 0.018, and 0.007, respectively). Serum albumin level (P < 0.001) and residual renal Kt/V value (P < 0.001) were significantly lower, but the serum C-reactive protein level (P = 0.005) was significantly higher, in PAD patients compared with non-PAD patients. Logistic regression analysis showed that serum albumin level (odds ratio = 1.485, P = 0.040) and residual renal Kt/V value (odds ratio = 1.725, P = 0.016) were independently associated with PAD. CONCLUSION: A high prevalence of PAD appeared among elderly PD patients in Macao. Serum albumin level and residual renal Kt/V value were independently related to PAD.

Risk factors associated with brachial-ankle pulse wave velocity among peritoneal dialysis patients in Macao.

BACKGROUND: Cardiovascular disease is the leading cause of mortality among peritoneal dialysis (PD) patients in Macao. Increased arterial stiffness determined by pulse wave velocity (PWV) has been established as an independent predictor of cardiovascular mortality in end-stage renal disease patients. The present study aims to investigate the relationship between arterial stiffness and its associated risk factors in chronic PD patients. METHODS: A total of 96 chronic PD patients (48 males/48 females) were included in the cross-sectional study. Arterial stiffness was assessed by brachial-ankle PWV (baPWV). Patients were divided into two subgroups according to mean baPWV value. On enrollment, clinical characteristics and biochemical parameters were collected. RESULTS: Compared with low baPWV group patients, high baPWV group patients were significant older (p<0.001) and more likely to have a high proportion of female gender (p=0.004) as well as previous CVD history (p=0.008). Serum albumin, pre-albumin levels and residual renal creatinine clearance (CCr) were significantly lower but the serum ferritin level was significantly higher in high baPWV group patients than in low baPWV group patients (all p<0.01). BaPWV was positively associated with age (r=0.534, p<0.001), Charlson comorbidity index (r=0.350, p<0.001) and serum ferritin level (r=0.340, p=0.001). Meanwhile, baPWV negatively correlated with serum albumin (r=-0.479, p<0.001), pre-albumin levels (r=-0.320, p=0.003) and residual renal CCr (r=-0.177, p=0.048). Age-adjusted partial correlation test found a significant correlation between baPWV and CRP (r=0.462, p<0.001). Multivariate regression analysis showed that baPWV was independently associated with age (p<0.001), serum albumin level (p=0.015), CRP (p=0.019) and residual renal CCr (p=0.045). CONCLUSION: Arterial stiffness, assessed by baPWV, had an independent correlation with age, serum albumin level, CRP level and residual renal CCr among PD patients in Macao.

The ratio of CRP to prealbumin levels predict mortality in patients with hospital-acquired acute kidney injury.

BACKGROUND: Animal and human studies suggest that inflammation and malnutrition are common in acute kidney injury (AKI) patients. However, only a few studies reported CRP, a marker of inflammation, albumin, prealbumin and cholesterol, markers of nutritional status were associated with the prognosis of AKI patients. No study examined whether the combination of inflammatory and nutritional markers could predict the mortality of AKI patients. METHODS: 155 patients with hospital-acquired AKI were recruited to this prospective cohort study according to RIFLE (Risk, Injury, Failure, Lost or End Stage Kidney) criteria. C-reactive protein (CRP), and the nutritional markers (albumin, prealbumin and cholesterol) measured at nephrology consultation were analyzed in relation to all cause mortality of these patients. In addition, CRP and prealbumin were also measured in healthy controls (n = 45), maintenance hemodialysis (n = 70) and peritoneal dialysis patients (n = 50) and then compared with AKI patients. RESULTS: Compared with healthy controls and end-stage renal disease patients on maintenance hemodialysis or peritoneal dialysis, patients with AKI had significantly higher levels of CRP/prealbumin (p < 0.001). Higher level of serum CRP and lower levels of albumin, prealbumin and cholesterol were found to be significant in the patients with AKI who died within 28 days than those who survived >28 days. Similarly, the combined factors including the ratio of CRP to albumin (CRP/albumin), CRP/prealbumin and CRP/cholesterol were also significantly higher in the former group (p < 0.001 for all). Multivariate analysis (Cox regression) revealed that CRP/prealbumin was independently associated with mortality after adjustment for age, gender, sepsis and sequential organ failure assessment (SOFA, p = 0.027) while the others (CRP, albumin, prealbumin, cholesterol, CRP/albumin and CRP/cholesterol) became non-significantly associated. The hazard ratio was 1.00 (reference), 1.85, 2.25 and 3.89 for CRP/prealbumin increasing according to quartiles (p = 0.01 for the trend). CONCLUSIONS: Inflammation and malnutrition were common in patients with AKI. Higher level of the ratio of CRP to prealbumin was associated with mortality of AKI patients independent of the severity of illness and it may be a valuable addition to SOFA score to independent of the severity of illness and it may be a valuable addition to SOFA score to predict the prognosis of AKI patients.

Efficacy of cytokine removal by plasmadiafiltration using a selective plasma separator: in vitro sepsis model.

More effective removal of pro- and anti-inflammatory cytokines may play an important role in the treatment of sepsis. Plasmadiafiltration (PDF) with a larger selective plasma separator was performed to study the cytokine and plasma protein permeability profiles of the membrane in an in vitro sepsis model. The in vitro sepsis model was constructed by exposure of human whole blood to bacterial lipopolysaccharide. EVACURE 2A, a selective plasma separator, was placed in the blood circuit of PDF. Sieving coefficients of cytokines and plasma protein were tested in post-dilution PDF mode at the following operating parameters: blood flow rate 150 mL/min; dialysate flow rate 33.33 mL/min; replacing fluid flow rate 6.67 mL/min; ultrafiltration rate 5 mL/min. An enzyme linked immunoadsorbent assay was used to measure the concentrations of tumor necrosis factor-α (TNF-α), high-mobility group box 1 protein (HMGB1), interleukin-1ß (IL-1ß), interleukin-1 receptor antagonist (IL-1ra), interleukin-2 (IL-2), interleukin-2 receptor (IL-2r), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10) in plasma and ultrafiltrate. Sieving coefficients of different solutes ranged from 0.1 to 1.0 at first, decreased 10%-60% after 1 h of PDF, and then remained stable. Total clearance rates of cytokines ranged from 15 to 80 mL/min. The concentrations of cytokines decreased 20-80% after 1 hour of PDF. The sieving coefficient of albumin was 0.1 at first and then decreased to 0.05 after 1 hour of therapy. Plasmadiafiltration with Evacure 2A plasma separator can effectively remove almost all of the inflammatory mediators with low albumin loss.

Intima-media thickness of the carotid artery and its correlation factors in maintenance hemodialysis patients: a cross-sectional study.

BACKGROUND: To investigate the relationship between the intima-media thickness of the carotid artery (CA-IMT) and its major risk factors in maintenance hemodialysis (MHD) patients. METHODS: Seventy-five MHD patients and 30 healthy volunteers were enrolled. The MHD patients were divided into 3 subgroups according to their CA-IMT value. RESULTS: CA-IMT values in the MHD group were significantly higher than those in the control group. The differences in age, systolic blood pressure (SBP), and levels of serum albumin, prealbumin, cholesterol and serum phosphate between the increased IMT group and the normal IMT group were significant. SBP and serum phosphate levels were also greater in the abnormal IMT group than those in the normal IMT group. Significant relationships were found between CA-IMT and age, SBP, and serum levels of phosphate, albumin and prealbumin. In multiple regression analysis, a high serum phosphate level, low serum prealbumin level and high SBP were significant independent risk factors of increased CA-IMT. CONCLUSIONS: CA-IMT was increased dramatically in MHD patients. A high serum phosphate level, low serum prealbumin level and high SBP may be associated with advanced arteriosclerosis.

Rational choice of peritoneal dialysis catheter.

The peritoneal catheter should be a permanent and safe access to the peritoneal cavity. Catheter-related problems are often the cause of permanent transfer to hemodialysis (HD) in up to 20% of peritoneal dialysis (PD) patients; in some cases, these problems require a temporary period on HD. Advances in connectology have reduced the incidence of peritonitis, and so catheter-related complications during PD have become a major concern. In the last few years, novel techniques have emerged in the field of PD: new dialysis solutions, better connectology, and cyclers for automated PD. However, extracorporeal dialysis has continued to improve in terms of methods and patient survival, but PD has failed to do so. The main reason is that peritoneal access has remained problematical. The peritoneal catheter is the major obstacle to wide-spread use of PD. Overcoming catheter-related problems means giving a real chance to development of the peritoneal technique. Catheters should be as efficient, safe, and acceptable as possible. Since its introduction in the mid-1960s, the Tenckhoff catheter has not become obsolete: dozens of new models have been proposed, but none has significantly reduced the pre-dominance of the first catheter. No convincing prospective data demonstrate the superiority of any peritoneal catheter, and so it seems that factors other than choice of catheter are what affect survival and complication rates. Efforts to improve peritoneal catheter survival and complication rates should probably focus on factors other than the choice of catheter. The present article provides an overview of the characteristics of the best-known peritoneal catheters.

Advances in the technology of automated, tidal, and continuous flow peritoneal dialysis.

Automated peritoneal dialysis (APD) has undergone substantial growth in recent years because of an increased demand for higher doses of peritoneal dialysis (PD) treatment and a need to improve quality of life for patients. The evolution of this treatment is closely linked with the development of new automatic machines and with recent advances in prescription and monitoring of PD treatment. In the present article, we describe the characteristics of the new generation of APD cyclers with particular regard to adequacy targets and safety. There is renewed interest in continuous-flow peritoneal dialysis (CFPD), because of a belief that new peritoneal access technologies will make the success of this modality a possibility. In the CFPD technique, a certain amount of fluid is constantly present in the abdomen, and constant inflow and outflow are maintained without interruption thanks to paired indwelling catheters. The PD solution is used either in a single pass or in a recirculation loop with a regeneration systems (sorbent cartridge or dialyzer).

Effectiveness of sodium hypochlorite in the prevention of catheter related infections.

Vascular access in hemodialysis is a major point of concern in the management of chronic patients. Although arteriovenous fistula remains as the access of first choice, tunneled central venous catheters are still commonly used. Infection remains the principal cause of catheter dysfunction or loss. Many protocols have been used in order to prevent exit site infections and bacteremia. We describe our experience with the use of sodium hypochlorite, an electrolytic chloroxidizer used as a topical disinfectant. It has been shown to be active against a broad spectrum of potential pathogens and has other specific advantages compared to other cleansing agents, including its non-toxic, non-irritating nature and its low cost. We conclude that sodium hypochlorite solution in different concentrations (10 and 50%) is effective in preventing exit site infections and bacteremia associated with tunneled central venous catheters in chronic hemodialysis patients.

Extracorporeal blood purification therapies for prevention of radiocontrast-induced nephropathy: a systematic review.

BACKGROUND: Radiocontrast-induced nephropathy (RCIN) causes acute kidney injury and increases mortality. Studies have examined the capacity of various forms of extracorporeal blood purification therapies for the prevention of RCIN, with conflicting results. We conducted a systematic review of published trials to determine whether periprocedural extracorporeal blood purification prevents RCIN. METHODS: We searched PubMed, the Cochrane Collaboration Database, EMBASE, and CINAHL through January 2006 and bibliographies of retrieved articles and consulted with experts to identify relevant studies. Published studies of extracorporeal blood purification for the prevention of RCIN in patients receiving radiocontrast were included. Two authors reviewed all citations. The primary end point is the incidence of RCIN, defined as an increase in serum creatinine concentration (>or=0.5 mg/dL [>or=44 micromol/L]). Results were combined on the risk ratio scale. Random-effects models were used. Sensitivity analyses were performed to evaluate the effects of extracorporeal blood purification modality, study design, and sample size. RESULTS: Eight trials (6 randomized controlled trials, 2 nonrandomized trials) were included in the analysis (pooled sample size, 412). Six trials assessed hemodialysis, whereas 1 trial each assessed continuous venovenous hemofiltration and continuous venovenous hemodiafiltration. The incidence of RCIN was 35.2% in the standard-medical-therapy group and 27.8% in the extracorporeal-blood-purification group. Extracorporeal blood purification did not decrease the incidence of RCIN significantly compared with standard medical therapy (risk ratio, 0.97; 95% confidence interval, 0.44 to 2.14); however, intertrial heterogeneity was high. Limiting analysis to only randomized trials did not eliminate heterogeneity, but limiting analysis to only hemodialysis trials did. Periprocedural hemodialysis did not decrease the incidence of RCIN. CONCLUSION: This critical analysis of the published literature suggests that periprocedural extracorporeal blood purification does not decrease the incidence of RCIN compared with standard medical therapy.