Randomized, controlled trial of glucose-sparing peritoneal dialysis in diabetic patients.

Glucose-containing peritoneal dialysis solutions may exacerbate metabolic abnormalities and increase cardiovascular risk in diabetic patients. Here, we examined whether a low-glucose regimen improves metabolic control in diabetic patients undergoing peritoneal dialysis. Eligible patients were randomly assigned in a 1:1 manner to the control group (dextrose solutions only) or to the low-glucose intervention group (IMPENDIA trial: combination of dextrose-based solution, icodextrin and amino acids; EDEN trial: a different dextrose-based solution, icodextrin and amino acids) and followed for 6 months. Combining both studies, 251 patients were allocated to control (n=127) or intervention (n=124) across 11 countries. The primary endpoint was change in glycated hemoglobin from baseline. Mean glycated hemoglobin at baseline was similar in both groups. In the intention-to-treat population, the mean glycated hemoglobin profile improved in the intervention group but remained unchanged in the control group (0.5% difference between groups; 95% confidence interval, 0.1% to 0.8%; P=0.006). Serum triglyceride, very-low-density lipoprotein, and apolipoprotein B levels also improved in the intervention group. Deaths and serious adverse events, including several related to extracellular fluid volume expansion, increased in the intervention group, however. These data suggest that a low-glucose dialysis regimen improves metabolic indices in diabetic patients receiving peritoneal dialysis but may be associated with an increased risk of extracellular fluid volume expansion. Thus, use of glucose-sparing regimens in peritoneal dialysis patients should be accompanied by close monitoring of fluid volume status.

Complications and outcomes of pandemic 2009 Influenza A (H1N1) virus infection in hospitalized adults: how do they differ from those in seasonal influenza?

BACKGROUND: It is unclear whether pandemic 2009 influenza A (pH1N1) infection caused more significant disease among hospitalized adults than seasonal influenza. METHODS: A prospective, observational study was conducted in adults hospitalized with polymerase chain reaction-confirmed pH1N1 infection in 2 acute-care general hospitals from June 2009 to May 2010 (n = 382). Complications and outcomes were described and compared with those in a seasonal influenza cohort (2007-2008, same hospitals; n = 754). RESULTS: Hospitalized patients with pH1N1 influenza were younger than those with seasonal influenza (mean age ± standard deviation, 47 ± 20 vs 70 ± 19 years) and fewer had comorbid conditions (48% vs 64%). The rate of positive immunofluorescence assay results was low (54% vs 84%), and antiviral use was frequent (96% vs 52%). Most patients in both cohorts developed complicated illnesses (67.8% vs 77.1%), but patients with pH1N1 influenza had higher rates of extrapulmonary complications (23% vs 16%; P = .004) and intensive care unit admission and/or death (patient age <35 years, 2.3% vs 0%; 35-65 years, 12.4% vs 3.2%; >65 years, 13.5% vs 8.5%; adjusted odds ratio [OR] 2.13; 95% confidence interval [CI], 1.25-3.62; P = .005). Patients who received antiviral treatment within 96 h after onset had better survival (log-rank test, P < .001). However, without timely treatment, the mortality risk was higher with pH1N1 infection (9.0% vs 5.8% for seasonal influenza; adjusted OR, 6.85; 95% CI, 1.64-28.65; P = .008]. Bacterial superinfection worsened outcomes. CONCLUSIONS: Adults hospitalized for pH1N1 influenza had significant complications and mortality despite being younger than patients with seasonal influenza. Antiviral treatment within 96 h may improve survival.

Anticoagulation during haemodialysis using a citrate-enriched dialysate: a feasibility study.

BACKGROUND: The feasibility of anticoagulating the extracorporeal circuit during haemodialysis using a simple citrate-enriched dialysate was evaluated in a prospective, randomised, cross-over study of 24 patients who were at high risk for bleeding. METHODS: A dialysate, with a citrate level of 3 mEq/L (1 mmol/L), was generated by adding citrate to the conventional liquid 'bicarbonate concentrate' of a regular, dual-concentrate, bicarbonate-buffered dialysate delivery system. Each of the 24 patients received two dialysis treatments. For anticoagulation of the extracorporeal circuit, one treatment used the citrate-enriched dialysate (Citrate Group), while the other treatment used conventional saline flushing (Saline Group). The order of the two treatments was randomised. With either method, a heparinized, saline-rinsed dialyser was used, and no heparin was administered during dialysis. RESULTS: Ninety-two per cent (22 out of 24) and 100% of patients tolerated the procedure well in the Citrate Group and the Saline Group, respectively. Eight per cent (two out of 24) of the treatments in each group had to be abandoned because of clotting in the extracorporeal circuit. Significantly less thrombus formation in the venous air traps was detected in the Citrate Group. No patients from either group suffered from hypocalcaemic or bleeding complications, but the immediate post-dialysis and 0.5-h post-dialysis plasma levels of ionised calcium and of magnesium were slightly lower in the Citrate Group than in the Saline Group. CONCLUSIONS: Our findings suggest that it is feasible to use the present simple citrate-enriched dialysate to dialyse patients safely and effectively. Furthermore, the approach is much simpler than a conventional, intermittent, saline-flushing method.

Timely initiation of dialysis for chronic kidney disease: perspective from four Asian countries.

Recommendations about when to initiate dialysis for end-stage kidney failure have been made by a number of expert groups. These recommendations have led to changes in clinical practice, yet they are not based on high level evidence. In fact, most reported studies argue that dialysis should be started early rather than late, many are confounded and a number have reached the opposite conclusion. Probably more important than a prescribed level of renal function at which dialysis is initiated is the widespread adoption of a structured approach to pre-dialysis care and the recognition of the importance of pre-dialysis patient education. One of the main determinants of optimal initiation of dialysis is the time of referral of the patient to a nephrologist or a renal unit. In particular, early referral of patients with chronic kidney disease allows a planned initiation of dialysis, using from the start permanent vascular or peritoneal dialysis access.

Randomized Controlled Trial on Adjunctive Lavage for Severe Peritonitis.

Background:In severe peritoneal dialysis (PD)-related peritonitis, patients' response to antibiotic can be poor. We postulated that adjunctive lavage may improve the outcome in severe cases by enhancing the removal of bacteria and inflammatory cells from the peritoneum.Methods:Severe PD peritonitis was defined as poor clinical response to empirical cefazolin/ceftazidime and a PD effluent (PDE) leukocyte count > 1,090/mm3 on day 3. Enrolled patients were randomized into either the lavage group (n = 20) or control group (n = 20). In the lavage group, continuous lavage by an automated PD machine from day 3 to 5 or 6 was performed, whereas the usual PD schedule was maintained in the control group. The primary outcome was treatment success. Post hoc analysis was also performed to compare the outcome between subgroups with different severity.Results:Baseline parameters were similar in the lavage and control groups, including PDE leukocyte count on day 3 (4,871/mm3 vs 4,143/mm3, p = 0.46). Treatment success rates were high in both groups (75% vs 70%, p = 0.72). C-reactive protein (CRP) on day 3 was found to be the only predictor of treatment failure and was used to stratify all patients into tertiles of severity. Whilst a significant decline in treatment success was evident across the tertiles of increasing CRP in the control group (100% vs 85.7% vs 28.6%, p = 0.005), treatment success was relatively maintained in the lavage group (85.7% vs 71.4% vs 66.7%, p = 0.43).Conclusions:Adjunctive lavage did not improve the overall outcome, although it may be beneficial for the more severe peritonitis patients who have high CRP.

ASPD: A prospective study of adequacy in Asian patients on long term, small volume, continuous ambulatory peritoneal dialysis.

BACKGROUND: The impact of small solute clearance on patient survival in continuous ambulatory peritoneal dialysis (CAPD) is not yet solidified. Previously, we demonstrated that CAPD using small volume (6 L) daily exchanges provides adequate dialysis for most Asian patients. METHODS: We conducted a prospective, long-term observational study to determine the optimal dialysis adequacy that may provide better patient survival for Asian patients who receive small-volume CAPD. We recruited 294 patients. The initial CAPD regime was 3 x 2-L exchanges daily. The same regime was maintained unless there was significant loss of ultrafiltration or fluid retention despite the use of hypertonic dialysate. RESULTS: Median study period was 38.9 (range 5 - 76.5) months, with 81% and 27% of patients remaining in the study at 24 and 48 months respectively. The overall survival rates at 2 and 4 years were 94.0% and 74.8% respectively. Our long-term data revealed that survival rate was related to Kt/V values. Survival rates were significantly higher for patients with total Kt/V > 2.0 than for patients with Kt/V < 1.7 (p = 0.02). The former group had lower body mass index and higher residual renal function and peritoneal Kt/V than the Latter group. On analysis using Cox proportional hazards regression models, cardiovascular disease (CVD), lower urine volume, and higher body mass index were independent predictors of mortality. Patients with higher renal Kt/V had a significantly lower risk of mortality (RR = 0.018, p = 0.01) after adjusting for the effects of CVD and diabetes mellitus. CONCLUSION: Our data recommend that 1.7 be the minimal target for total Kt/V in patients on long-term CAPD. Patients with high body mass index, low residual urine volume, and significant CVD need close monitoring.

A report with consensus statements of the International Society of Nephrology 2004 Consensus Workshop on Prevention of Progression of Renal Disease, Hong Kong, June 29, 2004.

This report summarizes the discussions of the International Society of Nephrology (ISN) 2004 Consensus Workshop on Prevention of Progression of Renal Disease, which was held in Hong Kong on June 29, 2004. Three key areas were discussed during the workshop: (1) screening for chronic kidney disease; (2) evaluation and estimating progression of chronic kidney disease; and (3) measures to prevent the progression of chronic kidney disease. Fifteen consensus statements were made in these three areas, as endorsed by the participants of the workshop. The ISN can make use of and take reference to these statements in formulating its policy for tackling chronic kidney disease, a disease with significant global impact.

Phosphorus-enriched hemodialysates: formulations and clinical use.

Although hyperphosphatemia is a cardinal feature of renal failure, the occasional patient suffering from end-stage renal disease (ESRD) may present with hypophosphatemia. For example, hypophosphatemia can develop in ESRD patients if they suffer from malnutrition or if they are aggressively dialyzed. Hypophosphatemia is commonly prevented or treated with the oral or the intravenous administration of soluble phosphate salts; however, determination of the required oral or intravenous dose is difficult. Under appropriate circumstances, phosphorus-enriched dialysates can also be employed for the purpose of phosphorus administration. Various preparations of soluble phosphate salts can be used to enrich hemodialysates.

Cardiovascular Protective Effects of Adjunctive Alternative Medicine (Salvia miltiorrhiza and Pueraria lobata) in High-Risk Hypertension.

Introduction. Hypertension in association with diabetes (DM), renal impairment (RI), and left ventricular hypertrophy (LVH) increases the risk of future cardiovascular events. We hypothesize, traditional herbal medicines Danshen and Gegen (D&G) have beneficial effects on atherogenesis in these high-risk hypertensive subjects. Subjects and Methods. 90 asymptomatic hypertensive subjects associated with LVH (63.3%), DM (62.2%), or RI (30%) were randomized to receive D&G herbal capsules 1 gm/day, 2 gm/day, or identical placebo capsules in double-blind and parallel fashion for 12 months. Brachial flow-mediated dilation (endothelium-dependent dilation, FMD) and carotid intima-media thickness (IMT) were measured by ultrasound. All data were analyzed using the Statistical Package for Social Sciences in Windows 16.0. Results. Their mean age was 55 ± 8 years, and 74.4% were male. After 12 months of adjunctive therapies and compared with baseline, there were no significant changes in blood pressure, heart rate, hematological, glucose, and creatinine profiles in both placebo and D&G groups. FMD improved significantly during D&G (P = 0.0001) and less so after placebo treatment (P = 0.001). There was a mild but significant decrease in carotid IMT after D&G (P < 0.001) but no significant changes after placebo. A trend of better improvement in FMD after higher versus lower D&G dosages was seen. D&G were well tolerated, with no significant adverse events or blood biochemistry changes. Conclusion. D&G adjunctive treatment was well tolerated and significantly improved atherogenesis in high-risk hypertensive patients, with potential in primary atherosclerosis prevention.

Viral clearance and inflammatory response patterns in adults hospitalized for pandemic 2009 influenza A(H1N1) virus pneumonia.

BACKGROUND: Little is known about the virological and inflammatory responses of severe pandemic 2009 influenza A(H1N1) virus pneumonia during antiviral treatment. METHODS: In a prospective observational study, we recruited consecutive adults hospitalized with confirmed pandemic 2009 H1N1 infection during a 16-week period. Nasopharyngeal aspirate and non-respiratory samples (blood, stool and urine) were collected at presentation, and serial nasopharyngeal flocked swabs (NPFS) and tracheal aspirates (TA) were collected after initiating oseltamivir treatment for quantitative viral RNA assay, using real-time reverse transcriptase-PCR. Serial plasma samples were collected for cytokine/chemokine assay using cytometric bead array. Patients with severe pneumonia (lung infiltrates and hypoxaemia) were compared to those with milder illnesses. RESULTS: A total of 66 patients were studied (mean age 43 ±20 years); 28 (42%) developed severe pneumonia, of whom 10 (15%) required intubation. Severe pneumonia was associated with older age, dyspnoea, delayed presentation >2 days from onset, extrapulmonary virus detection (13-28%) and higher viral concentration despite late-presentation (multiple linear regression, ß=0.94, 95% confidence interval 0.15-1.74; P=0.02). Patients with severe pneumonia exhibited slow viral clearance with oseltamivir treatment, particularly in the lower respiratory tract (median [interquartile range] durations of RNA positivity after antiviral initiation were NPFS 6.0 days [3.0-8.0], TA 11.0 days [7.8-14.3] versus milder illness group NPFS of 2.0 days [1.0-3.0] days; P<0.01). High viral load in lower respiratory tract despite upper-tract RNA negativity and viral rebound after stopping treatment were noted in some patients. H275Y mutation was absent. High plasma levels of interleukin (IL)-6, CXCL-8 (IL-8), CCL2 (monocyte chemoattractant protein-1) and soluble tumour necrosis factor receptor-1 were observed, which correlated with the extent and progression of pneumonia in hospital. CONCLUSIONS: In severe 2009 H1N1 pneumonia, viral clearance is slow with treatment, particularly in the lower respiratory tract. A more sustained antiviral regime appears warranted.