Bioincompatible Impact of Different Peritoneal Dialysis Fluid Components and Therapeutic Interventions as Tested in a Rat Peritoneal Dialysis Model

Peritoneal dialysis (PD) is associated with functional and structural changes of the peritoneal membrane. In this paper, we describe the impact of different factors contributing to peritoneal incompatibility of PD fluid installation including presence of a catheter, volume loading, and the PD fluid components itself. These factors initiate recruitment and activation of peritoneal immune cells such as macrophages and mast cells, as well as activation of peritoneal cells as mesothelial cells in situ. We provide an overview of PD-associated changes as seen in our rat PD-exposure model. Since these changes are partly reversible, we finally discuss therapeutic strategies in the rat PD model with possible consequences of long-term PD in the relevant human setting

Economic impact of extended time on peritoneal dialysis as a result of using polyglucose: the application of a Markov chain model to forecast changes in the development of the ESRD programme over time

BACKGROUND: The use of polyglucose as a peritoneal dialysis (PD) fluid extends time on PD treatment. It is anticipated, therefore, that the share of patients treated with PD will be positively influenced. The relationship between extension of PD treatment time and an increase of the PD treatment share, however, is complex and needs further investigation. In this paper, a Markov chain model was applied to investigate the impact of extended time on PD treatment for the PD share in all dialysis patients in The Netherlands. Furthermore, the economic impact of the extended time on treatment (ETOT) was explored. METHODS: Scenarios were forecast over a 10 year period using aggregate data from the End-Stage Renal Registry in The Netherlands (Renine). Three scenarios were simulated in which the median PD technique survival was extended by 8, 10 and 12 months. Two other scenarios explored the impact of the combined effect of ETOT of 10 months together with a 10% and 20% increase of PD inflow shares. Reductions of costs to society due to ETOT were estimated using Dutch cost data on renal replacement therapies. RESULTS: PD share increases from 30.0% in the null scenario to 34.5% in the scenario with an ETOT of 10 months and an increased PD inflow share of 20%. The reduction in total costs to society of the renal replacement therapies is 0.96%. The average societal costs per discounted patient year for haemodialysis (HD) are 84 100 euros. For PD, these costs are 60 300 euros. A shift from HD to PD results in average cost savings of 28% per patient year. CONCLUSIONS: In view of high dialysis costs to society, a reduction of 0.96% can be considered to be relevant for healthcare policy makers

Citrate confers less filter-induced complement activation and neutrophil degranulation than heparin when used for anticoagulation during continuous venovenous haemofiltration in critically ill patients

Background: During continuous venovenous haemofiltration (CVVH), regional anticoagulation with citrate may be superior to heparin in terms of biocompatibility, since heparin as opposed to citrate may activate complement (reflected by circulating C5a) and induce neutrophil degranulation in the filter and myeloperoxidase (MPO) release from endothelium. Methods. No anticoagulation (n = 13), unfractionated heparin (n = 8) and trisodium citrate (n = 17) regimens during CVVH were compared. Blood samples were collected pre- and postfilter; C5a, elastase and MPO were determined by ELISA. Additionally, C5a was also measured in the ultrafiltrate. Results: In the heparin group, there was C5a production across the filter which most decreased over time as compared to other groups (P = 0.007). There was also net production of elastase and MPO across the filter during heparin anticoagulation (P = 0.049 or lower), while production was minimal and absent in the no anticoagulation and citrate group, respectively. During heparin anticoagulation, plasma concentrations of MPO at the inlet increased in the first 10 minutes of CVVH (P = 0.024). Conclusion: Citrate confers less filter-induced, potentially harmful complement activation and neutrophil degranulation and less endothelial activation than heparin when used for anticoagulation during continuous venovenous haemofiltration in critically ill patients

CHANGING NURSING CARE TIME AS AN EFFECT OF CHANGED CHARACTERISTICS OF THE DIALYSIS POPULATION

Background: The population of dialysis patients is ageing. Dialysis nurses are confronted with geriatric patients with multiple comorbidities. Nurses are confronted with an increasing burden of care. Objectives: The present study focused on the question of whether, over time, the increasing age and comorbidities of the haemodialysis population increased nursing care time. Furthermore, we studied potential changes in the predictors of the required nursing time. Design: Observational study. Participants: A total of 980 dialysis patients from 12 dialysis centres were included. Measurements: Nurses filled out the classification tool for each patient and completed a form for reporting patient characteristics for groups of relevant haemodialysis patients at baseline and after 1 and four years. Changes in patient and dialysis characteristics were analysed, as well as the estimated nursing care time needed. Results: An increase in the nursing time needed for dialysis was largely due to decreased mobility, closing of the vascular access and a greater need for psychosocial attention and was most strongly present in incident dialysis patients. The time needed for dialysis decreased as patient participation increased and vascular access changed from catheters to fistulae. Over the four-year period, the average overall needed nursing care time per haemodialysis session did not change. Conclusions: Our study shows that the average nursing time needed per patient did not change in the four-year observation period. However, more time is required for incident patients; thus, if a centre has high patient turnover, more nursing care time is needed

The plasma level and biomarker value of neutrophil gelatinase-associated lipocalin in critically ill patients with acute kidney injury are not affected by continuous venovenous hemofiltration and anticoagulation applied

Introduction: Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of acute kidney injury (AKI), and levels reflect severity of disease in critically ill patients. However, continuous venovenous hemofiltration (CVVH) may affect plasma levels by clearance or release of NGAL by activated neutrophils in the filter, dependent on the anticoagulation regimen applied. We therefore studied handling of NGAL by CVVH in patients with AKI.Methods: Immediately before initiation of CVVH, prefilter blood was drawn. After 10, 60, 180, and 720 minutes of CVVH, samples were collected from pre- and postfilter (in- and outlet) blood and ultrafiltrate. CVVH with the following anticoagulation regimens was studied: no anticoagulation in case of a high bleeding tendency (n = 13), unfractionated heparin (n = 8), or trisodium citrate (n = 21). NGAL levels were determined with enzyme-linked immunosorbent assay (ELISA).Results: Concentrations of NGAL at inlet and outlet were similar, and concentrations did not change over time in any of the anticoagulation groups; thus no net removal or production of NGAL occurred. Concentrations of NGAL at inlet correlated with disease severity at initiation of CVVH and at the end of a CVVH run. Concentrations of NGAL in the ultrafiltrate were lower with citrate-based CVVH (P = 0.03) and decreased over time, irrespective of anticoagulation administered (P < 0.001). The sieving coefficient and clearance of NGAL were low and decreased over time (P < 0.001).Conclusions: The plasma level and biomarker value of NGAL in critically ill patients with AKI are not affected by CVVH, because clearance by the filter was low. Furthermore, no evidence exists for intrafilter release of NGAL by neutrophils, irrespective of the anticoagulation method applied

Reduction of Oxidative Stress in Chronic Kidney Disease Does Not Increase Circulating alpha-Klotho Concentrations

The CKD-associated decline in soluble α-Klotho levels is considered detrimental. Some in vitro and in vivo animal studies have shown that anti-oxidant therapy can upregulate the expression of α-Klotho in the kidney. We examined the effect of anti-oxidant therapy on α-Klotho concentrations in a clinical cohort with mild tot moderate chronic kidney disease (CKD). We performed a post-hoc analysis of a prospective randomized trial involving 62 patients with mild to moderate CKD (the ATIC study), all using an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) for 12 months. On top of that, the intervention group received anti-oxidative therapy consisting of the combination of pravastatin (40 mg/d) and vitamin E (α-tocopherol acetate, 300 mg/d) while the placebo was not treated with anti-oxidants. α-Klotho concentrations were measured at baseline and after 12 months of anti-oxidant therapy. Data were analysed using T-tests and Generalized Estimating Equations, adjusting for potential confounders such as vitamin D, parathyroid hormone, fibroblast-growth-factor 23 (FGF23) and eGFR. The cohort existed of 62 patients with an eGFR (MDRD) of 35 ± 14 ml/min/1.72 m2, 34 were male and mean age was 53.0 ± 12.5 years old. Anti-oxidative therapy did successfully reduce oxLDL and LDL concentrations (P <0.001). α-Klotho concentrations did not change in patients receiving either anti-oxidative therapy (476.9 ± 124.3 to 492.7 ± 126.3 pg/mL, P = 0.23) nor in those receiving placebo 483.2 ± 142.5 to 489.6 ± 120.3 pg/mL, P = 0.62). Changes in α-Klotho concentrations were not different between both groups (p = 0.62). No evidence was found that anti-oxidative therapy affected α-Klotho concentrations in patients with mild-moderate CKD

Citrate anticoagulation versus systemic heparinisation in continuous venovenous hemofiltration in critically ill patients with acute kidney injury: A multi-center randomized clinical trial

Introduction: Because of ongoing controversy, renal and vital outcomes are compared between systemically administered unfractionated heparin and regional anticoagulation with citrate-buffered replacement solution in predilution mode, during continuous venovenous hemofiltration (CVVH) in critically ill patients with acute kidney injury (AKI).Methods: In this multi-center randomized controlled trial, patients admitted to the intensive care unit requiring CVVH and meeting inclusion criteria, were randomly assigned to citrate or heparin. Primary endpoints were mortality and renal outcome in intention-to-treat analysis. Secondary endpoints were safety and efficacy. Safety was defined as absence of any adverse event necessitating discontinuation of the assigned anticoagulant. For efficacy, among other parameters, survival times of the first hemofilter were studied.Results: Of the 139 patients enrolled, 66 were randomized to citrate and 73 to heparin. Mortality rates at 28 and 90 days did not differ between groups: 22/66 (33%) of citrate-treated patients died versus 25/72 (35%) of heparin-treated patients at 28 days, and 27/65 (42%) of citrate-treated patients died versus 29/69 (42%) of heparin-treated patients at 90 days (P = 1.00 for both). Renal outcome, i.e. independency of renal replacement therapy 28 days after initiation of CVVH in surviving patients, did not differ between groups: 29/43 (67%) in the citrate-treated patients versus 33/47 (70%) in heparin-treated patients (P = 0.82). Heparin was discontinued in 24/73 (33%) of patients whereas citrate was discontinued in 5/66 (8%) of patients (P &#60; 0.001). Filter survival times were superior for citrate (median 46 versus 32 hour

The effect of online hemodiafiltration on infections: Results from the CONvective TRAnsport STudy

Background: Hemodialysis (HD) patients have a high risk of infections. The uremic milieu has a negative impact on several immune responses. Online hemodiafiltration (HDF) may reduce the risk of infections by ameliorating the uremic milieu through enhanced clearance of middle molecules. Since there are few data on infectious outcomes in HDF, we compared the effects of HDF with low-flux HD on the incidence and type of infections. Patients and Methods: We used data of the 714 HD patients (age 64 ±14, 62% men, 25% Diabetes Mellitus, 7% catheters) participating in the CONvective TRAnsport STudy (CONTRAST), a randomized controlled trial evaluating the effect of HDF as compared to low-flux HD. The events were adjudicated by an independent event committee. The risk of infectious events was compared with Cox regression for repeated events and Cox proportional hazard models. The distributions of types of infection were compared between the groups. Results: Thirty one percent of the patients suffered from one or more infections leading to hospitalization during the study (median follow-up 1.96 years). The risk for infections during the entire follow-up did not differ significantly between treatment arms (HDF 198 and HD 169 infections in 800 and 798 person-years respectively, hazard ratio HDF vs. HD 1.09 (0.88-1.34), P = 0.42. No difference was found in the occurrence of the first infectious event (either fatal, nonfatal or type specific). Of all infections, respiratory infections (25% in HDF, 28% in HD) were most common, followed by skin/musculoskeletal infections (21% in HDF, 13% in HD). Conclusions: HDF as compared to HD did not result in a reduced risk of infections, larger studies are needed to confirm our findings. Trial Registration: ClinicalTrials.gov NCT00205556