An economic evaluation of rt-PA locking solution in dialysis catheters.

In a recent randomized trial, weekly recombinant tissue plasminogen activator (rt-PA), 1 mg per lumen, once per week, and twice-weekly heparin as a locking solution (rt-PA/heparin) resulted in lower risks of hemodialysis catheter malfunction and catheter-related bacteremia compared with thrice-weekly heparin (heparin alone). We collected detailed costs within this trial to determine how choice of locking solution would affect overall health care costs, including the cost of locking solutions and all other relevant medical costs over the course of the 6-month trial. Nonparametric bootstrap estimates were used to derive 95% confidence intervals (CIs) and mean cost differences between the treatment groups. The cost of the locking solution was higher in patients receiving rt-PA/heparin, but this was partially offset by lower costs for managing complications. Overall, the difference in unadjusted mean cost for managing patients with rt-PA/heparin versus heparin alone was Can$323 (95% CI, -$935 to $1581; P=0.62). When the costs were extrapolated over a 1-year time horizon using decision analysis, assuming ongoing rt-PA effectiveness, the overall costs of the strategies were similar. This finding was sensitive to plausible variation in the frequency and cost of managing patients with catheter-related bacteremia, and whether the benefit of rt-PA on catheter-related bacteremia was maintained in the long term. In summary, we noted no significant difference in the mean overall cost of an rt-PA/heparin strategy as a locking solution for catheters compared with thrice-weekly heparin. Cost savings due to a lower risk of hospitalization for catheter-related bacteremia partially offset the increased cost of rt-PA.

Results of the HepZero study comparing heparin-grafted membrane and standard care show that heparin-grafted dialyzer is safe and easy to use for heparin-free dialysis.

Heparin is used to prevent clotting during hemodialysis, but heparin-free hemodialysis is sometimes needed to decrease the risk of bleeding. The HepZero study is a randomized, multicenter international controlled open-label trial comparing no-heparin hemodialysis strategies designed to assess non-inferiority of a heparin grafted dialyzer (NCT01318486). A total of 251 maintenance hemodialysis patients at increased risk of hemorrhage were randomly allocated for up to three heparin-free hemodialysis sessions using a heparin-grafted dialyzer or the center standard-of-care consisting of regular saline flushes or pre-dilution. The first heparin-free hemodialysis session was considered successful when there was neither complete occlusion of air traps or dialyzer, nor additional saline flushes, changes of dialyzer or bloodlines, or premature termination. The current standard-of-care resulted in high failure rates (50%). The success rate in the heparin-grafted membrane arm was significantly higher than in the control group (68.5% versus 50.4%), which was consistent for both standard-of-care modalities. The absolute difference between the heparin-grafted membrane and the controls was 18.2%, with a lower bound of the 90% confidence interval equal to plus 7.9%. The hypothesis of the non-inferiority at the minus 15% level was accepted, although superiority at the plus 15% level was not reached. Thus, use of a heparin-grafted membrane is a safe, helpful, and easy-to-use method for heparin-free hemodialysis in patients at increased risk of hemorrhage.

Independent effects of systemic and peritoneal inflammation on peritoneal dialysis survival.

Systemic inflammation, as evidenced by elevated inflammatory cytokines, is a feature of advanced renal failure and predicts worse survival. Dialysate IL-6 concentrations associate with variability in peritoneal small solute transport rate (PSTR), which has also been linked to patient survival. Here, we determined the link between systemic and intraperitoneal inflammation with regards to peritoneal membrane function and patient survival as part of the Global Fluid Study, a multinational, multicenter, prospective, combined incident and prevalent cohort study (n=959 patients) with up to 8 years of follow-up. Data collected included patient demographic characteristics, comorbidity, modality, dialysis prescription, and peritoneal membrane function. Dialysate and plasma cytokines were measured by electrochemiluminescence. A total of 426 survival endpoints occurred in 559 incident and 358 prevalent patients from 10 centers in Korea, Canada, and the United Kingdom. On patient entry to the study, systemic and intraperitoneal cytokine networks were dissociated, with evidence of local cytokine production within the peritoneum. After adjustment for multiple covariates, systemic inflammation was associated with age and comorbidity and independently predicted patient survival in both incident and prevalent cohorts. In contrast, intraperitoneal inflammation was the most important determinant of PSTR but did not affect survival. In prevalent patients, the relationship between local inflammation and membrane function persisted but did not account for an increased mortality associated with faster PSTR. These data suggest that systemic and local intraperitoneal inflammation reflect distinct processes and consequences in patients treated with peritoneal dialysis, so their prevention may require different therapeutic approaches; the significance of intraperitoneal inflammation requires further elucidation.

Effect of fish oil supplementation on graft patency and cardiovascular events among patients with new synthetic arteriovenous hemodialysis grafts: a randomized controlled trial.

CONTEXT: Synthetic arteriovenous grafts, an important option for hemodialysis vascular access, are prone to recurrent stenosis and thrombosis. Supplementation with fish oils has theoretical appeal for preventing these outcomes. OBJECTIVE: To determine the effect of fish oil on synthetic hemodialysis graft patency and cardiovascular events. DESIGN, SETTING, AND PARTICIPANTS: The Fish Oil Inhibition of Stenosis in Hemodialysis Grafts (FISH) study, a randomized, double-blind, controlled clinical trial conducted at 15 North American dialysis centers from November 2003 through December 2010 and enrolling 201 adults with stage 5 chronic kidney disease (50% women, 63% white, 53% with diabetes), with follow-up for 12 months after graft creation. INTERVENTIONS: Participants were randomly allocated to receive fish oil capsules (four 1-g capsules/d) or matching placebo on day 7 after graft creation. MAIN OUTCOME MEASURE: Proportion of participants experiencing graft thrombosis or radiological or surgical intervention during 12 months' follow-up. RESULTS: The risk of the primary outcome did not differ between fish oil and placebo recipients (48/99 [48%] vs 60/97 [62%], respectively; relative risk, 0.78 [95% CI, 0.60 to 1.03; P = .06]). However, the rate of graft failure was lower in the fish oil group (3.43 vs 5.95 per 1000 access-days; incidence rate ratio [IRR], 0.58 [95% CI, 0.44 to 0.75; P < .001]). In the fish oil group, there were half as many thromboses (1.71 vs 3.41 per 1000 access-days; IRR, 0.50 [95% CI, 0.35 to 0.72; P < .001]); fewer corrective interventions (2.89 vs 4.92 per 1000 access-days; IRR, 0.59 [95% CI, 0.44 to 0.78; P < .001]); improved cardiovascular event-free survival (hazard ratio, 0.43 [95% CI, 0.19 to 0.96; P = .04]); and lower mean systolic blood pressure (-3.61 vs 4.49 mm Hg; difference, -8.10 [95% CI, -15.4 to -0.85]; P = .01). CONCLUSIONS: Among patients with new hemodialysis grafts, daily fish oil ingestion did not decrease the proportion of grafts with loss of native patency within 12 months. Although fish oil improved some relevant secondary outcomes such as graft patency, rates of thrombosis, and interventions, other potential benefits on cardiovascular events require confirmation in future studies. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN15838383.

Prevention of catheter lumen occlusion with rT-PA versus heparin (Pre-CLOT): study protocol of a randomized trial [ISRCTN35253449].

BACKGROUND: Many patients with end-stage renal disease use a central venous catheter for hemodialysis access. A large majority of these catheters malfunction within one year of insertion, with up to two-thirds due to thrombosis. The optimal solution for locking the catheter between hemodialysis sessions, to decrease the risk of thrombosis and catheter malfunction, is unknown. The Prevention of Catheter Lumen Occlusion with rt-PA versus Heparin (PreCLOT) study will determine if use of weekly rt-PA, compared to regular heparin, as a catheter locking solution, will decrease the risk of catheter malfunction. METHODS/DESIGN: The study population will consist of patients requiring chronic hemodialysis thrice weekly who are dialyzed with a newly inserted permanent dual-lumen central venous catheter. Patients randomized to the treatment arm will receive rt-PA 1 mg per lumen once per week, with heparin 5,000 units per ml as a catheter locking solution for the remaining two sessions. Patients randomized to the control arm will receive heparin 5,000 units per ml as a catheter locking solution after each dialysis session. The study treatment period will be six months, with 340 patients to be recruited from 14 sites across Canada. The primary outcome will be catheter malfunction, based on mean blood flow parameters while on hemodialysis, with a secondary outcome of catheter-related bacteremia. A cost-effectiveness analysis will be undertaken to assess the cost of maintaining a catheter using rt-PA as a locking solution, compared to the use of heparin. DISCUSSION: Results from this study will determine if use of weekly rt-PA, compared to heparin, will decrease catheter malfunction, as well as assess the cost-effectiveness of these locking solutions.

Peritoneal Dialysate Glucose Load and Systemic Glucose Metabolism in Non-Diabetics: Results from the GLOBAL Fluid Cohort Study.

BACKGROUND AND OBJECTIVES: Glucose control is a significant predictor of mortality in diabetic peritoneal dialysis (PD) patients. During PD, the local toxic effects of intra-peritoneal glucose are well recognized, but despite large amounts of glucose being absorbed, the systemic effects of this in non-diabetic patients are not clear. We sought to clarify whether dialysate glucose has an effect upon systemic glucose metabolism. METHODS AND MATERIALS: We analysed the Global Fluid Study cohort, a prospective, observational cohort study initiated in 2002. A subset of 10 centres from 3 countries with high data quality were selected (368 incident and 272 prevalent non-diabetic patients), with multilevel, multivariable analysis of the reciprocal of random glucose levels, and a stratified-by-centre Cox survival analysis. RESULTS: The median follow up was 5.6 and 6.4 years respectively in incident and prevalent patients. On multivariate analysis, serum glucose increased with age (ß = -0.007, 95%CI -0.010, -0.004) and decreased with higher serum sodium (ß = 0.002, 95%CI 0.0005, 0.003) in incident patients and increased with dialysate glucose (ß = -0.0002, 95%CI -0.0004, -0.00006) in prevalent patients. Levels suggested undiagnosed diabetes in 5.4% of prevalent patients. Glucose levels predicted death in unadjusted analyses of both incident and prevalent groups but in an adjusted survival analysis they did not (for random glucose 6-10 compared with <6, Incident group HR 0.92, 95%CI 0.58, 1.46, Prevalent group HR 1.42, 95%CI 0.86, 2.34). CONCLUSIONS: In prevalent non-diabetic patients, random glucose levels at a diabetic level are under-recognised and increase with dialysate glucose load. Random glucose levels predict mortality in unadjusted analyses, but this association has not been proven in adjusted analyses.

[Comparative study of two teaching methods of a predialysis educational program]. / Etude comparative de deux méthodes d'enseignement d'un programme educatif en prédialyse.

The purpose of this quasi-experimental study was to compare two teaching methods of a predialysis educational program, namely on-site and by distance. This program was offered to patients with chronic kidney disease (CKD) stage 3. The experimental group one received the on-site program, whereas the experimental group two received the teaching program by distance. This study uses a pre-test post-test design. Measures included a Sociodemographic Information Form, the Degree of Knowledge Integration (Aucoin-Gallant, 1998), and the Knowledge Satisfaction Scale (Aucoin, 1998). In this study, both groups are homogenous from a sociodemographic perspective and have similar creatinine clearance values. Findings demonstrate an increase with knowledge integration and satisfaction with knowledge that is statistically significant for both groups of subjects. Participants in group two learned as much as participants in group one. This study highlights that knowledge integration leads to satisfaction in both groups of subjects. The results demonstrate that predialysis teaching delivered on-site or by distance promotes knowledge integration for patients with CKD stage 3.

The Benefit of a Glucose-Sparing PD Therapy on Glycemic Control Measured by Serum Fructosamine in Diabetic Patients in a Randomized, Controlled Trial (IMPENDIA).

BACKGROUND/AIMS: Poor glycemic control can lead to increased morbidity and mortality in peritoneal dialysis (PD) patients. Serum fructosamine may be a more reliable marker of glycemic control than HbA1c in dialysis patients. METHODS: We evaluated the effects of a glucose-sparing PD regimen on serum fructosamine. In the multicenter, controlled IMPENDIA trial, eligible diabetic PD patients were randomized (1:1) to a 24-hour combination of a glucose sparing regimen (n = 89) or a glucose-based therapy (n = 91). Serum fructosamine and HbA1c were measured at baseline, 3 months and 6 months; fructosamine measurements were corrected for serum albumin (AlbF). RESULTS: Serum fructosamine decreased from 297 to 253 µmol/l in the glucose-sparing group (95% confidence interval [CI] for the difference, -26 to -68, p < 0.001), and increased from 311 to 314 µmol/l in the glucose-only group (95% CI for the difference, -23 to +19, p = 0.87). The mean difference in change of fructosamine levels between groups at 6 months was 64 µmol/l (95% CI 29-99, p < 0.001). HbA1c decreased versus baseline in both groups (treatment difference 0.3%, p = 0.07). The correlation between AlbF and baseline fasting serum glucose was stronger than that seen between HbA1c and baseline fasting serum glucose (r = 0.47, p < 0.0001 and r = 0.31, p < 0.0001, respectively). CONCLUSION: A glucose-sparing regimen (P-E-N) improved glycemic control as measured by serum fructosamine. Further studies are needed to establish fructosamine targets that will reduce the morbidity risk related to hyperglycemia in PD patients.

A novel citrate anticoagulation regimen for continuous venovenous hemodiafiltration.

OBJECTIVE: Validation of a novel citrate anticoagulation regimen for continuous venovenous hemodiafiltration (CVVHDF). DESIGN AND SETTING: Prospective cohort trial in medicosurgical intensive care units of two university-affiliated teaching institutions. PATIENTS: Participants were patients at high risk for bleeding, with renal failure requiring CVVHDF without heparin. Fourteen patients completed the study. INTERVENTION: A convection-based citrate anticoagulation CVVHDF regimen using an isotonic replacement fluid containing citrate administered in predilution. A neutralizing solution of calcium chloride and magnesium sulfate was infused at the end of the circuit. Blood flow rate was set and kept at 125 ml/min, and the flow rate of the replacement fluid was initiated at 1250 ml/h and adjusted thereafter according to the monitoring of blood activated coagulation time (ACT), with a target between 180 to 220 s. MEASUREMENTS AND RESULTS: The average filter time-life was 44 h. Thrombosis of the proximal portion of the circuit (which was not anticoagulated) was the main reason for technique failure. A mean urea clearance of 21 ml/min was obtained. Electrolytes and acid-base balance were both well maintained. Six percent (16/287) of Ca(i) readings less than 0.3 mmol/l were associated with very high ACT levels (>300 s). CONCLUSIONS: This regimen is shown to be safe, efficacious, and convenient. Citrate anticoagulation should be monitored using postfilter ACT and/or ionized calcium with respective targets of 200-250 s or 0.3-0.4 mmol/l.

Rationale and design of the HepZero study: a prospective, multicenter, international, open, randomized, controlled clinical study with parallel groups comparing heparin-free dialysis with heparin-coated dialysis membrane (Evodial) versus standard care: study protocol for a randomized controlled trial.

BACKGROUND: Anticoagulation for chronic dialysis patients with contraindications to heparin administration is challenging. Current guidelines state that in patients with increased bleeding risks, strategies that can induce systemic anticoagulation should be avoided. Heparin-free dialysis using intermittent saline flushes is widely adopted as the method of choice for patients at risk of bleeding, although on-line blood predilution may also be used. A new dialyzer, Evodial (Gambro, Lund, Sweden), is grafted with unfractionated heparin during the manufacturing process and may allow safe and efficient heparin-free hemodialysis sessions. In the present trial, Evodial was compared to standard care with either saline flushes or blood predilution. METHODS: The HepZero study is the first international (seven countries), multicenter (10 centers), randomized, controlled, open-label, non-inferiority (and if applicable subsequently, superiority) trial with two parallel groups, comprising 252 end-stage renal disease patients treated by maintenance hemodialysis for at least 3 months and requiring heparin-free dialysis treatments. Patients will be treated during a maximum of three heparin-free dialysis treatments with either saline flushes or blood predilution (control group), or Evodial. The first heparin-free dialysis treatment will be considered successful when there is: no complete occlusion of air traps or dialyzer rendering dialysis impossible; no additional saline flushes to prevent clotting; no change of dialyzer or blood lines because of clotting; and no premature termination (early rinse-back) because of clotting.The primary objectives of the study are to determine the effectiveness of the Evodial dialyzer, compared with standard care in terms of successful treatments during the first heparin-free dialysis. If the non-inferiority of Evodial is demonstrated then the superiority of Evodial over standard care will be tested. The HepZero study results may have major clinical implications for patient care. TRIAL REGISTRATION: ClinicalTrials.gov NCT01318486.

Design of the fish oil inhibition of stenosis in hemodialysis grafts (FISH) study.

BACKGROUND: Arteriovenous grafts (AVG) are the predominant form of permanent vascular access used among hemodialysis (HD) patients in North America but suffer from high intervention and complication rates associated with vascular stenosis. The fish oil inhibition of stenosis in hemodialysis grafts (FISH) study evaluates the efficacy of fish oil in improving HD graft patency. METHODS: This study is a multi-center, randomized, double blind placebo-controlled clinical trial of 232 chronic HD patients who require a new graft access. Participants are randomized to fish oil versus placebo post-operatively. The primary endpoint is the proportion of AVG with loss of native patency within 12 months of creation. Secondary endpoints are aimed to determine the effect of fish oil on factors that may promote stenosis and thrombosis. Cumulative patency rates, survival analysis, and analysis of inflammatory markers and adverse events will provide a better understanding of the potential effect of fish oil on a patient's vascular access and cardiovascular system. The FISH study is registered at current controlled trials (www.controlled-trials.com) ISRCTN: 15838383. RESULTS: Details of the study protocol are described including mechanisms of reducing bias through randomization and double blinding, sample size determination, evaluation of patient adherence, access monitoring, and the safety of using fish oil. The main challenges of designing and implementing this study, including using a natural supplement as an intervention in modern medical practice and recruitment of graft recipients in the ;fistula first' environment are discussed. CONCLUSION: This is the first large, multicenter, randomized controlled trial of a natural supplement in preventing HD graft stenosis and thrombosis.

Acute renal failure in bone marrow transplant patients admitted to the intensive care unit.

BACKGROUND/AIMS: Review of bone marrow transplant (BMT) cases admitted to our intensive care unit (ICU) and to compare co-morbidity and outcome of BMT patients developing or not developing acute renal failure (ARF). METHODS: A case review of BMT patients admitted to the ICU (a 16-bed medico-surgical ICU in a tertiary care teaching institution) over a 4-year period. RESULTS: Between January 1994 and December 1998, 57 among 441 BMT patients (12.9%) were admitted to the ICU, mainly for respiratory distress (58%) and hypotension (32%). Forty-two patients (73.7%) presented ARF as defined as a doubling of serum creatinine. Compared to the 15 other patients, ARF patients had a higher APACHE II score (30 +/- 8 vs. 25 +/- 7, p < 0.05). For ARF vs. non-ARF patients, there was no difference in age (43.8 +/- 10.8 vs. 44.3 +/- 11.1 years), in requirement for mechanical ventilation (76 vs. 73%) and vasopressors (69 vs. 60%), and in prevalence of graft-versus-host disease (19 vs. 13%) or neutropenia (69 vs. 67%), but the prevalence of sepsis (83 vs. 60%) and liver failure (69 vs. 40%) was higher. Maximum serum bilirubin was markedly increased in ARF compared to non-ARF patients (p < 0.005). For both subgroups, no difference in the administration of potential nephrotoxic agents was identified. Usually, ARF was considered multifactorial by clinicians, with ATN being the most frequent diagnosis (55%). Maximum serum creatinine reached a mean of 330 +/- 130 micromol/l. In 74% of cases, ARF occurred concomitantly or after admission to the ICU. Oligoanuria was present in 38%, whereas polyuria was observed in 17%. Fourteen ARF patients (33%) required dialytic support. Mortality rates were significantly different in ARF vs. non-ARF patients (88 vs. 60%, p < 0.05). Predictive factors for the development of ARF were liver failure (odds ratio (OR) 5.9), low serum albumin (OR 1.2) and APACHE II score (OR 1.1), whereas variables predictive of mortality were mechanical ventilation (OR 14.8), ARF (OR 5.8), liver failure (OR 3.7), and APACHE II score (OR 1.2). CONCLUSIONS: This study confirms that ARF in BMT patients admitted to the ICU is frequent, multifactorial, related to liver failure, and that its development has a negative impact on outcome.