Clinical evaluation of performance, biocompatibility, and safety of vitamin E-bonded polysulfone membrane hemodialyzer compared to non-vitamin E-bonded hemodialyzer.

The vitamin E-bonded polysulfone membrane hemodialyzer (ViE™-21) was evaluated in a clinical study for regulatory submission. Seventeen patients on hemodialysis were treated with conventional high-flux hemodialyzers for 2 weeks (Pre-ViE phase) and switched to the ViE-21 for 36 sessions (ViE phase) followed by an additional 2 weeks on conventional hemodialyzers (Post-ViE phase). Reduction ratios of urea, creatinine, beta-2-microglobulin, albumin, and ultrafiltration coefficients (KUF) were measured once during the Pre-ViE phase and twice during the ViE phase. Moreover, biocompatibility markers [leucocyte count, platelet count, and activated complement factor (C3a) levels] were evaluated pre-dialysis, 15 min after initiation, and post-dialysis. During the study, type and number of adverse events (AEs), and device malfunctions were recorded. ViE-21 reduction ratios and KUF were not noticeably different than those of conventional hemodialyzers. Fluctuations of leucocyte counts and C3a concentrations were similar using ViE-21 and conventional hemodialyzers; however, the platelet count fluctuation was lower in ViE-21 sessions. The frequency of episodes of hypotension occurring during the ViE phase was lower than that occurring during the Pre- and Post-ViE phases. In conclusion, this study provided performance and safety data of the ViE-21 for regulatory application. The data suggest that vitamin E-bonded hemodialyzers are beneficial in lowering platelet activation and frequency of intradialytic hypotension. Larger randomized controlled trials are needed to confirm these findings.

Comparison of hypoalbuminemia-corrected serum calcium using BCP albumin assay to ionized calcium and impact on prescribing in hemodialysis patients
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BACKGROUND: Albumin-corrected calcium (cCa) is recommended over ionized calcium (iCa) in hemodialysis (HD) patients per the Kidney Disease: Improving Global Outcomes position statements due to cost and feasibility. Two common albumin assays, bromocresol green (BCG) and bromocresol purple (BCP), produce differing results in uremic patients. All previous studies compared iCa to cCa from a BCG assay. This study, using the BCP assay, aimed to compare cCa and total calcium, respectively, to iCa. We also sought to assess phosphate binders and dialysis prescribing patterns following abnormal calcium measurements. MATERIALS AND METHODS: Retrospective review of 122 stable chronic HD patients with iCa, serum calcium, and albumin measured together throughout 6 blood work periods for a total of 338 sets of comparison values. Payne and Jain calcium correction equations were used. Prescription changes within 2 weeks of abnormal iCa values were recorded. RESULTS: Mean iCa, cCa, and total calcium were 1.17 ± 0.08, 2.37 ± 0.16, and 2.28 ± 0.15 mmol/L, respectively. Total calcium and cCa compared to iCa had κ-coefficients of 0.19 and 0.08, respectively, for hypocalcemia, 0.19 and -0.02 for normocalcemia and 0.59 and 0.46 for hypercalcemia. 21 interventions were made in hypocalcemic patients using iCa as reference; however, if total or corrected calcium values were used, only 8 and 5 interventions, respectively, would result. CONCLUSION: When BCP assay is used, conventional correction equations should not be utilized in hemodialysis patients; uncorrected serum calcium has a better predictive value.
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Randomized controlled trial of mycophenolate mofetil in children, adolescents, and adults with IgA nephropathy.

BACKGROUND: Previous randomized controlled trials evaluating the efficacy of mycophenolate mofetil (MMF) in patients with immunoglobulin A nephropathy (IgAN) have produced varying results. STUDY DESIGN: Double-blind placebo-controlled randomized controlled trial. SETTING & PARTICIPANTS: 52 children, adolescents, and adults with biopsy-proven IgAN in 30 centers in the United States and Canada. Entry criteria: age older than 7 to younger than 70 years; urine protein-creatinine ratio (UPCR), ≥0.6g/g (males) or ≥0.8g/g (females); and estimated glomerular filtration rate ≥ 50mL/min/1.73m(2) (≥40mL/min/1.73m(2) if receiving angiotensin-converting enzyme inhibitor). Mean age, 32±12 (SD) years; 62% men; and 73% white. INTERVENTION: Lisinopril (or losartan) plus a highly purified omega-3 fatty acid (Omacor [Pronova Biocare]) was given to 94 patients for 3 months; 52 of the patients with persistent UPCR≥0.6g/g (males) and ≥0.8g/g (females) were randomly assigned to MMF or placebo (target dose, 25-36mg/kg/d) in addition to lisinopril/losartan plus Omacor. OUTCOMES: Change in UPCR after 6 and 12 months treatment with MMF/placebo and 12 months after the end of treatment. MEASUREMENTS: UPCR measured on 24-hour urine samples. Glomerular filtration rate estimated with the Schwartz (age < 18 years) or Cockcroft-Gault (age ≥ 18 years) formula. RESULTS: 44 patients completed 6 months of treatment with MMF (n=22) or placebo (n=22). The trial was terminated early at the recommendation of the Data Monitoring Committee because of the lack of benefit. No patient achieved a complete remission (UPCR<0.2g/g). Mean UPCRs at randomization and after 6 months were 1.45 (95% CI, 1.16-1.75) and 1.40 (95% CI, 1.09-1.70) for MMF and 1.41 (95% CI, 1.17-1.65) and 1.58 (95% CI, 1.13-2.04) for placebo, respectively. The mean difference in UPCR change between these groups (MMF minus placebo) was -0.22 (95% CI, -0.75 to 0.31; P=0.4). Adverse events were rare apart from nausea (MMF, 8.7%; placebo, 3.7%); one of these MMF patients withdrew. LIMITATIONS: Low patient enrollment and short follow-up. CONCLUSIONS: MMF did not reduce proteinuria significantly in patients with IgAN who had persistent proteinuria after lisinopril/losartan plus Omacor.

Use of electron-beam sterilized hemodialysis membranes and risk of thrombocytopenia.

CONTEXT: Thrombocytopenia is not widely recognized as a potential dialyzer-related complication. Following the observation of significant thrombocytopenia among 20 patients undergoing hemodialysis in a single dialysis unit after the introduction of dialyzers sterilized by electron beam (e-beam), a larger investigation was undertaken. OBJECTIVE: To determine the prevalence and etiology of thrombocytopenia in hemodialysis populations of 2 Canadian provinces (British Columbia and Alberta). DESIGN, SETTING, AND PARTICIPANTS: A cohort study of patients undergoing hemodialysis in British Columbia (n = 1706) and southern Alberta (n = 425) between April 1, 2009, and November 30, 2010. Retrospective analyses of historical patient, laboratory, and dialyzer data predating conversion to e-beam dialyzers were undertaken, with prospective collection of predialysis and postdialysis platelet counts before and after the change from e-beam to non-e-beam sterilized dialyzers in September 2009. MAIN OUTCOME MEASURE: Significant thrombocytopenia, defined a priori as postdialysis treatment platelet count of less than 100 × 10(3)/µL and a postdialysis decrease in platelet count of more than 15%. RESULTS: Among 1706 patients undergoing hemodialysis in British Columbia, 1411 (83%) were undergoing hemodialysis with e-beam sterilized dialyzers. Of 1706 patients, 194 (11.4%; 95% CI, 9.9%-12.9%) had postdialysis platelet counts of less than 100 × 10(3)/µL; 400 (23.4%; 95% CI, 21.5%-25.5%) had postdialysis decreases in platelet counts of more than 15%; and 123 (7.2%; 95% CI, 6.0%-8.6%) met both criteria. Among 425 patients in Alberta undergoing dialysis with polysulfone, e-beam sterilized dialyzers made by a different manufacturer, 46 (10.8%; 95% CI, 8.1%-14.3%) had platelet counts of less than 100 × 10(3)/µL; 156 (32.0%; 95% CI, 27.6%-36.7%) had decreases in platelet counts of more than 15%; and 31 (7.3%; 95% CI, 5.1%-10.3%) met both criteria. In multivariable analysis adjusting for patient and dialysis history characteristics, a significant association was observed between using an e-beam sterilized dialyzer and risk of significant thrombocytopenia (odds ratio [OR], 2.52; 95% CI, 1.20-5.29; P = .02). Compared with use of e-beam sterilized dialyzers, following the change to use of non-e-beam sterilized dialyzers, among 1784 patients, significant reductions were observed in postdialysis thrombocytopenia (120 patients [6.7%; 95% CI, 5.6%-8.0%; P < .001] had platelet counts of <100 × 10(3)/µL; 167 patients [9.4%; 95% CI, 8.1%-10.8%; P < .001] had decreases in platelet counts of >15%; and 38 patients [2.1%; 95% CI, 1.5%-2.9%; P < .001] met both criteria). Using generalized estimating equation modeling for repeated data with binary outcome, after adjusting for patient characteristics, the odds of significant thrombocytopenia were higher during the use of e-beam sterilized dialyzers than with use of non-e-beam sterilized dialyzers (OR, 3.57; 95% CI, 2.54-5.04; P < .001). CONCLUSION: In this cohort of patients undergoing hemodialysis in 2 Canadian provinces in 2009-2010, the use of e-beam sterilized dialyzers was associated with significant thrombocytopenia following dialysis.

Best possible medication history for hemodialysis patients obtained by a pharmacy technician.

BACKGROUND: Outpatients undergoing hemodialysis are at high risk for adverse drug events. Limited resources make it challenging for pharmacists to routinely obtain a best possible medication history (BPMH). OBJECTIVES: The primary objective was to determine whether, for patients undergoing hemodialysis, a pharmacy technician has the skills to obtain a BPMH that would allow a pharmacist to identify drug-related problems. The secondary objectives were to determine the number and types of medication discrepancies and drug-related problems identified and the time required by the technician to complete the BPMH. METHODS: All patients treated in the hemodialysis unit during the study period were included, except for those who required an interpreter or were unable to participate in an in-person interview. A single technician was taught how to interview patients according to a structured format. For each patient, the technician's BMPH was verified by a pharmacist. The agreement rate between technician and pharmacists was determined, along with the number and types of discrepancies and drug-related problems identified. RESULTS: The technician interviewed 99 patients. Of the 1334 medication orders reviewed, the technician and pharmacists agreed on all but 15 (agreement rate 98.9%). A total of 358 medication discrepancies were noted for 93 patients (3.8 discrepancies per patient). Of these, 210 (59%) were undocumented intentional discrepancies, and 148 (41%) were unintentional discrepancies (most commonly errors of commission). Of the 135 drug-related problems identified, the majority involved dosing problems or nonadherence. The technician required an average of 17 min for each interview. CONCLUSION: An adequately trained technician was capable of interviewing patients to create a BPMH. A variety of medication discrepancies and drug-related problems were identified. Generation of a BPMH by a technician is a useful approach allowing pharmacists to identify drug-related problems.

Citrate 4% versus heparin and the reduction of thrombosis study (CHARTS).

BACKGROUND AND OBJECTIVES: Citrate 4% has antithrombotic and antibacterial properties, which makes it a potentially superior alternative to heparin as an indwelling intraluminal locking agent. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Sixty-one prevalent hemodialysis (HD) patients dialyzing with a tunneled cuffed HD catheter were randomized in a pilot study to receive either heparin 5000 U/ml or citrate 4% as a locking agent after HD. The primary outcomes were the development of catheter dysfunction (defined as a blood pump speed <250 ml/min or the use of tissue plasminogen activator) and catheter-associated bacteremia. The secondary outcomes were the development of an exit-site infection or bleeding complications (either local or systemic). RESULTS: Citrate had comparable catheter dysfunction episodes to heparin (13/32 [41%] cases versus 12/29 [41%] cases, respectively). There were no differences in the development of catheter-associated bacteremia (2.2/1000 catheter days citrate versus 3.3/1000 catheter days heparin group; P = 0.607) or exit-site infection (2.2/1000 catheter days for both groups). CONCLUSIONS: The preliminary findings from our pilot study demonstrate that 4% citrate is effective in maintaining catheter patency and does not appear to have any increased incidence of infections. Because citrate is significantly cheaper and has a more favorable side effect profile than heparin, it can be considered a potentially better locking agent in HD catheters.