The CLEAR study: a 5-day, 3-g loading dose of mycophenolate mofetil versus standard 2-g dosing in renal transplantation.

BACKGROUND AND OBJECTIVES: Adequate early mycophenolic acid (MPA) exposure is associated with lower rates of acute rejection in renal transplantation. The aim of this randomized controlled trial was to determine if higher initial mycophenolate mofetil (MMF) doses increased the proportion of patients reaching therapeutic MPA levels (30 to 60 mg.h/L) by day 5. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: De novo renal transplant patients were randomized to receive intensified dosing of MMF (1.5 g twice daily on days 1 to 5, then 1.0 g twice daily) or standard dosing (1.0 g twice daily). All recipients received tacrolimus and prednisone. Full MPA areas under the curve (AUCs) were completed on days 3 and 5, whereas a limited sampling strategy was utilized at four subsequent time points. RESULTS: At day 5, 47.5% of the MMF 3-g arm achieved the MPA therapeutic window versus 54.4% of the MMF 2-g arm. However, MPA AUC levels were significantly higher in the 3-g arm at day 3 and 5. This resulted in a trend for fewer treated acute rejections at 6 months. Significantly more acute rejections (treated, biopsy-proven including and excluding borderline) occurred in patients with MPA AUC levels<30 mg.h/L compared with those >or=30 mg.h/L at day 5. No significant differences were seen in common adverse events. CONCLUSIONS: A limited intensified dose of MMF increased early MPA exposure and was well tolerated. Further studies are required to determine whether limited intensified MMF dosing can reduce acute rejection.

Quality of care among Aboriginal hemodialysis patients.

Registry data report racial differences in hemodialysis (HD) care, with ethnic minorities at a disadvantage. However, little information is available regarding Aboriginal HD patients specifically. This study sought to compare the quality of HD care between Aboriginal and non-Aboriginal patients in Canada. All adults who were established on HD for > or = 6 mo in a single Canadian province were included. Clinical information was obtained by patient interview and chart review, with race determined by self-report. Quality of HD care was assessed by small solute clearance, BP control, mineral metabolism, and anemia management. Of the 835 patients, 95 (11.4%) were Aboriginal. Aboriginal patients were significantly younger, were more likely to have diabetes as the cause of ESRD, and had a higher degree of comorbidity than non-Aboriginal patients. There were no differences between Aboriginal and non-Aboriginal patients for small solute clearance, anemia management, or use of permanent vascular access. Aboriginal patients, however, were less likely to achieve a target predialysis systolic BP of < 140 mmHg (29.5 versus 44.9%; P = 0.004), a target phosphate level of < 1.8 mmol/L (40.0 versus 67.3%; P < 0.0001), and a calcium-phosphate product < 4.4 mmol2/L2 (52.6 versus 72.7%; P < 0.001). Quality of care was found to be similar for Aboriginal compared with non-Aboriginal HD patients except for differences in predialysis systolic BP and mineral metabolism, which may be influenced by individual and cultural factors. Explanations for these differences and their impact on morbidity and mortality warrant further investigation.

Wait-listing for kidney transplantation among Aboriginal hemodialysis patients.

BACKGROUND: Although there has been rapid growth in the global prevalence of Aboriginal patients with end-stage renal disease (ESRD), these individuals have markedly lower rates of kidney transplantation for reasons that are unclear. We investigated barriers to kidney transplantation for Aboriginal patients treated with hemodialysis for ESRD in Canada. METHODS: All consenting adults in the province of Alberta, Canada, who had been established on hemodialysis therapy for 6 months or longer were interviewed by a physician. Data for transplantation referral, waiting list status, and the assessment process were determined from the regional transplant programs, with race defined by patient self-report. For purposes of this analysis, race was dichotomized as either Aboriginal or non-Aboriginal. RESULTS: Of 835 subjects, 100 (12%) were Aboriginal. Aboriginal patients were significantly younger and more likely to have diabetes mellitus as the cause of ESRD than non-Aboriginal patients. Although a greater proportion of Aboriginal patients were referred for transplantation assessment (60.6% versus 46.0%; P < 0.01), after adjustment, the likelihood of referral was similar for both racial groups (hazard ratio associated with Aboriginal race, 0.80; 95% confidence interval, 0.59 to 1.08). Aboriginal patients also were significantly less likely to be active on the transplant wait list than non-Aboriginal patients (adjusted hazard ratio, 0.46; 95% confidence interval, 0.27 to 0.78). Aboriginal subjects who had been referred for assessment were significantly more likely than non-Aboriginals to be in the process of completing the transplantation workup (69.6% versus 26.9%; P < 0.01) as opposed to being temporarily or permanently unsuitable for transplantation (30.4% versus 73.3%; P < 0.01). Although not statistically significant, median duration of the workup in progress in referred, but nonlisted, participants appeared longer in Aboriginal participants (954 versus 596 days; P = 0.07). CONCLUSION: The likelihood of referral for transplantation was similar between Aboriginal and non-Aboriginal people. However, Aboriginal people were approximately half as likely to be successfully activated to the transplant waiting list compared with non-Aboriginal people. These data suggest that the major barrier to transplantation in Aboriginal patients occurs after referral, but early in the course of evaluation for eligibility.

Extended reuse of polysulfone hemodialysis membranes using citric acid and heat.

The concomitant use of citric acid and prolonged exposure to heat (CAH) is an increasingly common alternative to purely chemical means of reusing dialyzers. However, there are no data on the effects of reprocessing dialyzers with CAH beyond 15 uses. Increasing the number of reuses with CAH cannot be systematically undertaken unless its safety is documented. We hypothesized that discarding polysulfone dialyzers after the 25th rather than the 15th use would result in increased clearance of beta2-microglobulin (beta2MG) without clinically significant changes in small solute clearance or albumin loss. We studied 15 Fresenius F80B polysulfone dialyzers in five chronic hemodialysis patients. Dialyzers were reprocessed using 1.5% citric acid solution heated to 95 degrees C. Representative fractional collection and 10 minute timed collections of dialysate were performed at baseline and during uses 5, 10, 15, 20, and 25 for each dialyzer. Dialysate-side urea, creatinine, and beta2MG clearances were calculated, and total albumin was measured in dialysate. We used a mixed model to adjust for repeated measures (both within a given dialyzer and for the multiple dialyzers per patient). Of the 15 dialyzers studied, 3 (20%) failed before the 25th use. There was no significant change in urea or creatinine clearance with additional reuse (overall p values 0.20 and 0.60, respectively). A sustained increase in beta2MG clearance was observed after the fifth treatment compared with the first use (p < 0.001). Fractional collection showed that dialysate albumin loss increased significantly with additional reuses (p < 0.001) but did not increase significantly above baseline until treatment 25. Reprocessing of polysulfone dialyzers with CAH 25 times significantly increased albumin loss and beta2MG clearance but did not appear to affect urea or creatinine clearance. Increasing the maximum number of uses to 20 may permit cost savings compared with current practice without additional risk.