A multicenter, randomized trial of increased mycophenolic acid dose using enteric-coated mycophenolate sodium with reduced tacrolimus exposure in maintenance kidney transplant recipients

Mycophenolic acid (MPA) dose is frequently reduced in tacrolimus-treated kidney transplant patients, but alternatively the recommended MPA dose can be maintained with reduced tacrolimus exposure. In a 6-month, multicenter, randomized, openlabel study, maintenance kidney transplant patients receiving MPA (mycophenolate mofetil 1g/d or enteric-coated mycophenolate sodium (EC-MPS) 720 mg/d) and tacrolimus were randomized to convert to EC-MPS 1,440 mg/d with reduced tacrolimus (n = 46), or receive EC-MPS 720 mg/d with unchanged tacrolimus (n = 48). Mean estimated GFR (eGFR, aMDRD) at Month 6 was 49.1 ± 11.1 and 44.7 ± 11.5 ml/min/1.73 m2 in the EC-MPS 1,440 mg and 720 mg groups, respectively (p = 0.07). The primary endpoint, change in eGFR from Day 0 to Month 6, was 2.48 ± 0.95 ml/min/1.73 m2 with EC-MPS 1,440 mg and -0.48 ± 0.93 ml/min/1.73 m2 with EC-MPS 720 mg (difference 2.96 ml/min/1.73 m2; 95% CI 0.32 - 5.60; p = 0.028). There were no deaths, graft losses or acute rejections. Adverse events were more frequent with EC-MPS 1,440 mg than 720 mg (66.7% vs. 44.7%, p = 0.034). Adverse events with suspected relation to EC-MPS occurred in 26.7% and 21.3% of patients, respectively (p = 0.59). Conversion of kidney transplant patients to increased MPA dosing using EC-MPS 1,440 mg/d, with reduced tacrolimus exposure, appears an effective immunosuppression strategy and may improve renal function. Adverse events overall, but not those with a suspected relation to EC-MPS, were higher with ECMPS 1,440 mg/d.     

Impact of Preoperative α-Fetoprotein Level on Disease-Free Survival After Liver Transplantation for Hepatocellular Carcinoma

Background

Preoperative α-fetoprotein (AFP) levels may have an influence on disease-free survival (DFS) of patients after liver transplantation for hepatocellular carcinoma (HCC) located on a cirrhotic liver.

Methods

Between 2000 and 2009, two groups were distinguished according to preoperative AFP level: normal-level group (<10?ng/ml) and increased-level group (>10?ng/ml). The increased-level group was further divided into three levels of preoperative AFP: 10–150, 150–500, and ≥500?ng/ml. DFS and recurrence rates were compared. All patients underwent transplantation using the preoperative 5/5 criteria.

Results

Of the 122 patients in this study, 63 had normal and 59 had increased preoperative AFP. There were no differences between the two groups concerning perioperative or pathologic data. Those with an increased preoperative AFP level had a significantly shorter 5-year DFS, and their recurrence rate was higher than that of the normal AFP group. The 5-year DFS and recurrence rates were 71 and 4?%, respectively, for those with normal AFP; 57 and 10?%, respectively, for those with AFP 10–150?ng/ml; 46 and 24?%, respectively, for those with AFP 150–500?ng/ml; and 28 and 62?%, respectively, for those with AFP ≥500?ng/ml.

Conclusions

This study shows the prognostic value of preoperative AFP levels on DFS after a liver transplant for HCC in a population of patients undergoing transplantation with the same preoperative criteria.     

Regional citrate anticoagulation in continuous venovenous haemodiafiltration using commercial solutions.

BACKGROUND: Treatment with trisodium citrate provides an effective means of regional anticoagulation during continuous renal replacement therapy (CRRT). We evaluated the efficacy, safety and cost of a regional citrate anticoagulation protocol using commercial solutions in 17 critically ill patients treated with continuous venovenous haemodiafiltration (CVVHDF). We performed a total of 22 sessions. METHODS: We delivered an A.C.D-A(541(R)) solution containing 112.9 mmol/l disodium citrate (3.22%) at a median rate of 260 (190-280) ml/h via the pre-filter port of a COBE PRISMA with an AN-69 dialyser, while adjusting the rate to maintain post-filtered ionized calcium (iCa(2+)) between 0.25 and 0.4 mmol/l. Plasma iCa(2+) was maintained at >1.1 mmol/l by infusion of calcium chloride at a median rate of 1.70 (1.36-2.27) mmol/h. The dialysate was easily modified according to the acid-base status of each patient. Both replacement and dialysate solutions were delivered at 1200 ml/h. Each session was scheduled for 48 h and biological parameters were assessed every 6 h. RESULTS: The mean dialyser survival was 39 +/- 11 h (median 41.5 h; range 13-48 h). We observed dialyser clotting in four cases (18%). There were no bleeding events or modifications of coagulation parameters. The citrate solution, replacement solution and dialysate were obtained as commercial products. Both the replacement and dialysate solutions contained calcium. The extra cost of this technique was 25 euro;/day as compared to anticoagulation with heparin. CONCLUSIONS: We designed an efficient method of regional citrate anticoagulation for CVVHDF by using commercial solutions. The monitoring of patients was as intensive as during heparin anticoagulation for CRRT. Because of the higher cost of this method, it should be proposed only for patients with high bleeding risk.     

Effect of mycophenolate mofetil monotherapy on T-cell functions and inosine monophosphate dehydrogenase activity in patients undergoing a kidney transplantation

The aim of this study was to assess the effects of 1 g of mycophenolate mofetil (MMF) on T-cell function and inosine monophosphate dehydrogenase (IMPDH) activity among patients undergoing kidney transplantation. Five patients undergoing renal transplantation from a living donor were enrolled in this study. Compared to baseline (before MMF intake), CD25 and CD71 expression were significantly decreased during the first hour following MMF intake. T-cell proliferation and IMPDH activity also decreased dramatically. Thereafter, all biomarker levels increased over time. At 4 hours, CD25 and CD71 levels, as well as IMPDH activity, returned to almost baseline values, whereas T-cell proliferation remained below baseline. Intracytoplasmic IL-2 expression remained unchanged after MMF ingestions. In conclusion, administration of 1 g of MMF was associated with a transient decrease in CD25 expression in addition to a temporary dramatic decrease in both T-cell proliferation and IMPDH activity.