Homocysteine, its metabolites, and B-group vitamins in renal transplant patients

Homocysteine, its metabolites, and B-group vitamins in renal transplant patients.BackgroundIncreased plasma total homocysteine (tHcy) levels are an independent risk factor for cardiovascular morbidity in patients with normal and impaired renal function, including stable renal transplant recipients (RTRs). Plasma concentrations of the metabolites of Hcy, such as cystathionine (Cys), methylmalonic acid (MMA), 2-methylcitric acid (MC), and its diasteromers MCI and MCII have been reported in only a few articles. We therefore looked for the serum concentration of these metabolites and their relationship to renal function, cardiovascular diseases, the immunosuppressive treatment, and serum concentrations of cobalamin and folate.MethodsFifty RTRs (mean age 50.4 ± 11.8 years, 35.9 ± 44.4 months after kidney transplantation) and 35 controls (NP; mean age 43.5 ± 14.4 years) were studied. Total Hcy and its metabolites were measured by gas chromatography-mass spectrometry (GC-MS).ResultsTotal Hcy, MMA, Cys, and MC were elevated twofold to sixfold as compared with NP, with a significant interrelationship between these compounds. With the exception of Cys, they were significantly correlated with serum creatinine. Serum folate levels were inversely correlated with tHcy, Cys and cobalamin with MMA and the ratio of MCI/MCII. There was no correlation between tHcy concentration and its metabolites with immunosuppressive treatment (CsA vs. FK506), clinical history, or current findings of cardiovascular complications and blood pressure profile.ConclusionProspective studies are needed to find out whether the lowering or normalization of serum concentrations of tHcy and its metabolites due to treatment with B vitamins should be achieved to reduce the cardiovascular risk and improve the long-term outcome of allografts and of patients

Bone disease after renal transplantation

We propose a probabilistic key predistribution scheme for wireless sensor networks, where keying materials are distributed to sensor nodes for secure communication. We use a two-tier approach in which there are two types of nodes: regular nodes and agent nodes. Agent nodes are more capable than regular nodes. Our node deployment model is zone-based such that the nodes that may end up with closer positions on ground are grouped together. The keying material of nodes that belong to different zones is non-overlapping. However, it is still possible for nodes that belong to different zones to communicate with each other via agent nodes when needed. We give a comparative analysis of our scheme through simulations and show that our scheme provides good connectivity figures at reasonable communication cost by using minimal flooding in key distribution. Moreover, we show that our scheme is scalable such that no extra overhead in incurred in case of increased number of nodes and sensor field size. Most importantly, simulation results show that our scheme is highly resilient to node captures

Tacrolimus-Based, Steroid-Free Regimens in Renal Transplantation: 3-Year Follow-Up of the ATLAS Trial

BACKGROUND: Long-term use of corticosteroids is associated with considerable morbidity, including cardiovascular and metabolic adverse effects. METHODS: This study evaluated the long-term efficacy and safety of two steroid-free regimens compared with a triple immunosuppressive therapy in renal transplant recipients. This was a 3-year follow-up to a 6-month, open-label, randomized, multicenter study. RESULTS: Data from 3 years were available for 421 (93.3%) of 451 patients in the original intent-to-treat population (143 tacrolimus/basiliximab [Tac/Bas], 139 tacrolimus/mycophenolate mofetil [Tac/MMF], and 139 tacrolimus/MMF/steroids [triple therapy]). In the time interval from 6 months to 3 years after transplantation, the incidence of biopsy-proven acute rejection was low and similar (Tac/Bas, 2.1%; Tac/MMF, 2.2%; triple therapy, 2.2%); Most rejection episodes occurred during the first 6 months of the study. Graft survival was high (Kaplan-Meier estimates: 92.7%, 92.5%, and 92.5%), as was patient survival (93.1%, 96.4%, and 97.0%). There were 10 graft losses (n=2, 4, and 4) and 12 patient deaths (n=5, 2, and 5). Renal function was well preserved throughout the study and similar between groups. There was a trend toward improved cardiovascular risk factors in the Tac/Bas group, including reduced total and low-density lipoprotein cholesterol and lower new-onset insulin use. There were no between-group differences in the incidence or type of adverse events. CONCLUSION: Higher rates of acute rejection early in treatment were seen with the steroid-free regimens, but this did not translate into poorer long-term outcomes, such as graft and patient survival and renal function. A trend for a more favorable cardiovascular risk profile was observed for steroid-free immunosuppression with Tac/Bas

Efficacy and safety of tacrolimus compared with ciclosporin A microemulsion in renal transplantation: 2 year follow-up results

BACKGROUND: Comparison studies of calcineurin inhibitors as cornerstone immunosuppressants in renal transplantation have demonstrated that tacrolimus consistently reduces acute rejection rates and, in some studies, also improves long-term renal outcome in comparison to cyclosporin A (CsA). The aim of the present 2 year follow-up of the European Tacrolimus vs Cyclosporin A Microemulsion Renal Transplantation Study was to investigate long-term clinical outcome in terms of rate of acute rejection, graft and patient survival and graft function. METHODS: The European Tacrolimus vs Cyclosporin A Microemulsion Renal Transplantation Study was a randomized, comparative 6 month trial of the calcineurin inhibitors tacrolimus and CsA in combination with both azathioprine and steroids. The intent-to-treat population (ITT) consisted of 286 patients in the tacrolimus arm and 271 in the CsA microemulsion (CsA-ME) arm. Whereas whole blood level targets were 10-20 and 5-15 ng/ml for tacrolimus and 100-400 and 100-200 ng/ml for CsA during months 0-3 and 4-6, respectively, during the investigator-driven follow-up after termination of the main study (months 7-24) no specific calcineurin inhibitor target levels were required. Follow-up data were collected at 2 years post-transplantation from 237 (82.9% of the ITT population) patients who received tacrolimus and 222 (81.9% of the ITT population) patients who received CsA-ME. RESULTS: Calculated on ITT populations, mortality (2.0% vs 3.3%; P<0.05 in Kaplan-Meier analysis) was lower, but rate of graft loss (9.3% vs 11.2%; P = 0.12 in Kaplan-Meier analysis) was not significantly different after 2 years with tacrolimus- vs CsA-ME-based immunosuppression. Biopsy-proven acute rejection was significantly lower (19.6%) with tacrolimus than with CsA-ME (37.3%) during months 0-6 (P<0.0001), but was not significantly different during months 7-12 and 13-24 of follow-up (1.7% and 0.8% with tacrolimus and 4.7% and 0.9% with CsA-ME, respectively). A composite endpoint consisting of graft loss, patient death and biopsy-proven acute rejection occurred significantly more frequently in CsA-ME patients than in tacrolimus patients (42.8% vs 25.9%; P<0.001) during 24 months follow-up. Renal function 2 years post-transplant, measured by serum creatinine concentrations, was significantly better in tacrolimus-based compared with CsA-ME-based immunosuppression (136.9 vs 161.6 micromol/l; P<0.01). Cornerstone immunosuppression remained unchanged in 82.5% and 66.2% of patients treated with tacrolimus and CsA-ME, respectively. At 2 years, more patients in the tacrolimus arm were off steroids and received calcineurin inhibitor monotherapy, and fewer tacrolimus patients remained on a triple immunosuppressive regimen. The cardiovascular risk profile was affected favourably in the tacrolimus arm, with lower cholesterol and triglyceride concentrations (despite less use of cholesterol-lowering drugs); no significant difference in requirement for antidiabetic medication was noted. CONCLUSIONS: The 2 year study results confirm that tacrolimus is a highly efficacious cornerstone immunosuppressant in kidney transplantation. Tacrolimus-based immunosuppression may induce long-term benefits with regard to graft function and graft survival. The overall side-effect profile is considered to be favourable

Efficacy and safety of tacrolimus compared with ciclosporin A in renal transplantation: three-year observational results

BACKGROUND: The European tacrolimus versus ciclosporin A microemulsion (CsA-ME) renal transplantation study showed that tacrolimus was significantly more effective in preventing acute rejection and had a superior cardiovascular risk profile at 6 months. METHODS: The endpoints of this investigator-initiated, observational, 36-month follow-up were acute rejection incidence rates, rates of patient and graft survival and renal function. An additional analysis was performed using the combined endpoints BPAR, graft loss and patient death. Data available from the original ITT population (557 patients; 286 tacrolimus and 271 CsA-ME) were analysed. RESULTS: A total of 231 tacrolimus and 217 CsA-ME patients participated. At 36 months, Kaplan-Meier-estimated BPAR-free survival rates were 78.8% in the tacrolimus group and 60.6% in the CsA-ME group, graft survival rates were 88.0% and 86.9% and patient survival rates were 96.6% and 96.7%, respectively. The estimated combined endpoint-free survival rate was 71.4% with tacrolimus and 55.4% with CsA-ME (P 6 mmol/L (26.3% versus 12.6%, P <or= 0.0003, chi-square test). CONCLUSIONS: Patients treated with tacrolimus had significantly higher combined endpoint-free survival rates and lower acute rejection rates with less immunosuppressive medication at 36 months