Background and objectives: The impact of posttransplantation anemia on patient survival, renal allograft survival, and rate of acute rejection is not known.Design, setting, participants, & measurements: A total of 1023 patients who underwent kidney transplantation at one center from January 1992 through June 2003 were retrospectively analyzed. Posttransplantation anemia was defined as mean hemoglobin <11 g/dl after 3 mo after transplantation. Data on demographics, pretransplantation dialysis, previous transplant history, pretransplantation hemoglobin, degree of HLA mismatch, and donor characteristics were collected. Some of the posttransplantation data that were collected in addition to the hemoglobin included delayed graft function; diabetes; hypertension; induction and maintenance of immunosuppressive regimen; posttransplantation infections; and use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, statins, aspirin, and ␤ blockers. Cox regression models were used to assess the effects of posttransplantation anemia on each outcome: Mortality, graft survival, and rate of acute rejection. Median follow-up time was 4 yr.Results: During the entire follow-up period, there were 89 (9%) deaths, 143 (14%) acute rejection episodes, and 235 (23%) kidney losses. In multivariate Cox regression models, being anemic after transplantation, after the first 90 d, was associated with increased overall mortality and increased renal allograft loss. Posttransplantation anemia was also associated with increased acute rejection rates.Conclusions: This study shows that posttransplantation anemia is associated with worse patient and graft survival and higher rates of acute rejection when compared with nonanemic renal transplant recipients.

SummaryBackground and objectives The optimal maintenance immunosuppressive regimen to improve long-term renal allograft function and graft survival is yet to be determined.Design, setting, participants, & measurements This observational study prospectively compared tacrolimus/ sirolimus with tacrolimus/mycophenolate mofetil in renal transplant recipients using a prednisone-free regimen with over 8.5 years of follow-up. Patients received methylprednisonlone and anti-IL2 receptor antagonist (Basiliximab) induction and were blindly randomized to either the tacrolimus/mycophenolate mofetil (n=45) or tacrolimus/sirolimus (n=37) groups. Outcome measures included patient and renal allograft survival, incidence of acute rejection, and estimated GFR.Results The tacrolimus/mycophenolate mofetil group compared with the tacrolimus/sirolimus group had overall better renal allograft survival (91% versus 70%, P=0.02); 13 patients (35.1%) in the tacrolimus/sirolimus group and 8 patients (17.8%) in the tacrolimus/mycophenolate mofetil group experienced biopsy-proven acute cellular rejection (P=0.07). By 3 months post-transplant, estimated GFR was significantly lower in the tacrolimus/ sirolimus group compared with the tacrolimus/mycophenolate mofetil group (47.7 versus 59.6 ml/min per 1.73 m 2 , P=0.0002), and this trend persisted throughout the follow-up period. Also, the slope of decline in the tacrolimus/ sirolimus group was significantly steeper than in the tacrolimus/mycophenolate mofetil group.Conclusions This study shows that, in a prednisone-free immunosuppressive regimen, long-term renal graft survival and function are significantly worse in the tacrolimus/sirolimus group than the tacrolimus/ mycophenolate mofetil group. The synergistic nephrotoxic effect and higher acute rejection rates in the tacrolimus/sirolimus compared with the tacrolimus/mycophenolate mofetil group adversely affect graft survival.

Tacrolimus and Sirolimus are commonly used maintenance immunesuppressants in kidney transplantation. Since their effects on immune cells and allograft molecular profiles have not been elucidated, we characterized the effects of Tacrolimus to Sirolimus conversion on frequency and function of T cells, and on graft molecular profiles. Samples from renal transplant patients in a randomized trial of 18 patients with late Sirolimus conversion and 12 on Tacrolimus maintenance were utilized. Peripheral blood was collected at 0, 6, 12 and 24-months post-randomization with T cell subpopulations analyzed by flow cytometry and T cell alloreactivity tested by IFN-γ ELISPOT. Graft biopsy samples obtained 24-months post-randomization were used for gene expression analysis. Sirolimus conversion led to an increase in CD4+25+++Foxp3+ regulatory T cells. While Tacrolimus-maintained patients showed a decrease in indirect alloreactivity over time post-transplant, Sirolimus conversion increased indirect alloreactive T cell frequencies compared to Tacrolimus-maintained patients. No histological differences were found in graft biopsies, but molecular profiles showed activation of the antigen presentation, IL-12 signaling, oxidative stress, macrophage-derived production pathways, and increased inflammatory and immune response in Sirolimus-converted patients. Thus, chronic immune alterations are induced after Sirolimus conversion. Despite the molecular profile being favorable to calcineurin inhibitor-based regimen, there was no impact in renal function over 30 months of follow-up.

Idiopathic membranous nephropathy (IMN) remains

Our data suggest that, in SPK recipients, long-term kidney allograft survival and function are not statistically different. A trend toward an increased rate of renal allograft loss was found in the Tac/SRL-treated group.