5 research outputs found
Withdrawal of cyclosporine or prednisone six months after kidney transplantation in patients on triple drug therapy: a randomized, prospective, multicenter study
Uncertainty exists regarding the necessity of continuing triple therapy
consisting of mycophenolate mofetil (MMF), cyclosporine (CsA), and
prednisone (Pred) after kidney transplantation (RTx). At 6 mo after RTx,
212 patients were randomized to stop CsA (n = 63), stop Pred (n = 76), or
continue triple drug therapy (n = 73). The MMF dose was 1000 mg twice
daily, target CsA trough levels were 150 ng/ml, and Pred dose was 0.10
mg/kg per d. Follow-up was until 24 mo after RTx. Biopsy-proven acute
rejection occurred in 14 (22%) of 63 patients after CsA withdrawal
compared with 3 (4%) of 76 in the Pred withdrawal group (P = 0.001) and 1
(1.4%) of 73 in the control group (P = 0.0001). Biopsy-proven chronic
rejection was present in one patient in the control group, in nine
patients after CsA withdrawal (P = 0.006 versus control group); and in
four patients after discontinuation of Pred (NS). Graft loss occurred in
two versus one patient after CsA or Pred withdrawal, respectively, and in
two patients in the control group (NS). Patients who successfully withdrew
CsA had a significantly lower serum creatinine during follow-up. Pred
withdrawal resulted in a reduction in mean arterial pressure, and the
total cholesterol/HDL ratio increased. In conclusion, rapid CsA withdrawal
at 6 mo after RTx results in a significantly increased incidence of
biopsy-proven acute and chronic rejection. Pred withdrawal was safe and
resulted in a reduction in mean arterial pressure. However, patient and
graft survival and renal function 2 yr after RTx were not different among
groups
PIRCHE-II is related to graft failure after kidney transplantation
Individual HLA mismatches may differentially impact graft survival after kidney transplantation. Therefore, there is a need for a reliable tool to define permissible HLA mismatches in kidney transplantation. We previously demonstrated that donor-derived Predicted Indirectly ReCognizable HLA Epitopes presented by recipient HLA class II (PIRCHE-II) play a role in de novo donor-specific HLA antibodies formation after kidney transplantation. In the present Dutch multi-center study, we evaluated the possible association between PIRCHE-II and kidney graft failure in 2,918 donor-recipient couples that were transplanted between 1995 and 2005. For these donors-recipients couples, PIRCHE-II numbers were related to graft survival in univariate and multivariable analyses. Adjusted for confounders, the natural logarithm of PIRCHE-II was associated with a higher risk for graft failure [hazard ratio (HR): 1.13, 95% CI: 1.04-1.23, p = 0.003]. When analyzing a subgroup of patients who had their first transplantation, the HR of graft failure for ln(PIRCHE-II) was higher compared with the overall cohort (HR: 1.22, 95% CI: 1.10-1.34, p < 0.001). PIRCHE-II demonstrated both early and late effects on graft failure in this subgroup. These data suggest that the PIRCHE-II may impact graft survival after kidney transplantation. Inclusion of PIRCHE-II in donor-selection criteria may eventually lead to an improved kidney graft survival
Allocation to highly sensitized patients based on acceptable mismatches results in low rejection rates comparable to nonsensitized patients
Whereas regular allocation avoids unacceptable mismatches on the donor organ, allocation to highly sensitized patients within the Eurotransplant Acceptable Mismatch (AM) program is based on the patient\'s HLA phenotype plus acceptable antigens. These are HLA antigens to which the patient never made antibodies, as determined by extensive laboratory testing. AM patients have superior long-term graft survival compared with highly sensitized patients in regular allocation. Here, we questioned whether the AM program also results in lower rejection rates. From the PROCARE cohort, consisting of all Dutch kidney transplants in 1995-2005, we selected deceased donor single transplants with a minimum of 1 HLA mismatch and determined the cumulative 6-month rejection incidence for patients in AM or regular allocation. Additionally, we determined the effect of minimal matching criteria of 1 HLA-B plus 1 HLA-DR, or 2 HLA-DR antigens on rejection incidence. AM patients showed significantly lower rejection rates than highly immunized patients in regular allocation, comparable to nonsensitized patients, independent of other risk factors for rejection. In contrast to highly sensitized patients in regular allocation, minimal matching criteria did not affect rejection rates in AM patients. Allocation based on acceptable antigens leads to relatively low-risk transplants for highly sensitized patients with rejection rates similar to those of nonimmunized individuals
Allocation to highly sensitized patients based on acceptable mismatches results in low rejection rates comparable to nonsensitized patients
Whereas regular allocation avoids unacceptable mismatches on the donor organ, allocation to highly sensitized patients within the Eurotransplant Acceptable Mismatch (AM) program is based on the patient's HLA phenotype plus acceptable antigens. These are HLA antigens to which the patient never made antibodies, as determined by extensive laboratory testing. AM patients have superior long-term graft survival compared with highly sensitized patients in regular allocation. Here, we questioned whether the AM program also results in lower rejection rates. From the PROCARE cohort, consisting of all Dutch kidney transplants in 1995-2005, we selected deceased donor single transplants with a minimum of 1 HLA mismatch and determined the cumulative 6-month rejection incidence for patients in AM or regular allocation. Additionally, we determined the effect of minimal matching criteria of 1 HLA-B plus 1 HLA-DR, or 2 HLA-DR antigens on rejection incidence. AM patients showed significantly lower rejection rates than highly immunized patients in regular allocation, comparable to nonsensitized patients, independent of other risk factors for rejection. In contrast to highly sensitized patients in regular allocation, minimal matching criteria did not affect rejection rates in AM patients. Allocation based on acceptable antigens leads to relatively low-risk transplants for highly sensitized patients with rejection rates similar to those of nonimmunized individuals