MPF is a reliable indicator of graft viability based on the rate of PNF and immediate renal allograft function, especially in marginal donors.
ABO-incompatible liver transplantation is usually contraindicated. The presence in the recipient of preformed anti-A/B antibodies located on endothelial cells raises the risk of antibody-mediated humoral rejection of the graft. We describe four successful cases of steroid withdrawal in adult patients who had living-donor liver transplantation from ABO-incompatible donors. Antirejection therapy included multiple perioperative plasmapheresis, splenectomy, and a triple immunosuppressive regimen with tacrolimus, methylprednisolone (MPSL), and cyclophosphamide or mycophenolate mofetil (MMF). The maintenance dose of immunosuppression did not differ from that of ABO-identical cases. After transplantation, intrahepatic arterial infusion therapy with prostaglandin E1 (PG E1) was used. As a result, all four patients were able to achieve long-term graft survival without steroid use. They all have good liver function and are leading normal lifestyles. Our experience with these four patients suggests the feasibility of controlling humoral rejection and other complications in adult ABO-incompatible living donor liver transplantations with intrahepatic arterial infusion of PGE1, splenectomy, and plasmapheresis with a regular base of immunosuppression protocol to prevent antibody-mediated humoral rejection.
Cyclosporine (CYA) and tacrolimus (TAC) are calcineurin inhibitors with similar action mechanisms. However, there have not been any detailed reports on the pharmacokinetic differences of relationship among are under the concentration time curve (AUC), peak concentration (C p ), and trough concentration (C t ), regarding CYA and TAC after oral administration in a controlled group. 1) AUC of CYA has been reported to be associated with clinical efficacy. [2][3][4][5] On the other hand, the relationship between AUC of TAC and the clinical efficacy of TAC has not been evaluated precisely. However, it is generally thought that AUC is the most reliable pharmacokinetic parameter to predict the clinical efficacy of calcineurin inhibitors including TAC. CYA blood concentration is often monitored by blood concentration at 2 h after administration (C 2 ) to be more significantly associated with AUC, 6) and TAC blood concentration is monitored by C t . It has yet to be explained why only AUC of CYA correlates more significantly with C 2 , and we could not clearly account for why the monitoring timings differ between CYA and TAC. Therefore, we investigated this issue to compare the blood concentration curve patterns and pharmacokinetic parameters of CYA and TAC in renal transplant recipients by using new pharmacokinetic parameters such as area under the trough level (AUTL) and area above the trough level (AATL). These parameters are parts of AUC and are dependent on C t and C p , respectively as described later. MATERIALS AND METHODSPatients Twelve hours of monitoring of CYA and TAC blood concentrations was performed on 20 patients who were administered a CYA microemulsion formulation at 41.8Ϯ 20.5 (meanϮS.D.) d after renal transplantation and on 24 patients who were administered TAC at 41.4Ϯ21.4 d after transplantation. This monitoring was routinely carried out once before hospital discharge. The CYA-administrated patients consisted of 11 males and 9 females aged 42.7Ϯ1.0 (meanϮS.D.) years, and the mean (S.D.) body weight of these patients was 53.5Ϯ10.0 kg. The TAC-administrated patients consisted of 15 males and 9 females aged 46.5Ϯ11.3 years, and their mean body weight was 52.3Ϯ9.9 kg ( Table 1). None of the patients had digestive or liver dysfunction, which may affect the absorption or metabolism of CYA or TAC. All patients received a triple immunosuppressive-drug regimen, which consisted of calcineurin inhibitors (CYA or TAC), methylprednisolone, and either mycophenolate mofetil or azathioprine. Other drugs known to affect the pharmacokinetics of CYA or TAC were not administered to these patients. Informed consent was obtained from all patients included in this study. The clinical efficacy of calcineurin inhibitors administered to renal transplant patients is considered to be a strong function of the area under the concentration time curve (AUC). Interestingly, monitoring timings of blood concentrations for two similar calcineurin inhibitors, cyclosporine (CYA; Neoral ® ) and tacrolimus (TAC; Prograf ® ) are different. ...
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