Storyboard

Transplantation replaces a dysfunctional organ or tissue with a functioning one from a donor. The main biological challenge is rejection: the recipient's immune system recognizes the donor's antigens (HLA, MHC) as foreign and mounts an alloreactive response. Matzinger's model describes this activation: donor APCs (in the graft) present foreign antigens to recipient T lymphocytes alloreactive clonal expansion (T_alo increases) graft damage. Immunosuppression (IS) suppresses k_prim and T_alo growth.

HLA compatibility is the most robust determinant of long-term rejection: each incompatibility at the A, B, DR loci increases the risk. The HLA_score (0 = fully matched, 6 = incompatible in A+B+DR bilaterally) predicts chronic rejection rate and 1020 year graft survival. Transplants with HLA_score = 0 have 10-year kidney graft survival 6070%, vs. 4050% with score = 6.

The reference immunosuppressant in solid transplantation is tacrolimus (calcineurin inhibitor): it blocks IL-2 and suppresses the proliferation of T_alo. The minimum C concentration (trough) is routinely measured: the therapeutic range varies by organ and time post-transplant (kidney: 812 ng/mL in the first 3 months; 58 ng/mL after one year). Pharmacokinetics are highly variable (Cl_tac 1060 L/h), determined mainly by the expression of CYP3A5.

Cold ischemia damage during organ preservation follows exponential kinetics over time: the longer the ischemia time, the greater the mitochondrial damage, the worse initial graft function (delayed graft function, DGF in kidney) and the worse long-term survival. The clinical limits are: kidney < 2436 h, liver < 1215 h, heart < 46 h. Preservation solutions (HTK, UW) and pulsatile hypothermic perfusion reduce k_isq.

The balance between insufficient (rejection) and excessive (opportunistic infections, tumors) immunosuppression is the greatest challenge of post-transplant follow-up. The Cox survival model integrates multiple predictors (HLA_score, IS level, baseline graft eGFR) to estimate the cumulative hazard function H(t) and graft survival S(t). Patients with a living donor and low HLA_score have S(t) at 10 years 6575%, those with a cadaveric donor with high incompatibility, 4555%.

>Model

ID:('ky', 60)

Description

ID:(0, 60)