Chronic renal allograft rejection is often associated with the presence of fibrin thrombi in the microcirculation. Our purpose was to evaluate the influence of chronic rejection on fibrinolytic regulators in plasma of renal allograft recipients. We evaluated the concentration and activities of tPA, uPA and PAI-I in plasma from kidney allograft recipients. We studied 64 patients who underwent kidney transplantation from cadaveric allograft donors. At the time of the study 38 patients had stable graft function for at least 6 months proceeding the study, and 26 recipients had biopsy-proven chronic rejection of the kidney transplant. Control group included 30 healthy blood donors. In kidney transplant recipients we found significantly higher plasma tPA activity (median: 0.99 IU/ml; range: 0-3.8 IU/ml) in comparison to healthy controls (median: 0.15 IU/ml; range: 0-2.8 IU/ml) (p = 0.002) as well as significantly lower plasma PAI-I activity (median: 7.06 U/ml; range: 0-33.2 U/ml) in comparison to healthy controls (median: 21.8 U/ml; range: 0-36.7 U/ml), (p = 0.0001). Among transplant recipients, PAI-I plasma activity in recipients with chronic graft rejection (median: 10.16 U/ml; range: 0-33.2 U/ml) was significantly higher than in patients with stable graft function (median: 4.83 U/ml; range: 0-22.9 U/ml), (p = 0.01). In transplant recipients with stable graft function and poorly controlled hypertension we found significantly higher PAI-I plasma activity in comparison to recipients with normal blood pressure (p = 0.006). In kidney transplant recipients there was a positive correlation between the dose of prednisone and PAI-I activity in plasma (p = 0.01) and an association between BMI value and plasma PAI-I activity (p = 0.008), as well as an association between BMI value and plasma tPA-Ant concentration (p = 0.006). Among transplant recipients, patients treated with ACE inhibitors had significantly lower uPA plasma activity than the rest of the group (p = 0.003). In recipients with stable graft function we found a correlation between CsA concentration and tPA activity (p = 0.04), as well as an association between the dose of CsA and uPA-Ant concentration in plasma (p = 0.049). In patients with chronic graft rejection we found a negative correlation between the dose of prednisone and uPA-Ant plasma level (p = 0.004). Renal allograft recipients have higher tPA and lower PAI-I activities in plasma in comparison to healthy individuals. Chronic allograft rejection, is as well as poorly controlled hypertension, seem to be associated with an increase PAI-I plasma activity. In kidney graft recipients there is a relation between the value of BMI and the activity and concentration of tPA-Ant as well as the value of BMI and the PAI-I activity in plasma. Poorly controlled hypertension is associated with an increase in PAI-I plasma activity. The results of our study suggest a stimulatory effect of CsA on tPA and PAI-I plasma activities as well as on uPA-Ant concentration, while prednisone in turn seems to enhance PAI-I activity in plasma and decrease uPA expression. In renal allograft recipients ACE inhibitors seem to reduce uPA plasma activity.

Adult↗

PubMed2000

Donor DNA can be detected in recipient tissues during rejection of allograft.

The main source of donor DNA in recipients of allograft are "passenger" cells. It is claimed that they are responsible for the posttransplantation microchimerism and prolongation of allograft survival. We have observed that besides cellular microchimerism, donor DNA can be found in the recipient tissues at the time of rejection of the allograft. In this study, we provide evidence for the presence in the recipient of both DNA in "passenger cells" and free DNA in tissues at the terminal stage of rejection. Male BN (RT1 n) rat heart or skin was transplanted to female LEW (RT1 l) rats followed by a vascularized bone marrow in a hindlimb transplant. In another group, heart and skin were transplanted followed by immediate i.v. infusion of donor-type bone marrow cells. CsA was given in a dose of 17 mg/kg body weight for 30 days, then the rats were followed up until day 100 unless rejection occurred earlier. LEW blood, spleen, mesenteric node and bone marrow cells were stained with moAb OX27 specific for BN but not LEW. Genomic male DNA was isolated and amplified with SRY oligonucleotide. At day 30 and day 100 cellular microchimerism was detected in blood, spleen, nodes and bone marrow cells. Donor DNA was detected in recipient skin, liver and heart extracts, as well as lymphoid organs, at the time of rejection of allograft, but not when the rats were maintained on CsA. Taken together, donor DNAwas detected in recipient tissues at the time of heart or skin rejection. It appeared to be released from cells of rejecting grafts and not from "passenger" cells, representing only a minor cellular mass compared with the graft.

Animals↗

PubMed2000