Impact of Early Blood Transfusion After Kidney Transplantation on the Incidence of Donor-Specific Anti-HLA Antibodies.

Little is known about the impact of posttransplant blood transfusion on the sensitization of anti-HLA antibodies and the formation of donor-specific antibodies (DSAs). The aims of our study were to determine the 1-year incidence of DSAs (assessed using a solid-phase assay) and antibody-mediated rejection (AMR) in kidney transplant patients who had or had not received a blood transfusion during the first year after transplantation. Included were 390 non-HLA-sensitized patients who had received an ABO-compatible kidney transplant and had not previously or simultaneously received a nonkidney transplant. Overall, 64% of patients received a red blood cell transfusion within the first year after transplantation, most within the first month. The overall 1-year incidence of DSAs was significantly higher in patients that had undergone transfusion (7.2% vs. 0.7% in patients with no transfusion, p < 0.0001). AMR occurred more often in the transfusion group (n = 15, 6%) compared with the nontransfusion group (n = 2, 1.4%; p = 0.04). Blood transfusion was an independent predictive factor for de novo DSA formation but not for AMR. Patients who had a transfusion and developed DSAs were more often treated with cyclosporin A (n = 10, 55.5%) rather than tacrolimus (n = 45, 19.4%; p = 0.0001). In conclusion, early posttransplant blood transfusion may increase immunological risk, especially in underimmunosuppressed patients.

Early steroid withdrawal compared with steroid avoidance correlates with graft failure among kidney transplant recipients with an history of diabetes.

BACKGROUND: Steroid minimization strategies attempt to reduce morbidity in kidney transplantation. Concern still exists regarding long-term outcomes using either steroid withdrawal or steroid avoidance regimens. METHODS: During a 10-year period, 572 primary kidney transplant recipients were treated with basiliximab, calcineurin inhibitors, and mycophenolate mofetil: 417 (72.9%) underwent a steroid-taper regimen over 2-3 months (steroid withdrawal) and 155 (27.1%), complete steroid avoidance (steroid avoidance). RESULTS: Despite no significant difference during the first 3 months (hazard ratio [HR], 1.23; P = .5349), steroid withdrawal recipients showed an increased risk of late acute rejection episodes (HR, 4.06; P = .0585), independent of recipient age >55 years (HR, 1.84; P = .0272). The risk of any adverse event was not different among steroid regimen groups (HR, 0.98; P = .8458), independent of recipient age >55 years (HR, 1.69; P = .0002), delayed graft function (DGF) (HR, 1.54; P = .0001), and positive donor Epstein-Barr virus serology (HR, 0.68; P = .0471). Intention-to-treat analyses revealed a significantly greater risk of graft failure only in diabetic recipients in the steroid withdrawal group (HR, 8.18; P = .0065), independent of confounding risk factors such as recipient age >55 years (HR, 1.99; P = .0244), >4 human leukocyte antigen-A, -B, and -DR incompatibilities (HR, 1.64; P = .0475), and DGF occurrence (HR, 2.63; P < .0001). CONCLUSION: Although both steroid minimization strategies were comparable regarding long-term safety and efficacy, an increased rate of graft failure was observed among diabetics who underwent steroid withdrawal compared with steroid avoidance.

Mechanism of activation and functional significance of the lipolysis-stimulated receptor. Evidence for a role as chylomicron remnant receptor.

In cultured human and rat cells, the lipolysis-stimulated receptor (LSR), when activated by free fatty acids (FFA), mediates the binding of apoprotein B- and apoprotein E-containing lipoproteins and their subsequent internalization and degradation. To better understand the physiological role of LSR, we developed a biochemical assay that optimizes both the activation and binding steps and, thus, allows the estimation of the number of LSR binding sites expressed in the livers of living animals. With this technique, a strong inverse correlation was found in rats between the apparent number of LSR binding sites in liver and the postprandial plasma triglyceride concentration (r = -0.828, p < 0.001, n = 12). No correlation existed between the number of LSR and plasma triglycerides measured in the same animals after 24 h of fasting. The same membrane binding assay was used to elucidate the mechanism by which FFA induce lipoprotein binding to LSR. The LSR activation step was mediated by direct interaction of FFA with LSR candidate proteins of apparent molecular masses of 115 and 90 kDa and occurred independently of the membrane lipid environment. The FFA-induced conformational shift that revealed the lipoprotein binding site remained fully reversible upon removal of the FFA. However, occupancy of the site by the apoprotein ligand stabilized the active form of LSR. Comparison of the effect of different FFA alone or in combination indicated that the same binding site is revealed by different FFA and that the length and saturation of the FFA monomeric carbon chain are critical in determining the potency of the FFA activating effect. We propose that the LSR pathway represents a limiting step for the cellular uptake of intestinally derived triglyceride-rich lipoproteins and speculate that FFA liberated by lipolysis initiate this process by altering the conformation of LSR to reveal the lipoprotein binding site.