A Randomized Controlled Clinical Trial Comparing Belatacept With Tacrolimus After De Novo Kidney Transplantation.

BACKGROUND: Belatacept, an inhibitor of the CD28-CD80/86 costimulatory pathway, allows for calcineurin-inhibitor free immunosuppressive therapy in kidney transplantation but is associated with a higher acute rejection risk than ciclosporin. Thus far, no biomarker for belatacept-resistant rejection has been validated. In this randomized-controlled trial, acute rejection rate was compared between belatacept- and tacrolimus-treated patients and immunological biomarkers for acute rejection were investigated. METHODS: Forty kidney transplant recipients were 1:1 randomized to belatacept or tacrolimus combined with basiliximab, mycophenolate mofetil, and prednisolone. The 1-year incidence of biopsy-proven acute rejection was monitored. Potential biomarkers, namely, CD8CD28, CD4CD57PD1, and CD8CD28 end-stage terminally differentiated memory T cells were measured pretransplantation and posttransplantation and correlated to rejection. Pharmacodynamic monitoring of belatacept was performed by measuring free CD86 on monocytes. RESULTS: The rejection incidence was higher in belatacept-treated than tacrolimus-treated patients: 55% versus 10% (P = 0.006). All 3 graft losses, due to rejection, occurred in the belatacept group. Although 4 of 5 belatacept-treated patients with greater than 35 cells CD8CD28 end-stage terminally differentiated memory T cells/µL rejected, median pretransplant values of the biomarkers did not differ between belatacept-treated rejectors and nonrejectors. In univariable Cox regressions, the studied cell subsets were not associated with rejection-risk. CD86 molecules on circulating monocytes in belatacept-treated patients were saturated at all timepoints. CONCLUSIONS: Belatacept-based immunosuppressive therapy resulted in higher and more severe acute rejection compared with tacrolimus-based therapy. This trial did not identify cellular biomarkers predictive of rejection. In addition, the CD28-CD80/86 costimulatory pathway appeared to be sufficiently blocked by belatacept and did not predict rejection.

Public survey of financial incentives for kidney donation.

BACKGROUND: One of the most fiercely debated strategies to increase the number of kidneys for transplantation is the introduction of financial incentives. As the success of such strategy largely depends on public support, we performed a public survey on this topic. METHODS: We developed a questionnaire on financial incentives for living kidney donation. We investigated the public opinion on two different fixed compensations: either life-long health insurance compensation or 25,000 euros. Furthermore, we investigated public preferences on the practical implementation: either the patient seeks a donor or the donor registers for donation at an independent institute. For all examples, health insurance companies would cover costs of treatment. TNS NIPO, a professional organization for market research, sent the survey to a response panel that is made representative for the general population. RESULTS: Five hundred fifty respondents (M/F: 60/40; median age: 46) filled out the questionnaire. Forty-six percent considered the situation wherein health insurance companies would introduce financial incentives to increase the number of living kidney donors undesirable (26% undesirable; 20% very undesirable), compared to 25% who perceived this as desirable (20% desirable; 5% very desirable). The option wherein the donor registers at an independent institute to donate to a patient on the list and in turn receives life-long health insurance compensation was chosen as most favourable. Of all respondents, 5.5% stated that there was a (very) great chance that they would donate a kidney in order to get compensation if such system were to be reality. CONCLUSION: Although almost half of the respondents (46%) were reluctant towards introducing a system with fixed compensation to increase the number of living kidney donors, still 25% of the general public reacted positively.