Differential impact of belatacept and cyclosporine A on central aortic blood pressure and arterial stiffness after renal transplantation.

Calcineurin inhibitors (CNI) are potent vasoconstrictors and induce an acceleration of arteriosclerosis, thus contributing to the cardiovascular risk after renal transplantation. The study compares the impact of belatacept and cyclosporine A (CsA) on arterial stiffness and central aortic blood pressure. We performed a case-control study in 46 patients (23 on belatacept and 23 on CsA) matched for age, body mass index, time after transplantation, and time on dialysis prior to transplantation. Pulse wave analysis (SphygmoCor, AtCor(®) ) was used to assess central aortic blood pressure, aortic augmentation pressure, and pulse wave velocity (PWV) as a marker of arterial stiffness. Assessment of vascular function was performed after a minimum of 20 months and a median follow-up of 81 months post-transplant. Peripheral systolic and diastolic blood pressure did not significantly differ in the two groups (p > 0.05 each). The central aortic augmentation pressure was higher in the CsA group (12.7 mmHg vs. 7.3 mmHg, p = 0.048). PWV as a measure of arterial stiffness did not differ in the two groups. Thus, belatacept is not associated with a significant difference in arterial stiffness compared to CsA after a median of 81 months post-transplant. It is associated, however, with a lower aortic augmentation pressure, a strong independent cardiovascular risk factor.

Protocol for Optimizing the Use of Kidneys From Donors With Seropositivity for Hepatitis C Virus in Seronegative Recipients.

BACKGROUND: The rapid identification of the viral load from hepatitis C virus (HCV) in seropositive donors enables the determination of their infection capacity and the subsequent design of a strategy to optimize the use of direct-action antivirals (DAA) in seronegative recipients. In 2017, we designed an optimization protocol; this study aims to assess its efficacy and safety. METHODS: This is a prospective, multicenter observational study that complies with the Declarations of Helsinki and Istanbul. Donors were HCV seropositive. The HCV and human immunodeficiency virus loads were immediately determined in the donors. For viremic donors, recipients were treated with DAA for 8 weeks. For nonviremic donors, DAA was started if a viral load was detected during the follow-up period. The minimum follow-up period was 6 months posttransplant. RESULTS: This study recruited 28 donors. Just over half of the donors (n = 15; 53.5%) had a nonactive history of injection drug use. Eight (22.4%) donors were viremic, and 20 (87.6%) were nonviremic; 13 (65%) had been treated previously. Nine grafts were ineligible for the protocol. We performed a total of 47 transplants. Procedure I (viremic donors) was performed in 13 recipients (27.7%). Posttransplant viremia was observed in 6 participants. Posttransplant viremia was low (<100 IU/mL) in 4 participants but high (36,000 and 138,000 IU/mL) in 2 participants who had initiated DAA after the transplant; all these patients had a sustained viral response. Seroconversion was observed in 11 of 13 (84.6%) patients. Procedure II (nonviremic donors) was undertaken in 34 (82.3%) patients. No positive viral loads were observed. Seroconversion occurred in 7 of 34 (20.5%) recipients. All recipients maintained kidney function at 6 months posttransplant, except 1 patient with a graft that had never been functional and another patient who died of pancreatitis. Both patients had received kidneys from nonviremic donors. CONCLUSIONS: Our experience supports the efficacy and safety of this protocol.

Targets of new immunosuppressants in renal transplantation.

Although current immunosuppression is highly effective in avoiding acute rejection, it is associated with nephrotoxicity, cardiovascular morbidity, infection, and cancer. Thus, new drugs dealing with new mechanisms, as well as minimizing comorbidities, are warranted in renal transplantation. Few novel drugs are currently under investigation in Phase I, II, or III clinical trials. Belatacept is a humanized antibody that inhibits T-cell co-stimulation and has shown encouraging results in Phase II and III trials. Moreover, two new small molecules are under clinical development: AEB071 or sotrastaurin (a protein kinase C inhibitor) and CP-690550 or tasocitinib (a Janus kinase inhibitor). Refinement in selecting the best combinations for the new and current immunosuppressive agents is probably the main challenge for the next few years.