In an open-label, multicenter trial, de novo kidney transplant recipients at low to medium immunological risk were randomized at week 7 posttransplant to remain on CsA (n = 100, controls) or convert to everolimus (n = 102), both with enteric-coated mycophenolate sodium and corticosteroids. The primary endpoint, change in measured GFR (mGFR) from week 7 to month 12, was significantly greater with everolimus than controls: 4.9 (11.8) mL/min versus 0.0 (12.9) mL/min (p = 0.012; analysis of covariance [ANCOVA]). Per protocol analysis demonstrated a more marked difference: an increase of 8.7 (11.2) mL/min with everolimus versus a decrease of 0.4 (12.0) mL/min in controls (p < 0.001; ANCOVA). There were no differences in graft or patient survival. The 12-month incidence of biopsy-proven acute rejection (BPAR) was 27.5% (n = 28) with everolimus and 11.0% (n = 11) in controls (p = 0.004). All but two episodes of BPAR in each group were mild. Adverse events occurred in 95.1% of everolimus patients and 90.0% controls (p = 0.19), with serious adverse events in 53.9% and 38.0%, respectively (p = 0.025). Discontinuation because of adverse events was more frequent with everolimus (25.5%) than controls (3.0%; p = 0.030). In conclusion, conversion from CsA to everolimus at week 7 after kidney transplantation was associated with a greater improvement in mGFR at month 12 versus CNItreated controls but discontinuations and BPAR were more frequent.

Imlifidase is a cysteine proteinase which specifically cleaves IgG, inhibiting Fc‐mediated effector function within hours of administration. Imlifidase converts a positive crossmatch to a potential donor (T cell, B cell, or both), to negative, enabling transplantation to occur between previously HLA incompatible donor‐recipient pairs. To date, 39 crossmatch positive patients received imlifidase prior to a kidney transplant in four single‐arm, open‐label, phase 2 studies. At 3 years, for patients who were AMR+ compared to AMR−, death‐censored allograft survival was 93% vs 77%, patient survival was 85% vs 94%, and mean eGFR was 49 ml/min/1.73 m2 vs 61 ml/min/1.73 m2, respectively. The incidence of AMR was 38% with most episodes occurring within the first month post‐transplantation. Sub‐analysis of patients deemed highly sensitized with cPRA ≥ 99.9%, and unlikely to be transplanted who received crossmatch‐positive, deceased donor transplants had similar rates of patient survival, graft survival, and eGFR but a higher rate of AMR. These data demonstrate that outcomes and safety up to 3 years in recipients of imlifidase‐enabled allografts is comparable to outcomes in other highly sensitized patients undergoing HLA‐incompatible transplantation. Thus, imlifidase is a potent option to facilitate transplantation among patients who have a significant immunologic barrier to successful kidney transplantation. Clinical Trial: ClinicalTrials.gov (NCT02790437), EudraCT Number: 2016‐002064‐13.

Summary In a 36‐month, open‐label, multicenter trial, 202 kidney transplant recipients were randomized at week 7 post‐transplant to convert to everolimus or remain on cyclosporine: 182 were analyzed to month 36 (92 everolimus, 90 controls). Mean (SD) change in measured GFR (mGFR) from randomization to month 36 was 1.3 (14.0) ml/min with everolimus versus −1.7 (15.4) ml/min in controls (P = 0.210). In patients who remained on treatment, mean mGFR improved from randomization to month 36 by 7.9 (11.5) ml/min with everolimus (n = 37) but decreased by 1.4 (14.7) ml/min in controls (n = 62) (P = 0.001). During months 12–36, death‐censored graft survival was 100%, patient survival was 98.9% and 96.7% in the everolimus and control groups, respectively, and 13.0% and 11.1% of everolimus and control patients, respectively, experienced mild biopsy‐proven acute rejection (BPAR). Protocol biopsies in a limited number of on‐treatment patients showed similar interstitial fibrosis progression. Donor‐specific antibodies were present at month 36 in 6.3% (2/32) and 18.0% (9/50) of on‐treatment everolimus and control patients with available data (P = 0.281). During months 12‐36, adverse events were comparable, but discontinuation was more frequent with everolimus (33.7% vs. 10.0%). Conversion from cyclosporine to everolimus at 7 weeks post‐transplant was associated with a significant benefit in renal function at 3 years when everolimus was continued.

The present study shows that 3 months of antihypertensive therapy with irbesartan or atenolol improves endothelium-dependent vasodilatation.