Donor-Specific Anti-Human Leukocyte Antigens Antibodies, Acute Rejection, Renal Function, and Histology in Kidney Transplant Recipients Receiving Tacrolimus and Everolimus

Abstract

Background: This analysis compared efficacy, renal function, and histology in kidney transplant recipients receiving tacrolimus (TAC) combined with everolimus (EVR) or mycophenolate (MPS). Methods: This was a retrospective analysis from a randomized trial in kidney transplant recipients who received a single 3 mg/kg dose of rabbit antithymocyte globulin (r-ATG), TAC, EVR, and prednisone (PRED; r-ATG/EVR, n = 85), basiliximab (BAS), TAC, EVR, and PRED (BAS/EVR, n = 102) or BAS, TAC, MPS, and PRED (BAS/MPS, n = 101). We evaluated the incidence of de novo donor-specific anti-human leukocyte antigens antibodies (DSA) and histology on protocol biopsies at 12 months, and the incidence of acute rejection, estimated glomerular filtration rate (eGFR) and proteinuria at 36 months. Results: At 12 months, there were no differences in de novo DSA (6.4 vs. 3.4 vs. 5.5%) or in subclinical inflammation (2.0 vs. 4.8 vs. 10.2%), interstitial fibrosis/tubular atrophy (57.1 vs. 58.5 vs. 53.8%) and C4d deposition (2.0 vs. 7.3 vs. 2.6%). At 36 months, there were no differences in the incidence of treatment failure (19.0 vs. 27.7 vs. 27.7%, p = 0.186), first biopsy-proven acute rejection (9.5 vs. 21.8 vs. 16.8%, p = 0.073), and urine protein/creatinine ratios (0.53 ± 1.05 vs. 0.62 ± 0.75 vs. 0.71 ± 1.24). eGFR was lower in the BAS/EVR compared to that in the BAS/MPS group (53.4 ± 20.9 vs. 50.8 ± 19.5 vs. 60.7 ± 21.2 mL/min/1.73 m², p = 0.017) but comparable using a sensitive analysis (49.5 ± 23 vs. 47.5 ± 22.6 vs. 53.6 ± 27.8 mL/min/1.73 m², p = 0.207). Conclusion: In this cohort, the use of EVR and reduced TAC concentrations were associated with comparable efficacy, renal function, and histological parameters compared to the standard-of-care immunosuppressive regimen.

The impact of everolimus in reducing cytomegalovirus events in kidney transplant recipients on steroid-avoidance strategy: 3-year follow-up of a randomized clinical trial

“…Different from studies demonstrating better renal function in patients on EVR versus MPS in combination with CsA, we observed no benefits on renal function. In agreement with our findings, previous studies using TAC instead of CsA also did not report renal function improvements in EVR regimens [29]. A possible explanation for this finding would be the potential lower nephrotoxic effect of therapeutic doses of TAC compared to CsA [30].…”

“…). Similar noncompliance to predetermined TAC levels were observed in previous studies . In fact, one of the challenges of this association in current clinical practice is to determine the optimal mTORi and calcineurin inhibitor concentrations to maintain a good efficacy–toxicity balance.…”

Prospective randomized study comparing everolimus and mycophenolate sodium inde novokidney transplant recipients from expanded criteria deceased donor

“…Previous studies have shown that renal function at 12 months was similar in patients receiving EVR or MPA in combination with TAC . The incomplete recovery of renal function observed from months 1 to 12 occurred despite comparable and low exposure to TAC.…”

Early conversion to a CNI-free immunosuppression with SRL after renal transplantation—Long-term follow-up of a multicenter trial

“…The results are mixed to this in the literature. Some trials reported a higher incidence of dnDSA under mTOR-Is [ 16 , 42 – 45 ] and some did not [ 18 , 46 , 47 ]. The largest multicenter study to date comparing mTOR-Is with CNIs following renal transplantation (TRANSFORM) showed no negative effect for the mTOR-I in terms of dnDSA incidence and antibody-mediated rejection at 12 months [ 18 ].…”