Early post-transplant conversion from tacrolimus to belatacept for prolonged delayed graft function improves renal function in kidney transplant recipients

Abstract

Prolonged delayed graft function (DGF) in kidney transplant recipients imparts a risk of poor allograft function; tacrolimus may be detrimental in this setting. We conducted a retrospective single center analysis of the first 20 patients converted to belatacept for prolonged DGF as part of a clinical protocol as a novel treatment strategy to treat prolonged DGF. Prior to conversion, patients underwent an allograft biopsy to rule out rejection and confirm tubular injury. The primary outcome was the estimated glomerular filtration rate (eGFR) at 12 months post-transplant; secondary outcome was the change in eGFR 30 days post-belatacept conversion. At 1 year post-transplant, the mean eGFR was 54.2 (SD 19.2) mL/min/1.73 m . The mean eGFR on the day of belatacept conversion was 16 (SD 12.7) mL/min/1.73 m and rose to 43.1 (SD 15.8) mL/min/1.73 m 30 days post-conversion (P<.0001). The acute rejection rate was 20% with 100% patient survival at 12 months post-transplant. There was one graft loss in the setting of an invasive Aspergillus infection that resulted in withdrawal of immunosuppression and transplant nephrectomy. Belatacept conversion for prolonged DGF is a novel treatment strategy that resulted in an improvement in eGFR. Additional follow-up is warranted to confirm the long-term benefits of this strategy.

Conversion to belatacept within 1‐year of renal transplantation in a diverse cohort including patients with donor‐specific antibodies

“…Conversion to belatacept in immunologically higher risk populations, including African Americans and patients with preformed DSA, has been questioned due to the higher observed rates of BPAR with belatacept and the underrepresentation or exclusion of these patients from early phase II and III trials . In our patient cohort, we observed a rejection rate of 9.4% at 1 year following conversion to belatacept, which is in line with previous studies reporting overall rejection rates ranging from 7.0% to 16.7% for patients receiving lymphocyte‐depleting induction . While BPAR is more common following conversion to belatacept compared with CNI continuation, rejection rates are similar to those reported with conversion to mechanistic target of rapamycin (mTOR) inhibitors in the CONVERT and ASCERTAIN trials …”

“…The results of our experience support a strategy of early conversion to belatacept for patients with a suitable clinical indication and suggest that conversion within the first year of transplant is associated with improved renal function and 1‐year allograft survival rates >90%. Other observational studies have suggested that conversion within 3 months of transplant results in greater eGFR improvement than later conversion, and conversion within 30 days of transplant may result in even greater eGFR benefit than conversion between 61 and 90 days . This suggests a continuous relationship between the duration of CNI exposure and accumulated irreversible endothelial dysfunction and that earlier CNI avoidance by means of conversion to belatacept may result in superior effects on allograft function.…”

“…In the landmark trial by Vincenti et al, a de novo CNI‐free regimen of belatacept, mycophenolate, and prednisone led to improved composite patient and allograft survival and a higher eGFR at 7‐years compared with a cyclosporine‐based regimen, despite higher rates of biopsy proven acute rejection (BPAR) with belatacept . Subsequent studies evaluated post‐transplant conversion from a CNI to belatacept and observed similar improvements in eGFR with belatacept relative to CNI maintenance, again with higher rates of early rejection …”

Alemtuzumab induction and belatacept maintenance in marginal pathology renal allografts

“…[24][25][26] Similar to previous literature, belatacept recipients experienced higher grades of rejections, but this did not contribute to short-term graft loss, except in one patient, in whom there were adherence concerns. A few studies have previously reported the outcomes of depleting induction in conjunction with belatacept; however, these have been conducted in patients receiving more optimal quality donor kidneys.…”

“…These improvement in eGFR of about 6 mL/min. [24][25][26] Similar to previous literature, belatacept recipients experienced higher grades of rejections, but this did not contribute to short-term graft loss, except in one patient, in whom there were adherence concerns. In our study, we also combined depleting induction with steroid withdrawal.…”