Impact of belatacept conversion on kidney transplant function, histology, and gene expression ‐ a single‐center study

Abstract

Prior studies on belatacept conversion from calcineurin inhibitor (CNI) have been limited by an absence of postconversion surveillance biopsies that could underestimate subclinical rejection, or a case-controlled design. A total of 53 adult patients with allograft dysfunction underwent belatacept conversion (median: 6 months) post-transplant. At a median followup = 2.5 years, patient survival was 94% with a death-censored graft survival of 85%. Seven (13%) patients had acute rejection (including 3 subclinical) at median 6 months postconversion. Overall, eGFR improved (P = <0.001) from baseline = 31AE15 to 40.2 AE 17.6 ml/min/1.73m 2 by 6 months postconversion, but then stayed stable. This improvement was also observed (P < 0.001) in comparison with a propensity matched control cohort on CNI, where eGFR stayed stable (mean~32ml/min/1.72m 2) over 2-year follow-up. Patients converted < 6 months post-transplant were more likely to have a long-term improvement in kidney function. Paired gene expression analysis of 30 (of 53) consecutive pre-and postconversion surveillance biopsies did not reveal changes in inflammation/acute injury; although atrophy-fibrosis score worsened (mean = 0.28 to 0.44; P = 0.005). Thus, improvement in renal function with belatacept conversion occurred early and then sustained in comparison with controls where renal function remained unchanged overtime. We were unable to show molecular signals that could be related to CNI administration and regressed after withdrawal.

Belatacept Use after Kidney Transplantation and Its Effects on Risk of Infection and COVID-19 Vaccine Response

“…At a median follow-up of 2.5 years, 64 adverse events had occurred during 88.5 p--y of belatacept exposure. Eight (15%) patients required hospitalization at post-conversion due to infection, with urinary-tract infections being the most common indication [ 38 ].…”

“…In a review by Yazdi et al, only two of 78 KTx converted from CNI-based to belatacept-based therapy had positive CMV viremia, without signs of infection [ 37 ]. In a study by Gupta et al, six of 53 (11.3%) converted KTx developed CMV-associated disease: of these, three were at high risk for CMV, i.e., the donor was CMV seropositive, the recipient was CMV seronegative, thus putting them at risk for primary CMV infection [ 38 ].…”

“…Gupta et al noted BKV viremia in one patient (1.9%) [ 38 ]. Bertrand et al focused on OIs in their study and considered polyomavirus-associated nephropathy as an OI, but not BKV viremia.…”

“…Gupta et al reported on 53 patients of which three (5.7%) developed Cryptococcus [ 38 ]. In the study by Brakemeier et al, among 69 patients, one developed Pneumocystis jirovecii pneumonia and one developed Candida septicemia [ 39 ].…”

“…In the study by Darres et al, 45 patients (20.5%) suffered from a bacterial infection that required hospitalization, including 18 (8.2%) cases of pyelonephritis and 12 (5.5%) of pneumonia [ 36 ]. Gupta et al, among 53 patients, reported that four (7%) developed a surgical wound infection, 13 (24.5%) a urinary-tract infection, three (5.7%) bacteremia, and one (1.9%) developed Clostridium difficile colitis [ 38 ].…”