Early conversion to belatacept after renal transplantation

Self Cite

Early conversion from a calcineurin inhibitor to belatacept has the potential to improve long-term renal allograft function; however, there remains limited experience with this strategy among African Americans and patients with preformed donor-specific antibodies (DSA). To examine these subgroups, we performed a single-center review of kidney transplant recipients converted to belatacept within 1-year of transplant between 01/2011 and 10/2017. All patients received lymphocyte-depleting induction with maintenance tacrolimus and mycophenolate +/− corticosteroids.Patients were switched to belatacept for clinical indication and followed from date of conversion until allograft failure or study conclusion. The primary endpoint at 1-year was a composite of allograft loss, biopsy proven rejection, de novo DSA formation, proteinuria, and declining renal function. Thirty-two patients were included in the review. The majority were African American, and 28.1% had DSA at transplant. Patient and allograft survival at 1-year was 96.9% and 93.8%, respectively, and estimated glomerular filtration rate improved from 41.9 to 58.4 mL/min. No African Americans or patients with pretreatment DSA developed rejection or allograft failure within 1-year. The only clinical variable correlated with suboptimal allograft function was baseline weight ≥80 kg (OR = 6.2; 95% CI, 1.2-32.3). Early conversion to belatacept appears safe for select patients with DSA and African Americans receiving lymphocyte-depleting induction. K E Y W O R D Sbelatacept, immunosuppressive agents, kidney transplantation, transplant rejection

Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 98%

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

Santeusanio

Bhansali

Weinberg

et al. 2020

Self Cite

“…[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.…”

Section: Discussionsupporting

confidence: 76%

“…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.…”

Section: Evidence Of Resolving Moderate Pathologic Changes Is Encourasupporting

confidence: 76%

Alemtuzumab induction and belatacept maintenance in marginal pathology renal allografts

Sparkes

Ravichandran

Opara

et al. 2019

We performed a prospective, 12‐month, single‐center, nonrandomized, open‐label pilot study to investigate the use of belatacept therapy combined with alemtuzumab induction in renal allografts with preexisting pathology, as these kidneys may be more susceptible to additional toxicity when exposed to calcineurin inhibitors posttransplant. Nineteen belatacept recipients were matched retrospectively to a cohort of tacrolimus recipients on the basis of preimplantation pathology. The estimated glomerular filtration rate was not significantly different between belatacept and tacrolimus recipients at either 3 or 12 months posttransplant (59 vs 45, P = 0.1 and 56 vs 48 mL/min/1.72/m2, P = 0.3). Biopsy‐proven acute rejection rates at 12 months were 26% in belatacept recipients and 16% in tacrolimus recipients (P = 0.7). Graft survival at 1 year was 89% in both groups. Alemtuzumab induction combined with either calcineurin inhibitor or costimulatory blockade therapies resulted in similar acceptable one‐year outcomes in kidneys with preexisting pathologic changes. Longer‐term follow‐up may be necessary to identify preferential strategies to improve outcomes of kidneys at a higher risk for poor function (ClinicalTrials.gov—NCT01496417).

“…For patients unable to change from a boosted HAART regimen, caution should be taken with medication dosing and CNI troughs should be carefully monitored. Belatacept, a novel T‐cell co‐stimulation blocking agent, has been used successfully in HIV‐infected recipients . If larger studies demonstrate safety and efficacy, belatacept may be another choice of immunosuppression in HIV patients on boosted PI‐based HAART.…”

Section: Discussionmentioning

confidence: 99%

Higher rates of rejection in HIV‐infected kidney transplant recipients on ritonavir‐boosted protease inhibitors: 3‐year follow‐up study

Rollins

Farouk

DeBoccardo

et al. 2019

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Rejection rates in HIV‐infected kidney transplant (KTx) recipients are higher than HIV‐negative recipients. Immunosuppression and highly active antiretroviral therapy (HAART) protocols vary with potentially significant drug‐drug interactions, likely influencing outcomes. This is an IRB‐approved, single‐center, retrospective study of adult HIV‐infected KTx patients between 5/2009 and 12/2014 with 3‐year follow‐up, excluding antibody‐depleting induction. A total of 42 patients were included; median age was 52 years, 81% male, 50% African American, 29% Hispanic, 17% Caucasian. The most common renal failure etiology was hypertensive nephrosclerosis (50%) with 5.8 median years of pre‐transplant dialysis. All patients received IL‐2 receptor antagonist, were maintained on tacrolimus (76%) or cyclosporine (17%), and 40% received ritonavir‐boosted PI‐based HAART (rtv+) regimen. Patient and graft survival at 3 years were 93% and 90%. At 1‐, 2‐, and 3‐year time points, median serum creatinine was 1.49, 1.35, and 1.67; treated biopsy‐proven rejection was 38%, 38%, and 40.5%; and 92% of episodes were acute rejection. At these time points, rejection rates were significantly higher with boosted PI HAART regimens compared to other HAART regimens, 59% vs 24% (P = 0.029), 59% vs 24% (P = 0.029), and 68% vs 24% (P = 0.01). Despite higher rejection rates, HIV‐infected KTx recipients have reasonable outcomes. Given significantly higher rejection rates using rtv+ regimens, alternative HAART regimens should be considered prior to transplantation.