INTRO: Calcineurin inhibitors have improved kidney transplant and recipient survival, their use has significant nephrotoxicity. Belatacept is a recently approved immunosuppressant that is not nephrotoxic but may be associated with increased rates of clinical and subclinical rejections. We reviewed our experience with belatacept conversion in hopes of identifying clinical and pathological characteristics that predicted favorable outcomes.

METHODS/RESULTS: Since 2013, we have converted 39 patients from a CNI based regimen to Belatacept: 32 for graft dysfunction, 5 for thrombotic microangiopathy, 2 for neurotoxicity, and 1 for bone marrow suppression. Patients were 53.1 (38.9 – 64) years old, 43.6% male and were converted at a median of 11.4 months (IQR: 3.4 -33.9) after transplant. After 153 days (18-468) on belatacept, serum creatinine improved significantly from 2.8 mg/dL (1.9 -3.4) to 2 mg/dL (1.5 -2.5) (p=0.0001) and includes renal recovery from dialysis dependence for one patient with severe TMA. To identify characteristic associated with response to conversion, we defined two groups- responders (≥ 30% reduction in creatinine) and nonresponders (<30% reduction in creatinine). we divided these patients into those with and without a 30% reduction in serum creatinine. The 36% patients who responded were significantly less likely to have vascular disease on pre-conversion biopsy (53.9% vs 91.3%, p=0.016) and more likely to have isometric tubular vacuolization (30.8% vs 4.4% p=0.047). The degree of fibrosis and glomerulosclerosis were not different between groups. In general, proteinuria improved but not significantly after conversion from 0.4 (0.18 – 0.8) to 0.35 (0.13 – 0.61) mg/mg of creatinine. There were three rejection episodes- 2 in patients who had DSA and were still on CNI at that time of rejection, and 1 patient who was converted for mTOR inhibitor intolerance 12 years out from transplant. One patient developed both BK viremia and CMV retinitis. A single patient was hospitalized for pneumonia after conversion, recovered completely but later had sudden cardiac death at home.

CONCLUSION: Most patients who were converted to belatacept had either stabilization or improvements in their renal function. While nearly all patients had improved renal function, patients with isometric vacuolization or lack of vascular disease on renal biopsy showed the largest gains. Overall conversion was safe though 7% experienced rejection.

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