*Purpose: Proteinuria develops in about 30% of kidney transplant recipients and is a strong predictor of graft loss. ACEis/ARBs can reduce proteinuria but are frequently associated with worsening hyperkalemia and reduction in estimated glomerular filtration rate (eGFR). Novel therapies are needed to reduce proteinuria and prevent graft loss in transplant recipients. While B7-1 is a well-known co-stimulatory signal that interacts with CD28 on T cells, B7-1 also plays an important role in glomerular proteinuria by promoting disease-associated podocyte migration. Abatacept has been shown to reduce proteinuria in patients with B7-1-positive glomerular disease by stabilizing β1-integrin activation in podocytes. The utility of belatacept in proteinuric kidney transplant (KT) recipients remains to be explored.

*Methods: In this phase I multicenter clinical trial, we recruited EBV IgG⁺ adult KT recipients at least 6 months post-transplant with an eGFR greater than 30ml/min/1.73m², proteinuria greater than 1g/day on CNI-based maintenance immunosuppression and no acute rejection on biopsy in the previous 6 months. Patients were converted from CNI to belatacept. The primary outcome was 25% reduction in proteinuria at 12 months.

*Results: Total of 15 KT recipients were included. 87% were male, 20% were black and 73% had received a deceased donor transplant. Diabetic nephropathy was the most common cause of ESKD. At enrollment, mean (±SD) eGFR was 45.2±13 ml/min/1.73m², mean urine protein/creatinine ratio was 2.5±0.4 g/g and 67% were on ACEis or ARBs. At 12 months, mean (±SD) eGFR was 43.7±13 ml/min/1.73m² and mean proteinuria was 1.7±1.8 g/g. Primary outcome was reached in 53% of the patients. Patients without diabetes mellitus (DM) had a trend towards more reduction in proteinuria, compared to patients with DM (-1.91±2.49 vs 0.1±1.3, mean difference of -1.8 with 95% confidence interval: -0.5 to 4.1). There was no difference between systolic (134±9 vs 129±16 mmHg) and diastolic blood pressures (75±7 vs 73±9 mmHg) at 12 months compared to baseline. During the study period, 13% of patients were newly started on ACEi or ARBs. None of the patients had allograft rejection or developed new donor-specific antibodies. One patient had sudden cardiac death thought to be unrelated to the treatment. One patient had worsening of proteinuria which led to discontinuation of belatacept.

*Conclusions: Belatacept conversion in proteinuric kidney transplant recipients was associated with stable allograft function and about half the patients achieved the primary outcome of 25% reduction in proteinuria. Patients without DM may experience greater reduction in proteinuria on belatacept.

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