Immune-globulin/prednisolone/unspecified steroids
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Lack of efficacy: 2 case reports In a study of 6 patients, 2 patients were described of whom, a 39-year-old man exhibited lack of efficacy during treatment with immune-globulin and prednisolone while being treated for active antibody-mediated rejection (AMR), and a 60-year-old woman exhibited lack of efficacy during treatment with immune-globulin and unspecified steroids for acute AMR [not all routes stated; dosages not stated]. The 39-year-old man (Case 1), who had end-stage renal disease (ESRD) secondary to IgA nephropathy status after 2 previous renal transplant, received his third kidney transplant donor in 2015. His initial urine output was good but anuria was observed within 12 hours. He received basiliximab induction, unspecified steroids and everolimus for maintenance immunosuppression. Dialysis was initiated on postoperative day (POD) 1. An open kidney biopsy on POD2 revealed acute tubular necrosis with thrombotic microangiopathy (TMA). Plasmapheresis, IV immune-globulin, and prednisolone were started; however, he did not respond to the treatment. Repeat biopsy on post operative (POD)12 corresponded to acute AMR. Donor specific antibodies (DSAs) specific for A68, B37, DQ5, and DP3 were observed by POD17. A biopsy on POD20 revealed AMR with TMA and diffuse C4d. Bortezomib on POD 24 and belatacept on POD20 were started. DSA specific for A68, B37, and DQ5 was decreased to undetectable by POD35, whereas DP3-specific antibodies were undetectable in 182 days . At the 30-month follow-up, DSA remained undetectable, and serum creatinine (sCr) and estimated glomerular filtration rate (eGFR) reduced. The 60-year-old woman (Case 2), who had ESRD due to progression of contrast-induced nephropathy, underwent renal transplant. She received antithymocyte globulin induction and everolimus plus mycophenolate mofetil for maintenance immunosuppression. After 24 hours, renal function deteriorated. Renal biopsy on POD6 revealed diffuse interstitial haemorrhage and focal necrosis with focal C4d staining. She was DSA positive (DQ7). After four days, she became positive for DR4, 14 and 52. She was treated with apheresis, immune-globulin, and unspecified steroids; however, no improvement was observed. After 3 days belatacept and bortezomib were initiated (off-label use). This rejection was treated with antithymocyte and additional steroids, in addition to ongoing belatacept and mycophenolate mofetil. After POD 39, there was no further detection of DSA until POD300. The treatment was discontinued after 204 days of treatment. However, the kidney function did not return and progressed to infarction, and was removed on POD 221. Jain D, et al. Reversing donor-specific antibody responses and antibody-mediated rejection with bortezomib and belatacept in mice and kidney transplant recipients. American 803520928 Journal of Transplantation 20: 2675-2685, No. 10, Oct 2020. Available from: URL: http://doi.org/10.1111/ajt.15881
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