Selective corticosteroid and calcineurin‐inhibitor withdrawal after pancreas–kidney transplantation utilizing thymoglobulin induction and sirolimus maintenance therapy

Abstract

Of 25 simultaneous pancreas-kidney transplant (SPK) recipients treated with thymoglobulin induction, sirolimus and reduced-dose cyclosporine (CsA), 18 low-immune responders (non-African-Americans, PRA < 30%) were withdrawn from prednisone on post-transplant day 5, whereas seven high-immune responders continued on prednisone. Most high- and low-immune responder recipients were converted from CsA to mycophenolic acid (MPA) at six months post-transplantation. At a mean follow-up of 28 +/- 10 months, two pancreas grafts were lost to pancreatitis. There were no patient or kidney graft losses, but one acute rejection episode. At 28 +/- 11 months, all 18 low-responder recipients remain steroid-free. Twenty recipients (14 low and six high-immune responders) were converted from CsA to MPA. During conversion, immune response was monitored by Flow-PRA and T-cell stimulation (Cylex) assays. Nineteen of 20 recipients displayed a post-conversion PRA of 0%, whereas one highly sensitized patient expressed a post-conversion PRA of 67%. Fifty-eight percent of individual T-cell stimulation scores were in the hypo-responsive range. Twelve of 18 low-immune responders are both steroid and CsA-free at a mean follow-up of 17 +/- 13 months, whereas five of seven high-immune responders remain CsA-free at a mean follow-up of 11 +/- 10 months. These data suggest that thymoglobulin induction with combined sirolimus and CsA maintenance therapy permits immunosuppression minimization in selected SPK recipients.

The metabolic and toxicological considerations for immunosuppressive drugs used during pancreas transplantation

“…Induction therapy with anti-thymocyte globulin followed by either sirolimus/reduced dose CSA (withdrawn at 6 months and conversion to MMF)/prednisone withdrawn or sirolimus/ reduced dose CSA/prednisone demonstrated encouraging survival rates at 1 year and 2 years in SPKT recipients [135][136][137]. Additionally, these protocols are associated with low immune response as assessed by flow-panel reactive antibody (PRA) and T-cell stimulation (Cylex) assays [136].…”

“…Additionally, these protocols are associated with low immune response as assessed by flow-panel reactive antibody (PRA) and T-cell stimulation (Cylex) assays [136]. Corticosteroids avoidance or withdrawal protocols after pancreas transplant have been used in many centers due to their effect on hyperglycemia.…”

Induction therapy in pancreas transplantation

“…Descriptive studies using different dosing strategies of thymoglobulin include the following: Knight et al . described the use of rabbit ATG at 1.5 mg/kg/d for 5 days with sirolimus/cyclosporine and a selective steroid taper maintenance for 6 months and were switched to mycophenolate/sirolimus and selective corticosteroid maintenance . Among 25 SPKs, kidney graft survival was 100% at 1 year, and two pancreatic allografts were lost during that time.…”

Role of simultaneous pancreas-kidney transplantation in the treatment of diabetes mellitus

“…A pécsi munkacsoport is ezt preferálja. A második leggyakrabban használt kombináció pedig mTOR-inhibitor-alapú, szteroid, ciklosporin-A, sirolimus [34]. A budapesti program ez utóbbi kombinációt használja.…”