Reversibility of tacrolimus-induced posttransplant diabetes: an illustrative case and review of the literature

Abstract

Tacrolimus is a potent immunosuppressive agent. It has been reported to have superior immunosuppressive efficacy when compared with the standard formulation of cyclosporine (CyA), 1 based on its ability to rescue patients with failing allografts under CyA-based therapy, 2,3 lower rejection rates when used as a primary immunosuppressive agent, 4,5 and longer projected half-life. 6 However, there have been reports of an increased incidence of posttransplant diabetes (PTDM) under tacrolimus-based therapy. 4,5 We have reported on the reversibility of tacrolimus-induced PTDM in our own renal transplant patients. 7,8 In this article, we present an illustrative case demonstrating the reversibility of PTDM and review both the published and unpublished literature. The data suggest that the initial incidence of PTDM in the renal transplant population may be higher under tacrolimus than under CyA-based therapy, but the final incidence is comparable. 9-11 ILLUSTRATIVE CASEThe patient was a 64-year old black female with end-stage renal disease secondary to hypertension, who received a kidney from her son. The allograft functioned immediately, and she never experienced rejection. Her serum creatinine, tacrolimus dosages and levels, prednisone dosages, fasting blood glucose levels, and insulin requirements are shown in Table 1. Basically, she was normoglycemic until 13 weeks after transplantation, when her fasting blood glucose level was 280 mg/dL. One week later, it was 555 mg/dL, and she was admitted to the hospital and started on insulin. As her tacrolimus and steroid dosages were tapered, her blood sugars normalized, and her insulin was tapered off by 26 weeks after transplantation. She continues to have normal renal function 1.5 years after transplantation, with a serum creatinine of 1.0 mg/dL, on tacrolimus 1 mg orally twice per day and no prednisone. Her tacrolimus level is 8.7 ng/mL, and her fasting blood glucose is 140 mg/dL. Review of the LiteratureThe initial and final incidences of PTDM in various studies of tacrolimus in renal transplantation are summarized in Table 2. The initial incidence ranged from 6% to 28.3%. and the final incidence ranged from 1.4% to 12.6%, with a reversibility of 37% to 83%. 1,4,5,[12][13][14][15] Subgroup analysis was performed in only one study, the American Phase III Multicenter Trial. It showed a higher incidence of PTDM in African American than in Caucasian recipients, and an association in all patients with higher tacrolimus levels and steroid doses. 4,5 Address reprint requests to Ron Shapiro, MD, 4th Floor Falk,

Results of Pancreas Transplantation After Steroid Withdrawal Under Tacrolimus Immunosuppression 1

“…In early reports using TAC in primary renal transplantation, the risk of insulin-dependent diabetes after transplantation (PTDM) was a justifiable concern (6,7,9), however, with concomitant dose reduction greater than 80% of patients experiencing PTDM experience complete reversal of this complication (8,13). However, these early observations may have led many centers to hesitate in using TAC for pancreas transplantation.…”

“…Of the 17 pancreases lost, 7 were due to pancreatitis at 4,8,8,8,8,12, and 76 days after transplantation; 6 were lost to allograft thrombosis at 1, 1, 1, 1, 4, and 4 days after transplantation; 2 were lost to sepsis at 21 and 22 days after transplantation; and 1 was lost due to humoral rejection at 22 days after transplantation. There were four kidneys lost within 3 months of transplantation.…”

“…In a more recent analysis of pancreas transplantation under TAC, in which adjuvant bone marrow administration was studied, we reported 1-and 3-year SPK graft survival rates of 86% and 80%, respectively (5). One of the early concerns associated with the use of TAC was its reported potential for diabetogenicity (6,7), although this is reversible in the majority of cases (8,9). As a consequence, the use of TAC for pancreas transplantation has only recently been adopted in some centers (3,5,(10)(11)(12).…”

Pediatric Renal Transplantation Under Tacrolimus-Based Immunosuppression1

“…Thus, it should be possible to reduce to a minimum the incidence of PTLD. Tacrolimus-induced PTDM is another important adverse event, but is readily reversible with gradual dosage reduction of tacrolimus and tapering or even discontinuing prednisone (25,26). Virtually all cases ofPTDM in the pediatric patients have been transient.…”

Pediatric Renal Transplantation Under Tacrolimus-Based Immunosuppression

“…Tacrolimus-induced PTDM is another important adverse event, but is readily reversible with gradual dosage reduction of tacrolimus and tapering or even discontinuing prednisone (25,26). Virtually all cases of PTDM in the pediatric patients have been transient.…”