How to assess for impaired glucose tolerance before transplantation and should these results influence the choice of calcineurin inhibitors?

The concern about post-transplant diabetes mellitus (DM) has resulted in strategies to identify patients at risk. A study published in this issue suggests that results from pretransplant oral glucose tolerance tests (OGTTs) should influence the choice of calcineurin inhibitor. This editorial commentary discusses the validity of the OGTT for the assessment of glucose tolerance in chronic kidney disease (CKD) and whether these results should guide the choice of Calcineurin inhibitor. It is well recognized that children (and adults) with chronic renal failure have abnormalities of insulin and glucose metabolism, namely glucose intolerance, inhibition of insulin secretion and insulin resistance (1). Insulin resistance is present in most children with end-stage renal disease, because of the accumulation of uremic toxins from reduced renal function (2). In response to insulin resistance the beta cell compensates by increasing the secretion of insulin. However, in patients with renal disease, numerous factors may impair this ability, resulting in impaired glucose tolerance (IGT). These include metabolic factors, such as secondary hyperparathyroidism and vitamin D deficiency (3, 4), decreased responsiveness to gastric inhibitory polypeptide (GIP) stimulus and impaired postprandial regulation of insulin-like growth factor binding protein-1. The patients underlying kidney disease may also contribute. Patients with cystinosis for example may have progressive deposition of cystine crystals in their pancreatic b-cells, leading to progressive deterioration of the insulin secretion and C-peptide production (5). Furthermore, certain treatments of CKD, such as growth hormone therapy, can worsen the peripheral insulin resistance (6–8). Rarely, growth hormone therapy can lead to frank diabetes (9). However, temporary worsening of peripheral insulin resistance associated with treatment with recombinant human growth hormone therapy for short stature in children with CKD is considered safe (10). Despite all these alterations of the glucose metabolism in CKD, post-transplant DM is rare after pediatric solid organ transplantation. In a large study on the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) database (11), only 36 of 1365 children (2.6%) in the NAPRTCS registry with renal transplant (Tx) reported between January 1992 and July 1997 developed post-transplant diabetes mellitus (PTDM). PTDM was defined as more than 2 wk of insulin therapy after transplantation. In that study, the risk for PTDM was associated with the use of Tacrolimus (Tac). There are several other reports about worsened glucose control post-transplantation in association with Tac when compared with cyclosporine (CyA) (12). However, Tac therapy results in a reduced risk for rejection episodes when compared with CyA, despite the increased prevalence of diabetes with a pooled odds ratio of 5.03 (13). There is only one randomized controlled clinical trial comparing the two calcineurin inhibitors in children, and the prevalence of diabetes was identical in both study arms at 3% (14). It therefore, remains unclear whether the use of Tac is associated with a higher risk of PTDM in children. The identification of children at high risk for the development of PTDM is important. Studies Pediatr Transplantation 2006: 10: 1–4 Copyright 2006 Blackwell Munksgaard