Impact of glucose metabolism abnormalities on histopathological changes in kidney transplant protocol biopsies

Abstract

The impact of post-transplant diabetes (PTDM) on kidney transplant histopathology has been poorly described. We examined the association of glucose metabolism abnormalities on the progression of histopathological changes in serial protocol biopsies. Helsinki University Hospital kidney transplant recipients during 2004-2006 were followed up. Patients with pre-existing diabetes or 2-h oral glucose tolerance test (OGTT) performed at 3 months, and protocol biopsies taken at 0 and 12 months were analyzed (n = 76). Diabetes was defined according to WHO/ADA. Histology was analyzed with chronic allograft damage index (CADI). Altogether 32 patients had pre-existing diabetes. In OGTT at 3 months, four showed PTDM, eight impaired glucose tolerance (IGT), two impaired fasting glucose, and 30 normal glucose tolerance. Patients with impaired glucose metabolism were older (P = 0.005), received grafts from older donors (P = 0.04), and had reduced renal function at 12 months (P = 0.003). In patients with IGT or PTDM, 2-h postload glucose values in OGTT correlated with CADI at 12 months (R = 0.84, P = 0.001) and with the change in CADI score between 0 and 12 months (R = 0.67, P = 0.025). Graft survival was reduced in patients with pre-existing diabetes (P = 0.01). Glucose abnormalities were associated with the progression of histopathological changes, especially in patients with already compromised kidneys, supporting the harmful role of PTDM to the kidney allograft.