Early peri-operative hyperglycaemia and renal allograft rejection in patients withoutdiabetes

Abstract

Background: Patients with diabetes have an increased risk for allograft rejection, possibly related to peri-operative hyperglycaemia. Hyperglycaemia is also common following transplantation in patients without diabetes. We hypothesise that exposure of allograft tissue to hyperglycaemia could influence the risk for rejection in any patient with high sugars. To investigate the relationship of peri-operative glucose control to acute rejection in renal transplant patients without diabetes, all patients receiving their first cadaveric graft in a single center were surveyed and patients without diabetes receiving cyclosporin-based immunosuppression were reviewed (n = 230). Records of the plasma blood glucose concentration following surgery and transplant variables pertaining to allograft rejection were obtained. All variables suggestive of association were entered into multivariate logistic regression analysis, their significance analysed and modeled.Results: Hyperglycaemia (>8.0 mmol/L) occurs in over 73% of non-diabetic patients following surgery. Glycaemic control immediately following renal transplantation independently predicted acute rejection (Odds ratio=1.08). 42% of patients with a glucose < 8.0 mmol/L following surgery developed rejection compared to 71% of patients who had a serum glucose above this level. Hyperglycaemia was not associated with any delay of graft function. Conclusion:Hyperglycaemia is associated with an increased risk for allograft rejection. This is consistent with similar findings in patients with diabetes. We hypothesise a causal link concordant with epidemiological and in vitro evidence and propose further clinical research.

2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2018

“…Another term, "posttransplantation diabetes mellitus" (PTDM) (97,98), describes the presence of diabetes in the posttransplant setting irrespective of the timing of diabetes onset. Hyperglycemia is very common during the early posttransplant period, with ;90% of kidney allograft recipients exhibiting hyperglycemia in the first few weeks following transplant (97)(98)(99)(100). In most cases, such stress-or steroidinduced hyperglycemia resolves by the time of discharge (100,101).…”

“…Most studies have reported that transplant patients with hyperglycemia and PTDM after transplantation have higher rates of rejection, infection, and rehospitalization (100,102,107).…”

Acute Hyperglycemic Exacerbation of Lung Ischemia–Reperfusion Injury Is Mediated by Receptor for Advanced Glycation End-Products Signaling

“…Although the blood glucose levels in hyperglycemic mice were slightly lower than that achieved previously (27), the level of hyperglycemia in the present study is similar to that of acute hyperglycemia among humans undergoing organ transplantation (37,38). Second, this study documents the protection conferred by RAGE deficiency by using RAGE 2/2 mice, and does not evaluate the result of direct blockage of native RAGE in WT mice (e.g., with the use of decoy sRAGE).…”

“…The dosing strategy used was based upon our previous experience, wherein we demonstrated hyperglycemia after a single dose of dextrose administration, which peaks at 30 minutes after injection and remains elevated after 60 minutes (27). In our hyperglycemic animals, a twofold increase in blood glucose level was achieved 30 minutes after dextrose injection, which is similar to stress-induced changes in blood glucose among human transplant recipients (37). During hyperglycemia, ischemia of the left lung was performed as described in MATERIALS AND METHODS.…”

“…Stress-induced hyperglycemia is also a well documented risk factor for morbidity and mortality among patients undergoing cardiothoracic care and transplant (33,(36)(37)(38). Thus, to simulate stress-induced hyperglycemia in the present study, acute perioperative hyperglycemia was induced in mice by intraperitoneal injection of dextrose.…”