Key words : Glucose, Immunosuppression, Renal transplant

Introduction
Diabetes after transplant (DAT) refers to the occurrence of diabetes in patients who did not have diabetes until after organ transplant. The estimated incidence at 1-year posttransplant ranges from 20% to 50% for kidney transplant recipients.¹ Kidney transplant recipients who develop DAT are reported to be at increased risk of infections, cardiovascular events, graft loss, and death.² Little is known about the incidence of this condition in our country of Tunisia. In this study, our objectives were to determine the incidence of DAT in a Tunisian population and to examine its effects on kidney transplant outcomes.

Materials and Methods

We retrospectively evaluated the medical records of 257 patients who underwent their first kidney transplant between 2008 and 2019 in our Department of Nephrology in Sahloul Hospital (Tunisia). Fifteen patients with diabetes mellitus before transplant were excluded from the analyses. Demographic data, cause of chronic renal failure, donor type, and immunosuppressive medications were collected from patient medical records. Laboratory data such as serum cholesterol and triglycerides, serum creatinine, glycemia, and 24-hour proteinuria at discharge were also collected. We reviewed whether patients developed DAT. Diabetes was defined according to the International Consensus Guidelines. For our analyses, we divided patients into those with and without DAT. Complication rates such as infection episodes, cardiovascular complications, and graft loss were recorded. Graft and patient survival rates were compared between the 2 groups.

Statistical analyses
Data of 257 patients were evaluated with SPSS for Windows (IBM SPSS Statistics version 21). For analysis of study groups, chi-square and Fisher exact tests were used. We used t test for normally distributed data and Mann-Whitney U test for nonnormally distributed data. Categorical data are presented as frequencies and percentages. Normally distributed data are presented as means ± standard deviation, and nonnormally distributed data are presented as medians and interquartile ranges (IQR). Significance was accepted as P ≤ .05.

Results
Of the 257 patients included in our study, 168 (65.4%) were male patients and 89 (34.6%) were female patients. The mean age was 32.9 ± 13.6 years. Cause of chronic kidney disease was chronic interstitial nephritis in 120 patients, glomerulonephritis in 47 patients, hypertensive nephrosclerosis in 17 patients, autosomal dominant polycystic disease in 4 patients, other causes in 15 patients, and unknown causes in 54 patients (Table 1). In 196 patients, initial renal replacement therapy was hemodialysis, with median treatment period of 17 months (IQR, 8-44). Of total patients, 247 received living related donor allografts and 10 received grafts from deceased donors. Immunosuppressive treatment consisted of tacrolimus in 145 patients, cyclosporine in 72 patients, and sirolimus in 6 patients (Table 1).

Of total patients, 56 (21.8%) developed DAT. Rates of DAT were 3.1%, 8.5%, and 12.5% at 3, 12, and 36 months posttransplant, respectively. As shown Table 2, significant differences were found between patients with and without DAT with regard to recipient age and body mass index. Recipients with DAT were older than those without DAT (P = .016). Body mass index was higher in recipients with DAT than in patients without DAT (P < .001). Median serum glucose level at discharge was significantly higher in the DAT group (P < .001). Median triglyceride level of patients with DAT was higher than in patients without DAT (P = .013). Laboratory data (serum cholesterol, serum creatinine at discharge, and 24-hour proteinuria) were similar in those with and without DAT (all P > .05).

Infectious episodes were not significantly different bet-ween groups (P = .430). Acute coronary syndrome episodes were not significantly different between groups (P = .118).

We observed no significant difference in graft loss at 5 years between the patients with DAT and those without DAT (P = .582). Median graft survival of patients with DAT was 53.3 months (IQR, 27.7-80.3), whereas median graft survival of patients without new-onset DAT was 44.5 months (IQR, 19.5-69.7). The 5-year patient survival rate in the patients with DAT was 87.5%. There was no significant difference in rate of death between the 2 groups (8.9% vs 9.0%; P = .566).

Discussion
Diagnostic criteria for DAT were standardized with the 2003 International Consensus Guidelines. With these criteria, DAT has been shown to affect 17% to 56% of renal transplant recipients.³ Our analysis found an incidence rate of 21.8%, which is similar to the international average.

The time of onset of DAT was similar to other reports, with greatest risk of DAT in the first year. A large US cohort of 11?659 patient showed incidence rates of 9.1%, 16%, and 24% at 3, 12, and 36 months posttransplant, respectively.⁴ However, our analysis found an incidence rate of only 12.5% in the first year.

Patient body mass index and age at transplant were significantly associated with development of DAT, which has also been reported in an Irish cohort by Tomkins and colleagues.⁵

Diabetes after transplant has been shown to be associated with an up to 3-fold increased risk of myocardial infarction, ischemic heart disease, or cardiovascular disease within 7 years after renal transplant.⁶

A major concern of DAT is its effect on patient and graft survival. Detriments to graft survival have been shown in large population-based studies. For example, in the United States, DAT was associated with higher rates of graft failure.⁴ However, in our study, graft survival was not affected by diabetes after transplant.

The development of DAT has been associated with mortality risk versus that shown in patients who do not develop DAT. We did not observe this finding in our retrospective analysis. In a study of 173 renal transplant recipients, 1-year patient survival rates in those with versus those without DAT were 83% versus 98%, respectively (P = .01).⁶ In contrast to earlier reports, a retrospective analysis of the Organ Procurement and Transplant Network/United Network for Organ Sharing database did not show a negative impact of DAT on transplant survival or mortality due to cardiovascular complications.⁷

Conclusions

Diabetes after transplant is a common complication after solid-organ transplant and has variably been reported to have an adverse impact on patient and allograft outcomes. The incidence and impact of DAT can be minimized through pre- and posttransplant screening to identify patients at higher risk.

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