Diabetes Mellitus as a Risk Factor for Delayed Graft Function

1. Diabetes Mellitus as a Risk Factor for Delayed Graft Function Reference: Parekh J, Bostrom A, Feng S. Diabetes mellitus: A risk factor for delayed graft function after deceased donor kidney transplantation. Am J Transplant. 2010;10:298–303.

2. Delayed Graft Function: A Unique Challenge in Kidney Transplant Recipients • Delayed graft function (DGF) poses a unique challenge in kidney transplant recipients and is defined as the need for dialysis within 1 week of transplantation with a prevalence rate of 4.7–64% in living donor transplants and deceased donors. • There exists a strong correlation of DGF with acute rejection and decreased graft survival. • It is regarded to be an independent risk factor for decreased graft survival. • The rate of 1-year graft survival in recipients with DGF and patients with immediate graft function are 87% and 95%, respectively (see Fig. 1). • At a 5-year survival rate, patients with DGF are 1.53 times more likely to suffer graft loss and 10% lower graft survival compared to patients with immediate graft function. • Patients with both acute rejection and DGF result in decreased long-term survival at 5 years compared to patients who have DGF or rejection alone, 50.1%, 65.5% and 71.2%, respectively.

4. Delayed Graft Function: Risk Factors • Many efforts have been made to understand the pathogenesis and the risk factors underlying the DGF. • The risk factors that were identified to cause DGF are grouped into donor, recipient and transplant categories. • The two most important risk factors responsible for DGF were the recipient’s diabetes and warm ischemia time. • The correlation of recipient’s diabetes and DGF is principally significant because diabetes is an increasingly common etiology of end-stage renal disease, accounting for as much as 22.3% of adult kidney transplants in recent years. • Keeping this in view, a study was conducted to investigate whether the recipient diabetes is a risk factor for DGF.

5. Method • The authors conducted a retrospective analysis of all deceased donor renal transplants recorded between 1 January 1994 and 1 December 2005. • Kidneys from deceased donors underwent cold storage followed by kidney transplantation into adults with graft survival of >7 days that resulted in a total of 51,046 transplants. • The authors collected the demographic and health information for donors, recipients and transplants. • Many of the variables were missed for which the authors performed two additional conditional logistic regression analyses to confirm that their primary analysis was not biased. Comparisons of diabetic and nondiabetic recipients were performed with simple t-tests or 2 tests.

6. Clinical Outcomes Donor Characteristics • From about 25,523 deceased donors, both the kidneys were transplanted into adults. • The transplanted kidneys from the donor resulted in immediate graft function (61%) in diabetic as well as nondiabetic recipients. • Donors contributing kidneys with dissimilar outcomes (one with DGF and one without DGF) was less frequent (29%) whereas DGF in diabetic as well as nondiabetic recipients was least frequent (10%).

7. Recipient Characteristics • Nondiabetic recipients exhibited higher immunological risk with increased frequency of previous kidney transplants (0.12 vs. 0.07, p<0.01), higher peak panelreactive antibodies (PRA) (15 vs. 12% p<0.01), greater human leukocyte antigen (HLA) (3.35 vs. 3.29 loci, p<0.01) and DR mismatch (0.96 vs. 0.94, p=0.02). • Cold ischemia time for nondiabetic and diabetic recipients was similar, 19.358.28 h vs.19.368.31 h, p=0.89, respectively. Risk Factors for Delayed Graft Function • The factors that were responsible for DGF among the recipient and the transplant were identified with univariate conditional logistic regression models and are shown in Table 1.

9. Recipient age was the only variable that was not correlated with DGF (odds ratio (OR) 0.98 per 10-year increase, 95% confidence interval (CI) 0.96–1.01, p=0.16). • Diabetes in the recipient posed a significant risk factor for DGF with an OR of 1.32, 95%CI of 1.23–1.42 and p<0.01. • The other factors of a recipient including male gender, prior kidney transplant, higher PRA were also correlated with DGF. • Race had a significant effect on DGF. • Transplant factors including HLA mismatch, DR mismatch and cold ischemia time were associated with DGF

10. The above factors which were identified by univariate models were analyzed together in multivariate models. • In addition to the above factors, three interaction terms cold ischemia time and diabetes, gender and diabetes, and race and diabetes were also included. • Table 2 depicts the final multivariate model obtained by backwards stepwise elimination of variables with a p>0.20. • It was shown that the recipient diabetic status remained independently correlated with DGF (OR 1.67, 95%CI 1.46–1.93, p<0.01). In addition to this, gender, Black and Asian races, peak PRA, HLA mismatch and cold ischemia time were independent risk factors for DGF.

11. Moreover, among the three interaction terms, the interaction of gender and recipient diabetes achieved a p Value <0.20 and remained in the final multivariate model. • This indicates that the increased risk of DGF posed by recipient diabetes is alleviated for male recipients. • A female diabetic recipient would be at increased odds of DGF compared to a nondiabetic woman (OR 1.67, 95%CI 1.46–1.91, p<0.01), whereas a male diabetic recipient would have diminished but still increased odds of DGF (OR 1.28, 95%CI 1.15–1.43, p<0.01) compared to a nondiabetic man.

12. Supplemental Analyses of Risk Factors for DGF • The other two additional models, which the authors designed to confirm that their primary analysis is not biased, also confirmed recipient diabetes to be a risk factor for DGF. • In addition, the interaction term for recipient diabetes and male gender emerged as a risk factor for DGF. Conclusion • Based on the above findings, recipient diabetes appears to be an independent risk factor for DGF after kidney allograft. • It is considered that a causal relationship exists in that diabetes potentiates ischemia/reperfusion injury and thereby increases the need for early posttransplant dialysis.