Transcript Diabetes Mellitus as a Risk Factor for Delayed Graft Function

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.
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.
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 identifi ed 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.
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
confi rm that their primary analysis was not biased. Comparisons of
diabetic and nondiabetic recipients were performed with simple ttests or 2 tests.
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%).
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 identifi ed with
univariate conditional logistic regression models and
are shown in Table 1.
• 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
• 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.
• Moreover, among the three interaction terms, the
interaction of gender and recipient diabetes achieved a
p Value <0.20 and remained in the fi nal 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.
Supplemental Analyses of Risk Factors for DGF
• The other two additional models, which the authors
designed to confi rm that their primary analysis is not
biased, also confi rmed 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 fi ndings, 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.