The influence of induction therapy and diabetes on graft failure after kidney transplant

Open Access
Author:
Farag, Hosam Abdelhameed
Graduate Program:
Public Health Sciences
Degree:
Master of Science
Document Type:
Master Thesis
Date of Defense:
June 11, 2015
Committee Members:
  • Nasrollah Ghahramani, Thesis Advisor
  • Christopher Hollenbeak, Thesis Advisor
Keywords:
  • induction therapy
  • diabetes
  • graft failure
  • kidney transplant
Abstract:
Background: Induction therapy plays a significant role in reducing the rate of acute rejection in kidney transplantation (KT). Understanding differences in outcomes associated with various induction agents may lead to improvement in long-term care. Our objective was to examine the association of various induction therapies and diabetes with the risk of graft failure and patient mortality after KT. Methods: We performed a retrospective cohort study using data from the United Network for Organ Sharing (UNOS) between 2000 and 2013. We included only kidney transplantation patients who were maintained only on tacrolimus, mycophenolate mofetil (MMF) and steroids. We had 92,829 patients who were categorized into four groups based on induction therapy: basiliximab (n=23,531), daclizumab (n=14,563), rabbit anti-thymocyte globulin (r-ATG) (n=51,497) and alemtuzumab (n=3,238). All patients. The primary outcomes were graft failure and patient mortality. Cox proportional hazards models were used to model time to event after adjusting for patients and disease characteristics. Results: Graft failure was significantly higher in the r-ATG group (HR=1.047; 95% CI, 1.007 to 1.088; P= 0.0201) than the basiliximab group. However, the daclizumab group had lower risk for graft failure (HR=0.922; 95 % CI, 0.879 to 0.968; P= 0.0009). Graft failure was non-significantly higher in alemtuzumab group (HR=1.099; 95% CI, 0.994 to 1.216; P=0.0666). Patient death was significantly lower in the daclizumab group (HR=0.892; 95% CI, 0.830 to 0.958; P=0.0018) than the basiliximab group, whereas, patient death was non-significantly higher in the r-ATG group (HR=1.041; 95% CI, 0.984 to 1.101; P=0.163) and the alemtuzumab group (HR=0.978; 95% CI, 0.837 to 1.142; P= 0.7786. Diabetic status has a significant impact on graft failure and patient death. Graft failure was significantly higher in Type 2 diabetes than Type 1 and new-onset diabetes while the patient death was significantly higher in Type1 diabetes than Type 2 and new-onset diabetes. Conclusion: Daclizumab has better long-term graft survival outcomes than basiliximab and antithymocyte globulin (r-ATG). It also has better long-term patient survival outcomes than basiliximab. In general IL2-RA receptor antagonists group (Basiliximab and Daclizumab) have better long-term graft survival outcomes than antithymocyte globulin (r-ATG) when tacrolimus, mycophenolate mofetil (MMF) and steroids were used as maintenance therapy. Type of diabetes has a significant impact on graft failure and patient death.