Mycophenolate mofetil vs. azathioprine is associated with decreased acute rejection, late acute rejection, and risk for cardiovascular death in renal transplant recipients with pre‐transplant diabetes

Abstract

Outcomes specifically in mycophenolate mofetil (MMF)-treated diabetic renal transplant patients have not been previously reported. This study compared acute rejection (AR), late acute rejection (LAR), patient survival [and specifically death from cardiovascular (CV), infectious and malignant causes], incidence of post-transplant malignancies, and graft loss in MMF- or azathioprine (AZA)-treated renal transplant patients with pre-transplant diabetes. Outcomes were compared between MMF- (n = 14 144) and AZA- (n = 3001) treated diabetic patients using the Scientific Registry of Transplant Recipients data on all U.S. adult renal transplants performed between 1995 and 2002. Statistical analyses included Kaplan-Meier survival analysis, Cox multivariable regression and chi-square tests. MMF patients had less AR compared with AZA-treated patients (23.5% vs. 28.3%, p < 0.001) and less risk for LAR over 4 yr [hazard ratio (HR): 0.64, 95% CI 0.44, 0.92; p = 0.02]. While time to any-cause death did not differ between the groups, MMF treatment was associated with a 20% decreased risk of CV death (HR: 0.80, 95% CI 0.67, 0.97; p = 0.020) compared with AZA treatment. MMF patients also had a lower incidence of malignancies than AZA patients (2.2% vs. 3.7%, p < 0.001). These results suggest treatment with MMF compared with treatment with AZA in diabetic transplant patients is associated with less AR, less risk of LAR, a decreased risk of CV death, and a lower incidence of malignancies.

Belatacept-versus Cyclosporine-Based Immunosuppression in Renal Transplant Recipients with Pre-existing Diabetes

“…The proportion of RTR-PD patients surviving with a functioning graft was numerically higher for belatacept versus cyclosporine at 1 year, particularly for the LI regimen, whereas similar composite patient/graft survival was observed in the belatacept and cyclosporine arms in the overall ITT population (16,17). Retrospective studies involving RTR-PD show 1-year patient and graft-survival rates in the approximate range of 85% to 95% (5,6,20) and 80% to 90% (4 -6), respectively. In this study, the 1-year patient survival rates were at the higher end of the range previously reported (5,6,20), and 1-year survival rates were slightly higher for belatacept LI-treated patients compared with cyclosporine-treated patients.…”

“…Retrospective studies involving RTR-PD show 1-year patient and graft-survival rates in the approximate range of 85% to 95% (5,6,20) and 80% to 90% (4 -6), respectively. In this study, the 1-year patient survival rates were at the higher end of the range previously reported (5,6,20), and 1-year survival rates were slightly higher for belatacept LI-treated patients compared with cyclosporine-treated patients. Belatacept patients in this analysis also had higher graft-survival rates than previously reported, whereas the rate for cyclosporine patients was within the range previously reported (4 -6).…”

Multiple Unrelated Malignancies Following Renal Transplantation: An Evaluation of Four Cases

“…The carcinogenic effects of AZA and CsA have been shown in various studies (20,21). In contrast, although unverified, it is foreseen that the carcinogenic effects of mycophenolate mofetil (5,22) and the mammalian target of rapamycin inhibitor group would be reduced (23). In both our cases and the previously reported multiple primary malignancy cases, conventional immunosuppressive regimens consisting of Pred, AZA and CsA were used.…”

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“…18 Additionally, the population analysis performed using the Scientific Registry of Transplant Recipients and UNOS database showed a significantly reduced incidence of any cancer, even solid cancers with mycophenolate mofetil compared with azathioprine. 19 While both cyclosporine and tacrolimus are associated with an increased risk of cancer via aberrant production of cytokines that regulate the processes promoting cancer growth, metastasis, and angiogenesis, there are some data to suggest that tacrolimus prevents vascular invasion in cell culture models and induce apoptosis in transgenic murine model. 20 Clinical studies such as the European and US multicenter trials comparing maintenance immunosuppression with cyclosporine versus tacrolimus were equivocal, showing no significant difference in cancer incidence between these 2 drugs.…”