Chronic allograft nephropathy uniformly affects recipients of cadaveric, nonidentical living-related, and living-unrelated grafts.

BACKGROUND: Chronic allograft nephropathy (CAN) remains a major barrier to long-term allograft survival. The authors retrospectively compared the development of CAN in recipients of cadaveric (CAD), living-related donor (LRD), and living-unrelated donor (LURD) transplants at their center. METHODS: The authors retrospectively examined the impact of various factors on the incidence of CAN using univariate and multivariate proportional hazards analysis in a single-center kidney transplant population. RESULTS: Between 1 January 1990 and 31 May 2000, 2,140 kidney-alone transplants were performed at the authors' center. The overall 5-year incidence of biopsy-proven CAN was 12.2% (n=203). Risk factors for CAN included the number of transplants (P=0.0001), acute rejection (P=0.0001), panel reactive antibody (P=0.0001), discharge creatinine (P=0.0001), 1-year creatinine (P=0.0015), delayed graft function (P=0.007), total human leukocyte antigen (HLA)-B and -DR mismatches (P=0.0005), recipient age (P=0.003), black donor race (P=0.001), black recipient race (0.0457), donor age (P=0.0053), cold storage time (P=0.019), and cytomegalovirus infections (P=0.002). Interestingly, although the LRD HLA-identical recipients had a significantly lower incidence of CAN (P=0.0015), the incidence of CAN in CAD and HLA-nonidentical LRD recipients did not differ. Graft survival was significantly worse in CAD recipients compared with all other groups (P<0.001). CONCLUSIONS: These results demonstrate the importance of immunologic and nonimmunologic factors on the development of CAN. The disparities in overall graft survival, despite the similarities in CAN rates, suggests that other factors, in addition to CAN, influence the increase in graft loss in CAD transplant recipients.

Mycophenolate mofetil versus enteric-coated mycophenolate sodium: a large, single-center comparison of dose adjustments and outcomes in kidney transplant recipients.

BACKGROUND: Although enteric-coated mycophenolate sodium (EC-MPS) was developed to reduce gastrointestinal (GI) side effects in kidney transplantation, a multicenter clinical trial of patients undergoing de novo renal transplantation found that efficacy failure and adverse GI event rates for EC-MPS were comparable with mycophenolate mofetil (MMF). A common strategy to mitigate mycophenolic acid-related GI adverse events includes dose manipulations such as split dosing, dose reduction, and discontinuation. Several studies have demonstrated that dose alterations with MMF are associated with poorer graft outcomes. METHODS: To determine whether there was a clinically significant difference in dose alterations and outcomes with EC-MPS compared with MMF, we conducted a retrospective study comparing MMF and EC-MPS in all consecutive kidney transplants (n=1709) between 2000 and 2006. RESULTS: Graft survival between MMF and EC-MPS patients was not different during the study period (P=0.9928). The incidence of biopsy-proven acute rejection at 2 years was higher in the MMF group (30.2% MMF vs. 21.9% EC-MPS, P=0.0004). The adjusted risk of dose reductions was significantly higher in MMF-treated patients (hazard ratio=1.703, P<0.0001). Similarly, the adjusted risk of drug discontinuation was higher in the MMF group (hazard ratio=1.507, P=0.0002). EC-MPS patients also demonstrated a trend toward a lower incidence of infections and a significantly lower incidence of fungal infections. CONCLUSION: EC-MPS was associated with fewer dose reductions or discontinuations, which may have translated into the observed significantly lower incidence of biopsy-proven rejection. EC-MPS has become the mycophenolic acid agent of choice at this large center.