Causes of graft loss beyond two years in the cyclosporine era

While CsA has improved renal-allograft survival rates in the first 2 years compared with Aza, Terasaki’s multicenter study (1) failed to show any difference in longterm graft survival in CsA-Pred versus Aza-Pred- treated recipients. The present study examines the longterm graft-survival rates at a single center using CsA immunosuppression and seeks to discern the causes of 58 graft losses among 343 patients with functioning grafts beyond 2 years posttransplantation. The 6-year primary and cadaveric actuarial graft survival at this institution is 59% with a graft half-life of 10 years, which is better than the 40% and 7.7 years, respectively, reported by Terasaki (1) for primary cadaveric recipients on Aza-Pred. It is also better than the 41%, 6-year survival and 5.5-year half-life for primary cadaveric recipients treated with CsA-Pred as reported in the multicenter study. (2) Less experience with the use of CsA may explain the latter comparison. Primary LRD grafts at this institution (2/3 haploidentical) have a 6- year actuarial survival of 77% and a half-life very closely approximating that of HLA-identical LRD grafts under Aza (23.4 years). These results demonstrate that CsA mitigates the effects of HLA incompatibility to reduce graft survival. The most common cause of graft loss beyond 2 years was chronic rejection (36.2%) followed by noncompliance (27.6%). Patient deaths resulted in 13 of the 58 graft losses; most of the deaths were related to cardiovascular diseases. Only 3 patients died from causes that could be attributed to CsA immunosuppression; 2 from sepsis and 1 from viral hepatitis. Acute rejection caused 8.6% of the graft losses on continuous CsA therapy. When immunologic risk factors were analyzed, the entire graft-loss group had a significantly higher proportion of retransplant patients than the graft-survival group (P<0.005), suggesting that prior transplantation imposes a higher risk for graft loss not only acutely but long term as well. However, retransplanted patients were significantly less likely to lose their grafts because of noncompliance (P<0.005). Male patients were found to be significantly more non- compliant.