Renal Allograft Histology at 10 Years After Transplantation in the Tacrolimus Era: Evidence of Pervasive Chronic Injury.

Abstract

Improving long-term renal allograft survival remains an important unmet need. To assess the extent of histologic injury at 10years after transplantation in functioning grafts, we studied 575 consecutive adult solitary renal transplants performed between 2002 and 2005: 77% from living donors and 81% maintained on tacrolimus-based immunosuppression. Ten-year graft survival was 59% and death-censored graft survival was 74%. Surveillance allograft biopsies were assessed at implantation, 5years, and 10years from 145 patients who reached 10years. At implantation, 5% of biopsies had major histologic abnormalities (chronic transplant glomerulopathy score>0, other chronic Banff scores≥2, global glomerulosclerosis>20%, or mesangial sclerosis≥2). This increased to 54% at 5years and 82% at 10years. Major lesions at 10years included the following: arteriolar hyalinosis (66%), mesangial sclerosis (67%), and global glomerulosclerosis > 20% (43%), with 48% of grafts having more than one major lesion. Transplant glomerulopathy and moderate-to-severe interstitial fibrosis were uncommon (12% each). Major lesions were associated with increased proteinuria and decreased graft function. In patients with diabetes at baseline, 52% had diabetic nephropathy/mesangial sclerosis at 10years. We conclude that almost all renal allografts sustain major histologic injury by 10years after transplantation. Much damage appears nonimmunologic, suggesting that new approaches are needed to decrease late injury.