Clinical significance of renal biopsies showing concurrent acute rejection and tacrolimus-associated tubular vacuolization

Transplantation. 1999 Jan 15;67(1):85-9. doi: 10.1097/00007890-199901150-00014.


Background: The clinical significance of biopsies showing both rejection and isometric tubular vacuolization has not been well defined in the literature.

Methods: The clinical picture, sequential histopathologic findings, and response to therapy were compared between 24 renal allograft biopsies showing both tubular vacuolization and rejection and 14 biopsies showing vacuolization alone.

Results: The rejection was categorized as grade 1 in 4/24 (16.6%), grade 2A in 10/24 (41.6%), and grade 2B in 10/24 (41.6%) cases (Banff schema, 1993-1995). Treatment with additional steroids and tacrolimus led to a decrease in the interstitial inflammation score (2.6+/-0.1 to 1.3+/-0.1, P<0.001), tubulitis score (2.6+/-0.1 to 1.1+/-0.1, P<0.001), and serum creatinine (4.4+/-2.2 mg/dl to 3.3+/-2.6 mg/dl, P=0.001). Complete response, partial response and no response to antirejection therapy were observed in 16/24 (66.7%), 3/24 (12.5%), and 5/24 (20.8%) patients, respectively. Although there was a rise in the plasma (1.4+/-0.2 ng/ml to 2.8+/-0.3 ng/ml, P<0.001) and whole blood (16.5+/-2.8 ng/ml to 31.2+/-5.7 ng/ml, P<0.001) tacrolimus levels, repeat biopsy showed no change in the size or extent of tubular vacuolization (mean score 2.88+/-0.19 vs. 2.83+/-0.21). The morphologic characteristics of the tubular vacuoles in these cases did not differ from those observed in 14 cases of tacrolimus nephrotoxicity not complicated by rejection.

Conclusion: Patients with concurrent acute rejection and tubular vacuolization usually benefit from increased immunosuppression. The pathogenesis of the vacuolization in this clinical setting is not clear, but may reflect immune-mediated tubular injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Biopsy
  • Female
  • Graft Rejection / pathology*
  • Humans
  • Immunosuppressive Agents / poisoning*
  • Kidney / pathology*
  • Kidney Transplantation*
  • Kidney Tubules / drug effects
  • Kidney Tubules / pathology*
  • Male
  • Middle Aged
  • Tacrolimus / poisoning*
  • Vacuoles / pathology*


  • Immunosuppressive Agents
  • Tacrolimus