Immunosuppressive regimen and interstitial fibrosis and tubules atrophy at 12 months postrenal transplant

Clin J Am Soc Nephrol. 2012 Jun;7(6):1010-7. doi: 10.2215/CJN.09030911. Epub 2012 Apr 5.

Abstract

Background and objectives: Chronic renal transplant dysfunction is histopathologically characterized by interstitial fibrosis and tubular atrophy. This study investigated the relative contribution of baseline donor, recipient, and transplant characteristics to interstitial fibrosis and tubular atrophy score at month 12 after renal transplantation.

Design, setting, participants, & measurements: This retrospective study includes all 109 consecutive recipients with adequate implantation and month 12 biopsies transplanted between April of 2003 and February of 2007. Immunosuppression regimen was tacrolimus and steroids (10 days) plus either sirolimus or mycophenolate mofetil.

Results: Average interstitial fibrosis and tubular atrophy score increased from 0.70 to 1.65 (P<0.001). In an adjusted multiple linear regression analysis, interstitial fibrosis and tubular atrophy score at month 12 was significantly related to donor type (donors after cardiac death versus living donor had interstitial fibrosis and tubular atrophy score+0.41, 95% confidence interval=0.05-0.76, P=0.02), baseline interstitial fibrosis and tubular atrophy, and immunosuppression regimen. Because of interaction between the latter two variables (P=0.002), results are given separately: recipients with a baseline interstitial fibrosis and tubular atrophy score of zero had a 0.60 higher score at month 12 (95% confidence interval=0.09-1.10, P=0.02) when mycophenolate mofetil-treated, whereas recipients with a baseline interstitial fibrosis and tubular atrophy score more than zero had a 0.38 higher score at month 12 (95% confidence interval=0.01-0.74, P=0.04) when sirolimus-treated. A higher score at month 12 correlated with a lower estimated GFR (ρ=-0.45, P<0.001).

Conclusions: These findings suggest that histologic assessment of a preimplantation biopsy may guide choice of immunosuppresion to maximize transplant survival and its interaction with type of immunosuppression.

MeSH terms

  • Adult
  • Aged
  • Atrophy
  • Biopsy
  • Drug Therapy, Combination
  • Female
  • Fibrosis
  • Graft Rejection / immunology
  • Graft Rejection / pathology
  • Graft Rejection / prevention & control*
  • Graft Survival / drug effects*
  • Humans
  • Immunosuppressive Agents / blood
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Transplantation* / adverse effects
  • Kidney Transplantation* / immunology
  • Kidney Tubules / drug effects*
  • Kidney Tubules / immunology
  • Kidney Tubules / pathology
  • Linear Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Mycophenolic Acid / analogs & derivatives
  • Mycophenolic Acid / therapeutic use
  • Netherlands
  • Proteinuria / etiology
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Sirolimus / therapeutic use
  • Steroids / therapeutic use
  • Tacrolimus / therapeutic use
  • Time Factors
  • Treatment Outcome

Substances

  • Immunosuppressive Agents
  • Steroids
  • Mycophenolic Acid
  • Sirolimus
  • Tacrolimus