Serial protocol biopsies to quantify the progression of chronic transplant nephropathy in stable renal allografts

Am J Transplant. 2001 May;1(1):82-8. doi: 10.1034/j.1600-6143.2001.010115.x.


Aim: To evaluate the utility of intimal thickness and interstitial width as a primary efficacy variable in the design of clinical trials aimed to modify the natural history of chronic allograft nephropathy.

Methods: A donor and a 4-month protocol biopsy were evaluated in 40 stable grafts according to the Banff schema. In 27 patients, a second protocol biopsy was done at 1 yr. Arterial intimal volume fraction (Vvintima/artery) and cortical interstitial volume fraction (Vvinterstitium/cortex) were estimated with a point counting technique.

Results: Chronic Banff scores increased during follow-up, while acute scores reached its peak at 4 months. Vvintima/artery and Vvinterstitium/cortex significantly increased at 4 months, but not at 1 yr. Vvintima/artery at 4 months correlated with donor Vvintima/artery (r = 0.57, p < 0.001), histocompatibility (r = 0.38, p = 0.01) and serum cholesterol (r = 0.31, p = 0.047). Vvinterstitium/cortex at 4 months correlated with recipient body surface area (r = 0.44, p = 0.004) and delayed graft function (p = 0.016). Power calculations showed that Vvintima/artery and Vvinterstitium/cortex allow an important reduction in minimum sample size of a hypothetical trial aimed to prevent chronic allograft nephropathy.

Conclusions: Intimal thickening and interstitial widening progresses rapidly during the first 4 months after transplantation and slowly thereafter. These parameters can be considered as a primary efficacy variable in trials aimed to prevent chronic allograft nephropathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / blood
  • Biopsy / methods*
  • Creatinine / blood
  • Disease Progression
  • Female
  • Graft Survival / physiology
  • Humans
  • Kidney Transplantation / pathology*
  • Male
  • Middle Aged
  • Monitoring, Physiologic
  • Renal Circulation / physiology
  • Retrospective Studies
  • Time Factors
  • Transplantation, Homologous
  • Tunica Intima / pathology


  • Biomarkers
  • Creatinine