title: Serial protocol biopsies to quantify the progression of chronic transplant nephropathy in stable renal allografts.
abstract: OBJECTIVE
  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.
authors.affiliation: Nephrology Department, Hospital de Bellvitge, Barcelona, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Moreso
authors.forename: M
authors.initials: M
authors.lastname: Lopez
authors.forename: A
authors.initials: A
authors.lastname: Vallejos
authors.forename: C
authors.initials: C
authors.lastname: Giordani
authors.forename: L
authors.initials: L
authors.lastname: Riera
authors.forename: X
authors.initials: X
authors.lastname: Fulladosa
authors.forename: M
authors.initials: M
authors.lastname: Hueso
authors.forename: J
authors.initials: J
authors.lastname: Alsina
authors.forename: J M
authors.initials: JM
authors.lastname: Grinyó
authors.forename: D
authors.initials: D
authors.lastname: Serón
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001706:Biopsy / Q000379:methods*; D003404:Creatinine / Q000097:blood; D018450:Disease Progression; D005260:Female; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D016030:Kidney Transplantation / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D012079:Renal Circulation / Q000502:physiology; D012189:Retrospective Studies; D013997:Time Factors; D014184:Transplantation, Homologous; D017539:Tunica Intima / Q000473:pathology
chemical_list: D015415:Biomarkers; D003404:Creatinine