title: Protocol core needle biopsy and histologic Chronic Allograft Damage Index (CADI) as surrogate end point for long-term graft survival in multicenter studies.
abstract: This study is an investigation of whether a protocol biopsy may be used as surrogate to late graft survival in multicenter renal transplantation trials. During two mycophenolate mofetil trials, 621 representative protocol biopsies were obtained at baseline, 1 yr, and 3 yr. The samples were coded and evaluated blindly by two pathologists, and Chronic Allograft Damage Index (CADI) score was constructed. At 1 yr, only 20% of patients had elevated (>l.5 mg/100 ml) serum creatinine, whereas 60% of the biopsies demonstrated an elevated (>2.0) CADI score. The mean CADI score at baseline, 1.3 +/- 1.1, increased to 3.3 +/- 1.8 at 1 yr and to 4.1 +/- 2.2 at 3 yr. The patients at 1 yr were divided into three groups, those with CADI <2, between 2 and 3.9, and >4.0, the first two groups having normal (1.4 +/- 0.3 and 1.5 +/- 0.6 mg/dl) and the third group pathologic (1.9 +/- 0.8 mg/dl) serum creatinine. At 3 yr, there were no lost grafts in the low CADI group, six lost grafts (4.6%) in the in the elevated CADI group, and 17 lost grafts (16.7%) in the high CADI group (P < 0.001). One-year histologic CADI score predicts graft survival even when the graft function is still normal. This observation makes it possible to use CADI as a surrogate end point in prevention trials and to identify the patients at risk for intervention trials.
authors.affiliation: Data Analysis Center, Division of Transplantation, Department of Surgery, University of Calgary, Alberta, Canada.
authors.forename: Serdar
authors.initials: S
authors.lastname: Yilmaz
authors.forename: Steven
authors.initials: S
authors.lastname: Tomlanovich
authors.forename: Timothy
authors.initials: T
authors.lastname: Mathew
authors.forename: Eero
authors.initials: E
authors.lastname: Taskinen
authors.forename: Timo
authors.initials: T
authors.lastname: Paavonen
authors.forename: Merci
authors.initials: M
authors.lastname: Navarro
authors.forename: Eleanor
authors.initials: E
authors.lastname: Ramos
authors.forename: Leon
authors.initials: L
authors.lastname: Hooftman
authors.forename: Pekka
authors.initials: P
authors.lastname: Häyry
mesh_terms: D001707:Biopsy, Needle / Q000379:methods* / Q000706:statistics & numerical data; D002908:Chronic Disease; D018450:Disease Progression; D005260:Female; D006084:Graft Rejection / Q000401:mortality / Q000473:pathology*; D006085:Graft Survival; D006801:Humans; D007668:Kidney / Q000502:physiology; D016030:Kidney Transplantation / Q000401:mortality*; D008297:Male; D015337:Multicenter Studies as Topic / Q000379:methods; D015588:Observer Variation; D011237:Predictive Value of Tests; D012307:Risk Factors; D012720:Severity of Illness Index