Protocol core needle biopsy and histological chronic allograft damage index as surrogate endpoint for Long-Term graft survival.
Following encouraging results from several single-center studies showing that early histological manifestations of chronic rejection are seen in the graft before a decline in transplant function, we tested this concept in a multicenter study and investigated whether protocol needle biopsy may be used as a surrogate to late graft survival in multicenter renal transplantation trials. During two mycophenolate mofetil trials, 621 representative protocol biopsies were obtained at baseline, 1 year, and 3 years. The samples were coded and evaluated blindly by two pathologists and a Chronic Allograft Damage Index (CADI) score was constructed. At 1 year only 20% of patients had elevated (>1.5 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 year and to 4.1 +/- 2.2 at 3 years. The patients at 1 year were divided into 3 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 pathological (1.9 +/- 0.8 mg/dL) levels of serum creatinine. At 3 years there were no lost grafts in the "low" CADI group, six lost grafts (4.6%) in the "elevated" CADI group, and 17 lost grafts (16.7%) in the "high" CADI group (P <.001). One-year histological CADI score predicts graft survival even when the graft function is still normal. This observation makes it possible to use CADI as a surrogate endpoint in prevention trials and to identify the patients at risk for intervention trials.
Hayry
P
P
University of Helsinki Hospital, Helsinki, Finland. pekka.hayry@helsinki.fi
Paavonen
T
T
Taskinen
E
E
Tomlanovich
E
E
Mathew
T
T
Navarro
M
M
Ramos
E
E
Hooftman
L
L
Vamvakopoulos
J
J
Aavik
E
E
Yilmaz
S
S
D001707:Biopsy, Needle / Q000379:methods*; D003404:Creatinine / Q000097:blood; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000473:pathology*; D006085:Graft Survival / Q000502:physiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology / Q000473:pathology*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017741:Survivors; D013997:Time Factors; D014184:Transplantation, Homologous / Q000473:pathology*
D007166:Immunosuppressive Agents; D003404:Creatinine; D009173:Mycophenolic Acid