Clinical predictors of renal allograft histopathology: a comparative study of single-lesion histology versus a composite, quantitative scoring system.
BACKGROUND
Progressive injury that is refractory to conventional immunosuppression remains the major hurdle to indefinite survival of transplanted organs. Several clinical risk factors of chronic renal allograft rejection have been identified; although some (e.g., acute rejection) are direct manifestations of immunological injury, others (e.g., donor age) have been more difficult to conceptually link with graft dysfunction.


METHODS
We conducted formal multivariate statistical analyses to reveal associations between established clinical risk factors and allograft histopathology. In a multicenter protocol biopsy-controlled study, 17 clinical risk factors were studied in relation to either the composite Chronic Allograft Damage Index (CADI) score or, to each of eight individual histological indices, using multiple linear regression with forward selection.


RESULTS
Nine clinical risk factors were not significantly associated with any histopathological index. Four (donor age, acute rejection, recipient age, and cold ischemia time) were associated both with the total CADI score and, to varying extents, with the individual histopathological indices. In our analysis, clinical risk factors accounted for, at best, only about 60% of the interindividual variation in histopathological score.


CONCLUSIONS
Our study reveals a missing link between specific clinical risk factors and early histopathological findings that are known to presage accelerated failure of clinically healthy grafts. Given the complex relationship between clinical risk factors, early histopathological changes, and graft outcome, we conclude that composite, quantitative histological indices are best suited to for evaluation of the histological status of the transplant.
Yilmaz
Serdar
S
Division of Transplantation, Department of Surgery, University of Calgary, Calgary, Alberta, Canada.
McLaughlin
Kevin
K
Paavonen
Timo
T
Taskinen
Eero
E
Monroy
Mauricio
M
Aavik
Einari
E
Vamvakopoulos
Joannis
J
Häyry
Pekka
P
D000328:Adult; D001706:Biopsy; D006084:Graft Rejection / Q000145:classification / Q000473:pathology*; D006801:Humans; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation / Q000145:classification / Q000473:pathology*; D016014:Linear Models; D008875:Middle Aged; D015999:Multivariate Analysis; D010336:Pathology / Q000379:methods*; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D014184:Transplantation, Homologous