The predictive value of kidney allograft baseline biopsies for long-term graft survival

Abstract

The effect of baseline histology and individual histologic lesions at the time of transplantation on long-term graft survival has been evaluated using different scoring systems, but the predictive capacity of these systems has not been adequately validated. All kidney recipients transplanted in a single institution between 1991 and 2009 who underwent a baseline kidney allograft biopsy at transplantation were included in this prospective study (N=548). All baseline biopsies were rescored according to the updated Banff classification, and the relationship between the individual histologic lesions and donor demographics was assessed using hierarchical clustering and principal component analysis. Survival analysis was performed using Cox proportional hazards analysis and log-rank testing. Mean follow-up time was 6.7 years after transplantation. Interstitial fibrosis, tubular atrophy, and glomerulosclerosis associated significantly with death-censored graft survival, whereas arteriolar hyalinosis and vascular intimal thickening did not. Notably, donor age correlated significantly with interstitial fibrosis, tubular atrophy, and glomerulosclerosis and associated independently with graft survival. On the basis of these findings, a novel scoring system for prediction of 5-year graft survival was constructed by logistic regression analysis. Although the predictive performance of previously published histologic scoring systems was insufficient to guide kidney allocation in our cohort (receiver operating characteristic area under the curve ≤0.62 for each system), the new system based on histologic data and donor age was satisfactory for prediction of allograft loss (receiver operating characteristic area under the curve = 0.81) and may be valuable in the assessment of kidney quality before transplantation.

Figure 1.

Association of death-censored graft survival and donor age, by Kaplan–Meier survival analysis. The P value is calculated with the log-rank test. TX, transplantation.

Figure 2.

Association of death-censored graft survival and selected individual histologic lesions in 542 baseline biopsies, by Kaplan–Meier survival analysis. P values are calculated with the log-rank test. TX, transplantation.

Figure 3.

Principal component analysis using the individual histologic lesions in baseline biopsies and the different donor demographics of 548 renal allograft recipients. This analysis illustrates the following dichotomy between the histologic lesions: (1) closely clustering lesions associating with donor age, such as glomerulosclerosis (gs), tubular atrophy (ct), and interstitial fibrosis (ci); and (2) other lesions, such as vascular intimal thickening (cv) and arteriolar hyalinosis (ah), that correlate less with donor age, but better with history of smoking, diabetes mellitus (DM), and hypertension (AHT) (also see Table 4). PRIN1, principal component 1; PRIN2, principal component 2.

Figure 4.

Association of death-censored graft survival with the previously proposed Remuzzi score, the total chronic Banff score, and the donor chronic damage score,, using Kaplan–Meier survival analysis, and the corresponding ROC curves for prediction of (death-censored) 5-year graft survival. TX, transplantation.

Figure 5.

Statistical evaluation of the Leuven donor risk score. (A) Association of death-censored graft survival with the newly constructed Leuven donor risk score, using Kaplan–Meier survival analysis. (B) ROC curves for prediction of (death-censored) 5-year graft survival based on the Leuven donor risk score in the historic cohort (n=181) and in the validation cohort (n=367). TX, transplantation.