Histopathologic Clusters Differentiate Subgroups Within the Nonspecific Diagnoses of CAN or CR: Preliminary Data from the DeKAF Study

Abstract

The nonspecific diagnoses 'chronic rejection' 'CAN' , or 'IF/TA' suggest neither identifiable pathophysiologic mechanisms nor possible treatments. As a first step to developing a more useful taxonomy for causes of newonset late kidney allograft dysfunction, we used cluster analysis of individual Banff score components to define subgroups. In this multicenter study, eligibility included being transplanted prior to October 1, 2005, having a 'baseline' serum creatinine ≤2.0 mg/dL before January 1, 2006, and subsequently developing deterioration of graft function leading to a biopsy. Mean time from transplant to biopsy was 7.5 ± 6.1 years. Of the 265 biopsies (all with blinded central pathology interpretation), 240 grouped into six large (n > 13) clusters. There were no major differences between clusters in recipient demographics. The actuarial postbiopsy graft survival varied by cluster (p = 0.002). CAN and CNI toxicity were common diagnoses in each cluster (and did not differentiate clusters). Similarly, C4d and presence of donor specific antibody were frequently observed across clusters. We conclude that for recipients with new-onset late graft dysfunction, cluster analysis of Banff scores distinguishes meaningful subgroups with differing outcomes.

Glomerular damage as a predictor of renal allograft loss

“…This finding agrees with recently published studies (25)(26)(27)(28)(29). Wavamunno et al (30) showed that endothelial and subendothelial ultrastructural abnormalities in glomerular and peritubular capillaries are sensitive early markers of CTG.…”

Chronic Calcineurin Inhibitor Nephrotoxicity—Lest We Forget

“…The DeKAF study of deteriorating kidneys biopsied for cause, has most recently reconfirmed the role of inflammation in biopsies from patients with chronic kidney dysfunction, no matter where it is found in the kidney, as a major predictor of graft loss in the first 3 years after transplantation (19). However a different publication from this study has identified CNI nephrotoxicity as the local pathological diagnosis in 30% of failing grafts and substantial arteriolar hyalinosis as a feature of two of the major groupings (20). The Mayo clinic series of 1-and 5-year protocol biopsies has also recently questioned the frequency, progressive nature and specificity of chronic CNI toxicity (21).…”

A Case of Late Kidney Allograft Failure

“…Moreover, allografts labeled as calcineurin inhibitor toxicity fared no worse than other grafts in the absence of this diagnosis (11). The preponderance of abnormalities in this study featured immunologic injury including acute rejection (12) and antibody-mediated injury (13). Moreover, the presence of inflammation in the allograft, in areas of fibrosis and TA, was an independent negative feature of allograft failure (14).…”