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Four Stages and Lack of Stable Accommodation in Chronic Alloantibody‐Mediated Renal Allograft Rejection in Cynomolgus Monkeys
Author(s) -
Smith R. N.,
Kawai T.,
Boskovic S.,
Nadazdin O.,
Sachs D. H.,
Cosimi A. B.,
Colvin R. B.
Publication year - 2008
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2008.02303.x
Subject(s) - medicine , chronic allograft nephropathy , glomerulopathy , kidney , transplantation , pathology , peritubular capillaries , nephropathy , kidney disease , kidney transplantation , antibody , immunology , proteinuria , endocrinology , diabetes mellitus
The etiology of immunologically mediated chronic renal allograft failure is unclear. One cause is thought to be alloantibodies. Previously in Cynomolgus monkeys, we observed a relationship among donor‐specific alloantibodies (DSA), C4d staining, allograft glomerulopathy, allograft arteriopathy and progressive renal failure. To define the natural history of chronic antibody‐mediated rejection and its effect on renal allograft survival, we now extend this report to include 417 specimens from 143 Cynomolgus monkeys with renal allografts. A subset of animals with long‐term renal allografts made DSA (48%), were C4d positive (29%), developed transplant glomerulopathy (TG) (22%) and chronic allograft arteriopathy (CAA) (19%). These four features were highly correlated and associated with statistically significant shortened allograft survival. Acute cellular rejection, either Banff type 1 or 2, did not correlate with alloantibodies, C4d deposition or TG. However, endarteritis (Banff type 2) correlated with later CAA. Sequential analysis identified four progressive stages of chronic antibody‐mediated rejection: (1) DSA, (2) deposition of C4d, (3) TG and (4) rising creatinine/renal failure. These new findings provide strong evidence that chronic antibody‐mediated rejection develops without enduring stable accommodation, progresses through four defined clinical pathological stages and shortens renal allograft survival.