Hyalinosis Lesions in Renal Transplant Biopsies: Time-Dependent Complexity of Interpretation

作者：Einecke G; Reeve J; Halloran P F^*

来源：American Journal of Transplantation, 2017, 17(5): 1346-1357.

DOI：10.1111/ajt.14136

• basic (laboratory) research
• science
• kidney transplantation
• nephrology
• graft survival
• biopsy
• microarray
• gene array
• glomerular biology and disease

Because calcineurin inhibitor (CNI) immunosuppressive drugs induce arteriolar hyalinosis (ah) in kidney transplants, ah lesions can potentially provide information about drug exposure. We studied the relationship of ah lesions to findings and outcomes in 562 indication biopsies taken 3 days to 35 years after transplant. Prevalence of ah lesions increased with time of biopsy after transplant (TxBx). The ah scores correlated with arterial intimal thickening and atrophy-fibrosis but, unlike atrophy-fibrosis, did not increase until after 500 days because of a background of ah1 lesions in early biopsies reflecting donor aging. Correlation of ah scores with other features varied with TxBxin early biopsies, donor age and related changes, and in very late biopsies, chronic antibody-mediated rejection and glomerulonephritis and associated lesions. After correction for TxBx, ah0 in intermediate time periods was associated with increased risk of T cell-mediated rejection and graft loss, probably because of underimmunosuppression and nonadherence. Thus, ah lesions in indication biopsies have multiple associations: donor age (early, usually ah1), chronic glomerular diseases (late, often ah2/3), and adequate exposure to CNIs at intermediate times. This threefold TxBx-dependent complexity must be considered when interpreting indication biopsies: ah lesions often indicate adequate CNI exposure, not toxicity, and unexpected ah0 should increase vigilance for nonadherence and underimmunosuppression.
Analysis of arteriolar hyalinosis in prospective indication kidney transplant biopsies, mostly from calcineurin inhibitor-treated patients, indicates that interpretation of these lesions is highly dependent on time posttransplant, donor age, and chronic glomerular disease, and once time is taken into account, the absence of hyalinosis is actually a risk for graft loss, probably reflecting nonadherence.

• 出版日期2017-5