title: Hyalinosis Lesions in Renal Transplant Biopsies: Time-Dependent Complexity of Interpretation.
abstract: 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 TxBx-in 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.
authors.affiliation: Department of Nephrology, Hannover Medical School, Hannover, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Einecke
authors.affiliation: Alberta Transplant Applied Genomics Centre, Edmonton, AB, Canada.|Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Reeve
authors.affiliation: Alberta Transplant Applied Genomics Centre, Edmonton, AB, Canada.|Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada.|Division of Nephrology and Transplant Immunology, Department of Medicine, University of Alberta, Edmonton, AB, Canada.
authors.forename: P F
authors.identifier: http://orcid.org/0000-0003-1371-1947
authors.initials: PF
authors.lastname: Halloran
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050379:Arteriolosclerosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D006085:Graft Survival; D006801:Humans; D006818:Hyalin / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000601:surgery*; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors; D055815:Young Adult
keywords: basic (laboratory) research/science; biopsy; glomerular biology and disease; graft survival; kidney transplantation/nephrology; microarray/gene array