title: Arteriolar lesions in renal transplant biopsies: prevalence, progression, and clinical significance.
abstract: Arteriolar hyalinosis in kidney transplants is considered the histopathologic hallmark of chronic calcineurin inhibitor (CNI) toxicity. However, the lesion is not specific. We assessed prevalence, progression, and clinical significance of arteriolar lesions in 1239 renal transplant sequential protocol biopsy samples and 408 biopsy for cause samples in 526 patients. Associations between arteriolar lesions and presumed risk factors, concomitant histopathologic lesions, demographic factors, and graft function were evaluated. The frequency of arteriolar lesions was stable during the first 2 years after transplantation, and increased thereafter (14.8% at 6 months versus 48.6% at >2 years; P < 0.0001). We were unable to find associations with diabetes, hypertension, or CNI therapy. However, patients with early arteriolar lesions received grafts from older donors (mean ± SD age, 54.4 ± 13.4 years versus 43.1 ± 16.6 years; P < 0.0001), and had inferior graft function (estimated glomerular filtration rate 55 ± 21 mL/min versus 63 ± 24 mL/min at 6 weeks, 53 ± 19 mL/min versus 60 ± 23 mL/min at 1 year, and 49 ± 19 mL/min versus 59 ± 22 mL/min at 2 years; P < 0.05). Evaluation of late biopsy samples from patients not receiving CNI therapy revealed a high prevalence of AH without clear-cut identifiable underlying cause. Reproducibility of arteriolar lesions was at best moderate (κ ≤ 0.62). Sampling error in sequential biopsy samples was frequent. In conclusion, in samples from sequential protocol biopsies and biopsies for cause in individual patients, arteriolar lesions in renal transplants not only increase over time without being specific for CNI toxicity but are affected by sampling error and limited reproducibility.
authors.affiliation: Institute of Pathology, Hannover Medical School, Hannover, Germany. verena.broecker@addenbrookes.nhs.uk
authors.forename: Verena
authors.initials: V
authors.lastname: Bröcker
authors.forename: Victoria
authors.initials: V
authors.lastname: Schubert
authors.forename: Irina
authors.initials: I
authors.lastname: Scheffner
authors.forename: Anke
authors.initials: A
authors.lastname: Schwarz
authors.forename: Marcus
authors.initials: M
authors.lastname: Hiss
authors.forename: Jan Ulrich
authors.initials: JU
authors.lastname: Becker
authors.forename: Ralph
authors.initials: R
authors.lastname: Scherer
authors.forename: Hermann
authors.initials: H
authors.lastname: Haller
authors.forename: Hans Heinrich
authors.initials: HH
authors.lastname: Kreipe
authors.forename: Michael
authors.initials: M
authors.lastname: Mengel
authors.forename: Wilfried
authors.initials: W
authors.lastname: Gwinner
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001160:Arterioles / Q000473:pathology; D001706:Biopsy; D016572:Cyclosporine / Q000097:blood; D003920:Diabetes Mellitus / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006818:Hyalin / Q000378:metabolism; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology; D007166:Immunosuppressive Agents / Q000097:blood; D007668:Kidney / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D016030:Kidney Transplantation / Q000473:pathology* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D015203:Reproducibility of Results; D012189:Retrospective Studies; D016559:Tacrolimus / Q000097:blood; D014019:Tissue Donors
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus