title: Subclinical toxicity of calcineurin inhibitors in repeated protocol biopsies: an independent risk factor for chronic kidney allograft damage.
abstract: The purpose of the prospective study was to determine the prevalence of subclinical toxicity of calcineurin inhibitors (CI) in repeated protocol renal allograft biopsies and to assess its impact on the development of chronic graft changes. A total of 424 biopsies were conducted in a cohort of 158 patients; of these biopsies, 158 were in the third week, 142 were in the third month and 124 were in the first year after transplantation. Histological signs of toxicity occurred in the third week in 33 (20.1%) patients, with persistence after CI dose reduction in the third month in 27 (19.0%) and in the first year in 23 (18.5%) patients. Of the toxic changes, 52% were clinically silent. At the end of the one-year follow-up, both subclinical and clinically manifest toxicity resulted in a similar progression of chronic changes quantified by Banff chronicity score and they significantly differed from the control group (P < 0.05). Subclinical toxicity affects a significant percentage of grafts; it occurs independently of dosage, blood level and type of applied CI. It is associated with the progression of chronic changes as early as in the first year after transplantation and represents an independent risk factor for chronic allograft damage. We report here our clinical approach to toxicity.
authors.affiliation: 3rd Department of Internal Medicine and Nephrology, University Hospital Olomouc, Olomouc, Czech Republic. karel.krejci@fnol.cz
authors.forename: Karel
authors.initials: K
authors.lastname: Krejcí
authors.forename: Tomás
authors.initials: T
authors.lastname: Tichý
authors.forename: Miroslav
authors.initials: M
authors.lastname: Hrubý
authors.forename: Pavel
authors.initials: P
authors.lastname: Horák
authors.forename: Hana
authors.initials: H
authors.lastname: Ciferská
authors.forename: Vladko
authors.initials: V
authors.lastname: Horcicka
authors.forename: Pavel
authors.initials: P
authors.lastname: Strebl
authors.forename: Sadek
authors.initials: S
authors.lastname: Al-Jabry
authors.forename: Petr
authors.initials: P
authors.lastname: Bachleda
authors.forename: Josef
authors.initials: J
authors.lastname: Zadrazil
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy / Q000379:methods*; D065095:Calcineurin Inhibitors; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000633:toxicity; D007676:Kidney Failure, Chronic / Q000188:drug therapy / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D014184:Transplantation, Homologous / Q000009:adverse effects*
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents