title: Increased Telomere Attrition After Renal Transplantation-Impact of Antimetabolite Therapy.
abstract: BACKGROUND
  The uremic milieu exposes chronic kidney disease (CKD) patients to premature ageing processes. The impact of renal replacement therapy (dialysis and renal transplantation [RTx]) or immunosuppressive treatment regimens on ageing biomarkers has scarcely been studied.
  
  
  METHODS
  In this study telomere length in whole blood cells was measured in 49 dialysis patients and 47 RTx patients close to therapy initiation and again after 12 months. Forty-three non-CKD patients were included as controls.
  
  
  RESULTS
  Non-CKD patients had significantly (P≤ 0.01) longer telomeres than CKD patients. Telomere attrition after 12 months was significantly greater in RTx patients compared to dialysis patients (P= 0.008). RTx patients receiving mycophenolate mofetil (MMF) had a greater (P= 0.007) degree of telomere attrition compared to those treated with azathioprine. After 12 months, folate was significantly higher in RTx patients than in dialysis patients (P< 0.0001), whereas the opposite was true for homocysteine (P< 0.0001). The azathioprine group had lower levels of folate after 12 months than the MMF group (P= 0.003).
  
  
  CONCLUSIONS
  The associations between immunosuppressive therapy, telomere attrition, and changes in folate indicate a link between methyl donor potential, immunosuppressive drugs, and biological ageing. The hypothesis that the increased telomere attrition, observed in the MMF group after RTx, is driven by the immunosuppressive treatment, deserves further attention.
authors.affiliation: Neurogenetics Division, Department of Molecular Medicine and Surgery, Karolinska Institutet, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Luttropp
authors.forename: Louise
authors.initials: L
authors.lastname: Nordfors
authors.affiliation: Wolfson Wohl Translational Research Centre, Institute of Cancer Sciences, University of Glasgow, United Kingdom.
authors.forename: Dagmara
authors.initials: D
authors.lastname: McGuinness
authors.affiliation: Division of Transplantation, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Wennberg
authors.affiliation: Wolfson Wohl Translational Research Centre, Institute of Cancer Sciences, University of Glasgow, United Kingdom.
authors.forename: Hannah
authors.initials: H
authors.lastname: Curley
authors.affiliation: NHS Greater Glasgow and Clyde, Glasgow Royal Infirmary, United Kingdom.
authors.forename: Tara
authors.initials: T
authors.lastname: Quasim
authors.affiliation: Division of Transplantation, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Genberg
authors.affiliation: Division of Transplantation, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Sweden.
authors.forename: John
authors.initials: J
authors.lastname: Sandberg
authors.affiliation: Division of Transplantation, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Sweden.
authors.forename: Isabella
authors.initials: I
authors.lastname: Sönnerborg
authors.affiliation: Neurogenetics Division, Department of Molecular Medicine and Surgery, Karolinska Institutet, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Schalling
authors.affiliation: Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Sweden.
authors.forename: Abdul Rashid
authors.initials: AR
authors.lastname: Qureshi
authors.affiliation: Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Bárány
authors.affiliation: Wolfson Wohl Translational Research Centre, Institute of Cancer Sciences, University of Glasgow, United Kingdom.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Shiels
authors.affiliation: Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Stenvinkel