title: Leptin, pre-existing vascular disease, and increased arteriovenous fistula maturation failure in dialysis patients.
abstract: BACKGROUND
  The adipocytokine leptin is an independent cardiovascular risk factor and exerts proatherogenic effect. Pre-existing vascular disease is an important cause of arteriovenous fistula (AVF) maturation failure. We explored the association between serum leptin, pre-existing vascular disease, and AVF maturation failure in incident hemodialysis patients.
  
  
  METHODS
  Vein samples from 62 patients were collected at the time of AVF creation. Pre-existing vascular disease was evaluated with histologic changes and immunohistochemical characteristics of cellular phenotypes in intima. AVF maturation failure was defined as an AVF that could not be used successfully by the third month after its creation.
  
  
  RESULTS
  The prevalence of body mass index ≥30 kg/m2was 17%, and AVF maturation failure occurred in 28 (45%) patients. Patients within the highest leptin tertile showed significantly higher maturation failure rate, independent of age, gender, diabetes, and body mass index. On histologic examination, significant differences in intimal hyperplasia (13.3 ± 4.5 vs 18.2 ± 5.2 vs 30.3 ± 14.3 μm) and medial thickening (76.8 ± 23.7 vs 103.9 ± 33.6 vs 109.3 ± 36.5 μm) were observed across leptin tertiles. Similarly, medial fibrosis was most severe in the highest tertile. According to the immunohistochemical staining, most intimal cells were α-smooth muscle actin-positive, vimentin-positive, desmin-negative myofibroblasts. However, in the lowest tertile, desmin-positive contractile smooth muscle cells were also frequently observed, suggesting relatively slow phenotypic changes in this group. Furthermore, as leptin tertiles increased, the expression of leptin receptor in the luminal border of intima was significantly decreased.
  
  
  CONCLUSIONS
  Obesity-related higher fistula maturation failure rate may be partly mediated by higher leptin level-associated pre-existing vascular diseases in end-stage renal disease patients. Decreased expression of leptin receptor may be related to this association.
authors.affiliation: Department of Internal Medicine, Kidney Research Institute, Hallym University Sacred Heart Hospital, Anyang, Korea; Department of Clinical Immunology, Hallym University Sacred Heart Hospital, Anyang, Korea.
authors.forename: Jwa-Kyung
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Department of Nephrology, Sahmyook Medical Center, Seoul, Korea.
authors.forename: Sun Ryoung
authors.initials: SR
authors.lastname: Choi
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Hallym University Sacred Heart Hospital, Anyang, Korea.
authors.forename: Won Yong
authors.initials: WY
authors.lastname: Lee
authors.affiliation: Department of Clinical Immunology, Hallym University Sacred Heart Hospital, Anyang, Korea.
authors.forename: Mi Jin
authors.initials: MJ
authors.lastname: Park
authors.affiliation: Department of Nephrology, Sahmyook Medical Center, Seoul, Korea.
authors.forename: Hyung Suk
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Kidney Research Institute, Hallym University Sacred Heart Hospital, Anyang, Korea.
authors.forename: Young Rim
authors.initials: YR
authors.lastname: Song
authors.affiliation: Department of Internal Medicine, Kidney Research Institute, Hallym University Sacred Heart Hospital, Anyang, Korea.
authors.forename: Hyung Jik
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Kidney Research Institute, Hallym University Sacred Heart Hospital, Anyang, Korea; Department of Clinical Immunology, Hallym University Sacred Heart Hospital, Anyang, Korea. Electronic address: imnksk@gmail.com.
authors.forename: Sung Gyun
authors.initials: SG
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D005260:Female; D006801:Humans; D006965:Hyperplasia; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000628:therapy*; D020738:Leptin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000150:complications / Q000175:diagnosis; D011446:Prospective Studies; D054411:Receptors, Leptin / Q000032:analysis; D006435:Renal Dialysis; D056910:Republic of Korea; D012307:Risk Factors; D017211:Treatment Failure; D015854:Up-Regulation; D014652:Vascular Diseases / Q000097:blood / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology; D014680:Veins / Q000737:chemistry / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery*
chemical_list: D015415:Biomarkers; C515448:LEPR protein, human; D020738:Leptin; D054411:Receptors, Leptin