title: Nonesterified fatty acids and development of graft failure in renal transplant recipients.
abstract: BACKGROUND
  Chronic transplant dysfunction is the most common cause of graft failure on the long term. Proteinuria is one of the cardinal clinical signs of chronic transplant dysfunction. Albumin-bound fatty acids (FA) have been hypothesized to be instrumental in the etiology of renal damage induced by proteinuria. We therefore questioned whether high circulating FA could be associated with an increased risk for future development of graft failure in renal transplant recipients (RTR). To this end, we prospectively investigated the association of fasting concentrations of circulating nonesterified FA (NEFA) with the development of graft failure in RTR.
  
  
  METHODS
  Baseline measurements were performed between 2001 and 2003 in outpatient RTR with a functioning graft of more than 1 year. Follow-up was recorded until May 19, 2009. Graft failure was defined as return to dialysis or retransplantation.
  
  
  RESULTS
  We included 461 RTR at a median (interquartile range [IQR]) of 6.1 (3.3-11.3) years after transplantation. Median (IQR) fasting concentrations of NEFA were 373 (270-521) μM/L. Median (IQR) follow-up for graft failure beyond baseline was 7.1 (6.1-7.5) years. Graft failure occurred in 23 (15%), 14 (9%), and 9 (6%) of RTR across increasing gender-specific tertiles of NEFA (P=0.04). In a gender-adjusted Cox-regression analysis, log-transformed NEFA level was inversely associated with the development of graft failure (hazard ratio, 0.61; 95% confidence interval, 0.47-0.81; P<0.001).
  
  
  CONCLUSIONS
  In this prospective cohort study in RTR, we found an inverse association between fasting NEFA concentrations and risk for development of graft failure. This association suggests a renoprotective rather than a tubulotoxic effect of NEFA. Further studies on the role of different types of NEFA in the progression of renal disease are warranted.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, Groningen, The Netherlands. a.klooster@umcg.nl
authors.forename: Astrid
authors.initials: A
authors.lastname: Klooster
authors.forename: H Sijbrand
authors.initials: HS
authors.lastname: Hofker
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
authors.forename: Jaap J
authors.initials: JJ
authors.lastname: Homan van der Heide
authors.forename: Reinold O B
authors.initials: RO
authors.lastname: Gans
authors.forename: Harry
authors.initials: H
authors.lastname: van Goor
authors.forename: Henri G D
authors.initials: HG
authors.lastname: Leuvenink
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000097:blood / Q000453:epidemiology / Q000503:physiopathology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000401:mortality / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011507:Proteinuria / Q000097:blood / Q000503:physiopathology; D012044:Regression Analysis; D012189:Retrospective Studies; D012307:Risk Factors; D014180:Transplantation; D014184:Transplantation, Homologous
chemical_list: D005230:Fatty Acids, Nonesterified