Plasma bilirubin and late graft failure in renal transplant recipients.
Exogenous bilirubin has been shown to protect against oxidative stress in ischemia-reperfusion injury. Oxidative stress has been implicated in the pathophysiology of chronic transplant dysfunction leading to late graft failure after renal transplantation. We prospectively investigated whether high endogenous bilirubin is protective against development of late graft failure in renal transplant recipients (RTR). Baseline data were collected between August 2001 and July 2003 in nonicteric outpatient RTR with a functioning graft for >1 year. At baseline, bilirubin and liver enzymes were measured using routine assays on a Merck Mega analyzer. Graft failure was prospectively recorded until May 19 2009. During follow-up for 7.1 [6.2-7.2] years, 55 RTR developed graft failure. We found that circulating levels of bilirubin are inversely associated with late graft failure in RTR (HR = 0.29 [95% CI: 0.16-0.52], P < 0.001). This association was independent of potential confounders, including creatinine clearance, urinary protein excretion, calcineurin inhibitors, and gender (HR = 0.31 [95% CI: 0.15-0.62] P = 0.001). Our findings are consistent with a protective effect of increased endogenous bilirubin against development of late graft failure in RTR. If our findings are confirmed by other studies, intervention with endogenous or exogenous bilirubin may be of interest for long-term preservation of renal function in RTR.
Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Petronella E
PE
Deetman
Dorien M
DM
Zelle
Jaap J
JJ
Homan van der Heide
Gerjan J
GJ
Navis
Reinold O B
RO
Gans
Stephan J L
SJ
Bakker
D001663:Bilirubin / Q000097:blood*; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D011446:Prospective Studies; D017211:Treatment Failure
D001663:Bilirubin