Plasma bilirubin and late graft failure in renal transplant recipients

Abstract

Summary 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.

High sensitive C-reactive protein and serum amyloid A are inversely related to serum bilirubin: effect-modification by metabolic syndrome

“…In a validation experiment (n = 80), we observed a strong correlation between total bilirubin and unconjugated bilirubin (Spearman’s r = 0.92, p  < 0.001), as well as between total bilirubin and conjugated direct bilirubin (Spearman’s r = 0.82, p  < 0.001). For the present study, we only used serum total bilirubin in keeping with other reports [29-31]. …”

Circulating bilirubin and defense against kidney disease and cardiovascular mortality: mechanisms contributing to protection in clinical investigations

“…Bilirubin is independently associated with a lower risk of late graft failure, even after cumulative adjustment for confounders (34). Bilirubin modulates the immune system, resulting in inhibition of chronic rejection in individuals with high concentrations of bilirubin (34,124). Therefore, both bilirubin and biliverdin inhibit acute T cell-mediated immune responses and thus could contribute to prevention of transplant organ rejection (81).…”

“…Bilirubin is independently associated with a lower risk of late graft failure, even after cumulative adjustment for confounders (34). Bilirubin modulates the immune system, resulting in inhibition of chronic rejection in individuals with high concentrations of bilirubin (34,124).…”

Low-Normal Free Thyroxine Confers Decreased Serum Bilirubin in Type 2 Diabetes Mellitus

“…In a validation experiment (n = 80), a strong correlation between total bilirubin and indirect bilirubin (Spearman's r = 0.92, p < 0.001), as well as between total bilirubin and direct bilirubin (Spearman's r = 0.82, p < 0.001) was found. For the current analyses we only used serum total bilirubin, in keeping with other studies (31)(32)(33).…”