Clinical Impact of Serum Bilirubin Levels on Kidney Transplant Outcomes

Abstract

Serum bilirubin, a potent endogenous antioxidant, has been associated with decreased risks of cardiovascular disease, diabetes, and kidney disease. However, the effects of serum bilirubin on kidney transplant outcomes remain undetermined. We analyzed 1628 patients who underwent kidney transplantations between 2003 and 2017. Patients were grouped into sex-specific quartiles according to mean serum bilirubin levels, 3-12 months post-transplantation. Median bilirubin levels were 0.66 mg/dL in males and 0.60 mg/dL in females. The intra-individual variability of serum bilirubin levels was low (9%). Serum bilirubin levels were inversely associated with graft loss, death-censored graft failure, and all-cause mortality, independent of renal function, donor status, and transplant characteristics. Multivariable analysis revealed that the lowest serum bilirubin quartile was associated with increased risk of graft loss (HR 2.63, 95% CI 1.67-4.16, P < 0.001), death-censored graft failure (HR 2.96, 95% CI 1.62-5.40, P < 0.001), and all-cause mortality (HR 2.07, 95% CI 1.01-4.23, P = 0.046). Patients with lower serum bilirubin were also at greater risk of late-onset rejection and exhibited consistently lower glomerular filtration rates than those with higher serum bilirubin. Serum bilirubin levels were significantly associated with transplantation outcomes, suggesting that bilirubin could represent a therapeutic target for improving long-term transplant outcomes.