Circulating bilirubin and defense against kidney disease and cardiovascular mortality: mechanisms contributing to protection in clinical investigations.
Unconjugated bilirubin is an endogenous circulating antioxidant, bound to albumin, and therefore is retained in the vascular compartment. Bilirubin has well-documented neurotoxic effects in infants; however, current evidence indicates mildly elevated bilirubin is associated with protection from cardiovascular disease and all-cause mortality in adults. Recent clinical studies show mildly elevated bilirubin is associated with protection from kidney damage and dysfunction, in addition to cardiovascular events and all-cause mortality in patients undergoing hemodialysis. This is the first review to examine the clinical evidence and summarize the potential mechanisms of action that link bilirubin to protection from kidney damage, subsequent kidney failure, and dialysis-related mortality. With this understanding, it is hoped that new therapies will be developed to prevent renal dysfunction and mortality from cardiovascular disease in at-risk individuals.
Heart Foundation Research Centre, Griffith Health Institute, Griffith University, Gold Coast, Australia; and.
Ai-Ching
AC
Boon
Heart Foundation Research Centre, Griffith Health Institute, Griffith University, Gold Coast, Australia; and a.bulmer@griffith.edu.au.
Andrew C
AC
Bulmer
School of Human Movement Studies, University of Queensland, St Lucia, Australia.
Jeff S
JS
Coombes
School of Human Movement Studies, University of Queensland, St Lucia, Australia.
Robert G
RG
Fassett
D000818:Animals; D001663:Bilirubin / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000401:mortality / Q000503:physiopathology / Q000517:prevention & control; D018450:Disease Progression; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology; D007674:Kidney Diseases / Q000097:blood* / Q000401:mortality / Q000503:physiopathology / Q000628:therapy; D006435:Renal Dialysis / Q000009:adverse effects / Q000401:mortality; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome; D015854:Up-Regulation
D015415:Biomarkers; D001663:Bilirubin
NADPH oxidase; all-cause mortality; antioxidant; bile pigment; hemodialysis; tetrapyrrole