Bilirubin concentration is positively associated with haemoglobin concentration and inversely associated with albumin to creatinine ratio among Indigenous Australians: eGFR Study
Introduction
Indigenous Australians have a higher burden of chronic non-communicable conditions, including anaemia, chronic kidney disease (CKD), diabetes and cardiovascular (CV) disease than other Australians [1]. Nationally reported statistics cannot adequately represent the variability within this population, including differences between the major indigenous ethnic groups (the Aboriginal and Torres Strait Islander peoples such as body composition or dyslipidaemia profile [2], [3]) or the geographical diversity with illness burden [4]. End stage chronic kidney disease is one chronic condition which disproportionately affects Indigenous Australian people than observed among non-Indigenous counterparts, occurring at a much younger age and for whom Indigenous females have almost twice the risk as Indigenous males [5]. It is recognised that additional mechanisms and markers of chronic disease risk are needed to explain the CV disease burden and risks within Indigenous Australian communities [6], [7].
We recently reported an inverse association of total serum bilirubin (inclusive of the pathological range > 20 μmol/L) with albumin to creatinine ratio (ACR) among participants of the eGFR Study [8], an adult Indigenous population living in diverse regions of Northern and Central Australia, stratified for good health, diabetes and CKD. Serum bilirubin is the end product of haem degradation, has anti-oxidant properties, and in low concentration is associated with chronic cardio-metabolic disease risk [9]. Although our finding of an inverse association of ACR and bilirubin was consistent with reports of a cohort of adults with diabetes from Asia [10], it was in contrast to findings of a United States population-based health survey which reported a positive association between albuminuria and bilirubin [11].
The prevalence and severity of anaemia within populations is an important health indicator [12]. Anaemia is a condition frequently reported among sub-populations of Indigenous Australians [13] and is associated with diabetes and chronic kidney disease [14]. Factors contributing to anaemia thus include poor quality diet, micronutrient absorption, the impact of anaemia related to co-morbid chronic conditions and red cell destruction. We hypothesised that serum bilirubin will be negatively associated with markers of cardio-metabolic disease in Indigenous Australians, a population known to have high risk for anaemia, diabetes, premature cardiovascular disease, and chronic kidney disease.
Section snippets
Participants
Participants were self-identifying adult Aboriginal and Torres Strait Islander (TSI) Australians from the baseline eGFR Study [15], recruited from > 20 sites in urban, regional and remote areas known to have a high background prevalence of dialysis-dependent end stage kidney (ESKD) disease. All who expressed an interest to participate were able to be stratified for inclusion, including those with diabetes or CKD. We excluded pregnant or breast feeding women, or participants with rapidly changing
Results
Diabetes, albuminuria (without significantly impaired eGFR) and hypertension were prominent findings observed among the 594 participants (Table 1). Aboriginal participants, who comprised 71% of the study cohort, had a higher frequency of anaemia, albuminuria and GFR < 60 mL/min/1.73m2 than TSI participants.
Discussion
We report four key findings in this analysis of associations between bilirubin and the chronic conditions of diabetes, CKD and anaemia, in a cohort of 594 Indigenous Australians recruited from more than twenty sites. First serum log-bilirubin was positively associated with haemoglobin concentration, and anaemia was also commonly observed in this cohort. Second, log-bilirubin concentrations was positively associated with total cholesterol and inversely associated with triglycerides. Third, the
Conclusions
Our findings show that serum bilirubin is associated with markers of chronic disease, including CKD, dyslipidaemia, albuminuria and anaemia among Indigenous Australians. Further work in this population is required to determine the normal range of bilirubin, including ascertainment of factors which may explain the lower bilirubin concentrations among Aboriginal participants; and prospectively determine any causal relationship of low serum bilirubin with chronic disease progression and evaluate
List of abbreviations
- ACEI-ARB
angiotensin converting enzyme inhibitor-angiotensin receptor blocker
- ACR
albumin to creatinine ratio
- ALP
alkaline phosphatase
- ALT
alanine transferase
- BMI
body mass index
- BP
blood pressure
- CKD
chronic kidney disease
- CRP
C-reactive protein
- CV
cardiovascular
- eGFR
estimated glomerular filtration rate
- ESKD
end stage kidney disease
- GGT
γ glutamyl transferase
- Hb
haemoglobin
- HBA1c
glycated haemoglobin
- Hct
haematocrit
- HDL
high density lipoprotein
- IDMS
isotope dilution mass spectrometry
- IQR
interquartile range
- MCV
mean corpuscle
Acknowledgments
Thanks to participants, study staff, community facilitators and investigators of the eGFR Study. Other eGFR Study Investigators are A Brown, R McDermott, K Warr, S Cherian and P Lawton. The eGFR Study was supported by the Australian National Health and Medical Research Council (NHMRC) #545205 and Sea-Swift Thursday Island. JH was supported by NHMRC Fellowship #1092576; LMB was supported by NHMRC Fellowship #1078477. FB was supported by NHMRC Program Grant #631947. The views expressed in this
Conflict of interest statement
All authors have no conflicts to declare.
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