Elsevier

Clinical Biochemistry

Volume 50, Issue 18, December 2017, Pages 1040-1047
Clinical Biochemistry

Bilirubin concentration is positively associated with haemoglobin concentration and inversely associated with albumin to creatinine ratio among Indigenous Australians: eGFR Study

https://doi.org/10.1016/j.clinbiochem.2017.08.011Get rights and content

Highlights

  • Bilirubin was positively associated with Hb and inversely associated with ACR

  • Bilirubin was not associated with other markers of kidney function apart from ACR

  • Bilirubin was lower in Aboriginal than Torres Strait Islander participants

  • Factors explaining this lower concentration requires further investigation

Abstract

Low serum bilirubin concentrations are reported to be strongly associated with cardio-metabolic disease, but this relationship has not been reported among Indigenous Australian people who are known to be at high risk for diabetes and chronic kidney disease (CKD).

Hypothesis: serum bilirubin will be negatively associated with markers of chronic disease, including CKD and anaemia among Indigenous Australians.

Method: A cross-sectional analysis of 594 adult Aboriginal and Torres Strait Islander (TSI) people in good health or with diabetes and markers of CKD. Measures included urine albumin: creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), haemoglobin (Hb) and glycated haemoglobin (HbA1c). Diabetes was defined by medical history, medications or HbA1c  6.5% or ≥ 48 mmol/mol. Anaemia was defined as Hb < 130 g/L or < 120 g/L in males and females respectively. A multivariate regression analysis examining factors independently associated with log-bilirubin was performed.

Results: Participants mean (SD) age was 45.1 (14.5) years, and included 62.5% females, 71.7% Aboriginal, 41.1% with diabetes, 16.7% with anaemia, 41% with ACR > 3 mg/mmol and 18.2% with eGFR < 60 mL/min/1.73m2. Median bilirubin concentration was lower in females than males (6 v 8 μmol/L, p < 0.001) and in Aboriginal than TSI participants (6 v 9.5 μmol/L, p < 0.001). Six factors explained 35% of the variance of log-bilirubin; Hb and cholesterol (both positively related) and ACR, triglycerides, Aboriginal ethnicity and female gender (all inversely related).

Conclusion: Serum bilirubin concentrations were positively associated with Hb and total cholesterol, and inversely associated with ACR. Further research to determine reasons explaining lower bilirubin concentrations among Aboriginal compared with TSI participants are needed.

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.

References (45)

  • A. Pasternack et al.

    Low serum bilirubin in chronic renal failre. Relation to haem metabolism

    Clin. Chem. Acta

    (1976)
  • K.E. Daenen et al.

    Association of HO-1 (GT)n promoter polymorphism and cardiovascular disease: a reanalysis of the literature

    Can. J. Cardiol.

    (2016)
  • R.P.F. Dullaart et al.

    A pro-inflammatory glycoprotein biomarker is associated with lower bilirubin in metabolic syndrome

    Clin. Biochem.

    (2015)
  • Australian Health Ministers' Advisory Council

    Aboriginal and Torres Strait Islander Health Performance Framework Report

    (2014)
  • B.L. Heitmann et al.

    Are there ethnic differences in the association between body weight and resistance, measured by bioelectrical impedance?

    Int. J. Obes.

    (1997)
  • S. McDonald

    Incidence and treatment of ESRD among indigenous people of Australasia

    Clin. Nephrol.

    (2010)
  • Z. Wang et al.

    Hypertension, dyslipidaemia, body mass index, diabetes and smoking status in aboriginal Australians in a remote community

    Ethn. Dis.

    (2003)
  • K. Rowley et al.

    Inflammation and vascular endothelial activation in an aboriginal population: relationships to coronary disease risk factors and nutritional markers

    Med. J. Aust.

    (2003)
  • J.T. Hughes et al.

    Cross-sectional associations of albuminuria among Aboriginal and Torres Strait Islander adults: the eGFR Study

    Nephrology

    (2016)
  • T.S. Perlstein et al.

    Serum total bilirubin level, prevalent stroke, and stroke outcomes: NHANES 1999–2004

    Am. J. Med.

    (2008)
  • G. Targher et al.

    Relationship of serum bilirubin concentrations to kidney function and albuminuria in the United States adult population. Findings from the National Health and nutrition examination survey 2001-2006

    Clin. Chem. Lab. Med.

    (2009)
  • WHO

    Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity

  • Cited by (0)

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