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1. Study Protocol - Accurate assessment of kidney function in Indigenous Australians: aims and methods of the eGFR Study

Author

Maple-Brown, LJ, Lawton, PD, Hughes, JT, Sharma, SK, Jones, GRD, Ellis, AG, Hoy, W, Cass, A, MacIsaac, RJ, Sinha, AK, Thomas, MAB, Piers, LS, Ward, LC, Drabsch, K, Panagiotopoulos, S, McDermott, R, Warr, K, Cherian, S, Brown, A, Jerums, G, O'Dea, K, Maple-Brown, LJ, Lawton, PD, Hughes, JT, Sharma, SK, Jones, GRD, Ellis, AG, Hoy, W, Cass, A, MacIsaac, RJ, Sinha, AK, Thomas, MAB, Piers, LS, Ward, LC, Drabsch, K, Panagiotopoulos, S, McDermott, R, Warr, K, Cherian, S, Brown, A, Jerums, G, and O'Dea, K

Abstract

BACKGROUND: There is an overwhelming burden of cardiovascular disease, type 2 diabetes and chronic kidney disease among Indigenous Australians. In this high risk population, it is vital that we are able to measure accurately kidney function. Glomerular filtration rate is the best overall marker of kidney function. However, differences in body build and body composition between Indigenous and non-Indigenous Australians suggest that creatinine-based estimates of glomerular filtration rate derived for European populations may not be appropriate for Indigenous Australians. The burden of kidney disease is borne disproportionately by Indigenous Australians in central and northern Australia, and there is significant heterogeneity in body build and composition within and amongst these groups. This heterogeneity might differentially affect the accuracy of estimation of glomerular filtration rate between different Indigenous groups. By assessing kidney function in Indigenous Australians from Northern Queensland, Northern Territory and Western Australia, we aim to determine a validated and practical measure of glomerular filtration rate suitable for use in all Indigenous Australians. METHODS/DESIGN: A cross-sectional study of Indigenous Australian adults (target n = 600, 50% male) across 4 sites: Top End, Northern Territory; Central Australia; Far North Queensland and Western Australia. The reference measure of glomerular filtration rate was the plasma disappearance rate of iohexol over 4 hours. We will compare the accuracy of the following glomerular filtration rate measures with the reference measure: Modification of Diet in Renal Disease 4-variable formula, Chronic Kidney Disease Epidemiology Collaboration equation, Cockcroft-Gault formula and cystatin C- derived estimates. Detailed assessment of body build and composition was performed using anthropometric measurements, skinfold thicknesses, bioelectrical impedance and a sub-study used dual-energy X-ray absorptiometry. A q

Published
2010

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

Author

Alan Cass, Jacquelyne T Hughes, Louise J. Maple-Brown, Richard J MacIsaac, Mark Thomas, Sandawana William Majoni, Kerin O'Dea, Ashim Sinha, Federica Barzi, G Rathnayake, Wendy E. Hoy, Graham R D Jones, Hughes, JT, Barzi, F, Hoy, WE, Jones, GRD, Rathnayake, G, Majoni, SW, Thomas, MAB, Sinha, A, Cass, A, MacIsaac, RJ, O'Dea, K, and Maple-Brown, LJ

Subjects
Male, Native Hawaiian or Other Pacific Islander, Clinical Biochemistry, 030232 urology & nephrology, 030204 cardiovascular system & hematology, Gastroenterology, Hemoglobins, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, eGFR, education.field_of_study, diabetes, General Medicine, Middle Aged, Creatinine, Hypertension, Female, bilirubin, medicine.symptom, Adult, cardiovascular risk, medicine.medical_specialty, Bilirubin, Population, Renal function, 03 medical and health sciences, Internal medicine, Diabetes mellitus, Diabetes Mellitus, medicine, Albuminuria, Humans, Renal Insufficiency, Chronic, education, ACR, business.industry, Australia, Albumin, medicine.disease, Indigenous, Cross-Sectional Studies, Endocrinology, chemistry, Kidney Failure, Chronic, business, Biomarkers, Kidney disease
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 > 3mg/mmol and 18.2% with eGFR < 60mL/min/1.73m 2 . Median bilirubin concentration was lower in females than males (6 v 8μmol/L, p < 0.001) and in Aboriginal than TSI participants (6 v 9.5μmol/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. Refereed/Peer-reviewed

Published
2017

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

Author

Hughes JT, Barzi F, Hoy WE, Jones GRD, Rathnayake G, Majoni SW, Thomas MAB, Sinha A, Cass A, MacIsaac RJ, O'Dea K, and Maple-Brown LJ

Subjects
Adult, Albuminuria blood, Albuminuria urine, Australia, Biomarkers blood, Biomarkers urine, Creatinine urine, Cross-Sectional Studies, Diabetes Mellitus blood, Diabetes Mellitus urine, Female, Humans, Hypertension blood, Hypertension urine, Kidney Failure, Chronic blood, Kidney Failure, Chronic urine, Male, Middle Aged, Renal Insufficiency, Chronic blood, Renal Insufficiency, Chronic urine, Risk Factors, Bilirubin blood, Hemoglobins metabolism, Native Hawaiian or Other Pacific Islander
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 ≥48mmol/mol. Anaemia was defined as Hb<130g/L or <120g/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>3mg/mmol and 18.2% with eGFR<60mL/min/1.73m 2 . Median bilirubin concentration was lower in females than males (6 v 8μmol/L, p<0.001) and in Aboriginal than TSI participants (6 v 9.5μmol/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., (Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Published
2017
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7. Progression of Kidney Disease in Indigenous Australians: The eGFR Follow-up Study.

Author

Maple-Brown LJ, Hughes JT, Ritte R, Barzi F, Hoy WE, Lawton PD, Jones GRD, Death E, Simmonds A, Sinha AK, Cherian S, Thomas MAB, McDermott R, Brown ADH, O'Dea K, Jerums G, Cass A, and MacIsaac RJ

Subjects
Adult, Aged, Albuminuria urine, Australia epidemiology, Creatinine urine, Female, Follow-Up Studies, Glomerular Filtration Rate, Humans, Longitudinal Studies, Male, Middle Aged, Renal Insufficiency, Chronic therapy, Young Adult, Disease Progression, Native Hawaiian or Other Pacific Islander, Renal Insufficiency, Chronic ethnology, Renal Insufficiency, Chronic physiopathology
Abstract

Background and Objectives: Indigenous Australians experience a heavy burden of CKD. To address this burden, the eGFR Follow-Up Study recruited and followed an Indigenous Australian cohort from regions of Australia with the greatest ESRD burden. We sought to better understand factors contributing to the progression of kidney disease. Specific objectives were to assess rates of progression of eGFR in Indigenous Australians with and without CKD and identify factors associated with a decline in eGFR., Design, Setting, Participants, & Measurements: This observational longitudinal study of Indigenous Australian adults was conducted in >20 sites. The baseline cohort was recruited from community and primary care clinic sites across five strata of health, diabetes status, and kidney function. Participants were then invited to follow up at 2-4 years; if unavailable, vital status, progression to RRT, and serum creatinine were obtained from medical records. Primary outcomes were annual eGFR change and combined renal outcome (first of ≥30% eGFR decline with follow-up eGFR<60 ml/min per 1.73 m(2), progression to RRT, or renal death)., Results: Participants (n=550) were followed for a median of 3.0 years. Baseline and follow-up eGFR (geometric mean [95% confidence interval], 83.9 (80.7 to 87.3) and 70.1 (65.9 to 74.5) ml/min per 1.73 m(2), respectively. Overall mean annual eGFR change was -3.1 (-3.6 to -2.5) ml/min per 1.73 m(2). Stratified by baseline eGFR (≥90, 60-89, <60 ml/min per 1.73 m(2)), annual eGFR changes were -3.0 (-3.6 to -2.4), -1.9 (-3.3 to -0.5), and -5.0 (-6.5 to -3.6) ml/min per 1.73 m(2). Across baseline eGFR categories, annual eGFR decline was greatest among adults with baseline albumin-to-creatinine ratio (ACR) >265 mg/g (30 mg/mmol). Baseline determinants of the combined renal outcome (experienced by 66 participants) were higher urine ACR, diabetes, lower measured GFR, and higher C-reactive protein., Conclusions: The observed eGFR decline was three times higher than described in nonindigenous populations. ACR was confirmed as a powerful predictor for eGFR decline across diverse geographic regions., (Copyright © 2016 by the American Society of Nephrology.)

Published
2016
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