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

Abstract

BackgroundThere 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/DesignA 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 questionnaire was performed for socio-economic status and medical history.DiscussionWe have successfully managed several operational challenges within this multi-centre complex clinical research project performed across remote North, Western and Central Australia. It seems unlikely that a single correction factor (similar to that for African-Americans) to the equation for estimated glomerular filtration rate will prove appropriate or practical for Indigenous Australians. However, it may be that a modification of the equation in Indigenous Australians would be to include a measure of fat-free mass.

Progression of Kidney Disease in Indigenous Australians: The eGFR Follow-up Study

“…The methods of the eGFR Baseline Study have been previously described in detail (11). The methods of follow-up are outlined below (details in the Supplemental Material).…”

Accurate Assessment of Kidney Function in Indigenous Australians: The Estimated GFR Study

“…The methods (Item S1) have been previously described in detail 8 . Participants were Indigenous Australians aged 18 years and above, recruited from urban, rural and remote centres within four geographical regions of Australia across five pre-defined strata of health, diabetes status and kidney function.…”

“…11 A potential limitation of our study is the use of iohexol clearance as the formal GFR measurement. 8 The study was designed with respect to what is practical and achievable in very remote regions of Australia. Collection over a time period longer than 4 hours was not practical, and this may explain reduced accuracy of eGFR in participants with reduced GFR.…”

Increased bone mineral density in Aboriginal and Torres Strait Islander Australians: Impact of body composition differences

“…The methods of the eGFR Study have been previously reported [10]. In brief, 600 Indigenous Caucasian participants) were excluded from this analysis of BMD.…”

“…Interviewer-administered questionnaires determined: cigarette smoking, alcohol use, diabetes diagnosis, self-reported fracture history. Non-fasting bloods were collected for analysis of HbA1c, creatinine and other measures [10]. Diabetes was defined as a previous diagnosis of diabetes or HbA1c≥6.5% [11].…”