Contribution of cardiometabolic risk factors to estimated glomerular filtration rate decline in Indigenous Australians with and without albuminuria - the eGFR Follow-up Study.

AIM: We assessed associations between cardiometabolic risk factors and estimated glomerular filtration rate (eGFR) decline according to baseline albuminuria to identify potential treatment targets in Indigenous Australians. METHODS: The eGFR Follow-up Study is a longitudinal cohort of 520 Indigenous Australians. Linear regression was used to estimate associations between baseline cardiometabolic risk factors and annual Chronic Kidney Disease Epidemiology Collaboration eGFR change (mL/min per 1.73m2 /year), among those classified with baseline normoalbuminuria (urine albumin-to-creatinine ratio (uACR) <3 mg/mmol; n = 297), microalbuminuria (uACR 3-30 mg/mmol; n = 114) and macroalbuminuria (uACR ≥30 mg/mmol; n = 109). RESULTS: After a median of 3 years follow-up, progressive declines of the age- and sex-adjusted mean eGFR were observed across albuminuria categories (-2.0 [-2.6 to -1.4], -2.5 [-3.7 to -1.3] and -6.3 [-7.8 to -4.9] mL/min per 1.72m2 /year). Although a borderline association was observed between greater baseline haemoglobin A1c and eGFR decline in those with macroalbuminuria (P = 0.059), relationships were not significant in those with microalbuminuria (P = 0.187) or normoalbuminuria (P = 0.23). Greater baseline blood pressure, C-reactive protein, waist-to-hip ratio and lower high-density lipoprotein cholesterol showed non-significant trends with greater eGFR decline in the presence of albuminuria. CONCLUSION: Over a 3 year period, marked eGFR decline was observed with greater baseline albuminuria. Cardiometabolic risk factors were not strong predictors for eGFR decline in Indigenous Australians without albuminuria. Longer follow-up may elucidate the role of these predictors and other mechanisms in chronic kidney disease progression in this population.

Comparison of creatinine and cystatin C based eGFR in the estimation of glomerular filtration rate in Indigenous Australians: The eGFR Study.

BACKGROUND: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation that combines creatinine and cystatin C is superior to equations that include either measure alone in estimating glomerular filtration rate (GFR). However, whether cystatin C can provide any additional benefits in estimating GFR for Indigenous Australians, a population at high risk of end-stage kidney disease (ESKD) is unknown. METHODS: Using a cross-sectional analysis from the eGFR Study of 654 Indigenous Australians at high risk of ESKD, eGFR was calculated using the CKD-EPI equations for serum creatinine (eGFRcr), cystatin C (eGFRcysC) and combined creatinine and cystatin C (eGFRcysC+cr). Reference GFR (mGFR) was determined using a non-isotopic iohexol plasma disappearance technique over 4h. Performance of each equation to mGFR was assessed by calculating bias, % bias, precision and accuracy for the total population, and according to age, sex, kidney disease, diabetes, obesity and c-reactive protein. RESULTS: Data were available for 542 participants (38% men, mean [sd] age 45 [14] years). Bias was significantly greater for eGFRcysC (15.0mL/min/1.73m2; 95% CI 13.3-16.4, p<0.001) and eGFRcysC+cr (10.3; 8.8-11.5, p<0.001) compared to eGFRcr (5.4; 3.0-7.2). Accuracy was lower for eGFRcysC (80.3%; 76.7-83.5, p<0.001) but not for eGFRcysC+cr (91.9; 89.3-94.0, p=0.29) compared to eGFRcr (90.0; 87.2-92.4). Precision was comparable for all equations. The performance of eGFRcysC deteriorated across increasing levels of c-reactive protein. CONCLUSION: Cystatin C based eGFR equations may not perform well in populations with high levels of chronic inflammation. CKD-EPI eGFR based on serum creatinine remains the preferred equation in Indigenous Australians.