THE ROLE OF TUMOUR NECROSIS FACTOR RECEPTOR 1 (TNFR1) IN THE PROGRESSION OF KIDNEY DISEASE IN INDIGENOUS AUSTRALIANS: THE EGFR FOLLOW-UP STUDY

ELM BARR^1,2, F BARZI¹, JT HUGHES^1,3, G JERUMS^4,5, WE HOY⁶, K O’DEA⁷, GRD JONES^8.9, PD LAWTON¹, ADH BROWN^7,10, EI EKINCI^1,4,5, A SINHA¹¹, A CASS¹, RJ MACISAAC^5,12, LJ MAPLE-BROWN^1,3

¹ Menzies School of Health Research, Darwin, Northern Territory; ²Baker Heart and Diabetes Institute, Melbourne, Victoria; ³Royal Darwin Hospital, Darwin, Northern Territory; ⁴Austin Health, Department of Endocrinology, Melbourne, Victoria; ⁵University of Melbourne, Department of Medicine, Melbourne, Victoria; ⁶The University of Queensland, Brisbane, Queensland; ⁷University of South Australia, Nutrition and Population Health, Adelaide, South Australia; ⁸St Vincent’s Hospital, SydPath, Sydney, New South Wales; ⁹University of New South Wales, Department of Medicine, Sydney, New South Wales; ¹⁰South Australian Health and Medical Research Institute, Indigenous Health, Adelaide, South Australia; ¹¹Cairns Base Hospital, Diabetes and Endocrinology, Cairns, Queensland; ¹²St Vincent’s Hospital Melbourne, Melbourne, Victoria.

Aim: To examine the relationship between tumour necrosis factor receptor 1 (TNFR1) and estimated glomerular filtration rate (eGFR) decline in Indigenous Australians.

Background: TNFR1 is a marker of chronic inflammation and predicts eGFR decline in people with diabetes. However, its role in Indigenous Australians with and without diabetes is not understood.

Methods: Between 2007 and 2011, 654 Indigenous men and women were recruited from urban, regional and remote Australia across diabetes and/or kidney function strata. Baseline measures included: TNFR1, serum creatinine, urine albumin-to-creatinine ratio (uACR) and HbA_1c. Diabetes was classified as present (HbA_1c ≥ 6.5% or physician-diagnosed diabetes) or absent (HbA_1c <6.5 %). eGFR was determined using the Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equation. Annual CKD-Epi eGFR change (ml/min/1.73m²/year) was calculated as follow-up CKD-Epi eGFR minus baseline CKD-Epi / follow-up time. Follow-up data were available for 550, and 470 had complete data on TNFR1, CKD-Epi eGFR, albuminuria and diabetes. Linear regression estimated eGFR change for quartiles (Q) of increasing TNFR1 adjusting for age, sex, CKD-Epi eGFR and uACR.

Results: Over a median of 3 years, there was no association between increasing TNFR1 and eGFR decline for those without diabetes (n=267). Among those with diabetes (n=203), compared to TNFR1 Q1 (773-1282 pg/ml), the eGFR decline (ml/min/1.73m²/year) was: -0.3 (95% CI -3.1 to 2.5; p=0.842) for Q2 (1283-1624 pg/ml), -1.1 (-3.8 to 1.6; p=0.436) for Q3 (1625-2136 pg/ml) and -5.2 (-8.1 to -2.2; p=0.001) for Q4 (2153-9264 pg/ml). Further adjustment for uACR attenuated the relationship for Q4 but it remained significant (-3.5; -6.4 to -0.5; p=0.022).

Conclusions: Higher baseline TNFR1 levels are associated with progression of kidney disease in Indigenous Australians with diabetes independent of albuminuria.