Qiao Jin1, Eric Sh Lau2, Andrea Oy Luk3, Risa Ozaki4, Elaine Yk Chow5, Tammy So6, Theresa Yeung7, Kit-Man Loo8, Cadmon Kp Lim9, Alice Ps Kong10, Wing Yee So11, Alicia J Jenkins12, Juliana Cn Chan13, Ronald Cw Ma14. 1. Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China. Electronic address: jinqiao@link.cuhk.edu.hk. 2. Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China. Electronic address: ericlau@link.cuhk.edu.hk. 3. Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China; Chinese University of Hong Kong-Shanghai Jiao Tong University Joint Research Centre in Diabetes Genomics and Precision Medicine, Chinese University of Hong Kong, Hong Kong, China. Electronic address: andrealuk@cuhk.edu.hk. 4. Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China. Electronic address: risaozaki@cuhk.edu.hk. 5. Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China. Electronic address: e.chow@cuhk.edu.hk. 6. Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China. Electronic address: sty020@ha.org.hk. 7. Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China. Electronic address: yhm538@ha.org.hk. 8. Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China. Electronic address: kitmanloo@yahoo.com.hk. 9. Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China. Electronic address: cadmonlim@cuhk.edu.hk. 10. Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China. Electronic address: alicekong@cuhk.edu.hk. 11. Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China. Electronic address: wingyeeso@cuhk.edu.hk. 12. Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; NHMRC Clinical Trial Centre, Faculty of Medicine and Health, University of Sydney, Australia. Electronic address: alicia.jenkins@ctc.usyd.edu.au. 13. Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China; Chinese University of Hong Kong-Shanghai Jiao Tong University Joint Research Centre in Diabetes Genomics and Precision Medicine, Chinese University of Hong Kong, Hong Kong, China. Electronic address: jchan@cuhk.edu.hk. 14. Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China; Chinese University of Hong Kong-Shanghai Jiao Tong University Joint Research Centre in Diabetes Genomics and Precision Medicine, Chinese University of Hong Kong, Hong Kong, China. Electronic address: rcwma@cuhk.edu.hk.
Abstract
BACKGROUND AND AIMS: Skin autofluorescence (SAF) can non-invasively assess the accumulation of tissue AGEs. We investigated the association between SAF and kidney dysfunction in participants with T2D. METHODS: Of 4030 participants consecutively measured SAF at baseline, 3725 participants free of end-stage kidney disease (ESKD) were included in the analyses. The association of SAF with incident ESKD or ≥30% reduction in estimated glomerular filtration rate (eGFR) was examined with Cox regression, linear mixed-effects model for the association with annual eGFR decline, and mediation analyses for the mediating roles of renal markers. RESULTS: During a median (IQR) 1.8 (1.1-3.1) years of follow-up, 411 participants developed the outcome. SAF was associated with progression of kidney disease (hazard ratio 1.15 per SD, 95% confidence interval [CI] [1.04, 1.28]) and annual decline in eGFR (β -0.39 per SD, 95% CI [-0.71, -0.07]) after adjustment for risk factors, including baseline eGFR and urinary albumin-creatinine ratio (UACR). Decreased eGFR (12.9%) and increased UACR (25.8%) accounted for 38.7% of the effect of SAF on renal outcome. CONCLUSIONS: SAF is independently associated with progression of kidney disease. More than half of its effect is independent of renal markers. SAF is of potential to be a prognostic marker for kidney dysfunction.
BACKGROUND AND AIMS: Skin autofluorescence (SAF) can non-invasively assess the accumulation of tissue AGEs. We investigated the association between SAF and kidney dysfunction in participants with T2D. METHODS: Of 4030 participants consecutively measured SAF at baseline, 3725 participants free of end-stage kidney disease (ESKD) were included in the analyses. The association of SAF with incident ESKD or ≥30% reduction in estimated glomerular filtration rate (eGFR) was examined with Cox regression, linear mixed-effects model for the association with annual eGFR decline, and mediation analyses for the mediating roles of renal markers. RESULTS: During a median (IQR) 1.8 (1.1-3.1) years of follow-up, 411 participants developed the outcome. SAF was associated with progression of kidney disease (hazard ratio 1.15 per SD, 95% confidence interval [CI] [1.04, 1.28]) and annual decline in eGFR (β -0.39 per SD, 95% CI [-0.71, -0.07]) after adjustment for risk factors, including baseline eGFR and urinary albumin-creatinine ratio (UACR). Decreased eGFR (12.9%) and increased UACR (25.8%) accounted for 38.7% of the effect of SAF on renal outcome. CONCLUSIONS: SAF is independently associated with progression of kidney disease. More than half of its effect is independent of renal markers. SAF is of potential to be a prognostic marker for kidney dysfunction.