Predicting Kidney Function Decline in Diabetes Patients

Diabetes, or type 2 diabetes in particular, is the leading cause of end-stage kidney disease and is highly prevalent in Asian populations. To advance timely clinical interventions, researchers around the world have devoted significant effort to discovering biomarkers that allow the identification of high risk individuals for early clinical intervention.

In a major study led by the endocrinology and diabetes team of CUHK’s Faculty of Medicine and joined by the University of Sydney and Western Sydney University, researchers have discovered that a unique DNA property can predict the decline of kidney function in diabetes patients over a 14-year follow-up period. The study was the largest and most detailed and included the longest follow-up period of its kind. The results have been published in the medical journal Diabetologia.

Telomere characteristics indicate the culprit of end-stage kidney disease

The telomere is the tail-end of DNA strands. It contains a repeat code sequence that shortens with each cell division. Loss of these repeat sequences is associated with the reduction of telomere length, which indicates cellular aging. A large-scale cohort study published in 2020, conducted by the endocrinology and diabetes team at the Faculty of Medicine, proved that reduced DNA telomere length is a useful biomarker linked to a higher risk of developing cardiovascular disease in patients with type 2 diabetes.

Starting from mid-age and with a baseline value of around 100 mL/min, the estimated glomerular filtration rate (eGFR), an indicator of kidney function, may decline by 1% every year in an average person due to aging. This rate of decline is doubled in an average patient with diabetes. A person is said to have end-stage kidney disease if the eGFR is lower than 15 mL/min, when dialysis may be needed.

In this study, researchers discovered that for each unit decrease in the rLTL (relative leukocyte telomere length), the risk of the patients developing end-stage kidney disease was increased by 20%. This association remained significant after adjusting for other factors such as age, sex and kidney function at baseline. Furthermore, a smaller rLTL at baseline was associated with a rapid decline of the eGFR of more than 4% every year, i.e., a loss of 40% of kidney function in 10 years. 

‘Silent killer’ be not proud

Prof. Ronald Ma, head for academic affairs of the Division of Endocrinology and Diabetes at the Department of Medicine and Therapeutics, said, ‘On top of traditional risk factors, our new findings supported the added value of DNA telomere length as a biomarker in identifying individuals with type 2 diabetes at high risk of end-stage kidney disease and rapid deterioration of kidney function for individualized and intensified treatment. Early intervention has been shown to delay the progression of kidney disease and prevent end-stage kidney disease in patients with diabetes.’

Prof. Juliana Chan, chair professor of Medicine and Therapeutics and founding director of the Hong Kong Institute of Diabetes and Obesity at CUHK, added, ‘The high-quality database, biobank and research methods provided our study with robust statistical power to demonstrate the biological significance of DNA telomere length. Given the silent nature of diabetes, discovering biomarkers on top of conventional risk factors will increase the precision of risk prediction for personalized management which will assist in preventing hospitalizations, disabilities and premature death.’