Shortened telomere length associated with ESKD and rapid eGFR decline in T2DM patients

Shortened relative leucocyte telomere length (rLTL) is associated with development of end-stage kidney disease (ESKD) and rapid decline of kidney function in Chinese patients with type 2 diabetes mellitus (T2DM), according to a 14-year study involving more than 4,000 individuals.

Researchers from the Chinese University of Hong Kong (CUHK) evaluated 4,085 Chinese patients with T2DM (mean age, 54.3 years; male, 45.4 percent) enrolled into the Hong Kong Diabetes Register between 1995 and 2007 who had baseline DNA and clinical follow-up data available. rLTL was measured using quantitative polymerase chain reaction assay. [Diabetologia 2021;doi:10.1007/s00125-021-05613-1]

Over a follow-up period of 14.1 years, 564 patients developed incident ESKD. These patients had significantly shorter rLTL at baseline compared with the 3,521 nonprogressors who did not develop ESKD during the follow-up period (∆∆C_t, 4.2 vs 4.7; p<0.001).

Each ∆∆C_t decrease in rLTL was found to be associated with a significantly increased risk of incident ESKD (hazard ratio [HR], 1.21; 95 percent confidence interval [CI], 1.13 to 1.30; p<0.001) on Cox regression analysis. “The association remained significant after adjusting for baseline sex, age, HbA_1c, lipids, renal function, and other risk factors,” the investigators reported.

Shorter rLTL at baseline was also independently associated with rapid decline in estimated glomerular filtration rate (eGFR) of >4 percent per year (unadjusted odds ratio [OR], 1.22; 95 percent CI, 1.15 to 1.30; p<0.001) (adjusted OR, 1.09; 95 percent CI, 1.01 to 1.17; p=0.024).

“Each ∆∆C_t decrease in rLTL was significantly associated with a 0.4 percent decline per year in eGFR,” the investigators noted.

According to the investigators, the current study is the largest prospective study to comprehensively evaluate the relationship between baseline rLTL and progression to chronic kidney disease and ESKD in patients with T2DM. “The follow-up period of 14 years is also the longest among similar studies,” they noted.

“Our new findings support the added value of telomere length, in addition to traditional risk factors, as a biomarker in identifying individuals with T2DM at high risk of ESKD and rapid deterioration of kidney function for individualized and intensified treatment,” said investigator Professor Ronald Ma of the Department of Medicine and Therapeutics, CUHK. “Early intervention has been shown to delay kidney disease progression and prevent ESKD in patients with T2DM.”