Aim/hypothesis: The relationship between peripheral blood leukocyte telomere length (LTL) and kidney dysfunction, especially in people with hypertension, remains unclear. No clinical study has explored the role of oxidative stress and inflammatory markers in the relationship between LTL and kidney dysfunction. Therefore, we examined the relationship between baseline LTL and albuminuria progression and/or rapid renal function decline in Chinese patients with or without hypertension, and investigated whether oxidative stress and inflammation play a mediating role in this relationship. Methods: We conducted a prospective study including 262 patients in a 7-year follow-up period from 2014 to 2021. Data on LTL, inflammation, oxidative markers, renal function, and urine protein levels were assessed. Kidney dysfunction was defined as either albuminuria progression, rapid decline in renal function, or the composite endpoint (albuminuria progression and rapid decline in renal function). Logistic regression and simple mediation models were used for the analysis. Results: In this cohort (mean age, 53.18±11.32 years; follow-up period, 5.97±1.16 years), 43, 22, and 59 patients developed albuminuria progression, rapid renal decline, and the composite endpoint of kidney dysfunction, respectively. Logistic regression analysis showed that each standard deviation decrease in the lower quartile (Q) of baseline LTL was correlated with an increased risk of albuminuria progression (odds ratio [OR]=1.493 [95% confidence interval (CI) 0.985, 2.263], P=0.059; OR=3.307 [95% CI 1.033, 10.586], P=0.044; Q2 vs. Q4); rapid renal function decline (OR=2.402 [95% CI 1.361, 4.239], P=0.002; OR=13.457 [95% CI 1.610, 112.472], P=0.016; Q1 vs. Q4); and the composite endpoint of kidney dysfunction (OR=1.797 [95% CI 1.244, 2.594], P=0.002; OR=4.062 [95% CI 1.426, 11.568], P=0.009; Q1 vs. Q4). Subgroup analyses showed that LTL was inversely associated with albuminuria progression and the composite endpoint of kidney dysfunction in patients with hypertension (OR=5.671 [95% CI 1.203, 26.726], P=0.028; OR=4.223 [95% CI 1.297, 13.753], P=0.017), but not in those without hypertension. The mediating analysis showed that tumor necrosis factor (TNF)-α partly mediated the relationship between LTL and rapid decline in renal function (direct effect: β= –0.6791 [–1.2145, –0.1438]; indirect effect: β= –0.2919 [–0.5190, –0.1177]). Conclusion: Baseline LTL could independently predict kidney dysfunction at follow-up, especially in participants with hypertension. TNF-α partially mediated the negative association between LTL and kidney dysfunction.

Background Experimental and epidemiological studies have indicated an association between diabetes exposure and an increased risk of liver cancer due to nonalcoholic steatohepatitis (NASH). However, to date, no systematic study has specifically investigated the burden of NASH-related liver cancer due to exposure to high fasting plasma glucose (HFPG) levels worldwide. Methods The number and rate of deaths and disability-adjusted life years (DALYs) from HFPG-induced NASH-related liver cancer were estimated based on the results of the 2019 Global Burden of Disease Study. The estimated annual percentage changes (EAPCs) for age-standardized death or DALYs rates were calculated using a generalized linear model with a Gaussian distribution to quantify the temporal trends in the global burden of NASH-related liver cancer attributable to HFPG. The strength and direction of the association between the sociodemographic index (SDI) and death or DALY rate were measured using Spearman’s rank-order correlation. Results Globally, approximately 7.59% of all DALY and 8.76% of all mortalities of NASH-related liver cancer in 2019 were due to HFPG. The age-standardized death and DALY rates of NASH-related liver cancer attributable to HFPG increased from 1990 to 2019. The corresponding EAPCs were 0.69 (95% UI 0.48–0.89), and 0.30 (95% UI 0.05–0.56), respectively. This increasing pattern was most obvious in the high- and low-SDI regions. The age-standardized mortality and DALYs rate of NASH-related liver cancer attributable to HFPG varies considerably worldwide, with the middle SDI region having the highest death and DALY rates in 2019 (DALY 0.96 [95% UI 0.23–2.18]; death 0.05 [95% UI 0.01–0.11]). Conclusion The burden of NASH-related liver cancer attributable to HFPG has increased over the past three decades, particularly in regions with high and low SDI.