Abstract
BackgroundANGPTL8, an important regulator of lipid metabolism, was recently proven to have additional intracellular and receptor-mediated functions. This study aimed to investigate circulating levels of ANGPTL8 and its potential association with the risk of kidney function decline in a cohort study.MethodsWe analysed 2,311 participants aged 40 years old and older from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Kidney function decline was defined as an estimated glomerular filtration rate (eGFR) less than 60 mL per minute per 1.73 m2 of body surface area, a decrease in eGFR of ≥ 30% from baseline, chronic kidney disease (CKD)-related hospitalization or death, or end-stage renal disease. The association between baseline ANGPTL8 levels and kidney function decline was assessed using multivariable-adjusted Cox proportional hazards models, and inverse possibility of treatment weight (IPTW) was utilized to prevent overfitting.ResultsThere were 136 (5.9%) cases of kidney function decline over a median of 3.8 years of follow-up. We found that serum ANGPTL8 levels at baseline were elevated in individuals with kidney function decline compared to those without kidney function decline during follow-up (718.42 ± 378.17 vs. 522.04 ± 283.07 pg/mL, p < 0.001). Compared with the first quartile, multivariable-adjusted hazard ratio (95% confidence intervals [CIs]) for kidney function decline was 2.59 (95% CI, 1.41–4.77) for the fourth ANGPTL8 quartile. Furthermore, compared with patients in the first ANGPTL8 quartile, those in the fourth ANGPTL8 quartile were more likely to report a higher stage of CKD (relative risk: 1.33; 95% CI, 1.01–1.74). The conclusions of the regression analyses were not altered in the IPTW models. Multivariable-adjusted restricted cubic spline analyses suggested a linear relationship of ANGPTL8 with kidney function decline (p for nonlinear trend = 0.66, p for linear trend < 0.001).ConclusionsParticipants with higher circulating ANGPTL8 levels were at increased risk for kidney function decline, highlighting the importance of future studies addressing the pathophysiological role of ANGPTL8 in CKD.
Highlights
Angiopoietin-like protein 8 (ANGPTL8), an important regulator of lipid metabolism, was recently proven to have additional intracellular and receptor-mediated functions
Elevated levels of plasma ANGPTL8 are associated with metabolic syndrome [45, 46], type 2 diabetes mellitus (T2DM) [4,5,6], non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) [7, 8], atherosclerosis [9, 10] and hypertension [11]
We found that serum ANGPTL8 levels at baseline were elevated in individuals with kidney function decline compared with those without kidney function decline during the follow-up (718.42 ± 378.17 vs. 522.04 ± 283.07 pg/mL, p < 0.001, Fig. 1)
Summary
ANGPTL8, an important regulator of lipid metabolism, was recently proven to have additional intracellular and receptor-mediated functions. Elevated levels of plasma ANGPTL8 are associated with metabolic syndrome [45, 46], type 2 diabetes mellitus (T2DM) [4,5,6], non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) [7, 8], atherosclerosis [9, 10] and hypertension [11]. Hypertension and atherosclerosis are important risk factors for future estimated glomerular filtration rate (eGFR) decline and the development of kidney disease [12, 13]. Chronic kidney disease (CKD) is a devastating condition that is reaching epidemic levels owing to the increasing prevalence of diabetes mellitus, hypertension and obesity, as well as the ageing of the population [14]. According to WHO global health estimates, CKD accounted for 12.2 deaths per 100,000 people, ranking fourteenth in the list of leading causes of death [15]
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