Effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on podocytes, inflammation, and oxidative stress in patients with diabetic nephropathy (DN)

Abstract

Objectives: To investigate the effects of a glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide on podocytes, inflammation, and oxidative stress in patients with diabetic nephropathy (DN).

Methods: Eighty-four DN patients treated by the department of endocrinology of the Affiliated Hospital of Hebei University during December 2017 and March 2019 were randomly assigned to a control group and a treatment group (n=42, respectively), with the control group prescribed with conventional DN medications and the treatment group receiving liraglutide treatment in addition to the conventional therapy. The course of treatment lasted for 12 weeks. hemoglobin A1c (HbA1C), body mass index (BMI), total cholesterol (TC), triglyceride (TG), urinary albumin excretion rate (UAER), urine podocalyxin (PCX), urine nephrin, as well as inflammation and oxidative stress markers such as tumor necrosis factor α (TNF-α), monocyte chemotactic protein-1 (MCP-1), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) were measured pre- and post-treatment for intergroup comparison.

Results: After 12 weeks of treatment, HbA1C, BMI, TC, and TG in both groups were reduced in comparison with the pre-treatment levels, with the levels in the treatment group lower than in the control group (p<0.05); reduced levels of UAER, PCX, and nephrin were detected in the two groups, with the treatment group exhibiting a significant reduction in these markers compared with the control group (p<0.05); the 12-week treatment led to decreases in the TNF-α, MCP-1, and MDA levels in both groups, with the decline in the treatment group exceeding that in the control group, whereas both groups had an increased level of GSH-Px, with the level in the treatment group higher than that in the control group, and the differences were statistically significant (p<0.05, respectively).

Conclusions: Liraglutide protects the kidneys and improves DN by inhibiting inflammation and oxidative stress, reducing urinary albumin excretion and podocyte damage and supporting renal function in addition to its hypoglycemic properties.

Keywords: Diabetic nephropathy (DN); Liraglutide; Nephrin; Podocalyxin (PCX).