Role of liraglutide and probiotics in managing ‎chronic kidney disease induced ‎‎in rats

Abstract

Background and objective: Chronic kidney disease (CKD) is an incurable disorder involving widespread inflammation and gut dysbiosis, which facilitates disease progression via the gut-kidney axis. Current therapies can only decelerate the course of the disease and may cause adverse effects. This study aimed to investigate the potential reno-protective effects and modulation of gut integrity by the glucagon-like peptide-1 receptor agonist liraglutide and probiotics, separately and in combination, in a rat model of CKD. Methods: CKD was induced in male rats (n=40) by intraperitoneal injection of high-dose folic acid. Animals were randomly distributed into five equal groups: control negative, control positive, liraglutide group, probiotics group, and combination group. Serum levels of creatinine, blood urea nitrogen, cystatin-C and C-reactive protein were measured. Histological assessment of the kidney and colon was also performed. Results: High-dosefolic acid significantly increased markers of impaired kidney function and systemic inflammation. Treatment with liraglutide, probiotics, and their combination significantly reduced these markers’ levels. Histopathological analysis revealed improved renal and gastrointestinal integrity in all treatment groups, with the combination treatment group demonstrating the most substantial recovery. Conclusion: The combination therapy effectively protected renal and intestinal tissues from the damage of high-dose folic acid. The current findings suggest potential additive or synergistic benefits of combining liraglutide with probiotics and support its use as a novel strategy for managing CKD via gut and renal regulation.