Miqat Abdulkadhim Jawad
1* 
, Hasan Haider Alsalamy
1 , Mudhafar Sami Khazal
2 1 Department of Biochemistry, College of Medicine, University of Karbala, Karbala, Iraq
2 Department of Medical Physiology, College of Medicine, University of Karbala, Karbala, Iraq
Abstract
Obesity is a major contributor to the development and progression of chronic kidney disease (CKD) and represents a global health problem. The pathophysiology of obesity-related kidney injury is fundamentally based on a vicious cycle of oxidative stress and the dysregulation of key adipokines, mainly adiponectin. Chronic obesity leads to a greater production of reactive oxygen species (ROS) that damage the glomerular filtration barrier, leading to podocyte loss and albuminuria. Paradoxically, with fat accumulation, the level of the renoprotective hormone adiponectin decreases, depriving the kidney of crucial anti-inflammatory and antioxidant defenses. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have recently become a breakthrough class of drugs with significant renal benefits beyond weight loss. While their indirect metabolic and anti-inflammatory systemic actions are well-established, emerging data from animal and in vitro models suggest potential target-specific pathways on the renal microenvironment, potentially modulating oxidative damage and restoring adiponectin signaling. Accumulating clinical trial data, including secondary analyses from cohorts investigating non-diabetic populations with obesity, demonstrate that these therapies effectively mitigate albuminuria and slow progressive glomerular strain, independently of classic metabolic dynamics. The present review gathers available literature to understand the molecular actions of GLP-1 RAs on the adiponectin–oxidative stress axis, emphasizing the relevance of these pathways in maintaining podocyte integrity and preventing tubulointerstitial fibrosis. This integrative paradigm positions GLP-1 RAs as a key element in managing obesity-related nephropathy, providing a promising option to lessen the clinical and economic burden of renal failure.
Implication for health policy/practice/research/medical education:
The increasing prevalence of obesity-related kidney disease requires a transition from traditional weight-management strategies to targeted organ-protective therapies. This review underlines the important mechanisms of renal protection by glucagon-like peptide-1 receptor agonists (GLP-1 RAs) by the regulation of the adiponectin-oxidative stress axis. GLP-1 RAs exert a dual-action pathway that maintains podocyte function and slows the progression of chronic kidney disease (CKD) by increasing systemic adiponectin and reducing renal oxidative damage. These insights support the early integration of GLP-1 RAs not only as metabolic regulators but also as essential renoprotective agents that can significantly reduce the long-term burden of renal failure and the subsequent need for renal replacement therapy in the obese population with respect to clinical practice and health policy.
Please cite this paper as: Jawad MA, Alsalamy HH, Khazal MS. Impact of GLP-1 receptor agonist therapy on oxidative stress and adiponectin axis: Implications for renal health in adults with obesity. J Nephropharmacol. 2027;16(1):e12887. DOI: 10.34172/npj.12887.