LMB2-treated NEP25 transgenic mice on an AIN93G diet exhibited significant increases in plasma Pi, PTH, and FGF23 levels, and marked reductions in bone mineral density, recapitulating CKD-MBD.
Does NKG2D signal blockade improve cardiorenal outcomes in models of podocyte injury, and does sMICA predict CKD progression?
NKG2D signal blockade improves cardiorenal outcomes in podocyte injury models, and sMICA serves as a potential non-invasive biomarker for CKD progression.
Introduction: Chronic kidney disease-mineral and bone disorder (CKD-MBD) represents a systemic complication of chronic kidney disease, contributing significantly to increased morbidity and mortality.Several experimental models of CKD-MBD have been widely used to induce CKD-MBD-like phenotypes.However, in patients with CKD, renal dysfunction is frequently driven by glomerular pathology, and existing models fail to recapitulate the complex pathophysiology of CKD-MBD.Thus, establishing a pathophysiologically relevant animal model is imperative for elucidating the mechanisms underlying CKD-MBD and developing effective therapeutic interventions.In this study, we aimed to establish a mouse model of CKD-MBD that recapitulates human pathophysiology, using Nephrin-hCD25 (NEP25) transgenic (Tg) mice.Methods: At 8 weeks of age, male NEP25 Tg mice were injected with LMB2 at a dose of 0.9 ng/g body weight.Throughout the study, mice had free access to standard mouse chow or modified AIN93G purified diet.All experiments were conducted with n=3-5, and each experiment was repeated at least three times.Results: Under standard diet conditions, LMB2-treated mice developed proteinuria and glomerulosclerosis.While plasma phosphate (Pi) levels remained unchanged compared to non-treated controls, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23) levels were significantly elevated.In contrast, under the AIN93G diet, LMB2treated mice exhibited significant increases in plasma Pi, PTH, and FGF23 levels.Furthermore, under the AIN93G diet, micro-computed tomography analysis revealed marked reductions in bone mineral density and deterioration of trabecular architecture in both cortical and cancellous bone compartments in LMB2-treated mice.In addition, in the vascular smooth muscle of LMB2-treated mice under the AIN93G diet, there was a significant increase in the mRNA expression of RUNX2 and SPP1.Conclusion: These findings indicate that NEP25 transgenic mice represent a valuable and reliable model for analyzing the pathophysiology of CKD-MBD.I have no potential conflict of interest to disclose.I did not use generative AI and AI-assisted technologies in the writing process.
Maruki et al. (Wed,) conducted a other in Chronic kidney disease-mineral and bone disorder (CKD-MBD). LMB2 injection and modified AIN93G purified diet vs. Non-treated controls and standard mouse chow was evaluated on Plasma Pi, PTH, FGF23 levels, and bone mineral density. LMB2-treated NEP25 transgenic mice on an AIN93G diet exhibited significant increases in plasma Pi, PTH, and FGF23 levels, and marked reductions in bone mineral density, recapitulating CKD-MBD.