PDF(Pubmed)
Abstract：
Chronic kidney disease (CKD) represents a major public health burden with increasing prevalence. Current therapies focus on delaying CKD progression, underscoring the need for innovative treatments. This necessitates animal models that accurately reflect human kidney pathologies, particularly for studying potential reversibility and regenerative mechanisms, which are often hindered by the progressive and irreversible nature of most CKD models. In this study, CKD was induced in mice using a 0.2% adenine-enriched diet for 4 weeks, followed by a recovery period of 1 or 2 weeks. The aim was to characterize the impact of adenine feeding on kidney function and injury as well as water and salt homeostasis throughout disease progression and recovery. The adenine diet induced CKD is characterized by impaired renal function, tubular injury, inflammation, and fibrosis. A significant decrease in urine osmolality, coupled with diminished aquaporin-2 (AQP2) expression and membrane targeting, was observed after adenine treatment. Intriguingly, these parameters exhibited a substantial increase after a two-week recovery period. Despite these functional improvements, only partial reversal of inflammation, tubular damage, and fibrosis were observed after the recovery period, indicating that the inclusion of the molecular and structural parameters is needed for a more complete monitoring of kidney status.
摘要：
慢性肾脏病（CKD）是主要的公共卫生负担，患病率不断增加。目前的治疗重点是延缓CKD进展，强调创新治疗的必要性。这就需要准确反映人类肾脏病理的动物模型，特别是研究潜在的可逆性和再生机制，这通常受到大多数CKD模型的进行性和不可逆性质的阻碍。在这项研究中,CKD在小鼠中使用0.2％腺嘌呤丰富的饮食诱导4周，然后是1或2周的恢复期。目的是表征腺嘌呤喂养在整个疾病进展和恢复过程中对肾功能和损伤以及水和盐稳态的影响。腺嘌呤饮食诱导的CKD的特点是肾功能受损，肾小管损伤,炎症,和纤维化。尿渗透压显著下降，伴随着水通道蛋白2（AQP2）表达和膜靶向减少，腺嘌呤处理后观察到。有趣的是，经过两周的恢复期，这些参数显着增加。尽管有这些功能改进，只是炎症的部分逆转，管道损坏,在恢复期后观察到纤维化，这表明需要包含分子和结构参数才能更完整地监测肾脏状态。
