Nephrology and Dialysis Unit, Meyer Children's Hospital, Florence, Italy.
Department of Biomedical, Experimental and Clinical Sciences "Mario Serio", University of Florence, Florence, Italy.
Pediatr Nephrol. 2022 Dec;37(12):2997-3008. doi: 10.1007/s00467-022-05504-6. Epub 2022 Mar 14.
Chronic kidney disease (CKD) is a global public healthcare concern in the pediatric population, where glomerulopathies represent the second most common cause. Although classification and diagnosis of glomerulopathies still rely mostly on histopathological patterns, patient stratification should complement information supplied by kidney biopsy with clinical data and etiological criteria. Genetic determinants of glomerular injury are particularly relevant in children, with important implications for prognosis and treatment. Targeted therapies addressing the primary cause of the disease are available for a limited number of glomerular diseases. Consequently, in the majority of cases, the treatment of glomerulopathies is actually the treatment of CKD. The efficacy of the currently available strategies is limited, but new prospects evolve. Although the exact mechanisms of action are still under investigation, accumulating data in adults demonstrate the efficacy of sodium-glucose transporter 2 inhibitors (SGLT2i) in slowing the progression of CKD due to diabetic and non-diabetic kidney disease. SGLT2i has proved effective on other comorbidities, such as obesity, glycemic control, and cardiovascular risk that frequently accompany CKD. The use of SGLT2i is not yet approved in children. However, no pathophysiological clues theoretically exclude their application. The hallmark of pediatric CKD is the inevitable imbalance between the metabolic needs of a growing child and the functional capacity of a failing kidney to handle those needs. In this view, developing better strategies to address any modifiable progressor in kidney disease is mandatory, especially considering the long lifespan typical of the pediatric population. By improving the hemodynamic adaptation of the kidney and providing additional beneficial effects on the overall complications of CKD, SGLT2i is a candidate as a potentially innovative drug for the treatment of CKD and glomerular diseases in children.
慢性肾脏病（CKD）是儿科人群中全球公共卫生关注的问题，其中肾小球疾病是第二大常见病因。尽管肾小球疾病的分类和诊断主要依赖于组织病理学模式，但患者分层应将临床数据和病因标准与肾活检提供的信息相结合。肾小球损伤的遗传决定因素在儿童中尤为重要，对预后和治疗有重要影响。针对疾病主要原因的靶向治疗方法可用于少数肾小球疾病。因此，在大多数情况下，肾小球疾病的治疗实际上是 CKD 的治疗。目前可用策略的疗效有限，但新的前景正在出现。尽管确切的作用机制仍在研究中，但越来越多的成人数据表明，钠-葡萄糖共转运蛋白 2 抑制剂（SGLT2i）在减缓糖尿病和非糖尿病肾脏疾病引起的 CKD 进展方面是有效的。SGLT2i 在其他合并症方面也已被证明有效，如肥胖、血糖控制和经常伴随 CKD 的心血管风险。SGLT2i 在儿童中尚未获得批准。然而，从理论上讲，没有病理生理学线索排除其应用。儿童 CKD 的特点是代谢需求不断增长的儿童与功能衰竭的肾脏之间的平衡不可避免，肾脏无法满足这些需求。从这个角度来看，制定更好的策略来解决任何可改变的肾脏疾病进展因素是强制性的，特别是考虑到儿科人群的典型长寿命。通过改善肾脏的血液动力学适应能力并为 CKD 的整体并发症提供额外的有益效果，SGLT2i 是一种有潜力的治疗儿童 CKD 和肾小球疾病的创新药物候选药物。
