Division of Nephrology and Hypertension, UCI Medical Centre, 101 The City Drive, Orange, California 92868, USA.
Nat Rev Nephrol. 2016 Jan;12(1):37-47. doi: 10.1038/nrneph.2015.180. Epub 2015 Nov 16.
Normal HDL activity confers cardiovascular and overall protection by mediating reverse cholesterol transport and through its potent anti-inflammatory, antioxidant, and antithrombotic functions. Serum lipid profile, as well as various aspects of HDL metabolism, structure, and function can be profoundly altered in patients with nephrotic range proteinuria or chronic kidney disease (CKD). These abnormalities can, in turn, contribute to the progression of cardiovascular complications and various other comorbidities, such as foam cell formation, atherosclerosis, and/or glomerulosclerosis, in affected patients. The presence and severity of proteinuria and renal insufficiency, as well as dietary and drug regimens, pre-existing genetic disorders of lipid metabolism, and renal replacement therapies (including haemodialysis, peritoneal dialysis, and renal transplantation) determine the natural history of lipid disorders in patients with kidney disease. Despite the adverse effects associated with dysregulated reverse cholesterol transport and advances in our understanding of the underlying mechanisms, safe and effective therapeutic interventions are currently lacking. This Review provides an overview of HDL metabolism under normal conditions, and discusses the features, mechanisms, and consequences of HDL abnormalities in patients with nephrotic syndrome or advanced CKD.
正常的高密度脂蛋白(HDL)活性通过介导胆固醇逆向转运,并通过其强大的抗炎、抗氧化和抗血栓功能,为心血管系统和整体提供保护。肾病范围蛋白尿或慢性肾脏病(CKD)患者的血清脂质谱以及 HDL 代谢、结构和功能的各个方面都可能发生深刻改变。这些异常反过来又可能导致心血管并发症和各种其他合并症的进展,如泡沫细胞形成、动脉粥样硬化和/或肾小球硬化。蛋白尿和肾功能不全的存在和严重程度、饮食和药物方案、预先存在的脂质代谢遗传疾病以及肾脏替代疗法(包括血液透析、腹膜透析和肾移植)决定了肾病患者脂质紊乱的自然病程。尽管与胆固醇逆向转运失调相关的不良影响以及对潜在机制的理解有所进展,但目前仍缺乏安全有效的治疗干预措施。这篇综述概述了正常条件下的 HDL 代谢,并讨论了肾病综合征或晚期 CKD 患者中 HDL 异常的特征、机制和后果。