Obesity-related glomerulopathy and podocyte injury: a mini review.
Obesity-related glomerulopathy and podocyte injury: a mini review.
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DOI：
10.2741/e441
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发表时间：
2012-01-01
期刊：
影响因子：
--
通讯作者：
Carpi A
中科院分区：
文献类型：
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作者：
Camici M;Galetta F;Abraham N;Carpi A
肥胖相关肾小球病变(ORG)在形态学上定义为局灶性节段性肾小球硬化和肾小球肿大。足细胞肥大和密度降低与蛋白尿有关，在部分患者中，蛋白尿处于肾病范围，并演变为肾功能衰竭。本文综述了足细胞损伤或功能障碍的发病机制，并列出了基于已报道的发病机制的药物靶向的新的可能的抗蛋白尿策略。其发病机制包括：肾素血管紧张素系统、纤溶酶原激活抑制物-1、脂代谢、脂联素、巨噬细胞和促炎细胞因子、氧化应激。建议的抗蛋白尿策略包括：AT2受体阻滞剂；脂肪因子补体C19肿瘤坏死因子相关蛋白-1阻滞剂；选择性PAI-1抑制剂；法尼类x受体激活；增加循环脂联素；选择性抗炎药物；更有效的抗氧化剂(血红素氧合酶、NOX4抑制剂)。然而，由于ORG是一种罕见的疾病，对肥胖蛋白尿症患者进行长期药物治疗的必要性应该仔细评估，并且仅限于进行性肾功能丧失的患者。
Obesity-related glomerulopathy (ORG) is morphologically defined as focal segmental glomerulosclerosis and glomerulomegaly. Podocyte hypertrophy and reduced density are related to proteinuria which in a portion of patients is in the nephrotic range and evolvs towards renal failure. This article reviews the pathogenetic mechanisms of podocyte injury or dysfunction and lists new possible antiproteinuric strategies based on pharmaceutical targeting of the reported pathogenetic mechanisms. The pathogenetic mechnisms discussed include: renin angiotensin system, plasminogen activation inhibitor-1 (PAI-1), lipid metabolism, adiponectin, macrophages and proinflammatory cytokines, oxidative stress. The proposed antiproteinuric strategies include: AT2 receptor blockers; adipokine complement C19 TNF-related protein-1 blocker; selective PAI-1 inhibitor; farnesoid x receptor activation; increase of circulating adiponectin; selective antiinflammatory drugs; more potent antioxidants (Heme oxigenase, NOX4 inhibitors). However, because ORG is a rare disease, the need for a long term pharmaceutical approach in obese proteinuric patients should be carefully evaluated and limited to the cases with progressive loss of renal function.