Lipid-lowering therapy in membranous nephropathy.

    Membranous nephropathy (MN) is a very common cause of nephrotic syndrome in adults, and lipid abnormalities are, therefore, frequently found in these subjects. Although efficient lipid-lowering therapy is available, almost nothing is known about the contribution of hyperlipidemia in the pathogenesis of progressive renal failure in MN. Studies in an experimental animal model of human MN, Heymann nephritis, have shown that lipids play an essential role in the pathogenesis of proteinuria. Local production of reactive oxygen species after subepithelial immune complex deposition leads to the formation of lipid peroxidation (LPO) adducts, which ultimately alter the composition of the glomerular basement membrane. As the magnitude of urinary protein excretion is associated with the long-term prognosis, a normalization of glomerular permselective properties has been used as a surrogate parameter for the beneficial effects of treatment. Probucol, a drug with LPO inhibitor potential, is able to reduce urinary protein excretion in rats with passive Heymann nephritis. In humans with MN, preliminary data also support this observation. It remains to be determined, however, if this intervention, which does not interfere with immune complex formation, will reduce the number of the patients reaching end-stage renal failure because of MN. In conclusion, lipids may contribute to glomerular injury in MN, as LPO might be an especially important factor, opening the possibility for new therapeutic interventions, thereby avoiding the side-effects of the currently used treatment regimen.

    膜性肾病多见于肾病综合症和脂质异常成年患者，是肾病综合症和脂质异常的常见病因。尽管目前不乏有效的降脂治疗，但是关于高脂血症在膜性肾病肾衰竭进程中的致病机理还不得而知。对人膜性肾病和Heymann肾炎的动物模型的研究表明，脂质在蛋白尿症的发病机理中发挥重要的作用。上皮下免疫复合物沉积后生成的活性氧簇局部产物导致脂质过氧化物生成的内收，并最终使肾小球基底膜的组成发生改变。由于尿蛋白数量与长期预后有关，就将肾小球的渗透选择性恢复正常作为治疗发挥疗效的指标。普罗布考具有抑制LPO的作用，能够降低passive Heymann nephritis大鼠的尿蛋白含量。在膜性肾病患者中的初步研究数据同样支持该研究结果。然而此项干预是否能够降低膜性肾病导致的达到肾衰竭晚期的病人数量还有待证实。总之，脂质可能参与膜性肾病的肾小球损伤，LPO可能是其中的一个特殊重要因子。开发新的治疗干预方式能够避免目前治疗中的副作用的发生。