PATHOPHYSIOLOGY OF AIDS GLOMERULOPATHY

慢性肾小球损伤已被描述为 艾滋病。为了确定其发病率，我们将对500人的尿液进行筛查 用灵敏的免疫化学技术检测艾滋病患者 亚临床和显性蛋白尿升高。二十五岁 有大量蛋白尿的艾滋病患者随后将接受 生理、形态测量和细胞生物学技术 阐明肾小球损伤的发病机制和程度。 因为特发性肾病综合征(INS)与 伴有类似的肾小球上皮细胞改变或 无局灶性和节段性肾小球硬化的25例患者 移民局将以相同的方式进行检查。分数间隙 分级大小的无电荷右旋糖苷和阴离子右旋糖苷 硫酸盐将被用来定义伤害的大小- 以及肾小球滤过器中的电荷选择屏障。 形态计量测定，包括肾小球滤过 表面积和上皮滤过缝隙密度将 与GFR和超滤量(KF)降低相关。 单抗将被用来确定各种不同水平的 淋巴细胞培养上清液中的细胞因子及其相互关系 这样的水平与肾小球损伤的程度有关。重组 干扰素和其他选定的细胞因子将被注入到 慕尼黑Wistar大鼠与显微穿刺术和形态计量学 用于确定前述人类是否 肾小球损伤是可以复制的。大鼠肾脏也将 用单抗检测以确定细胞因子- MHC等基因在肾细胞上的表达变化 抗原，这些变化将在人类活检中寻找 材料。为了确定损伤的过程，差异溶质 清除和细胞因子水平将在前后重复。 试图用环孢素抑制后者，然后在 在5年内有规律的间隔。过滤数据将是 用一个将肾小球毛细血管壁视为 一种多孔膜，有效浓度为 固定负电荷。膜参数来自于 将使用系列检查来监测受伤情况并确定 要么是不可挽回的进步的减刑。通过获得更多 我们希望定量描述与艾滋病相关的肾小球病变 以确定它代表的是非特定的还是独特的损伤 肾小球上皮细胞，可能是由细胞因子介导的。 加强我们对其发病机制的认识和 病理生理学可能导致有效的发展 心理治疗。

A chronic glomerular injury has been described in patients with AIDS. To determine its incidence we will screen urine of 500 AIDS patients with a sensitive immunochemical technique for subclinical as well as overt elevation of albuminuria. Twenty-five AIDS patients with heavy proteinuria will then be examined with physiologic, morphometric and cell biologic techniques to elucidate the pathogenesis and extent of the glomerular injury. Because the idiopathic nephrotic syndrome (INS) is associated with a similar alteration of glomerular epithelial cells with or without focal and segmental glomerulosclerosis, 25 patients with INS will be examined in identical fashion. Fractional clearances of uncharged dextrans of graded size and of anionic dextran sulfate will be used to define the magnitude of injury to the size- and charge-selective barriers in the glomerular filter. Morphometric determinations, including glomerular filtration surface area and epithelial filtration slit density will be correlated with lowered GFR and ultrafiltration capacity (Kf). Monoclonal antibodies will be used to determine levels of various cytokines in supernates of cultured lymphocytes, so as to relate such levels to the magnitude of glomerular injury. Recombinant interferons and other selected cytokines will be infused into the Munich Wistar rat and micropuncture and morphometric techniques used to determine whether the foregoing human glomerular injuries can be replicated. Rat kidney will also be examined with monoclonal antibodies to identify cytokine- mediated alteration of expression on renal cells of MHC and other antigens, and these alterations will be sought for in human biopsy material. To define the course of the injury, differential solute clearances and cytokine levels will be repeated before and after an attempt to inhibit the latter with cyclosporine, and then at regular intervals over a 5 year period. The filtration data will be analyzed with a model that treats the glomerular capillary wall as a heteroporous membrane with an effective concentration of fixed negative charges. The membrane parameters derived from serial examinations will be used to monitor the injury and define either remission of irrevocable progression. By obtaining a more guantitative description of AIDS-related glomerulopathy, we hope to determine whether it represents a non-specific or unique injury to glomerular epithelial cells, perhaps mediated by cytokines. Enhancement of our understanding of its pathogenesis and pathophysiology could lead to the development of efficacious therapy.