For nearly fifty years the proximal tubule has been known to reabsorb, process, and either catabolize or transcytose albumin from the glomerular filtrate. Innovative techniques and approaches have provided insights into these processes, and several genetic diseases, nonselective proximal tubule cell (PTC) defects, chronic kidney disease and acute PTC injury lead to significant albuminuria, reaching nephrotic range. Albumin is also known to stimulate PTC injury cascades. Thus, the mechanisms of albumin reabsorption, catabolism and transcytosis are being reexamined utilizing techniques that allow for novel molecular and cellular discoveries. Megalin, a scavenger receptor, cubilin, amnionless, and Dab2 form a nonselective multi-receptor complex that mediates albumin binding, uptake and directs proteins for lysosomal degradation following endocytosis. The neonatal Fc receptor mediates albumin transcytosis by its pH-dependent binding affinity in endosomal compartments. This transcytotic, reclamation, pathway minimizes urinary losses and cellular catabolism of albumin thus prolonging its serum half-life. It also serves as a PTC molecular sorting mechanism to preserve and reclaim physiologic albumin while allowing "altered" albumin that does not bind to FcRn to enter the lysosomal pathway. The clinical importance of PTC albumin metabolism has also increased as albumin is now being used to bind therapeutic agents to extend their half-life and minimize filtration and kidney injury. The purpose of this review is to update and integrate evolving information regarding the reabsorption and processing of albumin by proximal tubule cells including discussing genetic disorders and therapeutic considerations.

中文翻译：

---

近端小管对白蛋白的摄取和加工：生理学、病理学和治疗意义

近五十年来，已知近端小管从肾小球滤液中重吸收、加工和分解代谢或转胞吞白蛋白。创新的技术和方法提供了对这些过程的深入了解，一些遗传疾病、非选择性近端小管细胞 (PTC) 缺陷、慢性肾病和急性 PTC 损伤导致显着的蛋白尿，达到肾病范围。还已知白蛋白可刺激 PTC 损伤级联反应。因此，白蛋白重吸收、分解代谢和转胞吞作用的机制正在利用允许新的分子和细胞发现的技术重新检查。Megalin（一种清道夫受体）、cubilin、amnionless 和 Dab2 形成一种非选择性多受体复合物，介导白蛋白结合、摄取并指导蛋白质在内吞作用后被溶酶体降解。新生儿 Fc 受体通过其在内体区室中的 pH 依赖性结合亲和力介导白蛋白转胞吞作用。这种转胞吞、回收途径可最大限度地减少白蛋白的尿液流失和细胞分解代谢，从而延长其血清半衰期。它还作为一种 PTC 分子分选机制来保存和回收生理白蛋白，同时允许不与 FcRn 结合的“改变的”白蛋白进入溶酶体途径。PTC 白蛋白代谢的临床重要性也有所增加，因为白蛋白现在被用于结合治疗剂以延长其半衰期并最大限度地减少滤过和肾损伤。