PATHOBIOLOGY OF CAST NEPHROPATHY FROM HUMAN BENCE-JONES PROTEINS
PATHOBIOLOGY OF CAST NEPHROPATHY FROM HUMAN BENCE-JONES PROTEINS
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DOI：
10.1172/jci115629
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发表时间：
1992-02-01
影响因子：
15.9
通讯作者：
BOOKER, BB
中科院分区：
文献类型：
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作者：
SANDERS, PW;BOOKER, BB
肾衰竭是多发性骨髓瘤的常见症状，通常是由于管型肾病或“骨髓瘤肾”引起的。 为了了解这种病变，我们从志愿者的尿液中纯化了四种人类 Bence Jones 蛋白 (BJP)，这些志愿者要么没有肾功能障碍 (BJP1) 的证据，要么因管型肾病导致肾衰竭（BJP2、BJP3、BJP4）。 当直接注入体内大鼠肾单位时，BJP2、BJP3和BJP4通过在远端肾单位沉淀而产生管腔内阻塞；在亨利环尖端之前从未鉴定出蛋白管型。 阻塞与灌注液中 BJP 的浓度有关。 向灌注液中添加呋塞米以浓度依赖性方式增加阻塞。 用秋水仙碱预处理大鼠完全防止了灌注肾单位的梗阻和管型形成； β-lumicolchicine 不能预防梗阻。 从 β-lumicolchicine 处理和未处理的大鼠中纯化的 Tamm-Horsfall 糖蛋白在体外与 BJP3 共聚。 来自秋水仙碱处理的大鼠的Tamm-Horsfall糖蛋白不含唾液酸，并且在体外不与BJP3聚集。因此，管型形成的人BJP与Tamm-Horsfall糖蛋白共聚集并阻塞大鼠远端肾单位。 减少细胞外液量或添加速尿会加重肾内梗阻。 最后，通过减少分泌和改变 Tamm-Horsfall 糖蛋白的碳水化合物部分，秋水仙碱可防止大鼠肾单位管型形成和阻塞。
Renal failure is a common accompaniment of multiple myeloma and is usually due to cast nephropathy, or "myeloma kidney." To understand this lesion, four human Bence Jones proteins (BJP) were purified from the urine of volunteers who had either no evidence of renal dysfunction (BJP1) or renal failure from cast nephropathy (BJP2, BJP3, BJP4). When infused directly into the rat nephron in vivo, BJP2, BJP3, and BJP4 produced intraluminal obstruction by precipitating in the distal nephron; protein casts were never identified before the tip of the loop of Henle. Obstruction was related to the concentration of BJP in the perfusate. Addition of furosemide to the perfusate augmented obstruction in a concentration-dependent fashion. Pre-treatment of rats with colchicine completely prevented obstruction and cast formation of perfused nephrons; beta-lumicolchicine did not prevent obstruction. Tamm-Horsfall glycoprotein purified from beta-lumicolchicine-treated and untreated rats coaggregated with BJP3 in vitro. Tamm-Horsfall glycoprotein from colchicine-treated rats did not contain sialic acid and did not aggregate with BJP3 in vitro.Thus, cast-forming human BJP coaggregated with Tamm-Horsfall glycoprotein and obstructed the rat distal nephron. Intranephronal obstruction was aggravated by decreasing extracellular fluid volume or adding furosemide. Finally, by decreasing secretion and altering the carbohydrate moiety of Tamm-Horsfall glycoprotein, colchicine prevented intraluminal cast formation and obstruction of the rat nephron.