Urinary clusterin levels in the rat correlate with the severity of tubular damage and may help to differentiate between glomerular and tubular injuries
Urinary clusterin levels in the rat correlate with the severity of tubular damage and may help to differentiate between glomerular and tubular injuries
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DOI：
10.1007/s00441-002-0629-5
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发表时间：
2002-12-01
影响因子：
3.6
通讯作者：
Witzgall, R
中科院分区：
文献类型：
--
作者：
Hidaka, S;Kränzlin, B;Witzgall, R
胆固醇是一种分泌性糖蛋白，在几种类型的肾小管损伤后合成。因此，我们想知道尿中丛生蛋白的排泄是否可以作为判断肾小管损伤严重程度的一个参数。使用亲和纯化的兔抗血清提出的重组clusterin，我们建立了一种酶联免疫吸附试验，测定尿排泄的clusterin双侧肾缺血后，在（cy/+）大鼠模型的常染色体显性多囊肾病和FHH大鼠模型的局灶节段性肾小球硬化症。双侧肾缺血后，尿聚集素排泄量高于总蛋白和白蛋白排泄量，并与肾小管损害程度相关。雄性（cy/+）大鼠比年龄匹配的（+/+）大鼠分泌更多的clusterin，而雌性（cy/+）大鼠则没有，这一发现与雄性大鼠的疾病病程更快一致。FHH大鼠出现明显的蛋白尿和白蛋白尿，但没有排泄增加的聚集素水平。因此，尿簇蛋白水平可以作为肾小管损伤严重程度的有价值的标志物。此外，clusterin也可能有助于区分肾小管和肾小球形式的蛋白尿。
Clusterin is a secreted glycoprotein that is synthesized after several types of tubular injury. We therefore wondered whether the urinary excretion of clusterin could serve as a parameter to determine the severity of tubular damage. Using an affinity-purified rabbit antiserum raised against recombinant clusterin, we established an enzyme-linked immunosorbent assay to measure the urinary excretion of clusterin after bilateral renal ischemia, in the (cy/+) rat model of autosomal-dominant polycystic kidney disease and in the FHH rat model of focal segmental glomerulosclerosis. After bilateral renal ischemia, the urinary excretion of clusterin paralleled the excretion of total protein and albumin and correlated with the extent of tubular damage. Male (cy/+) rats, but not female (cy/+) rats, excreted more clusterin than age-matched (+/+) rats, a finding consistent with the more rapid course of the disease in males. FHH rats presented with pronounced proteinuria and albuminuria but did not excrete increased levels of clusterin. Urinary clusterin levels could therefore serve as a valuable marker for the severity of tubular damage. Furthermore, clusterin may also help to differentiate between tubular and glomerular forms of proteinuria.