Hagiyama Man, Nakatani Yoshihisa, Takashima Yasutoshi, Kato Takashi, Inoue Takao, Kimura Ryuichiro, Otani Tomoyuki, Sato Yasufumi, Mori Hideo, Arima Shuji, Ito Akihiko
Department of Pathology, Faculty of Medicine, Kindai University, Osakasayama, Japan.
Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Kindai University, Osakasayama, Japan.
Front Cell Dev Biol. 2019 Jun 27;7:111. doi: 10.3389/fcell.2019.00111. eCollection 2019.
Cell adhesion molecule 1 (CADM1) is an immunoglobulin superfamily member strongly expressed on renal tubular epithelia in the urinary tract. Enzymatic cleavage of its ectodomain increases in chronic kidney disease (CKD), and is assumed to contribute to tubulointerstitial lesion formation. Because the cleaved ectodomain fragments are likely to be released into the urine, a sandwich enzyme-linked immunosorbent assay (ELISA) system for urinary CADM1 was developed using two anti-ectodomain antibodies. Urinary CADM1 concentrations in patients with CKD based on various forms of glomerulonephritis and nephropathy ( = 127) were measured. A total of 44 patients (35%) had elevated CADM1 concentrations over the normal upper limit (362 pg/mL), with a mean of 1,727 pg/mL. Renal biopsy specimens of all patients were pathologically scored for tubulointerstitial lesions using epithelial degeneration, interstitial inflammation, and fibrosis. There were no correlations between urinary CADM1 concentrations and pathological scores or any widely used renal markers, including glomerular filtration rate (GFR), but there was a weak inverse correlation between pathological scores and GFR ( = 0.292). Notably, this correlation gradually increased in patients with increasing CADM1 concentrations, and reached a maximum (0.899) at a cutoff of 1,569 pg/mL. The results of this study suggest that urinary CADM1 is a useful marker indicating tubulointerstitial damage from elevated GFR levels in CKD.
细胞黏附分子1（CADM1）是免疫球蛋白超家族成员，在尿路的肾小管上皮细胞上强烈表达。在慢性肾脏病（CKD）中，其胞外域的酶解作用增强，推测这有助于肾小管间质病变的形成。由于酶解后的胞外域片段可能会释放到尿液中，因此利用两种抗胞外域抗体开发了一种用于检测尿中CADM1的夹心酶联免疫吸附测定（ELISA）系统。对基于各种形式肾小球肾炎和肾病的CKD患者（ = 127）的尿CADM1浓度进行了测量。共有44例患者（35%）的CADM1浓度超过正常上限（362 pg/mL），平均为1727 pg/mL。对所有患者的肾活检标本，根据上皮细胞变性、间质炎症和纤维化情况对肾小管间质病变进行病理评分。尿CADM1浓度与病理评分或任何广泛使用的肾脏标志物（包括肾小球滤过率（GFR））之间均无相关性，但病理评分与GFR之间存在弱负相关（ = 0.292）。值得注意的是，随着CADM1浓度升高，这种相关性在患者中逐渐增强，在截断值为1569 pg/mL时达到最大值 （0.899）。本研究结果表明，尿CADM1是一种有用的标志物，可指示CKD中因GFR升高导致的肾小管间质损伤。
