Tubulointerstitial lesion formation in chronic kidney disease mediated by renal adhesion molecule CADM1

慢性腎臓病では尿細管間質病変の重篤度が残腎機能を規定するが、腎生検以外にその重篤度を知るのは難しい。慢性腎臓病では尿細管上皮のIgCAM型接着分子cell adhesion molecule 1（CADM1）の細胞外切断（shedding）が亢進しており、上皮アポトーシスを誘導する。shedding産物である細胞外断片NTFに注目し、尿中CADM1濃度を測定するサンドイッチELISAを樹立した。尿細管間質病変の重篤度と糸球体濾過率とは、尿中NTF濃度が高ければ高い程、非常に強く逆相関した。従って、尿中CADM1濃度が高い時は糸球体濾過率から尿細管傷害の重篤度を推測できると判明した。In chronic kidney disease (CKD), tubulointerstitial damage correlates with progressive decline in renal function, but it is difficult to monitor the severity without renal biopsy. Tumor suppressor CADM1/TSLC1, an IgCAM-type adhesion molecule, is expressed on renal tubular cells, and its increased ectodomain shedding is suggested to contribute to tubular degeneration. A sandwich ELISA for urinary CADM1 was developed using two anti-ectodomain antibodies. Urinary CADM1 concentrations in patients with CKD were measured. Renal biopsy specimens of all patients were pathologically scored for tubulointerstitial lesions using epithelial degeneration, interstitial inflammation, and fibrosis. There was a weak inverse correlation between pathological scores and elevated GFR (eGFR). Notably, this correlation gradually increased in patients with increasing CADM1 concentrations. CADM1 appeared to be a useful marker indicating tubulointerstitial damage from eGFR levels in CKD.研究分野：実験病