Abstract
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 (n = 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 (R2 = 0.292). Notably, this correlation gradually increased in patients with increasing CADM1 concentrations, and reached a maximum R2 (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.
Highlights
Chronic kidney disease (CKD) is defined as a condition involving gradual loss of renal function over a period of months or years, and includes diverse diseases that are primarily inflammatory, immunological, metabolic, and circulatory (Webster et al, 2017)
To develop a sandwich enzyme-linked immunosorbent assay (ELISA) for urinary Cell adhesion molecule 1 (CADM1), we biotinylated one of the two antibodies to use as a detection antibody and used the other antibody as the capture antibody
We examined which antibody was suitable as the detection antibody using a recombinant soluble isoform of CADM1 fused with the Fc portion of human IgG1 (Koma et al, 2004), and optimized both the quantity of the capture antibody to be coated on the plate and the dilution factor for detecting the antibody
Summary
Chronic kidney disease (CKD) is defined as a condition involving gradual loss of renal function over a period of months or years, and includes diverse diseases that are primarily inflammatory, immunological, metabolic, and circulatory (Webster et al, 2017). Patients with CKD often must undergo renal biopsy to monitor the severity of tubulointerstitial damage as well as to facilitate a diagnostic pathological classification (Hsu et al, 2017). These protocols have been used because the marker molecules are probably released from damaged tubular cells into the urine, and are sensitive to subtle damages in tubular cells. They are not sufficient to reflect the entire scope of tubulointerstitial damages, including interstitial inflammation and fibrosis
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