Recent evidence has indicated that the lymphatic vessel endothelial hyaluronan receptor (LYVE-1) is implicated in chronic inflammation and the lymphatic immune response. The soluble form of LYVE-1 (sLYVE-1) is produced by ectodomain shedding of LYVE-1 under pathological conditions including cancer and chronic inflammation. In this study, 1014 consecutive patients who underwent coronary angiography from May 2015 to September 2015 were included to investigate whether serum sLYVE-1 is associated with coronary artery disease (CAD) and its concomitant diseases includes chronic kidney disease (CKD). Results showed that there was no significant difference in sLYVE-1 levels between patients with CAD and without. However, a significantly higher level of sLYVE-1 was seen in patients with renal dysfunction compared to those with a normal eGFR. Results were validated in a separate cohort of 259 patients who were divided into four groups based on their kidney function assessed by estimated glomerular filtration rate (eGFR). Simple bivariate correlation analysis revealed that Lg[sLYVE-1] was negatively correlated with eGFR (r = -0.358, p < 0.001) and cystatin C (r = 0.303, p < 0.001). Multivariable logistic regression analysis revealed that the increase in Lg[sLYVE-1] was an independent determinant of renal dysfunction (odds ratio = 1.633, p = 0.007). Therefore, renal function should be considered when serum sLYVE-1 is used as a biomarker for the detection of pathological conditions such as chronic inflammation and cancer. Further study is required to elucidate the exact role of sLYVE-1 in renal function.