Characteristics of included studies.

Background
Chronic kidney disease (CKD) is one of the leading causes of morbidity and mortality worldwide. Endothelial dysfunction has been suggested to be involved in the pathophysiology of CKD. Endocan, as an endothelial factor, has been shown to increase in several diseases. The current systematic review and meta-analysis was performed with the aim of determining the association between endocan levels and CKD.
Methods
Four international databases, including PubMed, Embase, Scopus, and Web of Science were searched for relevant studies. Afterward, screening and extraction of data were performed. We conducted a random-effect meta-analysis to calculate the standardized mean difference (SMD) and 95% confidence interval (CI) to compare circulating endocan levels between patients with CKD (including patients undergoing hemodialysis) and healthy controls. Subgroup analysis based on the specimen in which endocan was measured (serum or plasma) was also performed.
Results
After screening by title/abstract and full-text review by the authors, 20 studies were included. Meta-analysis revealed that serum endocan is higher in CKD patients compared to healthy controls (SMD 1.34, 95% CI 0.20 to 2.48, p-value<0.01). This higher endocan level was also observed in the subgroup of studies that measured plasma endocan while this was not the case for the subgroup of studies assessing serum endocan. Meta-analysis was also performed for comparison of CKD patients without other comorbidities and healthy controls, which resulted in the same conclusion of higher endocan levels in patients with CKD (SMD 0.74, 95% CI 0.52 to 0.95, p-value<0.01). Moreover, endocan was associated with cardiovascular diseases in CKD.
Conclusion
Our study demonstrated that endocan is significantly increased in patients with CKD. This can have clinical implications as well as highlight the need for future research investigating the diagnostic and prognostic role of endocan in CKD.