Evaluation of Circulating Glypican-4 in Patients with ESKD.

Key Points: Glypican-4 (GPC4) levels were strongly elevated in incident dialysis patients compared with individuals without evidence of kidney disease. Circulating GPC4 was significantly correlated with various parameters linked to adverse conditions commonly present in incident dialysis patients. No association was found between GPC4 and all-cause mortality in incident dialysis patients.

Background: Glypican-4 (GPC4) is a cell surface heparan sulfate proteoglycan that can be released into circulation under various clinical conditions. Elevated levels of circulating GPC4 have recently been associated with reduced kidney function and an increased risk of all-cause mortality across different patient populations. The potential of circulating GPC4 for assessing disease status or prognosis in patients with ESKD has not yet been explored and was addressed in this study.

Methods: This study included 187 patients starting chronic dialysis treatment. In addition, 108 control subjects with normal or mildly reduced kidney function, matched for sex and age, were included in the study. The median follow-up time of incident dialysis patients was 3.8 years. Blood samples were collected immediately before initiation of dialysis. Serum GPC4 levels were determined using an enzyme-linked immunosorbent assay.

Results: Serum GPC4 levels were approximately ten-fold higher in incident dialysis patients compared with controls, demonstrating excellent classification ability to distinguish between the two groups. Furthermore, circulating GPC4 was significantly positively correlated with creatinine and phosphate and significantly negatively correlated with estimated GFR, hemoglobin, erythrocytes, calcium, and cholinesterase in incident dialysis patients. There was no significant association between GPC4 levels and all-cause mortality in patients starting dialysis.

Conclusions: GPC4 levels were markedly elevated in patients initiating dialysis and were linked with several pathophysiologic characteristics commonly observed in ESKD. However, our findings did not indicate that elevated serum GPC4 levels serve as a significant predictor of all-cause mortality in this patient population.