Muendlein Axel, Brandtner Eva Maria, Schimpf Judith, Piribauer Michael, Geiger Kathrin, Heinzle Christine, Leiherer Andreas, Drexel Heinz, Freistätter Otto, Neyer Ulrich, Zitt Emanuel
Vorarlberg Institute for Vascular Investigation and Treatment, Feldkirch, Austria.
Department of Nephrology and Dialysis, Academic Teaching Hospital Feldkirch, Feldkirch, Austria.
Kidney360. 2025 Mar 10. doi: 10.34067/KID.0000000744.
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 end-stage kidney disease has not yet been explored and was addressed in the present study.
The 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.
Serum GPC4 levels were approximately 10-fold higher in incident dialysis patients compared to 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 glomerular filtration rate, 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.
GPC4 levels were markedly elevated in patients initiating dialysis and were linked with several pathophysiological characteristics commonly observed in end-stage kidney disease. However, our findings did not indicate that elevated serum GPC4 levels serve as a significant predictor of all-cause mortality in this patient population.
磷脂酰肌醇蛋白聚糖-4(GPC4)是一种细胞表面硫酸乙酰肝素蛋白聚糖,在各种临床情况下均可释放到循环中。最近,循环GPC4水平升高与不同患者群体的肾功能下降和全因死亡风险增加有关。循环GPC4在评估终末期肾病患者疾病状态或预后方面的潜力尚未得到探索,本研究对此进行了探讨。
该研究纳入了187例开始接受慢性透析治疗的患者。此外,还纳入了108例肾功能正常或轻度下降、年龄和性别匹配的对照受试者。新发病透析患者的中位随访时间为3.8年。在开始透析前立即采集血样。采用酶联免疫吸附测定法测定血清GPC4水平。
新发病透析患者的血清GPC4水平比对照组高约10倍,显示出区分两组的出色分类能力。此外,在新发病透析患者中,循环GPC4与肌酐和磷酸盐显著正相关,与估计肾小球滤过率、血红蛋白、红细胞、钙和胆碱酯酶显著负相关。开始透析的患者中,GPC4水平与全因死亡率之间无显著关联。
开始透析的患者GPC4水平显著升高,并与终末期肾病中常见的几种病理生理特征相关。然而,我们的研究结果并未表明血清GPC4水平升高是该患者群体全因死亡率的重要预测指标。