Imperial College Kidney and Transplant Institute, Hammersmith Hospital, London, UK.
Eur J Clin Invest. 2010 Dec;40(12):1067-73. doi: 10.1111/j.1365-2362.2010.02353.x.
Peritoneal fibrosis manifests clinically as membrane failure or encapsulating peritoneal sclerosis (EPS). There are no clinical or biochemical tests to determine the rate of progression of peritoneal fibrosis. CCL18/pulmonary and activation-regulated chemokine (PARC) is profibrotic and stimulates collagen production independent of the effect of transforming growth factor beta. This has not been studied in peritoneal dialysis (PD) patients.
We have prospectively studied 106 patients, free from infection/recent peritonitis. A high concentration of CCL18 was discovered by multiplex antibody arrays and quantified by ELISA. Serum and dialysate levels were examined for their prognostic values.
By multiple regression analysis, dialysate CCL18 (6·76 ± 0·66 μg 4 h⁻¹) correlated with increasing membrane transport status (TS) (P < 0·0001) and total glucose exposure/24 h (P = 0·033). Serum CCL18 correlated with high TS (P = 0·0001) and duration of PD (P = 0·001). After 12 months of follow-up, 57 patients remained on PD while 12 patients were transferred to haemodialysis (HD) and seven developed EPS. Patients who subsequently developed EPS had higher baseline dialysate CCL18 (11·5 ± 3·6 μg 4 h⁻¹ vs. 5·6 ± 0·82 μg 4 h⁻¹, P = 0·03) and serum CCL18 (156·9 ± 12·8 ng mL⁻¹ vs. 124·8 ± 12·2 ng mL⁻¹, P = 0·02) compared with the stable PD group.
This is the first report of high levels of CCL18 in the spent dialysate and serum from long-term PD patients. These levels correlated with dysfunction of peritoneal membrane transport status, therefore following CCL18 in a longitudinal study may be of interest.
腹膜纤维化临床上表现为膜衰竭或包裹性腹膜硬化症(EPS)。目前尚无临床或生化检测手段可用于确定腹膜纤维化的进展速度。CCL18/肺和激活调节趋化因子(PARC)具有促纤维化作用,可刺激胶原产生,且这种作用独立于转化生长因子β的影响。这一点尚未在腹膜透析(PD)患者中进行研究。
我们前瞻性研究了 106 例无感染/近期腹膜炎的患者。通过多重抗体阵列发现了高浓度的 CCL18,并通过 ELISA 进行定量。检测了血清和透析液中 CCL18 水平的预后价值。
通过多元回归分析,透析液 CCL18(6.76±0.66μg4 h-1)与膜转运状态(TS)升高相关(P<0.0001),与总葡萄糖暴露量/24 h 相关(P=0.033)。血清 CCL18 与高 TS(P=0.0001)和 PD 时间相关(P=0.001)。随访 12 个月后,57 例患者继续接受 PD 治疗,12 例患者转为血液透析(HD),7 例患者发生 EPS。随后发生 EPS 的患者基线时透析液 CCL18 更高(11.5±3.6μg4 h-1比 5.6±0.82μg4 h-1,P=0.03),血清 CCL18 更高(156.9±12.8ng mL-1比 124.8±12.2ng mL-1,P=0.02)。
这是首个报道长期 PD 患者透析液和血清中 CCL18 水平升高的研究。这些水平与腹膜膜转运状态功能障碍相关,因此在纵向研究中监测 CCL18 可能具有意义。