腹膜透析滤出液中游离mtDNA 与腹膜透析患者腹腔微炎症的相关性分析

The correlation between free mtDNA in outflow dialysate and peritoneal micro-inflammation in patients undergoing peritoneal dialysis

目的探讨腹膜透析滤出液中游离线粒体DNA(mitochondrial DNA,mtDNA)与腹膜透析(peritoneal dialysis,PD)患者腹膜及腹腔微炎症的相关性。方法收集行PD治疗的患者85例,分为A组(1.5%葡萄糖腹膜透析液治疗组)和B组[高浓度(2袋以上2.5%或4.25%)葡萄糖腹膜透析液治疗组]。检测血生化指标,腹膜透析滤出液中白细胞介素6(interleukin 6,IL-6)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素1β(interleukin 1β,IL-1β)及白细胞介素(interleukin 18,IL-18)及mtDNA。比较2组患者上述指标的差异;将mtDNA分别与临床参数做相关性分析;通过多元回归分析明确影响腹膜透析滤出液中mtDNA浓度的危险因素。结果B组患者透析龄长于A组(t=-2.206,P=0.030),血白蛋白(Alb)低于A组(t=2.635,P=0.010),腹膜透析滤出液中IL-6(t=-4.835,P<0.001)、TNF-α(t=-6.557,P<0.001)、IL-1β(t=-2.395,P=0.019)、IL-18(t=-2.318,P=0.023)及游离mtDNA(t=-3.920,P<0.001)均高于A组。腹膜透析滤出液中mtDNA与IL-6(r=0.721,P<0.001)、TNF-α(r=0.418,P<0.001)、IL-1β(r=0.771,P<0.001)、IL-18(r=0.634,P<0.001)及透析龄(r=0.240,P=0.030)均呈正相关,与Alb呈负相关(r=-0.319,P=0.003)。多元回归分析显示腹膜透析液中葡萄糖浓度升高(β=0.358,P=0.005)、长透析龄(β=0.292,P<0.001)及Alb降低(β=-0.272,P=0.027)是腹膜透析滤出液中mtDNA水平升高的危险因素。结论腹膜透析滤出液中mtDNA与PD患者腹膜及腹腔慢性微炎症状态相关。高浓度葡萄糖腹膜透析液、长透析龄及低蛋白血症是导致其水平升高的危险因素。

Objective To investigate the relationship between free mitochondrial DNA(mtDNA)level in outflow dialysate and chronic peritoneum inflammation in patients undergoing peritoneal dialysis(PD).Methods A total of 85 patients with PD for more than 6 months were enrolled and divided into group A(using dialysate with 1.5%glucose)and group B(using dialysate with 2.5%or 4.25%glucose more than twice a day).Blood samples were collected and serum biochemical parameters were tested.The outflow dialysate was collected to measure interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-18(IL-18)and free mtDNA in the fluid.The differences of these parameters were compared between the two groups.The correlation between mtDNA in outflow dialysate and clinical parameters was analyzed.Multivariate regression was used to define the risk factors for mtDNA in dialysate.Results PD duration was longer(t=-2.206,P=0.030)and serum albumin was lower(t=2.635,P=0.010)in group B than in group A.IL-6,TNF-α,IL-1β,IL-18 and free mtDNA in the dialysate were significantly higher in group B than in group A(t=-4.835,-6.557,-2.395,-2.318 and-3.920 respectively;P<0.001,<0.001,=0.019,=0.023 and<0.001 respectively).Free mtDNA level in the dialysate was positively correlated with the levels of IL-6,TNF-α,IL-1βand IL-18 in dialysate and PD duration(r=0.721,0.418,0.771,0.634 and 0.240 respectively;P<0.001,<0.001,<0.001 and=0.03 respectively),and was negatively correlated with serum Alb(r=-0.319,P<0.01).Multivari-ate linear regression showed that higher glucose concentration in dialysate (β=0.358, P=0.005), longer PD duration(β=0.292, P=0.000) and lower serum Alb concentration (β=-0.272, P=0.027) were the risk factors forhigher free mtDNA in outflow dialysate. Conclusion Elevated mtDNA in outflow dialysate is associatedwith chronic micro-inflammatory status of the peritoneum in PD patients. Higher glucose concentration in dialysate,longer PD duration and lower serum Alb concentration are the risk factors for higher free mtDNA inoutflow dialysate.