The Changes And Significance Of Effluent PAI-1,MMP-9,MMP-2,IL-6 And Other Biomarkers In Peritoneal Dialysis Associated Peritonitis

【Objectives】To analyze the variety of PAI-1,MMP-9,MMP-2,NGAL,CA125,IL-6 in peritoneal dialysate effluent(PDE)collected during peritoneal dialysis associated peritonitis(PDAP),especially to discuss the alteration of biomarkers in the patients who have peritoneal dialysis-associated peritonitis with delayed removal of the peritoneal catheter,and provide the evidences for the diagnosis and treatment of such patients.【Methods】From May 2016 to August 2019,33 patients who were diagnosed PDAP in our center were selected as peritonitis group.According to the response to antibiotic treatment of patients with peritonitis and whether or not pull out the peritoneal catheter,the peritonitis group was divided into three subgroups,including 11 cases in non-refractory PDAP group,8 cases in refractory PDAP conservative treatment effective group and 14 cases in the PDAP group with delayed extubation.Peritonitis group was divided into two subgroups according to whether EPS was combined,including 10 cases in EPS group and 23 cases in non-EPS group.23 patients with normal maintenance PD who were admitted to our hospital for non-infection reasons during the same period were selected as negative control group.The clinical data,serum and peritoneal dialysate effluent samples of all patients were collected.The serum IL-6 and PAI-1,MMP-9,MMP-2,NGAL and IL-6 in the dialysate of all patients were detected by enzyme linked immunosorbent assay(ELISA)on the day of admission and on the 7th day,and the CA125 in the dialysate was detected by electrochemistry immunoluminescent method,the samples collected at the 14th day from patients in the delayed extubation group could be detected in some methods.SPSS 23.0 was used for statistical analysis.【Results】1.PAI-1,MMP-9,NGAL,MMP-2,IL-6,WBC in effluent and IL-6、CRP in serum were increased after peritonitis.The correlation analysis showed that MMP-9 was positively correlated with WBC and neutrophils(r_s=0.43,P<0.05,r_s=0.45,P<0.05,respectively).The AUC of MMP-9 was 0.963(95%CI:0.911-1.000,P<0.001).When the concentration of MMP-9 was≥189.37pg/ml,the diagnostic sensitivity was 97.0%,and the specificity was 95.7%.The diagnostic sensitivity of IL-6 was 70.0%and the specificity was 73.3%.The diagnostic sensitivity of NGAL was 72.7%,and the specificity was 56.5%.2.In non-refractory PDAP group,the effluent MMP-9,CA125,WBC,and s erum CRP were significantly higher than those in the control group at admissio n,and the self-control showed that the effluent MMP-9,CA125,WBC,and ser um CRP were significantly reduced after treatment.There was no significant dif-ference in above indexes between the non-refractory PDAP group and the contr ol group at 7 days.3.In refractory PDAP conservative treatment effective group,the effluent M MP-9,PAI-1,WBC and serum CRP at admission were significantly higher than those in the control group.The self-control showed that the effluent PAI-1,MM P-9 and WBC was significantly reduced after treatment.Although serum CRP w-ere lower than before,the difference was not statistically significant.There was no significant difference in six biomarkers between the non-refractory PDAP gr-oup and refractory PDAP conservative treatment effective group.4.In the delayed extubation group,the levels of IL-6,MMP-2,MMP-9,P AI-1,WBC in the effluent and IL-6,CRP in the serum were significantly high-er than those in the control group,while the levels of effluent IL-6 in the dela-yed extubation group were significantly higher than those in the non-refractory group and refractory PDAP conservative treatment effective group.The results o-f self-control showed that the exudate NGAL increased at 7 days,while the ot her biomarkers were not significantly decreased.PAI-1,MMP-9,MMP-2,IL-6,WBC in the effluent,IL-6 and CRP in the serum were significantly higher than those in the control group at 7 days.Meanwhile,NGAL,MMP-2,pia-1,WBC,IL-6 in the effluent and CRP in the serum were also significantly higher than those in the non-refractory PDAP group.5.The level of IL-6 and PAI-1 in the effluent and serum CRP of EPS pati ents was significantly higher than that of non-EPS patients at admitting,while t-he level of CA125 in EPS group was lower.The self-control showed that the PAI-1,MMP-9,NGAL in the effluent and serum CRP decreased significantly af-ter treatment in non-EPS group,but not in EPS group.In EPS group,the PAI-1,MMP-9,MMP-2,NGAL,IL-6 in the effluent and IL-6,CRP in the serum w-ere significantly higher than those in the non-EPS group at day 7.6.The biomarkers of PDAP patients with delayed extubation were monitore-d dynamically within 14 days.There was no significant difference between the biomarkers before and after 0,7 and 14 days.【Conclusions】1.The effluent MMP-9 is one of the effective biomarkers for early diagnosis of PDAP,which is significantly better than NGAL,IL-6 and CA125.2.Dynamic monitoring of MMP-9 in effluent can reflect the clinical outco-me of peritonitis.3.The persistently elevated levels of effluent PAI-1,MMP-9,MMP-2 and I L-6 in PDAP reflect the severity of peritonitis,especially in PDAP with delaye-d extubation.4.High levels of PAI-1 and IL-6 in effluent may be the early predictors of EPS in peritonitis.