Matrix Metalloproteinase 7 Associated With Prognosis Of Peritoneal Dialysis Patients

As one of the major renal replacement therapies,Peritoneal dialysis(PD)have the advantages of home treatment and residual renal function protection,especially under the environment of the current novel coronavirus epidemic.More and more patients choose PD because of the advantages of easy management and isolation.With the optimization of management strategy and follow-up means,the PD vintage is getting longer,and about 3.9%of PD patients were over 10 years in Japan.However,urotoxin damage,glucose exposure,and inflammatory cytokine stimulation can all lead to and aggravate peritoneal damage with the prolongation of dialysis vintage,presenting as peritoneal fibrosis,ultrafiltration failure,and solute-clearance disorder,which are the main reasons for peritoneal dialysis failure and poor prognosis.More importantly,after the occurrence of ultrafiltration failure and solute-clearance obstruction,patients often present with severe and irreversible peritoneal dialysis complications,such as congestive heart failure(CHF)and hyperphosphatemia,which are the leading causes of readmission,cardio-cerebrovascular events,and all-cause death in PD patients.It is very important to find the related factors of peritoneal injury for estimating the peritoneal function and predicting the prognosis of PD.Matrix Metalloproteinase 7(MMP7)is the smallest Matrix Metalloproteinase,which can degrade a variety of extracellular matrix components and has a variety of biological activities.In chronic kidney disease,the expression of serum MMP7 is significantly increased,which is the pathological mediator of renal fibrosis.In patients with acute kidney injury,MMP7 is also highly expressed in urine,which can predict the occurrence and clinical prognosis of acute kidney injury.However,there is no research on the expression and role of MMP7 in peritoneal dialysis patients.Therefore,we conducted an ambispective cohort study in the peritoneal dialysis center of the department of nephrology,Nanfang Hospital,Southern Medical University.We enrolled 283 PD patients who were followed up every 3 or 6 months until death,PD withdrawal,or the end of the study.Clinical data,serum and peritoneal dialysate samples from baseline and follow-up points were collected,the expression level of MMP7 was detected,and clinical events such as congestive heart failure,hyperphosphatemia and death were also recorded to investigate the association between MMP7 and CHF and hyperphosphatemia.Our study found that MMP7 is highly expressed in serum and dialysate of PD patients,and there is a good correlation between serum and dialysate MMP7.Further analysis showed that baseline serum and dialysate MMP7 levels were tightly associated to the occurrence of CHF.PD Patients with the highest baseline MMP7 levels had the highest incidence of CHF.When the baseline serum MMP7 levels were higher than 6.95ng/ml,the risk of CHF incident was 1.96 times higher than the lowest group.Patients with higher baseline serum MMP7 levels were trend to use high glucose concentration dialysate,but did not increase peritoneal ultrafiltration volume.Baseline MMP7 levels were also significantly associated with PD withdrawal and combined end point.Further study showed that the serum phosphorus(SP)levels of PD patients were high before dialysis and decreased rapidly after dialysis.Among patients whose SP levels decreased to normal after dialysis(n=243),71 patients(29.6%)developed hyperphosphatemia again,primarily at 9(3.73-12)months after dialysis.The baseline alkaline phosphatase levels,dialysate calcium,total KT/V were lower,serum fibroblast growth factor 23(FGF23)levels,dialysate OSM were higher,and the peritoneal dialysis vintage were longer in the newly diagnosed hyperphosphatemia group.SP levels on 1 month after dialysis was positive associated with newly diagnosed hyperphosphatemia.The proportion of newly diagnosed hyperphosphatemia in different baseline serum and dialysate MMP7 groups was different,but the results were not statistically significant.There was a positive correlation between baseline dialysate MMP7 and average 12-month D/P P(r=0.353,P<0.001).To sum up,we found that MMP7 was highly expressed in serum and dialysate of PD patients.Baseline MMP7 levels were tightly associated to the occurrence of CHF,PD withdrawal,and combined end point.The association between MMP7 and peritoneal phosphorus clearance and hyperphosphatemia remains to be further studied.In conclusion,MMP7 plays a very important role in peritoneal dialysis,and its specific mechanism needs to be further studied.