| Background:Anti-neutrophil cytoplasmic antibody(ANCA)associated vasculitis(AAV)is a multisystemic autoimmune disease.The typical antigens of ANCA include proteinase-3(PR3)and myeloperoxidase(MPO).AAV includes granulomatosis with polyangiitis(GPA),microscopic polyangiitis(MPA),and eosinophilic granulomatosis with polyangiitis(EGPA).Epidemiological studies have shown racial differences in the clinical manifestations of AAV and ANCA specificity.PR3-ANCA and GPA are the most common in Western populations,while MPO-ANCA and MPA are dominant in East Asian countries.Rapidly progressive glomerulonephritis is a common manifestation of AAV,which is characterized by high end-stage renal disease(ESRD)and mortality rates in patients without proper treatment.Therefore,early identification of biomarkers associated with disease activity and prognosis of AAV is expected to promote early and optimal therapy in patients with AAV.Interleukin-8(IL-8)is able to increase neutrophil adhesiveness and promote neutrophil activation and formation of neutrophil extracellular traps(NETs),which could lead to microvascular endothelial injury and necrotizing vasculitis.It is overexpressed in multiple forms of cancer,respiratory diseases,and autoimmune diseases.Several clinical studies found that IL-8 is increasing in peripheral blood,urine and bronchoalveolar lavage fluid of AAV patients,which maybe corelated with disease activity.However,the subjects of these studies were mainly patients with GPA.In China,there has been no relevant report on IL-8 and AAV.In this study,72 patients with AAV were included,and investigate the clinical significance of IL-8 in MPO positive AAV.Method:A total of 72 patients with MPO positive AAV in department of Nephrology from April2015 to October 2019 were included.Information about demographic characteristics,laboratory parameters was all collected and reviewed from the electronic medical records system.Patients were divided into two groups based on whether they reached ESRD or death.According to the cut-off value of serum IL-8 level(12.35pg/m L),the patients were divided into two groups.Data on clinical features,laboratory parameters,renal histopathology characteristics and prognosis were analyzed retrospectively.Spearman correlation test was used to determine the correlations.Kaplan-Meier method was used for survival analysis,and log-rank test was used to compare the survival rates between the groups.COX hazard regression model was used to analyze the risk factors affected prognosis of AAV.P<0.05 was considered statistically significant.Result:1.In comparison with patients without outcome events,the levels of serum creatinine(Scr)(P<0.001),IL-8(P=0.021)and tumor necrosis factor-?(TNF-?)(P=0.002)were significantly higher in patients with outcome events,whereas hemoglobin were significantly lower(P=0.022).In multivariate COX regression model,IL-8(HR=1.006,P=0.037)and Scr(HR=1.002,P<0.001)were independent risk factors affected prognosis of AAV.2.Patients with high level of IL-8 presented higher level of Scr(P=0.001),Interleukin-6(IL-6)(P=0.001),TNF-?(P<0.001),C-reactive protein(CRP)(P<0.001),D-dimer(P=0.011),white blood cell count(P=0.005),?1-Globulin(P<0.001)and Birmingham Vasculitis Activity Score(BVAS)(P=0.004)than patients with low level of IL-8,and presented a lower level of albumin and hemoglobin(P=0.002,0.019,respectively).3.In Spearman correlation analysis,the serum IL-8 level was positively correlated with BVAS(r=0.383,P<0.001),CRP(r=0.515,P<0.001),IL-6(r=0.558,P<0.001),TNF-?(r=0.584,P<0.001),SCr(r=0.467,P<0.001),D-dimer(r=0.483,P<0.001),?1-Globulin(r=0.528,P<0.001)and white blood cell count(r=0.390,P=0.001),and negatively correlated with albumin(r=-0.428,P<0.001)and hemoglobin(r=0.360,P=0.002).4.Patients with high level of IL-8 had more serious systemic damage,and the proportion of chest damage was higher(P=0.025).5.The renal pathology types in low level of IL-8 group were mainly the Mixed class(P=0.033),while in the high level of IL-8 group,the main renal pathological types were the Crescent class(P=0.017).Patients with high level of IL-8 presented lower proportion of normal glomeruli than patients with low level of IL-8(P=0.038).6.Kaplan-Meier analysis had shown that patients with high IL-8 level had lower renal survival rate than patients with low IL-8 level(log-rank=10.500,P=0.001).Conclusion:1.The initial Scr and IL-8 levels were independent risk factors affected prognosis of AAV.2.The serum IL-8 level was positively correlated with BVAS,CRP,IL-6,TNF-?,which indicated disease activity of AAV.3.Patients with high level of IL-8 had more serious systemic damage and lower renal survival rate.Background:Nephrotic syndrome(NS)is the main cause of primary glomerular disease.Approximately half of patients with NS develop steroid-dependent NS(SDNS)or frequently relapsing NS(FRNS).About 10–20% of NS patients have steroid-resistant NS(SRNS),which have poor renal prognosis.These conditions are collectively referred to as refractory nephrotic syndrome(RNS).Recurrence is the biggest challenge in the long-term management of NS and an independent risk factor for renal prognosis.Patients with FRNS/SDNS or SRNS usually require long-term steroids or immunosuppressive therapy to maintain remission and reduce the frequency of relapse,which could increase the risk of serious side effects.Rituximab(RTX),a chimeric anti-CD20 monoclonal antibody,which can deplete B cells through antibody-dependent and complement-dependent cytotoxicity.RTX has been proven be safe and effective in lymphoma and immune-mediated diseases.Many studies have confirmed the efficacy and safety of RTX in the treatment of SDNS/FRNS and SRNS.However,the optimal dose of RTX on initial and maintenance stage,and the length of medication interval remain elusive.In this study,aim to explore the factors affecting the therapeutic effect of RTX,the efficacy and safety of RTX on 70 patients with RNS were retrospectively analyzed.Method:A total of 70 patients with RNS received RTX from October 2015 to July 2020 were enrolled.Clinical data at the time of initial diagnosis and initial RTX treatment were collected through the electronic medical records system.Patients were divided into different groups according to the dose of RTX,renal pathological type and clinical type.Data on clinical features,treatment options and prognosis between groups were analyzed retrospectively.Survival analysis was analyzed by Kaplan-Meier curve,and log-rank test was used to compare the survival rates between the groups.The risk factors affected the therapeutic effect of RTX were analyzed by COX regression model.P<0.05 was considered statistically significant.Result:1.According to the dose of RTX,the patients were divided into the high-dose(375mg/m2,3-4 doses and 1000 mg,2 doses)group and the low-dose(375mg/m2,1-2 doses and 1000 mg,1 dose)group,and there were no significant differences in remission rate,time to remission,recurrence rate and sustained remission time between the two groups.2.After RTX treatment,the complete remission rate of patients with different pathological types were statistically different(P<0.001),and the complete remission rate of patients in groups of Ms PGN(78.6%),MCNS(75.0%)and FSGS(60.0%)were significantly higher than those in group of MN(13.6%).The partial remission rate of MN patients(68.2%)was significantly higher than patients with MCNS(25.0%),Ms PGN(21.4%)(P=0.013).Kaplan-Meier survival analysis showed that the relapse-free survival rate of patients with MCNS was significantly lower than patients with MN(P =0.042).3.B cell depletion was defined as the frequency of CD19+B cell of total lymphocyte ?0.1%.There were no significant differences in the time to remission,remission rate,sustained remission time and recurrence rate between the group with or without B cell depletion.4.Compared to baseline,the number of patients with steroids(34 vs 52)and the dose of steroids [5.00(0.00-13.75)vs 20.00(11.25-25.00)mg/d] were significantly lower at 6 months after RTX treatment(P <0.001).At 12 months,the number of cases(21 vs 52)and dose [0(0-12.50)vs 20.00(11.25-25.00)mg/d] were significantly lower than baseline(P <0.001).5.Compared with SDNS/FRNS patients,SRNS patients took longer time to remission(P=0.017).There was no significant difference in total remission rate between the two groups.The complete remission rate was higher in patients with SDNS/FRNS(67.3% vs 0,P<0.001),while partial remission rate was higher in patients with SRNS than in patients with SDNS/FRNS(80.0% vs 29.1%,P<0.001).6.COX regression multivariate analysis showed that,the length of the time from onset(P=0.009,HR=1.072,95%CI:1.018-1.129)and SRNS(P=0.019,HR=0.443,95%CI:0.224-0.876)were risk factors affected the remission of patients with NS after RTX treatment.Conclusion:1.There was no significant difference between low dose of RTX group and high dose of RTX in the treatment on RNS.2.The efficacy of RTX in patients with steroid-resistant MN was inferior to other groups,and the patients of MCNS had lower relapse-free survival rate.3.The depletion and recovery of CD19+B cell did not predict the remission or relapse of NS.4.The dose of steroids and immunosuppressants in patients with NS was reduced after RTX treatment. |
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