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      Serum creatinine level and ESR values associated to clinical pathology types and prognosis of patients with renal injury caused by ANCA-associated vasculitis

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          Abstract

          The correlation between serum creatinine and erythrocyte sedimentation rate (ESR) values and clinical pathology and prognosis in patients with renal injury caused by anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis were analyzed. Eighty-six patients with ANCA-associated vasculitis (AAV) treated in the Affiliated Hospital of Qingdao University were enrolled in the study. Patients were assigned into an elderly group (n=45) or a non-elderly group (n=41) according to age. The serum creatinine (Scr) level was measured via the sarcosine oxidase method, and the erythrocyte sedimentation rate (ESR) was measured using the full-automatic ESR analyzer; the relationship between Scr and ESR values and the pathology type of patients was statistically analyzed. The mean levels of Scr and ESR in the 86 patients were 406.87±12.37 µmol/l and 83.83±7.64 mm/1 h, respectively. Importantly, the levels of Scr and the ESR in the elderly group were significantly higher than those in the non-elderly group (P<0.05). In addition, patients with high levels of Scr and accelerated ESR presented mainly the crescentic and sclerotic pathological types, while in the same patients the numbers of focal and mixed types were lower (P<0.05). Kaplan-Meier analysis showed that the survival rate in the elderly group was significantly lower than that in the non-elderly group, and likewise patients with high levels of Scr and accelerated ESR had significantly lower survival rates than those with low levels of Scr and normal ESR (P<0.05). The AUC of the Scr level was 0.901, the sensitivity 90.2%, the specificity 89.5% and the cut-off value was 392.5 µmol/l; while the AUC of the ESR level was 0.864, the sensitivity 89.2%, the specificity 88.5% and the cut-off value 72.8 mm/1 h. Logistic regression analysis showed that the levels of Scr (OR=2.315, P<0.01) and ESR (OR=1.847, P<0.01) were independent factors affecting the prognosis of patients. Based on our findings, the seric Scr level and the ESR are closely related to the clinicopathological features of the disease in patients with renal injury caused by ANCA-associated vasculitis, and they can be used as prognosis and treatment evaluation markers.

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          Long-term follow-up of patients with severe ANCA-associated vasculitis comparing plasma exchange to intravenous methylprednisolone treatment is unclear.

          Patients with antineutrophil cytoplasm antibody-associated vasculitis (AAV) requiring dialysis at diagnosis are at risk for developing end-stage renal disease (ESRD) or dying. Short-term results of a trial comparing plasma exchange (PLEX) to intravenous methylprednisolone (IV MeP) suggested PLEX improved renal recovery. Here we conducted long-term follow-up to see if this trend persisted. A total of 137 patients with newly diagnosed AAV and a serum creatinine over 500 μmol/l or requiring dialysis were randomized such that 69 received PLEX and 68 received IV MeP in addition to cyclophosphamide and oral glucocorticoids. The patients were followed for a median of 3.95 years. In each group there were 35 deaths, while 23 PLEX and 33 IV MeP patients developed ESRD. The hazard ratio for PLEX compared to IV MeP for the primary composite outcome of death or ESRD was 0.81 (95% confidence interval 0.53-1.23). The hazard ratio for all-cause death was 1.08 with a subhazard ratio for ESRD of 0.64 (95% confidence interval 0.40-1.05). Thus, although short-term results with PLEX are encouraging, the long-term benefits remain unclear. Further research is required to determine the role of PLEX in AAV. Given the poor outcomes of patients with severe AAV, improved treatment is urgently needed.
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            ANCA serotype and histopathological classification for the prediction of renal outcome in ANCA-associated glomerulonephritis.

            The phenotype of renal involvement in anti-neutrophil cytoplasmic antibodies (ANCA) vasculitis has a major influence on survival, and histological subgrouping of diagnostic renal biopsies has been proposed to aid in the prediction of renal outcome. We aimed to validate this histological subgrouping and to investigate the additional value of ANCA serotype in the prediction of renal outcome.
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              Neutrophil extracellular trap formation is associated with autophagy-related signalling in ANCA-associated vasculitis.

              Increasing evidence indicates that aberrant neutrophil extracellular trap (NET) formation could contribute to the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Recent research has provided evidence that a novel type of ANCA autoantibody, anti-lysosomal membrane protein-2 (LAMP-2) antibody, may have a pathogenic role in AAV. We have shown previously that anti-LAMP-2 antibody-stimulated NET formation contains autoantigens and anti-microbial peptides. The current study sought to determine whether LAMP-2, as a novel antigen of ANCA, was present on NETs in AAV patients, the influence of the anti-LAMP-2 antibody on the neutrophil apoptosis rate and the role of autophagy in anti-LAMP-2 antibody-induced NET formation. NET formation was assessed using immunofluorescence microscopy, scanning electron microscopy or live cell imaging. The neutrophil apoptosis rate was analysed using fluorescence activated cell sorting (FACS). Autophagy was detected using LC3B accumulation and transmission electron microscopy. The results showed that enhanced NET formation, which contains LAMP-2, was observed in kidney biopsies and neutrophils from AAV patients. The apoptosis rate decreased significantly in human neutrophils stimulated with anti-LAMP-2 antibody, and this effect was attenuated by the inhibitors of autophagy 3-methyladenine (3MA) and 2-morpholin-4-yl-8-phenylchromen-4-one (LY294002). The anti-LAMP-2 antibody-stimulated NET formation was unaffected by benzyloxycarbonyl-Val- Ala-Asp (OMe)-fluoromethylketone (zVAD-fmk) and necrostatin-1 (Nec-1), which are inhibitors of apoptosis and necrosis, respectively, but was inhibited by 3MA and LY294002. Moreover, the proportion of LC3BI that was converted to LC3BII increased significantly (P=0.0057), and massive vacuolizations that exhibited characteristics typical of autophagy were detected in neutrophils stimulated with anti-LAMP-2 antibody. Our results provide further evidence that autophagy is involved in ANCA-induced NET formation in human neutrophils.
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                Author and article information

                Journal
                Exp Ther Med
                Exp Ther Med
                ETM
                Experimental and Therapeutic Medicine
                D.A. Spandidos
                1792-0981
                1792-1015
                December 2017
                16 October 2017
                16 October 2017
                : 14
                : 6
                : 6059-6063
                Affiliations
                Department of Rheumatology and Clinical Immunology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266005, P.R. China
                Author notes
                Correspondence to: Dr Jibo Wang, Department of Rheumatology and Clinical Immunology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, Shandong 266005, P.R. China, E-mail: wangjiboqd@ 123456126.com
                [*]

                Contributed equally

                Article
                ETM-0-0-5306
                10.3892/etm.2017.5306
                5740565
                f1bf1b3b-33ce-4c1b-ad73-7db264bfc025
                Copyright: © Liang et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 20 June 2017
                : 05 October 2017
                Categories
                Articles

                Medicine
                anti-neutrophil cytoplasmic antibody-associated vasculitis,renal injury,creatinine,erythrocyte sedimentation rate,prognosis

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