The Study Of Noninvasive Monitoring Kidney Injury In Patients With Antineutrophil Cytoplasmic Antibody Associated Vasculitis

ObjectivesTo observe the characteristics of traditional Chinese medicine（TCM）syndrome and its relationship with clinical laboratory examination in antineutrophil cytoplasmic antibody（ANCA）associated vasculitis（AAV）patients with kidney injury for providing a TCM theory basis.Investigate the expression and changes of urine biomarkers of kidney injury in patients with AAV for the potential value of early diagnosis and treatment of AAV.Materials and MethodsThe clinical information of AAV patients with kidney injury were collected through four TCM diagnostic methods and then devided into different TCM syndrome types,clinical indicators were collected in AAV patients with kidney injury,the association between TCM syndrome and laboratory indicators was explored.Urine biomarkers including beta catenin（β-catenin）,interleukin-18（IL-18）,neutrophil gelatinase associated lipocalin（NGAL）and trehalase were detected by enzyme-linked immunosorbent assay.The urine biomarkers were compared to serum ANCN and other clinical indicators.The ROC curve of the urine biomarkers was established to evaluate the predictive value of diagnosis and disease activity of AAV patients.Results1.The distribution of TCM syndrome type in AAV patients with kidney injury was as follows:52（41.6%）patients were deficiency of both spleen and kidney（SKD）,as the biggest percent of TCM syndrome type,38（30.4%）patients were qi-yin deficiency（QYD）,19（15.2%）patients were endoretention of damp heat（EDH）,and 16（12.8%）patients were asthenia of pulmonosplenic qi（PSQA）.QYD and SKD often appeared in spring and winter,while QYD presented in summer frequently（P<0.05）.The decrease level of hemoglobin,albumin and complement C3 was statistically correlated with QYD,SKD and EDH,while D-dimer,serum creatinine values and BVAS increased statistically,on the contrary.Compared to QYD and to SKD,the differences of hemoglobin,D-dimer,serum creatinine values and BVAS in EDH were significant（P<0.05）.The levels of urinary IL-18 in the EDH patients（P<0.05）and SKD patients（P<0.01）with AAV kidney injury were significantly higher than those in PSQA patients and QYD patients.The form of onset showed acute kidney injury in majority of EDH patients,while chronic kidney disease in majority of SKD patients and QYD patients（P<0.01）.2.Blood stasis syndrome was contained in 65.6%（82 of 125 AAV patients with kidney injury）of TCM syndromes.The serum high mobility group box 1 protein（HMGB1）level,C-reactive protein（CRP）,D-dimer,ANCA and BVAS was significantly higher in AAV patients with kidney injury,and significantly higher in blood stasis syndrome of AAV patients with kidney injury than that in non-blood stasis syndrome patients（P<0.05）.The serum HMGB1 level was also positively correlated with CRP,D-dimer,ANCA and BVAS（P<0.01）.3.The levels of urinaryβ-catenin,IL-18,NGAL and trehalase in the AAV patients with kidney injury were significantly higher than those in the normal control peasons（P<0.01,P<0.01,P<0.05,P<0.01,respectively）.There was significant difference in urineβ-catenin,IL-18 and trehalase between the active AAV patients and the inactive AAV patients（P<0.01,P<0.05,P<0.01,respectively）.Compared to non-treatment patients,urineβ-catenin,IL-18 and trehalase levels were significantly decreased in the treatment patients（P<0.05）.Urinaryβ-catenin in AAV patients was positively correlated with urine microalbumin-to-creatinine ratio（ACR）,β2-microglobulin（β₂-MG）and serum creatinine,negatively correlated with glomerular filtration rate（P<0.05）.Urinary IL-18 in the active AAV patients was positively correlated with serum IL-18,ANCA and Birmingham Vasculitis Activity Score（BVAS）（P<0.05）.Urinary NGAL was positively correlated with ACR,blood urea nitrogen and Cystatin C（P<0.05）.Urinary trehalase was positively associated withβ₂-MG（P<0.05）.Urinaryβ-catenin,IL-18,NGAL and Trehalase in the active AAV patients was positively correlated with serumβ-catenin,IL-18,NGAL and Trehalase（P<0.05）.Area under the curve（AUC）of urineβ-catenin,trehalase and NGAL with ROC curve area statistic assay in diagnosis of kidney injury in AAV was 0.966（P<0.001）,0.752（P<0.05）and 0.903（P<0.001）,respectively.AUC of urineβ-catenin,IL-18,trehalase in judgment of AAV disease activity was either higher than serum ANCA and BVAS（P<0.05）,or no significant difference with ANCA and BVAS（P>0.05）.Conclusions1.Deficiency of both spleen and kidney followed by qi-yin deficiency was the most common TCM syndrome type in AAV patients with kidney injury.Renal demage was more severe in endoretention of damp heat,with positively correlated to.AAV disease activity,indicating the need for paying more attention and active treatment.2.Blood stasis syndrome presented high percent in AAV patients with kidney injury.The serum HMGB1 was positively correlated with CRP,D-dimer,ANCA and BVAS.Serum HMGB1 may be involved in the pathogenesis of blood stasis syndrome in AAV with kidney injury.3.The levels of urinaryβ-catenin,IL-18,NGAL and trehalase in the AAV patients with kidney injury were significantly higher,urinaryβ-catenin,IL-18,NGAL and Trehalase in the active AAV patients was positively correlated with that in serum.Urinaryβ-catenin,NGAL and trehalase may be biomarkers with high sensitivity and specificity for the diagnosis of AAV patients with kidney injury.Urinaryβ-catenin,IL-18 and trehalase may be biomarkers in judgment the activity in AAV disease.