The Relationship Between Urinary TWEAK Level And The Activity Of Lupus Nephritis

ObjectiveLupus nephritis,characterized by immune complex deposition and inflammatory cells infiltration in the kidney,is the most common and most serious complication of systemic lupus erythematosus,as its high mortality. Due to the unpredictable nature of lupus nephritis,it would be clinically valuable to discover a reliable biomarker for disease activity and progression.Recent studies have shown that tumor necrosis factor-like weak inducer of apoptosis(TWEAK) plays a major role in the pathogenesis of glomerular and tubulointerstitial injury.It induced glomerular cell apoptosis,tubular cell apoptosis and inflammatory cells infiltration, leading to renal injury.Evidences showed that the expression of TWEAK in kidney has correlation with some indicators which associated with disease activity of lupus nephritis.So we make a hypothesis that TWEAK has the potential to become a new biomarkers of lupus nephritis and urinary TWEAK level may reflect kidney disease activity.In this study,we compared the urinary TWEAK level of active lupus nephritis patients with that of rest lupus nephritis patients,then we analyzed the correlation between urinary TWEAK level and lupus nephritis renal activity index(AI). In addiction,we also analyzed the correlation between urinary TWEAK level and urinary MCP-1 level,which has been proven as a biomarker of lupus nephritis for predicting disease activity.The purpose is to test our hypothesis.MethodsThe patients are in Xiangya Hospital from October 2008 to March 2009,with a total of 46 cases,including 42 of female,4 of male,34 of which have a renal biopsy in Xiangya Hospital.Patients age from 14 to 53, weighing 43～68kg.The average blood pressure is 127/83mmHg. According to the 2000 SLE disease activity index(SLEDAI),patients with lupus nephritis were divided into non-active group and active group. Make semi-quantitative score of renal biopsy for every patient,basing on the 2000 Gary S.Hill kidneys of lupus nephritis activity index score standards,calculating activity index(AI),chronicity index (CI),glomerular activity index(GAI) and tubulointerstitial activity index(TIM).Classify biopsy result for evry patient in this study, according to the 2003 ISN / RPS Renal Pathology Classification of Lupus Nephritis.Then detect urinary TWEAK level and MCP-1 level for evry patient in this study by ELISA.1.Compare urinary TWEAK level and MCP-1 level of active group with those of non-active group.2.Analyze the correlations of urinary TWEAK level and urinary MCP-1 level with AI,CI,GAI,TIAI for evry patient.3.Make comparation of urinary TWEAK level and urinary MCP-1 level of patients with different renal pathology classifications.4.Analyze the correlation of urinary TWEAK level with urinary MCP-1 level.5.Analyze the specificity and sensitivity of urinary TWEAK level for predicting lupus nephritis activity,basing on its ROC curve.Results1.The urinary TWEAK level of active group is significantly higher than that of non-active group(10.29±1.81 pg/mgCr vs 2.14±0.30 pg/mgCr,p＜0.01).The urinary MCP-1 level of active group is higher than that of non-activegroup,either(103.60±15.79pg/mgCr vs 20.19±2.934pg/mgCr,p＜0.01).2.The urinary TWEAK level significantly correlated with AI (r=0.825,p＜0.01) while has no correlation with CI(p＞0.05).Its correlation with GAI or AI is significantly positive,either(r_GAI= 0.745,r_{TIAI=0.751,p＜0.01}.The urinary MCP-1 level significantly correlated with AI(r=0.800,p＜0.01) while has no correlation with CI(p＞0.05).Its correlation with GAI or AI is significantly positive,either(r_{GAI= 0.804,rTIAI=0.769,p＜0.01}3.uTWEAK levels do not vary between different WHO classes of LN.A comparison of uTWEAK levels with different WHO classes of lupus nephritis yielded no significant difference between the groups(p＞0.05)4.uTWEAK levels significantly correlated with uMCP-1 levels (r=0.809,p＜0.01) in active group.But in non-active group,uTWEAK levels has no correlation with uMCP-1 levels(p＞0.05).5.The ROC curve of uTWEAK shows:uTWEAK at cut-off point is 4.34pg/mgCr,specificity 92.31%,sensitivity 69.70%,likelihood ratio 9.06,Youden's Index 0.62,positive predictive value 72.73%.Area under the ROC curve is 0.79±0.06.ConclusionsUrinary TWEAK level of patient with lupus nephritis not only prompts whether the patient is undergoing a flare or with chronic stable disease,but also reflects kidney disease activity.TWEAK may be useful as a novel biomarker of lupus nephritis for predicting disease activity.