| Objective:To investigate the clinical risk factors for unresponsive common approaches on the treatment of class IV LN.Methods:The class IV LN patients were confirmed by renal biopsy,treated with glucocorticoid and common immunosuppressive agents and followed-up for more than 6 months.They were divided into two groups according to curative effect after being treated 6 months.The differences between the divided groups were analyzed by means of demographic characteristics,clinical manifestations,laboratory tests,autoantibodies,pathologic indicators,treatment regimens and outcomes.The possible influencing risk factors on the class IV LN,were analyzed by Kaplan-Meier,and the independent risk factors were analyzed by multivariate COX regression modeling.Results:A total of 198 patients with complete data and regularly followed-up were enrolled.They were divided into two groups: 50(25.25%)patients belonged to nonresponse group and 148(74.75%)patients belonged to response group.There was no significant difference between two groups in responsive rate under various common induction therapies.And then,the risk factors,which influencing the curative effects of class LN IV patients were further explored.Results showed that compared with the response group,the nonresponse group had a higher rate of photosensitization,renal dysfunction,moderate proteinuria,the anti-RNP positive,renal glomerular sclerosis,CI,chronic interstitial lesions,interstitial cellular infiltration and NNV(P<0.05).Kaplan-Meier results showed that a decreasing response happened in the group with a higher rate of renal dysfunction,chronic lesions and interstitial cellular infiltration(Log Rank P<0.05).Then multivariate COX regression model investigated that renal dysfunction was an independent risk factor for poor curative effect.Conclusions:Under the treatment of common induction therapy,the class IV LN patients with baseline renal dysfunction have a terrible curative effect.In addition,it is possible that the baseline anti-RNP positive,chronic interstitial lesions,interstitial cellular infiltration or NNV are the risk factors for unresponsive treatment.Objective:1.To clarify the expression of Wnt/β-Catenin signaling pathway in lupus nephritis(LN).2.To discuss the possible pathologic mechanism of Wnt /β-Catenin signaling pathway in LN and to develop an understanding of the pathogenesis of LN.Methods:1.Chosing various of kidney sample slices from acute kidney injury and chronic kidney disease patients as nephropathy group,while kidney sample slices 3 cm adjacent to the cancer without infiltration as the control group.The elements of The Wnt /β-Catenin signaling pathway between two groups was compared by Immunohistochemistry to find the differences.2.Chosing the active LN patients dignosed with kidney biopsy as the target population,while the normal people from medical center as normal control group,and other kidney diseases instead of LN as the non-LN(NLN)group.To compair the differences of The Wnt/β-Catenin signaling pathway between LN group and normal control group,LN group and NLN group respectively;To divide the LN group who have been follewed up for more than 6 months into two groups: effective group and Invalid group,compairing which to find the differences in protein level.3.Chosing the active LN patients dignosed with kidney biopsy as the target population,while the normal people from medical center as normal control group.The elements of The Wnt/β-Catenin signaling pathway between two groups were compared by RT-PCR to find the differences in m RNA level.Results:1.A total of 37(71.2%)person and 15(28.8%)person were enrolled in nephropathy group and normal control group,respectively.With Immunohistochemistry,our date showed that the average optical density of β-catenin in the nephropathy group was significantly higher than the normal control group(P=0.032).However,there were no statistically significant in wnt1、DKK1 between the two groups.2.A total of 18(49%)person and 19(51%)person were enrolled in LN group and normal control group.The age and gender of the two groups were matched.With ELISA,LN group had a significantly higher level of 24 h urinary protein,creatinine,IFN-αthan the normal control group.However,there was no statistically significant in Wnt1,β-catenin and DKK1.We further analysed the differences of Wnt1,β-catenin and DKK1 in serum between LN group and NLN group.18(34%)person and 45(66%)person were enrolled in LN group and NLN group,respectively.The age and gender of the two groups were matched,our date showed that LN group had a higher expression of β-catenin but a lower expression of wnt1 than NLN group.In addition,there were no statistically significant in others.At the same time,we divided LN group according the therapy effect into two group:the effective group and invalid group.There were 8(47%)person reached complete remission or partical remission after therapy named effective group,while 10(53%)were not reached clinical remission named invalid group.Compairing the two groups,we investigated that the urea nitrogen,24 h urinary protein and β-catenin were significantly higher than the invalid group.Though there was no statistically significant in creatinine but it had a higher level in Invalid group.In addition,Wnt1 and DKK1 had no statistically significant between the two groups.3.A total of 15(53.6%)person and 13(46.4%)person were enrolled in LN group and normal control group,respectively.The age and gender of the two groups were matched.With RT-PCR,our date showed that LN had a higher significant level of 24 h urinary protein than normal control group.However,there were no statistically significant in Wnt1,β-cateni and DKK1.Conclusion:1.The wnt /β-Catenin signaling pathway maybe actived in LN,accompanied by the increase of β-catenin and the transcription of wnt target genes,which were related to the curative effect of LN patients.Who had a lower curative effect for LN drugs had a higher level of expression of wnt/β-catenin signaling pathway.2.Our study combined with previous studies suggested that wnt/ β-catenin signaling pathway triggered LN and aggravated disease progression through multiple pathogenesis.It maight lead to renal interstitial fibrosis by promoting renal epithelial cells and podocytes epithelial inolved cell mesenchymal changes(EMT),and the deposit of renal interstitial collagen fibers.In addition,It could mediate immune microenvironment changes by promoting the differentiation of T cells into Treg cells and interacting with TLR7 / My D88 / NF-KB pathway in dendritic cells(DC).3.Wnt/β-Catenin signaling pathway maight play a key role in LN curative effect or relapse.A developmental understanding of the pathogenesis of LN provides a way for us to find better and accurate targeted therapies. |
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