| Part I Relationship between dyslipidemia and clinical pathological features of children with IgANObjective:The clinical and pathological data of children with primary IgAN in our hospital were retrospectively analyzed,and the relationship between them and dyslipidemia was discussed,so as to provide a scientific basis for the clinical treatment and predicting the prognosis of children with IgAN.Methods:The data of children with primary IgAN diagnosed for the first time in the department of pediatric nephrology and rheumatology of Shandong provincial hospital from February 1,2016 to August 31,2020 were retrospectively collected.They were grouped according to the presence or absence of dyslipidemia.The clinical and pathological characteristics of the two groups were analyzed and compared.The risk factors of IgAN children with dyslipidemia were analyzed by Logistic regression.Results:(1)General data:125 children with IgAN were included in this study,including 86 males and 39 females,with an average age of 9.01±2.39 years.The average course of disease before renal biopsy was 1(0.73,3)month,the average body mass index was 17.35(15.77,19.59).There were 20 patients(16%)with hypertension,93 patients(74.4%)with gross hematuria,14 patients(11.2%)with acute kidney injury(AKI),47 patients(37.6%)with nephrotic-range proteinuria,20 patients(16%)with hypoproteinemia,75 patients(60%)with dyslipidemia.Hematuria with nonnephrotic-range proteinuria was the most common clinical classification(53.6%).Oxford pathological classification M1(51.2%),E1(55.2%)and S1(55.2%)were more common.Except IgA(100%),C3 deposition(64%)was most common in immune complex deposition.(2)Comparison between normal blood lipid group and dyslipidemia group:The systolic blood pressure,diastolic blood pressure,the proportion with hypertension and with nephrotic-range proteinuria in dyslipidemia group were higher than those in normal blood lipid group(All P<0.05).The proportion of gross hematuria in dyslipidemia group was lower(P<0.05),and the course of disease before renal biopsy was shorter than that in normal blood lipid group(P<0.01).The proportion of hematuria with nephrotic-range proteinuria in dyslipidemia group was higher than that in normal blood lipid group(P<0.05).Blood urea nitrogen,blood uric acid and 24-hour urinary protein quantification in dyslipidemia group were higher than those in normal blood lipid group,while serum albumin was lower(all P<0.01).Compared with normal blood lipid group,the proportion of endothelial cell proliferation(E),segmental glomerulosclerosis(S)and crescent formation(C)in dyslipidemia group was higher,and the proportion of non-M0EOS0TOC0 was higher(all P<0.01).(3)The logistic regression analysis showed that elevated systolic blood pressure(OR=1.102,95%CI 1.040～1.168,P<0.01),decreased serum albumin(OR=0.74,95%CI 0.65～0.843,P<0.01)and with endocapillary hypercellularity(E)(OR=6.651,95%CI 2.103～21.037,P<0.01)were risk factors for dyslipidemia in children with IgAN.Conclusion:The proportion of IgAN children with dyslipidemia is high.IgAN children with dyslipidemia have more serious laboratory abnormalities and renal pathological damage.Elevated systolic blood pressure,decreased serum albumin and with endocapillary hypercellularity(E)were risk factors for dyslipidemia in children with IgAN.Part Ⅱ Changes and clinical significance of TWEAK in urine of children with IgAN.Objective:To explore the changes and clinical significance of TWEAK in the urine of IgAN children by detecting the levels of TWEAK in the urine and analyzing the clinical and pathological data.Methods:The data of children who were first diagnosed with primary IgAN and successfully collected urine samples in the department of Pediatric Nephrology and Rheumatology of Shandong provincial hospital from February 1,2016 to August 31,2020 were retrospectively collected.The levels of TWEAK in urine was detected by ELISA.The levels of urine TWEAK were compared according to the clinical and pathological data.According to the urine TWEAK level of IgAN children,IgAN children were divided into high TWEAK group and low TWEAK group.The clinical and pathological characteristics of the two groups were analyzed and compared.Correlation analysis was carried out on the indexes with statistical significance among the groups.Results:(1)The urine TWEAK level in IgAN group was higher than that in normal control group(P<0.05).(2)Comparison of urine TWEAK levels among different clinical and pathological indexes of children with IgAN:The urine TWEAK level of nephrotic-range proteinuria group was higher than that of nonnephrotic-range proteinuria group(P<0.01).The urine TWEAK level of the high total cholesterol group was higher than that of the normal total cholesterol group(P<0.01).The urine TWEAK level of M1 group was higher than that of M0 group(P<0.05),and the urine TWEAK level of C1+C2 group was higher than that in C0 group(P<0.01).The level of urine TWEAK in>1 lesion group was higher than that of ≤1 lesion group and normal control group(all P<0.01).In terms of immune complex deposition types,except for IgA deposition(100%),urinary TWEAK levels in IgG,FRA,IgM,complement C3 and complement C1q immunofluorescence negative and positive groups were not statistically significant(all P>0.05).(3)Comparison of clinical and pathological indexes between high TWEAK group and low TWEAK group.The proportion of with nephrotic-range proteinuria(P<0.05),serum total cholesterol(P<0.01),24-hour urinary protein quantification(P<0.01)in high TWEAK group were higher than those in low TWEAK group,and serum albumin was lower than low TWEAK group(P<0.05).In high TWEAK group,the proportion of crescent formation C1+C2 was higher than that in C0 group,and the proportion of IgAN children with>1 lesion in high TWEAK group was higher than that in low TWEAK group(all P<0.05).There was no significant difference in the proportion of negative and positive deposition of IgG,FRA,IgM,complement C3 and complement Clq between high TWEAK group and low TWEAK group(all P>0.05).(4)Correlation analysis.Urine TWEAK level was negatively correlated with serum albumin(r=-0.488,P<0.01),and positively correlated with 24-hour urinary protein quantification(r=0.509,P<0.01),serum total cholesterol(r=0.471,P<0.01),mesangial cell proliferation(r=0.485,P<0.01)and crescent formation(r=0.475,P<0.01)in IgAN children.Conclusion:The level of urine TWEAK increased in IgAN children,and is correlated with clinicopathological indexes such as serum albumin,24-hour urinary protein quantification,serum total cholesterol,mesangial cell proliferation and crescent formation.The level of urine TWEAK can reflect the severity of the disease in children with IgAN to a certain extent.Part Ⅲ Effect and mechanism of TWEAK on lipid deposition and CXCL16 expression in podocytesObjective:The effects of TWEAK and PTL on lipid deposition and CXCL16 protein expression in podocytes were observed by culturing mouse podocytes in vitro and using TWEAK and NF-κB inhibitor parthenolide(PTL).The factors affecting lipid deposition in podocytes and their regulatory mechanisms were preliminarily explored.Methods:The mouse podocytes were cultured in vitro and incubated respectively with TWEAK,oxLDL,and/or PTL for 12 h,24 h and 48 h.The expression of CXCL16 was detected by Western blot and immunofluorescence.Dil-oxLDL staining was detected by immunofluorescence assay.Results:(1)TWEAK can induce podocyte injury,and the podocyte injury is reduced after PTL intervention.(2)Compared with the control group,the intracellular lipid accumulation in mouse podocytes treated with TWEAK was higher.After incubation with PTL,the intracellular lipid accumulation was significantly reduced.(3)Compared with the control group,the expression of CXCL16 protein in mouse podocytes treated with TWEAK was significantly increased.After incubation with PTL,the expression of CXCL16 was significantly reduced.Conclusion:TWEAK may regulate the expression of CXCL16 in podocytes through NF-κB pathway and affect the uptake of oxLDL by podocytes,mediating podocyte injury.Inhibition of NF-κB pathway may protect podocytes. |
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