Therapeutic effect of mycophenolate mofetil or cyclophosphamide in children with Henoch-Schönlein purpura nephritis of different age groups / 中国当代儿科杂志

OBJECTIVES@#To investigate the difference in the therapeutic effect of mycophenolate mofetil (MMF) or cyclophosphamide (CTX) in children with Henoch-Schönlein purpura nephritis (HSPN) of different age groups.@*METHODS@#A retrospective analysis was conducted on the clinical data of 135 children with HSPN who were treated with MMF or CTX in the Department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics, from October 2018 to October 2020. According to the immunosuppressant used, they were divided into two groups: MMF group and CTX group, and according to the age, each group was further divided into two subgroups: ≤12 years and >12 years, producing four groups, i.e, the ≤12 years MMF subgroup (n=30), the >12 years MMF subgroup (n=15), the ≤12 years CTX subgroup (n=71), and the >12 years CTX subgroup (n=19). All children were followed up for at least 12 months, and the above groups were compared in terms of clinical outcomes and the incidence rate of adverse reactions.@*RESULTS@#There was no significant difference in the complete response rate between the MMF group and the CTX group after 3, 6, and 12 months of treatment (P>0.05). There were no significant difference in the complete response rate and the incidence rate of adverse reactions between the >12 years MMF subgroup and the ≤12 years MMF subgroup at 3, 6, and 12 months of treatment (P>0.05). The >12 years CTX subgroup had a significantly lower complete response rate than the ≤12 years CTX subgroup at 6 and 12 months of treatment (P<0.05). The >12 years CTX subgroup had a significantly higher incidence rate of adverse reactions than the >12 years MMF subgroup (P<0.05).@*CONCLUSIONS@#The efficacy and adverse reactions of MMF are not associated with age, but the efficacy of CTX is affected by age, with a higher incidence rate of adverse reactions. CTX should be selected with caution for children with HSPN aged >12 years.

Clinical characteristics, pathology, and prognosis of children with diffuse endocapillary proliferative Henoch-Schönlein purpura nephritis / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical characteristics, pathology, and prognosis of children with diffuse endocapillary proliferative Henoch-Schönlein purpura nephritis (DEP-HSPN).@*METHODS@#A retrospective analysis was performed on the clinical, pathological, and prognosis data of 44 children with DEP-HSPN and 765 children without DEP-HSPN. The children with DEP-HSPN were diagnosed by renal biopsy in Jiangxi Provincial Children's Hospital from January 2006 to December 2021.@*RESULTS@#Among the 809 children with purpura nephritis, 44 (5.4%) had DEP-HSPN, with a mean age of (8±3) years, and there were 29 boys (65.9%) and 15 girls (34.1%). Compared with the non-DEP-HSPN group, the DEP-HSPN group had a significantly shorter time from onset to renal biopsy and a significantly higher proportion of children with respiratory infection or gross hematuria, and most children had nephrotic syndrome. The DEP-HSPN group had significantly higher levels of 24-hour urinary protein, urinary protein grading, microscopic hematuria grading, serum creatinine, and blood urea nitrogen and significantly lower levels of serum albumin and complement C3 (P<0.05). The DEP-HSPN group had a higher pathological grading, with predominant deposition of IgA in the mesangial area and capillary loops, and higher activity scores in the modified semi-quantitative scoring system (P<0.05). The Kaplan-Meier survival analysis showed that there was no significant difference in the renal complete remission rate between the two groups (P>0.05).@*CONCLUSIONS@#Children with DEP-HSPN have a rapid onset, severe clinical manifestations and pathological grading, and high activity scores in the modified semi-quantitative scoring system. However, most of the children with DEP-HSPN have a good prognosis, with a comparable renal complete remission rate to the children without DEP-HSPN.

A five-year follow-up study on the clinicopathology of 130 children with Henoch-Sch?nlein purpura nephritis / 中华肾脏病杂志

Objective:To analyze the clinicopathologic features and prognosis of children with Henoch-Sch?nlein purpura nephritis (HSPN).Methods:The clinicopathological data of children with HSPN who were followed up for more than 5 years and underwent renal biopsy in Jinling Hospital affiliated to Medical School of Nanjing University from January 2001 to June 2015 were retrospectively analyzed. The follow-up endpoint event was defined as estimated glomerular filtration rate (eGFR)<90 ml·min -1·(1.73 m 2) -1. Participants were divided into two groups according to whether the children had reached the primary endpoint event or not. Cox proportional hazards model was used to analyze the influencing factors of renal poor prognosis in children with HSPN. Kaplan-Meier survival curve method was used for survival analysis, and log-rank test was used to compare the difference of renal cumulative survival rate between segmental sclerosis/adhesion (S1) group and non-segmental sclerosis/adhesion (S0) group. Receiver operating characteristic curve (ROC curve) and area under the curve ( AUC) were used to evaluate the diagnostic value. Results:A total of 130 children with HSPN were enrolled in the study. The median onset age was 11.7(8.6, 13.3) years old, of whom 71 cases were males (54.6%). At a median follow-up time of 100.0(75.8, 119.0) months, 12 cases (9.23%) with HSPN reached the primary endpoint event. Compared with the non-endpoint event group, the endpoint event group had higher proportion of hypertension, higher levels of 24-hour urinary protein, serum cholesterol, serum uric acid, and serum creatinine, and lower levels of serum albumin (all P<0.05). There was no statistical difference in treatment between the two groups (all P>0.05). In terms of pathological features, compared with the non-endpoint event group, the endpoint event group had higher proportion of mesangial hyperplasia (M1), S1, tubular atrophy/interstitial fibrosis (T1/T2) and Glomerulus-Bowman's capsule adhesion (all P<0.05). Multivariate Cox regression model showed that S1 was significantly correlated with renal poor prognosis ( HR=7.739, 95% CI 1.422-42.114, P=0.018). As was revealed in a Kaplan-Meier plot, renal cumulative survival rate in the S1 group was significantly lower than that in the S0 group (log-rank χ2=17.069, P<0.001). The ROC curve showed S1 accurately predicted the outcome ( AUC=0.710, 95% CI 0.549-0.872) with specificity of 0.667(95% CI 0.349-0.901) and specificity of 0.754(95% CI 0.667-0.829). Conclusions:S1 is an independent risk factor affecting renal poor prognosis and has a diagnostic value.

Similarities and differences in the pathogenesis of Henoch-Sch?nlein nephritis and IgA nephropathy / 国际儿科学杂志

IgA vasculitis is a common autoimmune disease mediated by IgA in childhood, which can involve many systems.Henoch-Sch?nlein purpura nephritis(HSPN)is one of the main complications.Both HSPN and IgA nephropathy(IgAN)are common glomerulonephritis in children, but the former is the most common secondary glomerulonephritis and the latter is one of the most persistent diseases in primary glomerulonephritis.There are differences in clinical phenotype and prognosis.This article reviews the relevant literature, and summarizes the similarities and differences in the pathogenesis of HSPN and IgAN, so as to better understand the two diseases.

Diagnostic value of combined detection of urine and plasma kidney injury markers in children with Henoch-Sch?nlein purpura nephritis / 中华检验医学杂志

Objective:To investigate the clinical significance and the diagnostic value of detecting kidney injury biomarkers in urine and serum of children with Henoch-Sch?nlein purpura nephritis (HSPN).Methods:A total of 216 children with untreated HSPN, who were admitted in Beijing Children′s Hospital of Capital Medical University from January 2018 to December 2019, were recruited in this retrospective study. Two hundred and sixteen healthy children were selected as the healthy control group. We determined the levels of six biomarkers of kidney injury, including transferrin (TRF), immunoglobulin (IgG), microalbumin (mAlb), alpha-1 microglobulin (α1-MG), N-acetyl-β-D-glucosaminidase (NAG) in urine and cystatin C (CysC) in serum. The data from the two groups were analyzed, the diagnostic value of each biomarker was evaluated and a logistic regression model for the diagnosis of HSPN was established. In addition, 60 children with HSPN, who were admitted to our hospital from November 2021 to February 2022 and 60 healthy children, who underwent healthy check up in the same period were included to validate the diagnostic performance of the established logistic model. Receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of each biomarker.Results:The urine levels of TRF, IgG, mAlb, α1-MG and NAG and the serum level of CysC were significantly higher in the HSPN group than those in healthy control group (all P<0.05). The area under the ROC curve (AUC) of TRF, IgG, mAlb, α1-MG, NAG and the serum levels of CysC was 0.749, 0.719, 0.810, 0.648, 0.828 and 0.790 (all P<0.05). Logistics regression analysis showed that IgG, mAlb and TRF were the three diagnostic determinants of HSPN ( OR=1.083, 1.105, 1.704,all P<0.001), and the AUC was 0.916 of the established logistic model based on these three biomarkers. The sensitivity was 87.4% and the specificity reached 96.2%. The logistic model was validated by independent cohorts, and the AUC was 0.973, the sensitivity was 95.0% and the specificity was 98.3%. Conclusions:The levels of urine TRF, IgG, mAlb, α1-MG, NAG and serum CysC were higher in children with HSPN. The established logistic regression model based on three biomarkers including IgG, mAlb and TRF in this study has satisfactory clinical value in diagnosing HSPN in children.

Efficacy and safety of leflunomide in treatment of Henoch-Sch?nlein purpura nephritis with nephrotic proteinuria in children / 中国小儿急救医学

Objective:To compare the efficacy and safety of leflunomide(LEF)to mycophenolate mofetil(MMF)and cyclophosphamide(CTX)in the treatment of Henoch-Sch?nlein purpura nephritis(HSPN)in children with nephrotic proteinuria.Methods:Thirty-nine children who were diagnosed as HSPN with nephrotic proteinuria were randomly divided into three groups: LEF group, MMF group and CTX group.Each group had 13 children.Proteinuria, hematuria, adverse effect and cost were followed up at 1, 3, 6 and 9 months of medication.Results:Proteinuria and hematuria were significantly decreased in each group at 1, 3, 6 and 9 months of medication.Compared to CTX group, proteinuria and hematuria in LEF group and MMF group were lower at 9 months.It was probably associated with one child whose proteinuria did not completely return to normal at 9 months and another child who suffered from a relapse of proteinuria and hematuria at 6.5 months in CTX group.The results suggested that the efficacy of LEF and MMF was slightly better than CTX.During the observation period, all children were well tolerated and no serious adverse reactions occurred.One case showed a slight increase of alanine aminotransferase at 1 month, and returned to normal range at 3 months without any medication in MMF group.The cost of LEF group was(8 231±665)RMB and CTX group was(11 523±469)RMB which was significantly lower than(19 953±386)RMB in MMF group.Conclusion:LEF is as effective as MMF and CTX in the treatment of HSPN with nephrotic proteinuria in children.The adverse reactions of LEF are mild, and the cost is cheaper.LEF is worth popularizing in clinical practice.

Clinicopathological feature analysis of diffuse endocapillary proliferative Henoch-Schonlein purpura nephritis in children / 中华实用儿科临床杂志

Objective:To investigate the clinicopathological features, treatment and short-term prognosis of diffuse endocapillary proliferative Henoch-Schonlein purpura nephritis (DEP-HSPN) in children.Methods:Clinicopathological data of children with DEP-HSPN diagnosed by renal biopsy in the First Affiliated Hospital of Zhengzhou University from January 2012 to December 2019 were retrospectively analyzed.Children with HSPN with segmental endocapillary proliferation (non DEP-HSPN) and matched with the gender, age and pathological grade at the ratio of 1∶2 in the same period were recruited as controls.Results:(1) A total of 42 cases of DEP-HSPN were pathologically confirmed, accounting for 5.9% of the 712 children with HSPN during the same period.Thirty-nine newly treated cases were included, with the mean age of (8.9±3.2) years old, and the gender ratio was 1.79∶1.00.There were 21 cases of nephrotic syndrome, 14 cases of hematuria and albuminuria, 2 cases of acute glomerulonephritis, 1 case of rapid progressive nephritis and 1 case of isolated proteinuria.Pathological findings were accompanied by diffuse prolife-ration of mesangial and endocapillary.There were 13, 22 and 4 cases with pathological gradeⅡb, Ⅲb and Ⅳb, respectively.(2) Compared with non DEP-HSPN subjects, DEP-HSPN patients had a shorter course from renal symptoms to renal biopsy, and a higher incidence of nephrotic albuminuria, hypoalbuminemia, hypocomplementemia, hypertension and anemia.The main clinical type was nephrotic syndrome.The levels of D-dimer, 24-hour urinary protein (24 h UP) and urea nitrogen were significantly higher in DEP-HSPN group ( Z=-2.416, -2.595, -2.019, all P<0.05), while the red blood cells, hemoglobin, serum albumin, C 3 and glomerular filtration rate (eGFR) were significantly lower ( t=-2.499, -3.746, 2.836, -3.410, 3.236, all P<0.05). Besides, the glomerular C 3 deposition was higher than those in non DEP-HSPN subjects ( Z=-1.977, P<0.05). (3)The urinary protein remission rate in DEP-HSPN group was significantly reduced at 1 month follow-up [37.0%(10/27 cases) vs.62.5%(40/64 cases), P<0.05]. There was no significant difference between the 2 groups at 3 months, and the urinary protein remission was relieved at 6 months in both groups.There was no significant difference in hematuria remission between the 2 groups at the end of follow-up. Conclusions:Clinical manifestation of DEP-HSPN is severe, which is easy to be complicated with hypertension, anemia, hypocomplementemia C 3 and so on, and the hypercoagulable state is obvious.The degree of glomerular complement C 3 deposition was high in DEP-HSPN group.Urinary protein can be relieved slowly within 1 month after active treatment, but can be relieved at 6 months.

Study on Regulatory Action of Addition and Subtraction of Therapy of Zidiantang to Mmune Inflammatory Factors of Children with Purpura Nephritis / 中国实验方剂学杂志

Objective:To observe clinical effect of addition and subtraction therapy of Zidiantang to purpura nephritis in children （syndrome of blood fever） and regulatory action to immune inflammatory factors. Method:One hundred and twenty-five patients were randomly divided into control group （61 cases） and observation group （64 cases） by random number table. A total of 57 patients in control group completed the therapy （2 patients were falling off or missing visit and 2 was eliminated）， 59 patients in observation group completed the therapy （3 patients were falling off or missing visit and 2 was eliminated）. Both groups' patients got comprehensive measures of western medicine. Patients in control group got Xueniaoan capsule， 1 to 4 grains/time， 3 times/day. Patients in observation groups got addition and subtraction therapy of Zidiantang， 1 dose/day. The treatment was continued for 2 months and the follow up was recorded for a month. Purpura and urinalysis were recorded for every week. And disappearance of purpura， hematuria and proteinuria were compared for 3 months. Before treatment， and at the first， second and during the follow up， scores of 24 h urine protein quantification （24 hup） and syndrome of blood fever were graded. Levels of microalbuminuria （mAlb）， urinary <italic>β</italic>₂-microglobulin （<italic>β</italic>₂-MG）， cystatin C（CysC）， globulin A1（IgA1）， IgG， complement C3， Th17 cells， Treg cells， interleukin-17 （IL-17）， IL-21， IL-10 and transforming growth factor-<italic>β</italic>₁ （TGF-<italic>β</italic>₁） were detected before and after treatment. Result:At the first month of treatment， disappearance rate of purpura in observation group was higher than that in control group （<italic>P</italic><0.05）. Before treatment， and at the first， second and during the follow up， disappearance rate of hematuria and albuminuria were higher than those in control group （<italic>P</italic><0.05）， and scores of 24 h urine protein quantification （24 hup） and syndrome of blood fever were lower than those in control group （<italic>P</italic><0.01）. Levels of mAlb， <italic>β</italic>₂-MG， CysC， IgA1， IgG， Th17， Th17/Treg， IL-17， IL-21 and TGF-<italic>β</italic>₁ were lower than those in control group （<italic>P</italic><0.01）， and levels of C3， CD4⁺， Treg and IL-10 were higher than those in control group （<italic>P</italic><0.01）. Conclusion:On the basis of conventional western medicine treatment， addition and subtraction therapy of Zidiantang can promote the purpura to subside， improve the syndrome symptoms of blood fever， regulate the immune inflammatory reaction， reduce the inflammatory damage of kidney， thus reduce the hematuria and proteinuria， and play a role in protecting the renal function.

Changes of new urinary biomarkers in children with Henoch-Schonlein purpura nephritis / 上海交通大学学报（医学版）

Objective • To evaluate the changes of urinary angiotensinogen (UAGT), fibroblast-specific protein-1 (FSP-1) and thrombin in the children with Henoch-Schonlein purpura nephritis (HSPN). Methods • Fourteen children with HSPN (HSPN group), 28 children with Henoch-Schonlein purpura (HSP) but without renal injury (HSP group) and 23 children with normal urinalysis (control group) were included in the study. Ten HSPN children before treatment (untreated group), 9 HSPN children after glucocorticoid (GC) pulse therapy (GC group) and 8 HSPN children after GC and cyclophosphamide (CTX) double pulse therapy (GC+CTX group) were also selected in the study. Clinical information and fresh morning urine samples were collected from all the children. UAGT, FSP-1 and thrombin in urine were measured by kits. Urine creatinine (Ucr) was also measured for correction. Results • UAGT/ Ucr and FSP-1 in HSPN group were significantly higher than those in HSP group and control group (P0.05), but thrombin levels in HSPN group and HSP group were both significantly higher than that in control group (P<0.05). UAGT/Ucr in HSPN untreated group had no significant difference, compared with GC group, while it was significantly higher than that in GC+CTX group (P=0.000). FSP-1 in untreated group was significantly higher than that in GC group, but had no significant difference, compared with GC+CTX group. There was no significant difference in thrombin among the 3 HSPN groups. Conclusion • UAGT/Ucr, FSP-1 and thrombin all increase in the urine of HSPN children, and UAGT/Ucr and FSP-1 may reflect the treatment effect to some extent. [Key words]

Clinical Efficacy of Modified Zhibo Dihuangwan in Treatment of Purpura Nephritis with Deficiency of Liver and Kidney Yin in Children / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of modified Zhibo Dihuangwan on henoch-schonlein purpura nephritis with deficiency of liver and kidney yin in children (HSPN) and its effect on immune inflammatory response and hypercoagulable state. Method:Totally 120 patients were randomly divided into observation group (60 cases) and control group (60 cases) by random number table. Patients in two group was orally given prednisolone acetate tablets, 1.5-2 mg·kg-1·d-1, 2 times. Four weeks later, the drug was taken orally every other day, and the dosage decreased gradually after 4 weeks. Besides, patients in control group was intravenously dripped with cyclophosphamide, 8-12 mg·kg-1·d-1, for 2 days, and stopped for 2 weeks before another treatment course. The treatment lasted for 6 months. In the control group,Dabuyin Wan was taken orally,3 g/time,3 times/d.Patients in observation group was also added with modified Zhibo Dihuang Wan, 1 doe/day. The treatment lasted for 6 months. Urine routine was tested once a month, and disappearance time and rate of hematuria and albuminuria were recorded. The 24 h urine protein quantification, levels of microalbuminuria (mAlb) and urinary β2-microglobulin (β2-MG) were assessed before and after treatment. Furthermore, deficiency of liver and kidney Yin was scored, and levels of T lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+), fibrinogen (FIB), D-dimer (D-D), fibrin degradation products (FDP), interleukin-2 (IL-2), interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-10 (IL-10) were detected. Result:The clinical efficacy in observation group was superior to that in control group (Z=2.078，P<0.05). Disappearance times of hematuria and albuminuria of children in observation group were shorter than those in control group (P<0.01). The disappearance rate of proteinuria in observation group was 90.48%（38/42）, which was higher than 69.77%（30/43） in control group (χ2=5.694，P<0.05). The 24 h urinary protein quantity, mAlb and levels of β2-MG, FIB, D-D and FDP in observation group were lower than those in control group (P<0.01). The levels of CD3+, CD4+, IL-2 and IFN-γ and the ratio of CD4+/CD8+ in observation group were higher than those in control group (P<0.05), while the CD8+, IL-4 and IL-10 were lower than those in control group (P<0.05). The efficacy in observation group was better than that in control group (Z=2.106，P<0.05). Conclusion:In addition to conventional western medicine therapy, modified Zhibo Dihuang Wan have an effect on HSPN with deficiency of liver and kidney Yin in children by promoting the disappearance of albuminuria and hematuria, shortening the course of disease, improving T lymphocyte subpopulation, reducing inflammatory reaction and correcting hypercoagulable state of blood, with better clinical efficacy and syndrome effect of traditional Chinese medicine.

Clinical manifestations and pathological characteristics of Hen(o)ch-Sch(o)nlein purpura nephritis combined with hyperuricemia in children / 中华实用儿科临床杂志

Objective To analyze the relationship of clinical manifestations and pathological characteristics of Henoch-Sch(o)nlein purpura nephritis combined with hyperuricemia in children.Methods A retrospective study was conducted in 50 children with Henoch-Sch(o)nlein purpura nephritis who hospitalized at Department of Nephrology,Affiliated Children's Hospital,Capital Institute of Pediatrics from January 2014 to May 2018.The differences between the hyperuricemia group(19 cases)and the normal uric acid group (31 cases),were compared in age,sex,blood pressure,serum albumin,24-hour urinary protein,serum creatinine,triglyceride,cholesterol,high density lipoprotein,low density lipoprotein,serum uric acid,estimated glomerular filtration rate,and renal pathological characteristics,and the short-term prognosis was analyzed.Results (1) The average urinary protein in the hyperuricemia group and the normal uric acid group was (91.67 ±90.37) mg/(kg · d) and (64.62 ±43.28) mg/(kg · d),respectively and the difference was statistically significant between the both groups(t =2.04,P =0.047);and the morbidity with massive proteinuria in hyperuricemia group and normal uric acid group was 18/19 cases (94.7％)and 17/31 cases (54.8％),respectively and the difference was statistically significant between the both groups (x2 =8.930,P =0.003).(2)In all cases,there were 4 cases of glomerular pathological grade Ⅱ,43 cases of grade Ⅲ and 3 cases of grade Ⅳ.The pathological grading of hyperuricemia group and normal uric acid group was mainly grade Ⅲ,including 16/19 cases (84.2％) in hyperuricemia group and 27/31 cases (87.1％) in normal uric acid group,4 cases of grade Ⅱ in normal uric acid group and 3 cases of grade Ⅳ in hyperuricemia group,the pathological grade of hyperuricemia group was relatively severe (x2 =7.358,P =0.025).There was no significant difference about the degree of global sclerosis and mesangial proliferation between hyperuricemia group and normal uric acid group(x2 =2.426,P =0.119,x2 =0.043,P =0.836,respectively);7/19 cases (36.8％) had severe foot process lesions in hyperuricemia group,which was significantly higher than that in normal uric acid group [4/31 cases(12.9％)] (x2 =3.934,P =0.047).In hyperuricemia group,tubulointerstitial lesions were found in 9/19 cases (47.4％) of (+) grade and 10/19 cases (52.6％) of (+ +) grade,and 12/31 cases (38.7％) had normal tubulointerstitium in normal uric acid group,(+) and (+ +) grade lesions were also less than those in the hyperuricemia group (x2 =10.694,P =0.005).The mean scores of tubular atrophy and interstitial fibrosis were significantly higher in hyperuricemia group than that in normal uric acid group(t =2.36,P =0.001).(3) The interval from renal biopsy to final visit was 10.0 months and 10.5 monthsin hyperuricemia group and normal uric acid group respectively (P =0.85).In hyperuricemia group,complete remission was found in 5/19 cases (26.3％),slight abnormality in 10/19 cases (52.6％),severe abnormality in 4/19 cases (21.1％).Howe-ver,in normal uric acid group,complete remission was found in 19/31 cases (61.3 ％),10/31 cases (32.3 ％) of slight abnormalities and 2/31 cases (6.5％)of severe abnormalities.The non-remission cases in the hyperuricemia group were significantly higher than those in the normal uric acid group (x2 =7.878,P =0.042).Conclusions Urinary protein was higher in children with Henoch-Sch(o)nlein purpura nephritis complicated with hyperuricemia,the pathological of renal tubulointerstitium and glomerulus and the foot process change are more serious than those of patients with normal uric acid.Therefore,hyperuricemia may be used as a risk factor for poor prognosis.

Prediction of pathological grading of Henoch＿Sch?nlein purpura nephritis in children based on Fisher step-Wise discriminant analysis / 中华实用儿科临床杂志

Objective To establish the pathological grades of Henoch-Sch?nlein purpura nephriti(s HSPN) in children with diagnostic prediction models by stepwise Fisher discriminant in children. Methods Based on the in-vestigation of 28 clinical indicators from 144 cases with HSPN came from Children′s Hospital of Chongqing Medical University,the sensitive indicators were found and stepwise Fisher discriminant model was established and its accuracy in predicting the pathological classification of HSPN was tested. Results There were 5 laboratory indicators and clini-cal manifestations with different pathological grades of HSPN. In children with pathological gradeⅡ,ⅢandⅣ,5 indi-cators were screened(P<0. 05)and stepwise Fisher discriminant models were established. And the correct rate of comprehensive diagnosis was(61. 371 ± 8. 740)% in 100 random sampling diagnostic simulations;in children with pathological gradeⅢa and Ⅲb,5 indicators were also screened(P<0. 05)and stepwise Fisher discriminant models were established. And the correct rate of comprehensive diagnosis was(68. 015 ± 5. 736)% in 100 random sampling diagnostic simulations. Conclusions The stepwise Fisher discriminant models established in this research have a better diagnostic accuracy in forecasting for pathological grade of HSPN,and have a certain guiding value on early treatment and prognosis evaluation of children with newly diagnosed HSPN.

Changes of B cell-activating factor and a proliferation-inducing ligand in serum of children with Hen（o）ch-Sch(o)nlein purpura nephritis / 中华实用儿科临床杂志

Objective To investigate the changes of B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) in serum of children with Hen(o)ch-Sch(O)nlein purpura nephritis (HSPN),and to explore their role in the pathogenesis of children HSPN.Methods A total of 28 children with HSPN who were before treatment were selected in Department of Pediatrics Nephrology and Rheumatology,Shengjing Hospital of China Medical University from November 2017 to August 2018.Sixteen children with Hen(O)ch-Sch(O)nlein purpura were selected as HSP group,and 20 healthy children were selected as healthy control group.Followed the HSPN guideline to cure the patients for 6-8 weeks.The clinical data were collected.Serum levels of BAFF and APRIL were measured by adopting enzyme-linked immunosorbent assay (ELISA).Results (1) Changes of serum BAFF level:the serum levels of BAFF in HSPN children were significantly lower than those in the HSP group and the healthy control group [HSPN group (0.652 ± 0.360) μg/L,HSP group (1.276 ± 0.459) μg/L,healthy control group (1.285 ± 0.299) μg/L,F =17.519,P =0.000].Moreover,the serum levels of BAFF in before treatment were significantly lower than those in after treatment [before treatment (0.652 ± 0.360) μg/L,after treatment (0.860 ± 0.262) μg/L,P ＜ 0.05).However,there were no significant di-fferences in the serum levels of BAFF between HSP group and healthy control group (P ＞ 0.05).(2)Changes of serum APRIL level:the serum levels of APRIL in HSPN and HSP children were both significantly higher than those in healthy control group,but there were no marked differences between the 2 groups [HSPN group (2.285 ± 1.015) μg/L,HSP group (2.609 ± 1.264) μg/L,healthy control group (1.677 ±0.118) μg/L,F =3.647,P =0.016].There were no significant differences in the serum levels of APRIL between before treatment and after treatment [before treatment (2.285 ± 1.015) μg/L,after treatment (2.042 ± 0.695) μg/L,P ＞ 0.05].(3) Pearson correlation analysis results showed that the serum levels of BAFF were negatively correlated with 24 h urinary protein,urinary microalbumin,and urine red blood cell count (r =-0.587,-0.608,-0.515,all P ＜ 0.05).The serum levels of APRIL were positively correlated with serum IgA (r =0.588,P ＜ 0.05).Conclusions The level of serum BAFF decreased and APRIL increased in children with HSPN,which was related to the degree of renal involvement.It suggests that BAFF and APRIL may be related to the pathogenesis of HSPN in children.

Diagnosis and treatment of children with purpura nephritis / 国际儿科学杂志

Henoch-Schonlein purpura nephritis is the most common secondary renal disease in children,which is caused by immune complex mediated glomerular injury.Most children show mild symptoms,only presenting as microscopic hematuria or microalbuminuria,and a few children show renal insufficiency.The diagnosis of purpura nephritis is clear at home and abroad.Both clinical classification and pathological grading have consensus,but there is no unified treatment on the international at present.Early diagnosis and treatment have a profound effect on prognosis.Especially for the continuous proteinuria,multi-drug treatment should be taken to reduce the probability of progression to chronic renal insufficiency.

Clinical Effect of Jiawei Xijiao Dihuang Tang on Henoch-Schonlein Purpura Nephritis of Children with Blood Heat and Stasis Syndrome / 中国实验方剂学杂志

Objective:To observe the clinical effect of Jiawei Xijiao Dihuang Tang on Henoch-schonlein purpura nephritis of children with blood heat and stasis syndrome and the inflammatory factors and coagulation function. Method:One hundred and twenty-two patients were divided into control group (60 cases) and observation group (62 cases) by random number table. Patients in control group got prednisolone acetate tablets every day, 1.5-2 mg·kg-1·d-1, after 4 weeks, of the treatment, and the 4 weeks dosage decreased progressively. Patients in control group also got dipyridamole tablets, 3-5 mg·kg-1·d-1, and compound rutin tablets, 1 tablet/day, 3 times/days. In addition to the therapy of control group, patients in observation group were also given Jiawei Xijiao Dihuang Tang, 1 dose/day. And one course of treatment was 12 weeks. Before and after treatment, blood heat and stasis syndrome were graded. And levels of urinary β2 microglobulin (β2-MG), 24-hour urine protein quantitative (24 h UmAlb), microalbuminuria (mAlb), cystatin C (CysC), platelet count (PLT), plasma prothrombin time (PLT), plasma prothrombin time (PT), activated partial thromboplastin time (APTT), interleukins-2 (IL-2), IL-4, IL-10, tumor necrosis factor-α (TNF-α), von willebrand factor (vWF), platelet activating factor (PAF), thrombomodulin (TM), plasma fibrinogen (FIB), urine RBC and urine protein (PRO) were detected. Result:The total clinical effect in observation group was 95.16%, which was higher than 81.54% in control group (χ2=5.466, Pχ2=12.052, Pβ2-MG, 24 h UmAlb, mAlb and CysC were higher than those in control groups (PPPα and vWF, PAF and TM were lower than those in control groups, but level of IL-2 was higher than that in control groups (PConclusion:In addition to the hormone therapy, Jiawei Xijiao Dihuang Tang can protect renal function, relieve symptoms of proteinuria and hematuria, with the effects of resisting inflammation and alleviating coagulation function.

Changes of B cell-activating factor and a proliferation- inducing ligand in serum of children with Henöch-Schönlein purpura nephritis / 中华实用儿科临床杂志

Objective@#To investigate the changes of B cell-activating factor (BAFF) and a proliferation- inducing ligand (APRIL) in serum of children with Henöch- Schönlein purpura nephritis (HSPN), and to explore their role in the pathogenesis of children HSPN.@*Methods@#A total of 28 children with HSPN who were before treatment were selected in Department of Pediatrics Nephrology and Rheumatology, Shengjing Hospital of China Medical University from November 2017 to August 2018.Sixteen children with Henöch-Schönlein purpura were selected as HSP group, and 20 healthy children were selected as healthy control group.Followed the HSPN guideline to cure the patients for 6-8 weeks.The clinical data were collected.Serum levels of BAFF and APRIL were measured by adopting enzyme-linked immunosorbent assay (ELISA).@*Results@#(1)Changes of serum BAFF level: the serum levels of BAFF in HSPN children were significantly lower than those in the HSP group and the healthy control group[ HSPN group (0.652±0.360) μg/L, HSP group (1.276±0.459) μg/L, healthy control group (1.285±0.299) μg/L, F=17.519, P=0.000]. Moreover, the serum levels of BAFF in before treatment were significantly lower than those in after treatment [before treatment (0.652±0.360) μg/L, after treatment (0.860±0.262) μg/L, P<0.05). However, there were no significant di-fferences in the serum levels of BAFF between HSP group and healthy control group (P>0.05). (2)Changes of serum APRIL level: the serum levels of APRIL in HSPN and HSP children were both significantly higher than those in healthy control group, but there were no marked differences between the 2 groups [HSPN group (2.285±1.015) μg/L, HSP group (2.609±1.264) μg/L, healthy control group (1.677±0.118) μg/L, F=3.647, P=0.016]. There were no significant differences in the serum levels of APRIL between before treatment and after treatment [ before treatment (2.285±1.015) μg/L, after treatment (2.042±0.695) μg/L, P>0.05]. (3)Pearson correlation analysis results showed that the serum levels of BAFF were negatively correlated with 24 h urinary protein, urinary microalbumin, and urine red blood cell count (r=-0.587, -0.608, -0.515, all P<0.05). The serum levels of APRIL were positively correlated with serum IgA(r=0.588, P<0.05).@*Conclusions@#The level of serum BAFF decreased and APRIL increased in children with HSPN, which was related to the degree of renal involvement.It suggests that BAFF and APRIL may be related to the pathogenesis of HSPN in children.

Role of p300 in the pathogenesis of Henoch-Schonlein purpura nephritis and as a new target of glucocorticoid therapy in mice / 中华医学杂志(英文版)

Background@#Henoch-Schonlein purpura nephritis (HSPN) is a very common secondary kidney disease of childhood. Its pathogenesis and the treatment mechanism of glucocorticoid have not been fully elucidated. The aim of this study was to determine the relationship between p300 and the pathogenesis, glucocorticoid therapy in mice with HSPN, respectively.@*Methods@#Forty-eight C57BL/6N male mice, weighing 18 to 20 g, were selected (3–4 weeks old, n = 8 per group). The mice in the normal control group (Group I) were given normal solvent and the HSPN model group (Group II) were given sensitizing drugs. The mice in Group III were injected intraperitoneally with dexamethasone after being given sensitizing drugs. Meanwhile, mice in Groups IV, V and VI with conditional knockout of p300 were also given normal solvent, sensitizing drugs and dexamethasone. The levels of serum IgA, creatinine, and circulating immune complex (CIC) concentrations, 24 h urinary protein and urinary erythrocyte in C57 wild mice, and p300 conditional knockout mice in each group were measured. The expression of p300 in renal tissues and the expression of glucocorticoid receptor (GR) α and β, transforming growth factor (TGF)-β1, and activator protein (AP)-1 after dexamethasone treatment were determined by real-time polymerase chain reaction and Western blotting.@*Results@#Compared with the normal solvent control group (Group I), the expression of p300 mRNA in the model group (Group II) was significantly up-regulated. Western blotting further confirmed the result. Urinary erythrocyte count, 24 h urinary protein quantification, serum IgA, CIC, and renal pathologic score in Group V were distinctly decreased compared with non-knockout mice in Group II (9.7 ± 3.8 per high-power field [/HP] vs. 18.7 ± 6.2/HP, t = 1.828, P = 0.043; 0.18 ± 0.06 g/24 h vs. 0.36 ± 0.08 g/24 h, t = 1.837, P = 0.042; 18.78 ± 0.85 mg/mL vs. 38.46 ± 0.46 mg/mL, t = 1.925, P = 0.038; 0.80 ± 0.27 μg/mL vs. 1.64 ± 0.47 μg/mL, t = 1.892, P = 0.041; 7.0 ± 0.5 vs. 18.0 ± 0.5, t = 1.908, P = 0.039). Compared with non-knockout mice (Group III), the level of urinary erythrocyte count and serum IgA in knockout mice (Group VI) increased significantly after treatment with dexamethasone (3.7 ± 0.6/HP vs. 9.2 ± 3.5/HP, t = 2.186, P = 0.024; 12.38 ± 0.26 mg/mL vs. 27.85 ± 0.65 mg/mL, t = 1.852, P = 0.041). The expression level of GRα was considerably increased in the knockout group after dexamethasone treatment compared with non-knockout mice in mRNA and protein level (t = 2.085, P = 0.026; t = 1.928, P = 0.035), but there was no statistically significant difference in the expression level of GRβ between condition knockout and non-knockout mice (t = 0.059, P = 0.087; t = 0.038, P = 1.12). Furthermore, the expression levels of glucocorticoid resistance genes (AP-1 and TGF-β1) were notably increased after p300 knockout compared with non-knockout mice in mRNA and protein level (TGF-β1: t = 1.945, P = 0.034; t = 1.902, P = 0.039; AP-1: t = 1.914, P = 0.038; t = 1.802, P = 0.041).@*Conclusions@#p300 plays a crucial role in the pathogenesis of HSPN. p300 can down-regulate the expression of resistance genes (AP-1 and TGF-β1) by binding with GRα to prevent further renal injury and glucocorticoid resistance. Therefore, p300 is a promising new target in glucocorticoid therapy in HSPN.

Clinical manifestations and pathological characteristics of Henöch-Schönlein purpura nephritis combined with hyperuricemia in children / 中华实用儿科临床杂志

Objective@#To analyze the relationship of clinical manifestations and pathological characteristics of Henoch-Schönlein purpura nephritis combined with hyperuricemia in children.@*Methods@#A retrospective study was conducted in 50 children with Henoch-Schönlein purpura nephritis who hospitalized at Department of Nephrology, Affiliated Children′s Hospital, Capital Institute of Pediatrics from January 2014 to May 2018.The differences between the hyperuricemia group(19 cases)and the normal uric acid group(31 cases), were compared in age, sex, blood pressure, serum albumin, 24-hour urinary protein, serum creatinine, triglyceride, cholesterol, high density lipoprotein, low density lipoprotein, serum uric acid, estimated glomerular filtration rate, and renal pathological characteristics, and the short-term prognosis was analyzed.@*Results@#(1)The average urinary protein in the hyperuricemia group and the normal uric acid group was (91.67±90.37) mg/(kg·d) and (64.62±43.28) mg/(kg·d), respectively and the difference was statistically significant between the both groups(t=2.04, P=0.047); and the morbidity with massive proteinuria in hyperuricemia group and normal uric acid group was 18/19 cases(94.7%)and 17/31 cases(54.8%), respectively and the difference was statistically significant between the both groups(χ2=8.930, P=0.003). (2)In all cases, there were 4 cases of glomerular pathological grade Ⅱ, 43 cases of grade Ⅲ and 3 cases of grade Ⅳ.The pathological grading of hyperuricemia group and normal uric acid group was mainly grade Ⅲ, including 16/19 cases (84.2%) in hyperuricemia group and 27/31 cases (87.1%) in normal uric acid group, 4 cases of grade Ⅱ in normal uric acid group and 3 cases of grade Ⅳ in hyperuricemia group, the pathological grade of hyperuricemia group was relatively severe (χ2=7.358, P=0.025). There was no significant difference about the degree of global sclerosis and mesangial proliferation between hyperuricemia group and normal uric acid group(χ2=2.426, P=0.119, χ2=0.043, P=0.836, respectively); 7/19 cases (36.8%) had severe foot process lesions in hyperuricemia group, which was significantly higher than that in normal uric acid group [4/31 cases(12.9%)](χ2=3.934, P=0.047). In hyperuricemia group, tubulointerstitial lesions were found in 9/19 cases (47.4%) of (+ ) grade and 10/19 cases (52.6%) of (+ + ) grade, and 12/31 cases (38.7%) had normal tubulointerstitium in normal uric acid group, (+ )and (+ + )grade lesions were also less than those in the hyperuricemia group(χ2=10.694, P=0.005). The mean scores of tubular atrophy and interstitial fibrosis were significantly higher in hyperuricemia group than that in normal uric acid group(t=2.36, P=0.001). (3) The interval from renal biopsy to final visit was 10.0 months and 10.5 monthsin hyperuricemia group and normal uric acid group respectively (P=0.85). In hyperuricemia group, complete remission was found in 5/19 cases (26.3%), slight abnormality in 10/19 cases (52.6%), severe abnormality in 4/19 cases (21.1%). Howe-ver, in normal uric acid group, complete remission was found in 19/31 cases (61.3%), 10/31 cases (32.3%) of slight abnormalities and 2/31 cases (6.5%)of severe abnormalities.The non-remission cases in the hyperuricemia group were significantly higher than those in the normal uric acid group(χ2=7.878, P=0.042).@*Conclusions@#Urinary protein was higher in children with Henoch-Schönlein purpura nephritis complicated with hyperuricemia, the pathological of renal tubulointerstitium and glomerulus and the foot process change are more serious than those of patients with normal uric acid.Therefore, hyperuricemia may be used as a risk factor for poor prognosis.

Prediction of pathological grading of Henoch-Schönlein purpura nephritis in children based on Fisher stepwise discriminant analysis / 中华实用儿科临床杂志

Objective@#To establish the pathological grades of Henoch-Schönlein purpura nephritis(HSPN) in children with diagnostic prediction models by stepwise Fisher discriminant in children.@*Methods@#Based on the investigation of 28 clinical indicators from 144 cases with HSPN came from Children′s Hospital of Chongqing Medical University, the sensitive indicators were found and stepwise Fisher discriminant model was established and its accuracy in predicting the pathological classification of HSPN was tested.@*Results@#There were 5 laboratory indicators and clinical manifestations with different pathological grades of HSPN.In children with pathological grade Ⅱ, Ⅲ and Ⅳ, 5 indicators were screened (P<0.05) and stepwise Fisher discriminant models were established.And the correct rate of comprehensive diagnosis was (61.371±8.740)% in 100 random sampling diagnostic simulations; in children with pathological grade Ⅲa and Ⅲb, 5 indicators were also screened (P<0.05) and stepwise Fisher discriminant models were established.And the correct rate of comprehensive diagnosis was (68.015±5.736)% in 100 random sampling diagnostic simulations.@*Conclusions@#The stepwise Fisher discriminant models established in this research have a better diagnostic accuracy in forecasting for pathological grade of HSPN, and have a certain guiding value on early treatment and prognosis evaluation of children with newly diagnosed HSPN.

Changes and significance of serum midkine in children with allergic purpura and purpura nephritis / 中国小儿急救医学

Objective@#To investigate the role of midkine(MK)in the pathogenesis of Henoch-Schonlein purpura(HSP) and Henoch-Schonlein purpura nephritis(HSPN).@*Methods@#In the case group, 35 cases were hospitalized in the pediatric kidney rheumatism immunology ward of Shengjing hospital affiliated to China Medical University from December 2016 to January 2018.Among them, 10 cases were HSP, 25 were HSPN.According to quantitative level of 24-hour urine protein, HSPN group was divided into HSPN(nephrotic level of proteinuria)group of 15 cases and HSPN(non-nephrotic level of proteinuria)group of 10 cases.The control group consisted of 12 healthy cases who underwent physical examination at outpatient department in the same period in the developmental pediatric clinic of our hospital.Blood samples were collected to detect MK.The other clinical datas including renal function, 24-hour urine protein quantitative, immunoglobulin, etc were collected.The serum MK and renal function indexes were compared among groups.The correlation between MK and various clinical indicators was analyzed, and the receiver operating characteristic(ROC) curve was used to analyze the diagnostic significance of MK for HSP and HSPN.@*Results@#MK level of case group was higher than that of healthy control group[(289.34±160.70)pg/ml vs.(100.03±56.75)pg/ml, P<0.05]. Moreover, the difference of MK concentration among the HSPN(nephrotic proteinuria)group, the HSPN(non-nephrotic proteinuria)group and the HSP group was still statistically significant[(449.91±141.91)pg/ml vs.(244.04±89.15)pg/ml vs.(175.94±46.30)pg/ml, P<0.05]. MK was positively correlated with urine microalbumin(r=0.54), IgA(r=0.132), IgE(r=0.304), urine β2 microglobulin(r=0.483), 24-hour urine protein /body weight(r=0.503), and urine transferrin level(r=0.509)in the case group(P<0.05). According to the ROC curve, the area under ROC of MK for predicting the diagnosis of HSP was 0.908(95%CI 0.828-0.988). The optimal value in predicting the diagnosis of HSP was 182.762 pg/ml, with sensitivity and specificity of 81.4% and 91.7%.The area under ROC of MK in predicting HSPN was 0.947(95%CI 0.888-1.000), and the optimal value of predicting HSPN was 218.186 pg/ml, with sensitivity and specificity of 84.0% and 95.5%.@*Conclusion@#MK may be involved in the pathogenesis of HSP and HSPN.It can provide the basis for clinical diagnosis of HSP and HSPN, and has significance in evaluating the degree of renal damage of HSPN.