Angiotensin-converting Enzyme Gene Insertion/Deletion Polymorphism in Children with Henoch-Schonlein Purpua Nephritis

This study investigated the relationship between angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism and the occurrence, severity, prognosis of HSPN. The polymorphism of ACE gene in 103 HSPN cases and 100 healthy children was studied by using the polymerase chain reactions (PCR). Its relation to the clinical manifestation, pathological classification and prognosis of HSPN was analyzed accordingly. The results showed that: (1) there was a significantly higher frequency for DD genotype in HSPN children (P<0.01); (2) DD genotype was more frequently seen in HSPN children with gross hematuria and massive proteinuria (P<0.05), while DI genotype was more common in HSPN children group with renal insufficiency (P<0.05); (3) although mesangial proliferative lesion was most frequently observed in 21 biopsied HSPN children, and DD genotype frequency was still higher in children with severe pathology (Class Ⅲ Ⅳ); (4)II genotype was significantly frequent in HSPN children with complete remission in the follow-up of 32 HSPN children. It was concluded that the deletion allele of ACE gene might play a role, at least to some extent, in the occurrence, deterioration and progression in juvenile HSPN.

Childhood Henoch-Schnlein Purpura Nephritis and IgA Nephropathy: One Disease Entity?——A Clinico-pathologically Comparative Study

Summary： In order to characterize their relationship through clinicopathological comparison between IgA nephropathy and Henoch-Schoenlein purpura nephritis （HSPN）, 31 children with IgA nephrop- athy aged between 3 to 15 years and 120 children with HSPN aged between 4 to 15 years were compared with each other in clinical manifestation, blood biochemistry, serum immunology and followup study. Renal pathological findings under light microscope, immunofluorescence and electronic microscope were analyzed and also compared between 31 children with IgA nephropathy and 32 biopsied children with HSPN. The results showed that the onset age was over 12 years in 25.8 % children with IgA nephropathy, but only 10 % in HSPN （P〈0.05）. The clinical patterns of IgA nephropathy and HSPN were similar, but extra-renal manifestations were more often in HSPN, all of them had skin purpura, 59 % had gastrointestinal symptoms and 47 % suffered from arthralgia, compared with only abdominal pain in 3.2 % children with IgA nephropathy. The renal pathological investigation showed global sclerosis in 35.5 % of IgA nephropathy and 3.1% of HSPN, mesangial sclerosis in 41.9 % of IgA nephropathy and 6.3 % of HSPN, but endothelial proliferation in 65.6 % of HSPN and 29 % of IgA nephropathy （all P〈0.01）. Thin basement membrane nephropathy was only found in 6. 5 % children with IgA nephropathy, no in HSPN. The electronic dense deposits in HSPN were sparse, lodse and wildly spread in glomerular mesangium, subendothelial area and even intra basement membrane, but it was dense, lumpy and mostly limited in mesangium and paramesangium in IgA nephropathy. Predominant IgA deposits were found in 81.2% of HSPN, and overwhelming IgG deposits in 12.5 % of HSPN with relatively weak IgA deposits, moreover 6.3 % of HSPN showed linear IgG deposits in glomerular capillary. Totally 71. 9 G of HSPN had IgG deposits in glomeruli and only 19.4% of IgA nephropathy showed glomerular IgG deposits （P〈0. 01）. No IgG deposit was observed in 81. 6 % of IgA nephropathy, among them most showed IgA and IgM and/or C3 deposits, moreover overwhelming IgG deposits and linear IgG deposits couldn＇t be found in IgA nephropathy. Mean 20 months follow-up showed complete remission in 72.5% of HSPN, but only 19.4% in IgA nephropathy after 34 months follow-up. Moreover, 64.5 % of IgA nephropathy had consistent hematuria and proteinuria and 16. 1% had active nephritides （P〈0.05）. It was concluded that significant clinico-pathological difference was found between HSPN and IgA nephropathy, which didn＇t support the one disease entity hypothesis. HSPN and IgA nephropathy are probably two diseases with similar immune abnormalities.

Controlled study on therapeutic effect of vessel pricking therapy and western medication for treatment of henoch-schonlein purpura nephritis

Objective To compare the difference of therapeutic effects between vessel pricking therapy and Prednisone for treatment of henoch-schonlein purpura nephritis（HSPN）.Methods Seventy cases of acute purpura nephritis syndrome were randomly divided into an observation group （40 cases） and a control group （30 cases）.Patients in observation group were differentiated into sthenic and asthenic syndromes.Vessel pricking therapy was applied at Hégǔ（合谷 LI 4）,Qūchí（曲池 LI 11）,Xuèhǎi（血海 SP 10） etc.by three-edged needle for sthenic symptom;shallow needling was used at Píshū（脾俞 BL 20）,Shènshū（肾俞 BL 23）,Zúsānlǐ（足三里 ST 36） etc.by filiform needle for asthenic syndromes.The control group was treated with oral administration of Prednisone.The symptom score of TCM,24 h urinary protein,red blood cell count of urinary sediment of both groups were observed before and after treatment and therapeutic effects were compared.Results The total effective rate of 92.5%（37/40） in observation group was superior to that of 80.0%（24/30） in control group,and there was a significant difference between two groups （P0.05）;the symptom score of TCM,24 h urinary protein,red blood cell count of urinary sediment were all improved in both groups after treatment （all P0.05）,and moreover,the improvement in observation group was superior to that of control group （all P0.05）;after treatment,the symptom score of TCM of sthenic syndrome was lower than that of asthenic syndrome in observation group （P0.05）.Conclusion Vessel pricking therapy has a significant therapeutic effect for treatment of HSPN,superior to that of oral administration of Prednisone,and the therapeutic effect is better for treating sthenic syndrome than for asthenic syndrome.

Gene polymorphism in IL-1 receptor antagonist affects its production by monocytes in IgA nephropathy and Henoch-Schonlein nephritis

Objective To define the functional significance of IL-1 receptor antagonist (IL-1ra) gene polymorphism and to investigate, the production of IL-1ra by monocytes from individuals with different genotypes of IL-1.Methods The genotype of IL-1ra was detected by polymerase chain reaction (PCR). Peripheral monocytes obtained from patients with immunoglobin A nephropathy (IgAN), Henoch-Schonlein purpura nephritis (HSPN) and normal subjects were matched in sex and age between the IL1RN-2 allele carriers and non-carriers. The secretion of IL-1ra, IL-1α and IL-1β in the supernatant of GM-CSF (10ng/ml) treated and untreated monocytes were measured by ELISA.Results The secretion of IL-1ra by monocytes stimulated with GM-CSF was significantly higher in the IL1RN-2 allele non-carriers than those of carriers both in IgAN (21.55±3.08 vs 13.85±2.24ng/ml, P<0.001) and HSPN (23.72±6.68 vs 12.67±2.24ng/ml, P<0.01) as well as in normal controls (20.29±1.45 vs 10.51±2.3ng/ml, P<0.001). All showed no significant differences in monocyte secretion of IL-1α and IL-1β by GM-CSF stimulation between the IL1RN-2 allele carriers and non-carriers. Conclusions These results indicate that a functional correlation of the IL1RN-2 allele and IL-1ra production is present in patients with IgAN and HSPN. This gene polymorphism control of IL-1ra production may contribute to the variety of clinical responses to inflammatory stimulation in individuals with different genotype of IL-1ra.

Role of p300 in the pathogenesis of Henoch-Schonlein purpura nephritis and as a new target of glucocorticoid therapy in mice

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.

过敏性紫癜患儿尿液、血清NGAL的表达及意义

目的检测过敏性紫癜(Henoch-Schonlein puroura,HSP)患儿尿液、血清中性粒细胞明胶酶相关脂质运载蛋白(Neutrophil gelatinase-associated lipocalin,NGAL)的水平,进一步探讨其在肾小管间质损伤中的意义。方法随机选取2013年7月至2014年2月首次住院的过敏性紫癜患儿40例,分为尿检正常组及紫癜性肾炎(Henoch-Schonlein puroura nephritis,HSPN)组,同时选取20例年龄与性别相匹配的门诊健康体检者为对照组。采用ELISA检测尿液及血清NGAL,紫癜性肾炎组完善肾小管间质病理分级,所有数据进行统计学分析。结果紫癜性肾炎组及尿检正常组尿液NGAL、血清NGAL、尿视黄醇结合蛋白(Retinol binding protein,RBP)及尿胱抑素C(Cystatin C,CysC)水平均高于正常对照组,紫癜性肾炎组尿液NGAL、血清NGAL、尿RBP及尿CysC高于尿检正常组,差异有统计学意义(P<0.05);HSP尿液NGAL与尿CysC呈正相关(r=0.702,P=0.041),紫癜性肾炎组尿液NGAL与肾小管间质病理级别呈正相关(r=0.720,P=0.036)。结论 NGAL可能参与过敏性紫癜的发病,尿液NGAL水平在一定程度上反映HSP肾小管间质损伤程度,可作为新型的有用的标记物。

Mycophenolate mofetil plus prednisone for inducing remission of Henoch-Sch?nlein purpura nephritis: a retrospective study

Objective： The treatment of Henoch-Schonlein purpura （HSP） with moderate proteinuria remains con- troversial. We retrospectively analyzed the efficacy of immune suppressants, with a particular emphasis on myco- phenolate mofetil （MMF）. Methods： Ninety-five HSP patients with moderate proteinuria （1.0-3.5 g/24 h） after at least three months of therapy with angiotensin-converting enzyme inhibitor （ACEI） or angiotensin receptor blocker （ARB） were divided into three groups： an MMF group （n=33） that received MMF 1.0-1.5 g/d combined with prednisone （0.4-0.5 mg/（kg.d））, a corticosteroid （CS） group （n=31） that received full-dose prednisone （0.8-1.0 mg/（kg.d））, and a control group （n=31）. Patients in the MMF and CS groups continued to take ACEI or ARB at the original dose. The patients in the control group continued to take ACEI or ARB but the dose was increased by （1.73±0.58）-fold. The patients were followed up for 6-78 months （median 28 months）. Results： The baseline proteinuria was higher in the MMF group （（2.1±0.9） g/24 h） than in the control group （（1.6±0.8） g/24 h） （P=0.039）. The proteinuria decreased sig- nificantly in all groups during follow-up, but only in the MMF group did it decrease significantly after the first month. At the end of follow-up, the proteinuria was （0.4±0.7） g/24 h in the MMF group and （0.4±0.4） g/24 h in the CS group, significantly lower than that in the control group （（0.9±1.1） g/24 h）. The remission rates in the MMF group, CS group, and control group were respectively 72.7%, 71.0%, and 48.4% at six months and 72.7%, 64.5%, and 45.2% at the end of follow-up. The overall number of reported adverse events was 17 in the MMF group, 30 in the CS group, and 6 in the control group （P〈0.001）. Conclusions： MMF with low-dose prednisone may be as effective as full-dose prednisone and tend to have fewer adverse events. Therefore, it is probably superior to conservative treatments of adult HSP patients with moderate proteinuria.