Henoch-Schönlein Purpura Nephritis Research Articles

Efficacy of steroid and immunosuppressant combined therapy in Chinese patients with Henoch–Schönlein purpura nephritis: A retrospective study

Suitable and efficient treatments for Henoch-Schönlein purpura nephritis (HSPN) with proteinuria remains unclear. Whether steroids combined with immunosuppressive agents improves prognosis compared to steroid therapy alone also remains controversial. This study explored whether combined therapy reduces proteinuria in HSPN patients with different pathological features. Chinese patients (n = 84) diagnosed with HSPN with proteinuria by renal biopsy between 2010 and 2019 were retrospectively studied. Patients were grouped into the steroid group (control) or the combined steroid and immunosuppressant group. Estimated glomerular filtration rate (eGFR) (mL/min/1.73 m2/y) and proteinuria were measured. The primary outcome progression was analyzed using Kaplan–Meier survival curves. The effect of the combined therapy on renal outcome was analyzed by multivariable Cox regression. Propensity score matching and sensitivity analysis were used to explore whether pathological features impacted prognosis. Patients who received combined steroid and immunosuppressant therapy were more likely to recover from HSPN and had proteinuria <3 g/24 h (P = 0.02) or 1 g/24 h (P = 0.03). Multiple Cox regression analysis confirmed that this decrease was independent of renin–angiotensin system blockers. Further sensitivity analysis showed that combined therapy was effective in patients with crescents (P = 0.02). However, combined steroid and immunosuppressant therapy was not more effective in patients with endocapillary hypercellularity (E), tubular atrophy/interstitial fibrosis (T), or segmental sclerosis (S). Combined steroid and immunosuppressant therapy was significantly associated with HSPN remission, and more effectively decreased proteinuria during the initial disease phase.

Off-label use of tacrolimus in children with glomerular disease: Effectiveness, safety and pharmacokinetics.

Glomerular diseases are leading causes of end-stage renal disease in children. Tacrolimus is frequently used off-label in the treatment of glomerular diseases. The effectiveness, safety and pharmacokinetic data of tacrolimus in the treatment of glomerular diseases in children are reviewed in this paper to provide evidence to support its rational use in clinical practice. The remission rates in previously published studies were different. In 19 clinical trials on children with nephrotic syndrome, the overall remission rate was 52.6-97.6%. In four clinical trials on children with lupus nephritis, the overall remission rate was 81.8-89.5%. In a pilot study with paediatric Henoch-Schönlein purpura nephritis patients, the overall remission rate was 100.0%. Infection, nephrotoxicity, gastrointestinal symptoms and hypertension are the most common adverse events. Body weight, age, CYP3A5 genotype, cystatin-C and daily dose of tacrolimus may have significant effects on the pharmacokinetics of tacrolimus in children with glomerular disease. More prospective controlled trials with long follow-up are needed to demonstrate definitely the effectiveness, safety and pharmacokinetics of tacrolimus in children with glomerular diseases.

Preventive Effect of Tonsillectomy on Recurrence of Henoch-Schönlein Purpura Nephritis after Intravenous Methylprednisolone Pulse Therapy.

Henoch-Schönlein purpura (HSP) is regarded as a benign and self-limiting vasculitis characterized by purpura, arthritis, and gastrointestinal symptoms; however, about one third of the patients develop HSP nephritis (HSPN), the most serious long-term complication. Since 2013, we have proposed that tonsillectomy in addition to intravenous methylprednisolone pulse therapy (IVMP) be performed in all patients with HSPN, similar to immunoglobulin A nephropathy (IgAN) patients because both diseases are considered to a share common pathogenesis. Herein, we retrospectively reviewed the clinical courses of 71 Japanese children with HSPN (34 boys; median age at diagnosis, 6.7 years; median follow-up period, 5.6 years) who had received initial treatment with IVMP (15-20 mg/kg; on 3 consecutive days/week for 3 weeks) followed by oral prednisolone (initially 1 mg/kg; tapered off within 12 months) and achieved clinical remission (i.e., disappearance of both proteinuria and hematuria). The patients were divided into two groups: 31 patients receiving tonsillectomy after IVMP between 2013 and 2017 (tonsillectomy group) and 40 patients receiving IVMP monotherapy between 2003 and 2012 (IVMP group). For the 2 years after IVMP therapy, the rate of HSPN recurrence (i.e., persistent proteinuria combined with hematuria requiring additional treatments) after clinical remission was significantly lower in the tonsillectomy group than the IVMP group (0% vs. 19%, P < 0.05). Despite the short follow-up period in the tonsillectomy group, this study provides the evidence that tonsillectomy may be beneficial for preventing recurrence of HSPN from clinical remission with IVMP therapy in Japanese children.

Safety and Efficacy Evaluation of Traditional Chinese Medicine (Qingre-Lishi-Yishen Formula) Based on Treatment of Regular Glucocorticoid Combined with Cyclophosphamide Pulse in Children Suffered from Moderately Severe Henoch-Schonlein Purpura Nephritis with Nephrotic Proteinuria.

Objective At present, the most appropriate management of Henoch–Schonlein purpura nephritis (HSPN) with nephrotic-range proteinuria still remains controversial; thus, the purpose of this study is to evaluate safety and efficacy of traditional Chinese medicine (TCM), Qingre-Lishi-Yishen Formula (QLYF), integrated with regular oral glucocorticoid and cyclophosphamide intravenous pulse therapeutic regimen in children suffered from moderately severe HSPN with nephrotic proteinuria. Methods From 1 January 2012, to 1 January 2016, totally 150 hospitalized children suffered from HSPN with nephrotic proteinuria were included. All were treated with glucocorticoid and cyclophosphamide, and 100 of them were treated with integrative traditional Chinese decoction QLYF. Patients were followed up for 2 years. Rate of adverse event occurrence, short-term clinical effects, long-term clinical effects, and TCM therapeutic evaluation were all compared. Results Total adverse event rate was lower in the QLYF group (χ2 = 5.357, p = 0.022); rates of respiratory infection, urinary infection, poor appetite, hepatotoxity, cardiotoxicity, and neutropenia were all decreased in patients who received QLYF (p = 0.022); rates of respiratory infection, urinary infection, poor appetite, hepatotoxity, cardiotoxicity, and neutropenia were all decreased in patients who received QLYF (p = 0.022); rates of respiratory infection, urinary infection, poor appetite, hepatotoxity, cardiotoxicity, and neutropenia were all decreased in patients who received QLYF (p = 0.022); rates of respiratory infection, urinary infection, poor appetite, hepatotoxity, cardiotoxicity, and neutropenia were all decreased in patients who received QLYF (p = 0.022); rates of respiratory infection, urinary infection, poor appetite, hepatotoxity, cardiotoxicity, and neutropenia were all decreased in patients who received QLYF (p = 0.022); rates of respiratory infection, urinary infection, poor appetite, hepatotoxity, cardiotoxicity, and neutropenia were all decreased in patients who received QLYF (Conclusion Compared with merely using regular oral glucocorticoid plus cyclophosphamide pulse therapeutic regimen, the therapeutic regimen that integrates QLYF with the abovementioned western medicine might be a safe means to decrease the occurrence rate of adverse events and improve short-term and long-term clinical effects in children who suffered from moderately severe HSPN with nephrotic proteinuria.

Analyses of ultrasound-guided percutaneous pediatric kidney biopsy results: A single center experience

Aim: Percutaneous pediatric kidney biopsies (KB) performed in our center for the past 5 years were evaluated retrospectively. The relationship was examined between histopathological results and variables such as age, gender and ethnicity (Turkish and Syrian children).Material and Methods: A total 330 ultrasound-guided percutaneous pediatric KBs were performed in our center between January 2015 and September 2019. The study included 318 pediatric patients comprising 152 females and 178 males with a mean age of 9.50 ± 4.89 years (range, 2 months- 18 years). Indications, results and complications of the KBs were retrospectively evaluated. Histopathological results were statistically compared between genders and three age groups (0-2, 2-12 and 12-18 years of age). Comparisons were made between the ethnicities and histopathological results.Results: The most common indication for KB was nephrotic syndrome (n: 220, 66.7%). In the biopsy results, the most common primary (n: 230, 69.7%) and secondary (n: 74, 22.4%) glomerular diseases were focal segmental glomerulosclerosis (n: 101, 30.6%) and Henoch-Schonlein purpura nephritis (n: 41, 12.4%), respectively. A statistically significant relationship was determined between the biopsy results and age and gender. No statistically significant relationship was observed between the biopsy results and ethnicity.Conclusion: KB is an important intervention for the identification of glomerular diseases, requiring appropriate treatment in children. The ethnic origin of the patients had no effect on the frequency of the type of the diseases.

Diagnosis and treatment of children with purpura nephritis

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. Key words: Children; Purpura nephritis; Diagnosis; Treatment

Dermatomyositis combined with IgA vasculitis: A case report

Dermatomyositis (DM) is an autoimmune disease characterized by muscle involvement of the proximal extremities and specific skin involvement, like Gottron sign and heliotrope rash. HenochSchonlein purpura (IgA vasculitis) nephritis is characterized by hematuria and/or proteinuria clinically, with histologic evidence of IgA nephropathy, and also can be clinically characterized by non-thrombocytopenic purpura, presenting with petechiae and ecchymosis on the skin and mucous membranes, often involving multiple organs and systems, accompanied by abdominal pain, joint swelling and pain, and renal lesions. We reported here a patient with symmetric muscle weakness in her proximal limbs and typical Gottron sign, whose laboratory examination showed elevated creatine kinase (CK) level and myogenic damage electromyographically, which were concomitant with dermatomyositis. We applied prednisone combined with cyclophosphamide, and the patient's muscle strength, interstitial lung disease and all improved gradually. The patient gradually developed severe hepatic damage [significantly increased glutamic-pyruvic transaminase (ALT), glutamic oxalacetic transaminase (AST) and bilirubin], high fever (body temperature fluctuated between 38.0-39.2 °C), thrombocytopenia (limb distal purplish rash, some slightly protruded from the skin surface, some fused into a piece, which did not fade with pressure) and intractable diarrhea (waterlike stool, antidiarrheal drug treatment was not good), with new onset of the skin lesions on multiple areas of her body, as well as abrupt occurrence of massive proteinuria, which resulted in huge challenges in the following diagnosis and treatment. After extensive differential diagnosis from various directions, including pathological biopsies, it finally came out to be dermatomyositis combined with IgA vasculitis, which had been rarely reported. Both cellmediated immunity to muscle antigens and immune-complex disease might participate in the pathogenesis. There was evidence that they were immune complex diseases. Several immune mechanisms played an important role in the pathogenesis of both DM and IgA vasculitis. We conducted a substantial literature review of the above diseases. The purpose of our study is to strengthen the clinical understanding of such complicated diseases, and to highlight the importance of pathological biopsy in the diagnosis (renal biopsy pathology gave us a definite diagnosis). And what is more important is that seizing the opportunity to initiate treatment can control the disease and improve the prognosis.

The limited role and risky profile of Rituximab in nephritis associated with Henoch-Schönlein purpura

Adult-onset IgA vasculitis or Henoch-Schönlein purpura (HSP) is a systemic vasculitis characterized by IgA1-dominant deposits. The symptoms include cutaneous purpura, ankle arthritis, enteritis and nephritis. HSP nephritis (HSPN) can be severe and refractory to corticosteroids with/without immunosuppressive agents. The concept of depletion of antibody producing B cell with Rituximab is appealing despite the uncertainity of HSP pathogenesis. In the present case report; we describe our experience with Rituximab treatment in a patient with this disease. Our patient had different triggering factors for her relapses and lately Rituximab itself. Review of the literature indicates that autoantibodies to Gd-IgA1 did not decrease with Rituximab therapy and others indicated an inherited predisposition for higher levels in patients with progressive disease. Our findings confirm the limited role and risky profile of Rituximab in treatment of HSP. &#x0D; Keywords: HSP, IgA, Rituximab, vasculitis.

Predicting renal outcomes in immunoglobulin A vasculitis nephritis; from ISKDC classification to Oxford MEST-C classification

Immunoglobulin A vasculitis nephritis (IgAVN) or Henoch-Schönlein purpura nephritis (HSPN) is the most common type of secondary IgA nephropathy (IgAN), particularly in children. Overall, its prognosis is good, but in a significant number of cases, it does lead to chronic kidney disease (CKD) and end-stage renal disease (ESRD). Various classifications exist to predict the long-term outcome of kidney disease in these diseases, but none is universally accepted. We searched PubMed, Web of Science Embase, EBSCO, Scopus and directory of open access journals (DOAJ) with keywords of Henoch-Schönlein purpura nephritis, immunoglobulin A vasculitis nephritis, immunoglobulin A nephropathy, IgA vasculitis, extracapillary proliferation, IgA nephropathy, leukocytoclastic vasculitis, endstage renal disease, Oxford classification, crescent and childhood IgA vasculitis. IgAVN in children presents most often with crescents and endocapillary proliferation, with relapsing and remitting course clinically. Due to morphological resemblance of IgAVN and IgAN, the Oxford MEST-C scores could be applied for determining the long-term outcomes in the former disease. A critical concern in applying Oxford classification for IgAVN is that limited number of children with IgAVN exists in any one center and also a relatively short period of follow-up. Hence, further work in this regard is necessary. Preliminary evidence suggests that Oxford MEST-C classification is valid in predicting long-term kidney outcomes in children with IgAVN and the classification can also be used in adults. However, further, large scale, multicenter, international collaborative studies are needed to address the unmet issues.

Changes of coagulation and fibrinolysis system in children with Henoch-Schonlein purpura nephritis and its clinical significance

Objective To investigate the changes of coagulation and fibrinolysis system in children with Henoch-Schonlein purpura nephritis and its clinical significance. Methods From January 2013 to December 2016, 73 children with Henoch-Schonlein purpura inthe First People's Hospital of Huzhouwere selected as the Henoch-Schonlein purpura group, 73 children with Henoch-Schonlein purpura nephritis were selected as the Henoch-Schonlein purpura nephritis group, and 73 healthy children were selected as the control group.Antithrombin III activity (AT III), fibrinogen degradation products (FDP), plasma D-dimer (D-D), prothrombin activator inhibitor-1 (PAI-1), tissue plasminogen activator (t-PA), fibrinogen (FIB) levels and 24-hour urinary protein excretion were measured in three groups. Results The levels of FIB, AT III%, FDP, D-D, PAI-1 and t-PA in the Henoch-Schonlein purpura group and the Henoch-Schonlein purpura nephritis group[(2.89±0.76)g/L, (3.51±0.81)g/L; (145.72±8.46)%, (163.24±9.05)%; (1.31±0.67)mg/L, (1.54±0.72)mg/L; (0.87±0.52)mg/L, (1.18±0.67)mg/L; (66.47±2.58)ng/L, (91.02±3.24)ng/L; (16.34±0.98)μg/L, (12.35±1.06)μg/L]were higher than those in the control group[(1.88±0.54)g/L, (119.48±8.92)%, (0.92±0.33)mg/L, (0.32±0.18)mg/L, (31.25±3.02)ng/L, (6.82±0.75)μg/L](t=9.256, 18.236, 4.462, 8.540, 75.760, 65.912; 14.306, 29.423, 6.688, 10.591, 115.297, 36.387, all P 0.05). The 24-hour urinary protein excretion was positively correlated with AT III%, FDP, D-D and IL-33 in patients with Henoch-Schonlein purpura nephritis (r=0.502, 0.546, 0.483, all P 0.05). Conclusion Patients with purpuric nephritis are in a state of hypercoagulability and hyperfibrinolysis, and coagulation and fibrinolysis disorders are closely related to renal damage in patients. Key words: Purpura, Henoch-Schonlein; Nephritis; Antithrombin III activity; Fibrinogen degradation products; Plasma D dimer

Changes of B cell-activating factor and a proliferation-inducing ligand in serum of children with Hen(o)ch-Sch(o)nlein purpura nephritis

Objective To investigate the changes of B cell-activating factor (BAFF) and a proliferation- inducing ligand (APRIL) in serum of children with Henoch- Schonlein 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 Henoch-Schonlein 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). (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. Key words: Henoch- Schonlein purpura nephritis; Child; B cell-activating factor; Proliferation-inducing ligand

Comparison of clinical characteristics of diffused capillary endothelial proliferative Henoch-Schonlein purpura nephritis children with or without crescents formation

Objective To compare the clinical features of diffuse capillary endothelial proliferative Henoch-Schonlein purpura nephritis (DEP-HSPN) with or without crescent formation. Methods The clinical data of 110 children with DEP-HSPN admitted to Dalian Central Hospital and the First Affiliated Hospital of Dalian Medical University from January 2008 to January 2018 were analyzed retrospectively.Among them, 24 cases were divided into non crescentic group and 86 cases into crescentic group.The clinical characteristics and prognosis of the two groups were statistically analyzed. Results The clinical manifestations of children without crescent body formation group were all type III.There were 35 cases of type III and 51 cases of type V in the crescent body formation group.Compared with non-crescent formation group, the proportion of gross hematuria(83.7%(72/86) vs.29.2%(7/24), χ2=10.396), urine red blood cell count ((112.4±20.3)/HP vs.(45.2±10.6)/HP, t=9.697), 24 h urine protein ((2471.6±242.0) mg/d vs.(1358.5±109.3) mg/d, t=6.372) and serum creatinine ((44.9±9.6) μmol/L vs.(32.3±5.2) μmol/L, t=5.390) increased significantly, the serum albumin ((22.8±3.8) g/L vs.(35.1±5.7) g/L, t=4.806)decreased significantly (all P 0.05). Conclusion When DEP-HSPN is accompanied by crescent formation, gross hematuria, urinary erythrocyte count and the proportion of massive proteinuria increase significantly.Combined immunosuppressive therapy in acute stage and long-term sequential treatment in remission stage can achieve good prognosis. Key words: Glomerulo nephritis; Henoch-Schonlein purpura; Endocapillary proliferation; Children

Parents’ Resilience Affects Condition of Children With Henoch-Schönlein Purpura Nephritis

The impact of parents’ resilience on the condition of children with Henoch-Schönlein purpura nephritis (HSPN) is still unknown. In this cross-sectional study, the mental resilience was investigated by CD-RISC in 146 parents between April 2016 and January 2017. The average resilience was 56.37 ± 11.62 and negatively correlated with children’s 24-hour urinary protein, serum creatinine, and recurrent frequency (P < 0.001). Furthermore, the higher the parents’ resilience, the lower the incidence of edema (P < 0.001), nephritis/nephrotic syndrome (P = 0.002), and renal insufficiency (P = 0.001) in children. In conclusion, parents’ resilience level is generally low and has an adverse impact on the condition of HSPN children.

MiR-29b expression is altered in crescent formation of HSPN and accelerates Ang II-induced mesangial cell activation

MicroRNA-29b (miR-29b) has been suggested to possess pro-inflammatory activity, which can partially be explained by the repression of tumor necrosis factor alpha protein three antibody (TNFAIP3). Meanwhile, it also promotes thyroid cell proliferation via Smad signaling pathways. The present study aimed to elucidate the role of miR-29b in Henoch Schönlein purpura nephritis (HSPN) and its underlying molecular mechanism in angiotensin II (Ang II)-induced human glomerular mesangial cell (HGMC) activation. We evaluated miR-29b expression in 35 HSPN renal tissues based on crescent formation, glomerular sclerosis, interstitial fibrosis, thrombosis formation and capillary loop necrosis. Meanwhile, HGMCs were cultured, treated with Ang II and then transfected with LV-hsa-miR-29b-1 to induce miR-29b overexpression or LV-hsa-miR-29b-3p-inhibition to inhibit miR-29b expression. Finally, we examined the effects of miR-29b on cell proliferation and release of inflammatory mediators. We observed that miR-29b expression was significantly higher in the crescent group than in the no crescent group. MiR-29b overexpression induced the release of intercellular adhesion molecule-1, interleukin-1β (IL-1β), IL-6, IL-8, the increase of CyclinA2, CyclinD1, and cell proliferation. It also could inhibit the expressions of TNFAIP3 and NF-kappa-B-repressing factor (NKRF). Correspondingly, miR-29b inhibition produced the opposite effects and increased the expression of TNFAIP3 and NKRF. MiR-29b expression is altered in crescent formation of HSPN and accelerates Ang II-induced mesangial cell proliferation and release of inflammatory mediators.

Beneficial Effects of Qingzixiaoban Granule on Henoch-Schönlein Purpura Nephritis Mice through Inhibiting Immune Complex Deposition and Th2 Immunodeviation.

Background Henoch–Schönlein purpura nephritis (HSPN) is the principal cause of morbidity and mortality in Henoch–Schönlein purpura (HSP). However, there is no absolute consensus for the best management of severe HSPN till now. Qingzixiaoban Granule (QZXB GR), a traditional Chinese medicine formula, has been applied to treat HSP in clinical in China. However, the therapeutic effects and potential mechanism of QZXB GR on HSPN is still unknown. Methods A Gliadin plus Indian Ink-induced HSPN mice model was established. Renal histopathologic changes and the subcutaneous hemorrhage on left legs were assessed. Hematuria and proteinuria were determined using hemocytometer and bicinchoninic acid assay, respectively. The serum circular immune complex and interleukin-6 were quantified by ELISA. Using blood biochemical analyzer, the renal biochemical parameters, including serum total protein, albumin, creatinine, and blood urea nitrogen, were measured. The deposition of immune complex in renal tissues and the lymphocyte subsets in peripheral blood and spleen was investigated by immunohistochemistry and flow cytometry. Results QZXB GR treatment significantly ameliorated renal injury in HSPN mice, by attenuating renal histopathological changes, reducing subcutaneous hemorrhage, decreasing proteinuria/hematuria, regulating renal biochemical parameters, and inhibiting the release of serum interleukin-6. Furthermore, QZXB GR treatment significantly decreased the level of serum circular immune complex, decreased immune complex IgA and IgG deposition in renal tissue, and suppressed Th2 immunodeviation. Conclusion QZXB GR could prevent renal injury in HSPN mice, and its renoprotective mechanism might be exerted partly through suppressing immune complexes deposition and Th2 immune deviation.

Clinical effect of double filtration plasmapheresis combined with glucocorticoid and immunosuppressant in treatment of children with severe Henoch-Schönlein purpura nephritis

To study the clinical effect and safety of double filtration plasmapheresis (DFPP) combined with double pulse therapy with methylprednisolone (MP) and cyclophosphamide (CTX) in the treatment of children with severe Henoch-Schönlein purpura nephritis (HSPN). A total of 60 children with severe HSPN who were admitted to the hospital from January 2014 to March 2018 were enrolled and were randomly divided into an observation group and a control group (n=30 each). In addition to routine treatment, the children in the control group were given MP+CTX pulse therapy. Those in the observation group were given DFPP treatment in addition to the treatment in the control group, with three courses of treatment in total. After three courses of treatment, the two groups were compared in terms of 24-hour urinary protein, urinary microproteins, renal function parameters, adverse reactions, and clinical outcome. After three courses of treatment, the observation group had significantly greater reductions in 24-hour urinary protein, urinary albumin, urinary immunoglobulin G, urinary β2-microglobulin, serum creatinine, and blood urea nitrogen than the control group (P<0.05). After the treatment ended, the observation group had a significantly shorter time to achieve remission than the control group (P<0.05). No serious adverse reactions, such as hemorrhagic cystitis, thrombocytopenia, and hemolysis, were observed, and there was no significant difference in the overall incidence rate of adverse reactions between the two groups (P>0.05). Compared with MP+CTX pulse therapy alone in the treatment of severe HSPN in children, DFPP combined with MP+CTX pulse therapy can further alleviate renal injury and improve clinical outcome and does not increase the incidence rate of adverse reactions.

Clinical Effect of Total Glucosides of Paeonia as the adjuvant therapy on Hematuria and Proteinuria Purpura Nephritis and Its Effect on Serum Cytokines

Objective To investigate the efficacy of total glucosides of paeony (TGP) in the treatment of hematuria and proteinuria purpura nephritis (HSPN) and serum interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta) and interleukin-18 (IL-18). Methods From June 2017 to December 2018, 64 cases of children with primary hematuria and proteinuria purpura nephritis admitted to the department of pediatrics affiliated hospital of Xuzhou medical university were selected as study subjects, and were divided into control group (33 cases) and observation group (31 cases) according to random number method.The children in the control group were given oral administration of poniasone acetate, and the observation group was treated with TGP on the basis of the control group.Both groups received continuous treatment for 4 weeks.Two groups′ before and after treatment expression level of serum interleukin-6, interleukin-1β and interleukin-18, and level of clinic indicator such as Urinary red biood cell (URBC), 24 hour urinary protein quantity, urinary immune globulin G (IGU), micro-albuminuria (urinary microalbumin, MAU), α-Microglobulin (α1-MG) and urinary transferrin (TFRU) is made a comparison. Results After 4weeks of treatment, the total clinical effective rate of the observation group (93.5% (29/31)) was significantly higher than that of the control group (72.7% (24/33)), and the difference between the two groups was statistically significant (χ2=4.868, P 0.05). After treatment, in the observation group, Serum IL-6 ( (16.68±6.83) ng/L and (32.24±6.99) ng/L, t=12.373), IL-1β((63.83 ±8.97)ng/L and (85.59±9.42) ng/L, t=9.758), IL-18((64.52±5.46) ng/L and (88.50±5.54) ng/Ll, t=18.899), 24 h urinary protein quantification (0.3 (0.21, 0.36) g/24 h and 1.0 (0.65, 1.23) g/24 h, Z=-4.861), URBC (15.30 (3.80, 36.80)×106/L and 168.9 (58.4, 324.0)×106/L, Z=-4.840), were lower than before treatment (all P<0.05); After treatment, in the control group, Serum IL-6 ((23.62±5.95) pg/ml and (33.44±4.68) pg/ml, t=9.149), IL-1β ((68.67±6.31) pg/ml and (86.59±8.71) pg/ml, t=10.617), IL-18((71.25±9.69) pg/ml and (89.87±6.68) pg/ml, t=11.506), 24 h urinary protein quantification (0.42 (0.33, 0.56) g/24 h and 0.94 (0.74, 1.25) g/24 h, Z=-5.013), URBC (57.00 (39.25, 77.50)×106/L and 145.60 (58.20, 360.85)×106/L, Z=-4.762), were lower than before treatment (all P<0.05). The difference between the two groups was statistically significant (P<0.05). Conclusion The adjuvant effect of total glucoside of white peony root on hematuria and proteinuria purpura nephritis is significant, which can reduce the level of hematuria and proteinuria and improve the renal symptoms of children.Its mechanism of action may be to reduce renal inflammation and protect the kidney by down-regulating the expression of serum IL-6, IL-1 and IL-18. Key words: Total glucosides of paeonia; Henoch-Schonlein purpura nephritis; Interleukin1β; Interleukin18; Interleukin6

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.

Does MEST-C score predict outcomes in pediatric Henoch-Schönlein purpura nephritis?

Children with Henoch-Schönlein purpura nephritis (HSPN) have an increased risk of chronic kidney disease (CKD). Renal biopsy diagnostic of HSPN is graded using the International Study of Kidney Disease in Children criteria, which do not predict outcomes. The 2016 Oxford Classification's MEST-C scoring system predicts outcomes in adults with histologically identical IgA nephropathy, but evidence of its utility in pediatric HSPN is lacking. Our hypothesis was that MEST-C scores predict outcomes in children with HSPN. A retrospective cohort analysis of data from 32 children with HSPN who underwent renal biopsy was performed. We used logistic regression and receiver operator characteristic curves to analyze the ability of MEST-C to predict the composite outcome of hypertension (blood pressure ≥ 95% for age/sex/height), CKD (estimated glomerular filtration rate < 90mL/min/1.73m2), or proteinuria (urine protein-to-creatinine ratio > 0.2mg/mg). The median age at diagnosis was 7.9years (IQR 5.8, 11.7); 56% were male, 19% were Hispanic, and 9% were Black. After a median follow-up of 2.7years, 38% of patients (n = 12) reached the outcome. S1 score was significantly associated with the outcome (OR 7.9, 95% CI 1.5-42.6). S1 accurately predicted the outcome (area under the curve 0.72, 95% CI 0.55-0.88) with 58.3% sensitivity and 85.0% specificity, indicating a positive predictive value of 70.0% and a negative predictive value of 77.3%. S1 accurately predicted our composite outcome of hypertension, CKD, and proteinuria in a diverse cohort of U.S. children with HSPN. Further investigation is warranted to validate these findings.

Clinical manifestations and pathological characteristics of Henöch-Schönlein purpura nephritis combined with hyperuricemia in children

Objective To analyze the relationship of clinical manifestations and pathological characteristics of Henoch-Schonlein purpura nephritis combined with hyperuricemia in children. Methods A retrospective study was conducted in 50 children with Henoch-Schonlein 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-Schonlein 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. Key words: Child; Hyperuricemia; Henoch-Schonlein purpura nephritis; Pathology