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.

MEST-C pathological score and long-term outcomes of child and adult patients with Henoch-Sch\xf6nlein purpura nephritis

BackgroundHenoch-Schönlein purpura nephritis (HSPN), a small-vessel vasculitis, shares renal pathological features with immunoglobulin A nephropathy. Oxford classification of immunoglobulin A nephropathy pathology has been updated to the MEST-C score, but its application in HSPN remains unresolved.MethodsTwo hundred and thirteen patients with biopsy-proven HSPN were retrieved from the Seoul National University Hospital between 2000 and 2017. Renal outcome risks (i.e., end-stage renal disease or doubling of serum creatinine) were evaluated according to MEST-C scores after stratification by age: 113 children aged < 18 years (9.2 ± 3.6 years) and 100 adults aged ≥18 years (38.6 ± 18.3 years). We pooled our data with four previous cohort studies in which MEST or MEST-C scores were described in detail.ResultsTwenty-one child (19%) and 16 adult (16%) patients reached the renal outcome during the median follow-up periods of 12 years and 13 years, respectively (maximum 19 years). In children, M1 and T1/T2 scores revealed worse renal outcomes than did M0 and T0 scores, respectively, whereas the T score was the only factor related to worse outcomes in adult patients after adjusting for multiple clinical and laboratory variables. The pooled data showed that M1, S1, and T1/T2 in children and E1 and T1/T2 in adults were correlated with poorer renal outcomes than those of their counterpart scores.ConclusionsThe Oxford classification MEST-C scores can predict long-term renal outcomes in patients with HSPN.

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.

Involvement of activated cytotoxic T lymphocytes and natural killer cells in Henoch-Schönlein purpura nephritis.

ObjectivesImmunoglobulin A vasculitis/Henoch–Schönlein purpura (IgAV/HSP) is a major cause of vasculitis in children. It is often accompanied by nephritis (HSPN) and could progress to chronic kidney disease. Galactose‐deficient IgA1 was recently reported to be involved in the pathogenesis of HSPN, for which immunosuppressive drugs are considered key treatment. However, the involvement of immune cells in the development of HSPN remains unclear.MethodsWe compared gene expressions of peripheral blood mononuclear cells (PBMCs) among healthy controls (n = 10), IgAV/HSP patients (n = 21) and HSPN patients (n = 8), which required nephritis development within 3 months of IgAV/HSP onset. Immunohistochemistry analysis and flow cytometry were performed to assess renal biopsy specimens and PBMCs, respectively. Serum CX3CL1 levels were measured by ELISA.Results GNLY and GZMB expressions increased in HSPN patients, consistent with increased number of glomerular granulysin‐ and/or granzyme B‐positive cells demonstrated by immunohistochemistry analysis. Additionally, circulating cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells were activated with the up‐regulated surface expressions of human leucocyte antigen DR (HLA‐DR) and CX3CR1 in HSPN patients with severe proteinuria. Renal biopsies demonstrated increased number of CD8+ cells and/or CD56+ cells and up‐regulated expression of glomerular CX3CL1, a specific ligand for CX3CR1, along with increased serum CX3CL1 level.ConclusionActivated CTLs and NK cells play roles in the development of nephritis in IgAV/HSP patients and can be used as novel biomarkers for HSPN.

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.

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.

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.

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

Histological prognostic factors in children with Henoch-Schönlein purpura nephritis.

The management of IgA vasculitis with nephritis (IgAVN) remains controversial because of the difficulty to identify prognostic factors. This study reports the prognosis of children with IgAVN in relation to histological parameters. All children with IgAVN diagnosed between 2000 and 2015 in three pediatric nephrology centers were included. The following histological parameters were analyzed: mesangial proliferation (MP), endocapillary proliferation (EP), crescents, active, or chronic tubular and interstitial lesions (TIa lesions/TIc lesions), and segmental glomerulosclerosis (GS). Clinical and biological data were collected at the time of renal biopsy. The primary endpoint was IgAVN remission defined as a proteinuria < 200mg/l without renal failure. One hundred fifty-nine children were included with a median age of 7.6years. Acute glomerular or TI lesions including MP, EP, crescents, and TIa lesions were observed, respectively, in 81%, 86%, 49%, and 21% of patients. Chronic glomerular lesions including GS and TIc lesions were observed in 6 and 7% of patients. Median initial proteinuria was 330mg/mmol, albuminemia 32g/l, and eGFR 110ml/min/1.73m2. One hundred twelve (70%) patients were in remission at the end of a median follow-up of 37.4months. Chronic lesions were significantly associated with the absence of remission in multivariate analysis, whereas EP, crescents and TIa were not associated with a poor prognosis. Of children with IgAVN, 30% present a persistent renal disease at the end of a 3-year follow-up. Chronic histological lesions, but not EP or crescents, are associated with a bad prognosis and must be evaluated in IgAVN histological classification.

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.

Risk factors associated with IgA vasculitis with nephritis (Henoch-Schönlein purpura nephritis) progressing to unfavorable outcomes: A meta-analysis.

ObjectiveTo identify risk factors associated with unfavorable outcomes in children with IgA vasculitis with nephritis (Henoch-Schőnlein purpura nephritis)(IgA-VN)MethodsPubMed, Embase, and Web of Science databases were searched for studies, published in English through February 2019. The data were extracted to perform pooled analysis, heterogeneity testing, subgroup analysis, sensitivity analysis, and publication bias analysis.ResultsThis meta-analysis showed that, older age at onset (WMD 1.77, 95% CI 0.35–3.18, p = 0.014), lower glomerular filtration rate (GFR; WMD -23.93, 95% CI -33.78- -14.09, p<0.0001), initial renal manifestations with nephrotic syndrome (OR 1.74, 95% CI 1.12–2.70, p = 0.013), with nephritic-nephrotic syndrome (OR 4.55, 95% CI 2.89–7.15, p<0.0001) and renal biopsy with crescentic nephritis (International Study of Kidney Disease in Children [ISKDC] grades III-V) (OR 3.85, 95% CI 2.37–6.28, p<0.0001) were significant risk factors associated with poor outcomes in IgA-VN, whereas initial clinical features with hematuria (OR 0.33, 95% CI 0.16–0.69, p = 0.003) and mild proteinuria±hematuria (OR 0.46, 95% CI 0.28–0.75, p<0.0001) were associated with progression to good outcomes. By contrast, gender, hypertension and initial renal manifestations of acute nephritic syndrome were not significantly associated with poor outcomes in IgA-VN.ConclusionThis meta-analysis showed that older age at onset, lower GFR, initial renal features of nephrotic syndrome and nephritic-nephrotic syndrome and renal biopsy with crescentic nephritis (ISKDC grades III-V) were predictive of poor prognosis in children with IgA-VN.

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.

Patient Outcomes of Henoch–Schönlein Purpura Nephritis According to the New Semiquantitative Classification

Background: A new semiquantitative classification (SQC) for pediatric Henoch–Schönlein nephritis (HSN) was defined recently. The outcomes of pediatric HSN patients are reevaluated according to the new classification. Methods: Primary kidney biopsies from 80 HSN patients were scored using the new SQC. The International Study of Kidney Disease in Children (ISKDC) and SQC classifications were compared in terms of the patient outcomes. Outcomes were defined as: Outcome A (n = 44) patients with no sign of renal disease, Outcome B (n = 32) patients with minor urinary abnormalities, and Outcome C (n = 4) patients with active renal disease. Results: The patients with outcome C had significantly higher biopsy scores and chronicity indices than patients in group A. There was no significant difference in areas under the curve between total biopsy SQC scores and ISKDC findings. Conclusions: Our results suggest that the modified SQC is not more sensitive than ISKDC classification for predicting the outcome in HSN cases.