Purpura Nephritis Research Articles

The Clinicopathological Characteristics of Henoch-Schönlein Purpura Nephritis with Presentation of Nephrotic Syndrome

Background: Henoch-Schönlein purpura nephritis (HSPN) is a common vasculitis involving the kidneys, with a lower incidence in adults. Meanwhile, nephrotic syndrome (NS) can appear in HSPN. However, the clinicopathological features and renal outcome of adult-onset HSPN presenting with NS (NS-HSPN) have not been well clarified. Methods: A total of 191 HSPN patients were prospectively analyzed and comparisons were made between NS-HSPN and non-NS-HSPN. Multivariate Cox regression analysis was carried out to find the unfavorable factors of renal outcome of NS-HSPN. Results: Among the 191 patients, 44 (23.0%) had NS-HSPN. Apart from edema and abdominal pain, patients with NS-HSPN tended to have lower levels of erythrocytes and hemoglobulin in blood as well as a greater number of erythrocytes in urine (p < 0.05). Mesangial proliferation was the most common pathological lesion in HSPN and the rates of crescent formation were significantly different, with 54.5% in NS-HSPN and 33.3% in non-NS-HSPN (p < 0.05). Notably, 18.2 and 4.8% of patients reached the composite endpoints in the NS-HSPN and non-NS-HSPN groups, respectively (p < 0.05), demonstrating that NS-HSPN patients were more likely to progress to end-stage renal disease and had a worse outcome. We also found that hypertension, estimated glomerular filtration rate (eGFR), cystatin, and tubular atrophy/interstitial fibrosis (HR > 1, p < 0.05) at onset were correlated with adverse outcome in NS-HSPN. Conclusion: NS-HSPN had more severe clinicopathological manifestations and poorer prognosis. The adverse predictors of NS-HSPN principally depend on clinicopathological presentation rather than on different therapies, and hypertension, eGFR, cystatin, and tubular atrophy/interstitial fibrosis can serve as independent risk factors in NS-HSPN.

Diagnostic Value of Urinary miR-152-5p in Patients with IgA Nephropathy with Elevated Proteinuria Levels.

The current study aims to observe the correlation between the expression of miR-152-5p in urine samples and the condition of IgA nephropathy (IgAN). From January 2017 to October 2017, 40 patients with IgAN, 10 patients with mild glomerular lesions, 10 patients with membranous proliferative glomerulonephritis type I, 10 patients with focal segmental glomeruloscle-rosis, 10 patients with Henoch-Schonlein purpura nephritis, and 10 patients with lupus nephritis. Meanwhile, 25 healthy controls were also included in the physical examination center of our hospital. The expression level of miR-152-5p was detected by RT-qPCR. The correlation between the expression level of miR-152-5p and patholog-ical Haas grading and urinary protein was analyzed. The expression level of miR-152-5p in IgA nephropathy patients was higher than that in other types of glomerulonephritis and healthy control group (p < 0.0001). Meanwhile, the level of miR-152-5p in IgAN patients with high score (p < 0.01) was significantly increased. Furthermore, the level of miR-152-5p was positively corre-lated with the level of urinary protein and the degree of renal pathological damage (r2 = 0.89, p < 0.01). The expression of urinary miR-152-5p is positively correlated with IgA nephropathy, which provides a new way for early diagnosis and treatment of IgA nephropathy with elevated proteinuria.

Effect of miR-21 on the expression of interleukin-10 in B cell of patients with Henoch-Schonlein purpura

Objective: To investigate the effect of microRNAs (miR)-21 on the expression of interleukin (IL)-10 in B cell of patients with Henoch-Schonlein purpura (HSP). Methods: From March 2016 to January 2017, twenty-four children with HSP hospitalized in rheumatology and immunology department of Shenzhen Children's Hospital were enrolled into the study, including 12 males and 12 females. Patients were divided into purpura nephritis group (HSPN, 14 cases) and non-nephritis group (NHSPN, 10 cases). The age-matched 34 healthy children were included as the control group for prospective cohort study. The expression levels of IL-10 in peripheral blood B cells (CD19(+)), transitional B cells (CD19(+) CD24(hi)CD38(hi)) and naïve B cells (CD19(+)CD24(int)CD38(int)) from patients with HSP and healthy children were detected by flow cytometry (FCM). Expression of microRNAs related to IL-10 in B cells were quantitated by real-time PCR, including miR-21-5p, miR-106a-5p, miR-98-3p, miR-142-3p, miR-142-5p, miR-98-5p, miR-155-5p and miR-let7b-5p. Agomir negative control-FAM and agomir-21-5p-FAM were transfected into B cells from patients with HSP. The uptake of miRNA by B cells was observed by laser scanning confocal microscope and FCM, and the expression of IL-10 was detected by FCM after transfection. For quantitative data of normal distribution, t test was used for two samples comparison and multiple comparisons among three groups were conducted by ANOVA. Spearman test was used for correlation analysis. Results: (1) The CD19(+) B cells and its two populations at different differentiation stages all could express IL-10. The expression levels of IL-10 in three B cell populations in patients were significantly lower than those in healthy controls (1.4±0.2 vs. 2.4±0.3, t=3.501, P<0.01; 1.2±0.2 vs. 2.2±0.3, t=2.688, P<0.05; 1.6±0.3 vs. 2.7±0.4, t=2.498, P<0.05). Compared with healthy control and NHSPN groups, the expression of IL-10 in CD19(+) B cells from patients within HSPN group was the lowest, and the difference was statistically significant (1.1±0.2 vs. 2.4±0.3, 1.8±0.3, t=4.006, 2.362, P<0.001, P<0.05). (2) The expression of miR-21-5p in B cell in patients with HSPN was lower than that in healthy control group (1.2±0.9 vs. 3.5±2.8, t=2.962, P<0.01). There was no significant change in the other microRNAs. (3) The expression of IL-10 was positively correlated with the expression of miR-21-5p in the B cells of patients with HSP (r=0.778, P<0.001). (4) The expression of IL-10 in B cells of miR-21-5p group was significantly higher than that in negative control group (2.7±0.2 vs. 1.6±0.3, t=3.091, P<0.05). Conclusion: The insufficient expression of miR-21-5p in peripheral blood B cells of patients with HSP is one of the reasons for the reduction of IL-10 expression in B cells.

Differential expression of long non-coding RNA and mRNA in children with Henoch-Schönlein purpura nephritis.

Long non-coding RNAs (lncRNAs) serve an essential role in regulating immunological functions. However, their impact on Henoch-Schönlein purpura nephritis (HSPN), has remained elusive. The present study determined the expression of lncRNAs and mRNAs in the peripheral blood of 6 children with HSPN and recruited 4 healthy children for comparative study. High-throughput sequencing revealed outstanding differences in lncRNA and mRNA expression, which were verified through reverse transcription-quantitative polymerase chain reaction. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to investigate the associated biological functions and possible mechanisms of lncRNAs and mRNAs in HSPN. A total of 820 differentially expressed lncRNAs between the two groups were identified, of which 34 were upregulated and 786 were downregulated. Simultaneously, a total of 3,557 mRNAs were also identified to be differentially expressed, of which 1,232 were upregulated and 2,325 were downregulated. The results revealed that the expression of lncRNAs including ENST00000378432, ENST00000571370, uc001kfc.1 and uc010qna.2 was decreased in HSPN patients compared with that in healthy controls. These lncRNAs were associated with the p53 signaling pathway and apoptosis-associated genes (AKT2, tumor protein 53, phosphatase and tensin homolog and FAS). Further studies of those lncRNAs will be performed to elucidate their functions in apoptosis. Complete raw data files were deposited in the Gene Expression Omnibus (GEO) at National Center for Biotechnology information under the GEO accession no. GSE102114 (www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE102114).

Henoch-schonlein Purpura Nephritis with Renal Interstitial Lesions.

ObjectiveTo investigate the clinical pathology and prognosis & outcome of Henoch-Schonlein purpura nephritis (HSPN) with renal interstitial lesions.MethodsAll 148 patients were analyzed for clinical, renal pathological, and prognostic features. Patients with no, mild, and moderate- severe renal tubulo-interstitial lesions were included in group A, B and C, respectively.ResultsThe estimated glomerular filtration rate (eGFR) of group B was significantly lower than that of group A. The levels of serum creatinine and blood urea nitrogen in group C were significantly higher than those in groups A and B. Clinical type II was correlated with pathological types II and IIIa; pathological type IV and IIIb were correlated with clinical type VI and IV. There were significant differences in the level of red blood cells in urinary sediment, levels of urine occult blood and in the prognosis among the 3 groups.ConclusionClinically, Type II is the most common cause; pathologically, Type IIIa is more common. The severity of renal tubulo-interstitial lesions is positively correlated with a decline in renal function and GFR. There is a correlation between the severity of renal tubulo-interstitial lesions and the severity of hematuria. Most patients with HSPN have a good prognosis.

Significance of histological crescent formation in patients with IgA vasculitis (Henoch-Sch\xf6nlein purpura)-related nephritis: a cohort in the adult Chinese population

BackgroundIgA vasculitis (IgAV, formerly Henoch-Schönlein purpura) is a type of systemic vasculitis. This study aimed to explore the clinicopathological features, treatment and renal outcomes of adult IgAV-related nephritis (Henoch-Schönlein purpura nephritis) patients with different degrees of crescent formation.MethodsAdult patients with biopsy-proven IgAV-related nephritis in Nanjing Jinling Hospital were enrolled and divided into three groups as follows: control (no crescents, n = 257), group 1 (crescents < 25%, n = 381), and group 2 (crescents ≥25%, n = 60). The clinicopathological features, treatment and renal outcomes were compared among the three groups.ResultsThere were no significant differences in gender and age at biopsy among the three groups. Groups with more crescents had shorter renal durations and higher prevalence of macroscopic hematuria, proteinuria and nephrotic syndrome than the control group. The presence of renal insufficiency at biopsy was similar, whereas laboratory findings indicated that patients with ≥25% crescents had higher levels of serum creatinine and blood urea nitrogen than the control and group 1. Histologically, the incidence of glomeruli-Bowman’s capsule adhesion and capillary necrosis were proportional to the degree of crescent formation. Patients with more crescents received more positive immunosuppressive therapies. During follow-up, the levels of proteinuria and hematuria were in remission after treatment, and patients without crescents had lower levels of proteinuria. At the last follow-up, the renal function had deteriorated in the control and group 1, whereas the levels of serum creatinine at biopsy and last follow-up were similar in group 2. There was a significant difference in renal survival from end-stage renal disease (ESRD) or 50% decline in renal function among the three groups (log-rank, P = 0.030). However, no association between crescent formation and renal outcomes was found after adjusting potential confounders.ConclusionsAdult IgAV-related nephritis patients with more crescents had more-severe renal manifestations and worse treatment responses, whereas the proportions of crescents were not associated with higher risks for ESRD or 50% decline in renal function. A more suitable pathological classification standard is needed to predict renal prognosis.

Correlation between endocapillary proliferative and nephrotic-range proteinuria in children with Henoch-Schönlein purpura nephritis.

The endocapillary proliferative (EP) lesion is not included in theInternational Study of Kidney Disease in Children(ISKDC) pathological classification of Henoch-Schönlein purpura nephritis (HSPN). The main objective of the study was to determine the pathological importance of EP in the development of proteinuria in children with Henoch-Schönlein purpura nephritis (HSPN). The pathological features of 148 HSPN children with nephrotic-range proteinuria were investigated retrospectively. Urinary IgG, transferrin, and albumin levels were measured by immunonephelometry. The correlations between EP lesion and 24-h proteinuria, urinary IgG, urinary transferrin, and urinary albumin were analyzed. Renal biopsy specimens were immunohistochemically stained for nephrin and podocalyxin. Of the total 581 cases of children with HSPN who underwent renal biopsy, 148 cases (25.5%) presented with nephrotic-range proteinuria. The pathological types of HSPN with nephrotic-range proteinuria were categorized as IIb, IIIa, IIIb, IIIb with diffuse EP, IVb, pure focal EP type, and pure diffuse EP type. Among these types, pure diffuse EP type accounted for 7.4%. The levels of 24-h proteinuria and urinary albumin were the highest in pure diffuse EP type among all pathological types, and the percentage of EP correlated with 24-h proteinuria and urinary albumin levels. 24-h proteinuria was significantly higher in pure diffuse EP type relative to HSPN IIb type, and significantly higher in IIIb with EP, compared with HSPN IIIb. Nephrin, but not podocalyxin, was downregulated in EP segment. EP is an independent pathogenic factor in HSPN with nephrotic-range proteinuria. Downregulation of nephrin in EP segment is a potential molecular mechanism of nephrotic-range proteinuria. Albumin is the major urinary protein component in HSPN with EP.

Analysis of curative effect by Captopril in Henoch-Schönlein purpura nephritis characterized by mild proteinuria

Objective To explore the activation of renin-angiotensin system (RAS), efficiency and safety of Captopril, and the predictor of therapeutic activity for Henoch-Schonlein purpura nephritis(HSPN) characterized by mild proteinuria. Methods A total of 71 children who were hospitalized in Children′s Hospital Affiliated to Capital Institute of Pediatrics from July 2014 to January 2017 were involved, with the diagnosis of HSPN and the characteristic of mild proteinuria. The cases were divided into 2 groups, one as Captopril group, the other as case control group.The patients were followed up for 6 months.Forty healthy children were assigned as healthy control group.Blood pressure, urinary protein excretion, levels of urinary angiotensinogen (AGT)and transforming growth factor β1(TGF-β1), and the side effects of Captopril were surveyed.The therapeutic effects of these groups were analyzed by Kaplan-Meier survival curve. Results (1) Clinical characteristics: in the 71 cases, 43 cases were male, 28 cases were female, aged from 3 years to 14 years and 7 months.A total of 32 cases (45.1%) had manifested with isolated proteinuria, 39 cases (54.9%) were with hematuria and proteinuria. The volume of 24 hours′ urinary protein was 4.2-23.5 mg/(m2·h)[median 9.6(7, 12) mg/(m2·h)] at the beginning. (2) The level of urinary AGT: the levels of urinary AGT in the children with HSPN were significantly higher than those of the healthy control group(Z=-3.010, P=0.003). (3) Curative effect: there was no significant difference in age, disease staging, mean arterial pressure(MAP), levels of urinary of proteinuria and estimated glomerular filtration rate (eGFR) between the patients with or without Captopril.The proteinuria was relieved in 88.57% cases of Captopril group(35 cases), and the proportion was 80.55% in the case control group(36 cases), and there was no significant difference between the 2 groups. The levels of proteinuria were decreased significantly in the children of Captopril group 2 months after the enrollment, and there was a statistical significance (Z=2.010, P=0.044). But in the patients of each group, the levels of urinary protein excretion (Z=-2.127, P=0.030; Z=-2.639, P=0.010), TGF-β1(Z=-2.126, P=0.030; Z=-2.058, P=0.040) at the onset were significantly higher in the children with persistent proteinuria compared to those with remission of proteinuria completely, and there was a statistical significance.(4)Side effect: among 35 cases with therapy of Captopril, 4 cases(11.42%) were verified to have adverse reaction (hypotension, dry cough and abnormal renal function), with mild symptom. Conclusion The overall prognosis of children of HSPN presenting as mild proteinuria are not improved completely by Captopril. The occurrence of adverse effects for Captopril is seldom and less severe. The level of urinary protein excretion , TGF-β1 and AGT at the onset have some relevance with the prognosis of the patients of HSPN. Key words: Henoch-Schonlein purpura nephritis; Captopril; Angiotensinogen; Transforming growth factor β1

Clinical significance of serum and mesangial galactose-deficient IgA1 in patients with IgA nephropathy.

IntroductionGalactose-deficient IgA1 (Gd-IgA1) is a critical pathogenic factor for IgA nephropathy (IgAN), but its value as a disease-specific biomarker remains controversial. We aimed to clarify the clinical significance of Gd-IgA1 in patients with IgAN.MethodsWe retrospectively reviewed 111 patients who were diagnosed with IgAN based on the findings of renal biopsies (RB) at Showa University Hospital since 2007. Serum Gd-IgA1 (s-Gd-IgA1) at the time of RB was compared among 111 IgAN patients, 18 Henoch-Schönlein purpura nephritis (HSPN) patients, 29 lupus nephritis (LN) patients, 28 ANCA-associated vasculitis (AAV) patients, and 13 minimal change disease (MCD) patients using ELISA with an anti-human Gd-IgA1-specific monoclonal antibody (KM55). We also immunohistochemically stained paraffin-embedded sections for mesangial Gd-IgA1 (m-Gd-IgA1) deposition using KM55.ResultsAlthough levels of s-Gd-IgA1 were comparable among IgAN and HSPN, s-Gd-IgA1 levels were significantly elevated in patients with IgAN compared with LN, AAV and MCD (IgAN vs. HSPN, LN, AAV, and MCD: 16.2 ± 9.1 vs. 14.2 ± 10.8, p = 0.263; 12.7 ± 9.4, p = 0.008; 13.1 ± 7.3, p = 0.059; and 8.2 ± 4.8 μg/mL, p<0.001, respectively). Mesangial-Gd-IgA1 deposition was specifically detected in IgAN or HSPN. The increase in s-Gd-IgA1 significantly correlated with m-Gd-IgA1 positivity in patients with IgAN, and s-Gd-IgA1 elevation and m-Gd-IgA1 deposition were evident in patients with histopathologically advanced IgAN. Moreover, s-Gd-IgA1 levels were significantly higher in IgAN patients with glomerular sclerosis and tubulo-interstitial lesions. Mesangial-Gd-IgA1 intensity negatively correlated with eGFR in IgAN. Multivariate analysis selected s-Gd-IgA1 elevation as a significant risk factor for a 30%-reduction in eGFR in IgAN (HR, 1.37; 95% CI, 1.02–1.89; p = 0.038).ConclusionsAlthough IgAN and HSPN remain difficult to differentiate, s-Gd-IgA1 elevation and m-Gd-IgA1 deposition are reliable diagnostic factors that reflect IgAN severity. Serum-Gd-IgA1 could serve as a predictor of renal outcomes in IgAN. Thus, Gd-IgA1 could be significant biomarker for patients with IgAN.

Steroid- and immunosuppressant-based protocol of Henoch-Schönlein purpura nephritis without angiotensin inhibitors in the acute phase: case series with correlation to histology.

The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines suggest initially using angiotensin-converting-enzyme inhibitors (ACE-Is) and/or angiotensin receptor blockers (ARBs) to treat Henoch-Schönlein purpura nephritis (HSPN). However, these guidelines might overlook the potential benefits of aggressive therapy. Therefore, we evaluated the efficacy of an HSPN protocol that primarily uses steroids and immunosuppressants, without ACE-Is or ARBs. We determine treatment intensity based on International Study of Kidney Diseases in Children (ISKDC) grading. Fifty-one patients were treated with our protocol that primarily uses steroids and immunosuppressants. ACE-Is and ARBs were not used in the acute phase, including before renal biopsy. We evaluated the proteinuria disappearance rate, duration to proteinuria disappearance, and estimated glomerular filtration rate (eGFR) at the time of last observation and compared them to those in previous reports. Proteinuria disappeared in 49 patients (96%) within a median of 5 months. The median eGFR was 116.0 mL/min/1.73 m2 at the time of last observation. Six of 51 patients had acute kidney injury (eGFR <90 mL/min/1.73 m2) before treatment, but all recovered during the observation period (median 52 months). Our steroid- and immunosuppressant-based protocol without ACE-Is or ARBs in the acute phase of HSPN had almost equivalent efficacy to that in previous studies that used ACE-Is and/or ARBs with steroids and immunosuppressants.

Progress of the relationship between Streptococcus infection and Henoch-Schönlein purpura, purpura nephritis

Group A streptococcus (GAS) is the most common pathogens of human streptococcal infection.It is considered that GAS infection is one of the important factors leading to Henoch-Schonlein purpura (HSP). It can promote the occurrence of Henoch-Schonlein purpura nephritis(HSPN), and aggravate HSPN.Hemolysin, protease and superantigen involved in the pathogenesis of GAS.Research progress of the relationship between streptococcal infection and HSP and HSPN are summarized as follows. Key words: Group A streptococcus; Antistreptolysin O; Henoch-Schonlein purpura; Henoch-Schonlein purpura nephritis

Expression and significance of endothelial microparticles in children with Henoch-Schönlein purpura

To study the expression and significance of endothelial microparticles (EMPs) in children with Henoch-Schönlein purpura (HSP). A total of 100 previously untreated children with HSP were classified to Henoch-Schönlein purpura nephritis (HSPN) group (n=40) and non-nephritis group (n=60). Thirty healthy children who underwent physical examination were enrolled as control group. Serum levels of EMPs, T helper 17 cells (Th17), and interleukin-17 (IL-17) were compared between groups. The HSPN and non-nephritis groups had significantly higher levels of Th17 and IL-17 than the control group, and the HSPN group had the highest levels (P<0.05). The HSPN and non-nephritis groups had a significantly higher level of EMPs than the control group, and the HSPN group had the highest level (P<0.05). In the HSPN group, the levels of Th17 and IL-17 were positively correlated with the level of EMPs (r=0.830 and 0.644 respectively; P<0.05). EMPs play an important role in the pathogenesis of HSP. The increase in EMPs might be one of the reasons for renal involvement in children with HSP.

119. The management of pregnant women with chronic kidney disease: An 8-year review in a tertiary care center

Objective The management and treatment of kidney disease has advanced, and women who are pregnant and give birth have also increased recently. On the other hand, pregnancy with kidney disease causes preeclampsia (19–30%), intrauterine fetal death (16–20%), postpartum renal failure (3–5%). The purpose of this study was to review the maternal and neonatal outcomes in pregnant women with chronic kidney disease (CKD), and to evaluate the appropriate management that may contribute to obstetric outcomes. Methods We conducted a retrospective review of 126 births and 129 neonates in 110 CKD patients who were seen at Osaka University Hospital between January, 2010, and December, 2017. Results The mean patient age was 33.5 (18–49) years, and the nulliparity rate was 61%. The most frequent disease was IgA nephropathy (43/126; 34%) and the second was lupus nephritis and renal transplantation (both were 15/126; 12%). Second trimester abortion and preterm delivery occurred in 5% and 20% of the patients, respectively. There was no maternal and neonatal death. Fetal growth restriction and preeclampsia occurred in 10% and 25% of the patients, respectively. Two patients with lupus nephritis and one with Henoch-Schonlein purpura nephritis had severe preeclampsia occurred before 20 weeks gestation. sFlt1/PlGF ratio were 427, 865 and 1183, respectively. Conclusions To predict and prevent the adverse events in the care of pregnant women with CKD is important for good maternal and neonatal outcomes. Furthermore, Henoch-Schonlein purpura nephritis that had been already ameliorated may be also a risk factor for severe preeclampsia.

Clinical impact of endocapillary proliferation according to the Oxford classification among adults with Henoch-Sch\xf6nlein purpura nephritis: a multicenter retrospective cohort study

BackgroundHenoch-Schönlein purpura nephritis (HSPN) is a form of small vessel vasculitis associated with purpura and IgA deposition in the glomeruli. The International Study of Kidney Disease in Children (ISKDC) classification predicts renal prognosis in children with HSPN, but not in adults. Additionally, it is not well known whether the Oxford classification 2016 and/or the Japanese Histologic classification (JHC) are associated with renal outcome. Herein, we investigated the relationship between pathological characteristics and renal outcome among adult patients with HSPN.MethodsA multicenter retrospective cohort study was conducted in adult patients with HSPN who underwent renal biopsy between 2004 and 2014. Two nephrologists classified each patient according to the Oxford classification 2016, JHC, and the ISKDC classification. Renal outcome was defined by a 30% decline in the eGFR and/or end-stage kidney disease.ResultsWe enrolled 74 adult patients with HSPN (mean age, 47.8 ± 17.4 years; mean eGFR, 76.4 ± 25.8 ml/min/1.73 m2; median proteinuria, 1.40 [IQR: 0.70–2.38] g/day). During a mean follow-up period of 68.0 ± 33.0 months, fourteen patients (18.9%) reached the renal outcome, and all 14 had received immunosuppressive therapy. The log-rank test revealed that event-free renal survival was significantly shorter in patients with endocapillary proliferation (E1) according to the Oxford classification than in those with E0 (p = 0.0072). However, the JHC, ISKDC classification and other Oxford lesions could not demonstrate a significant difference in event-free renal survival. In a multivariate Cox model adjusted for clinical and pathological factors, age (HR, 1.57; 95% CI, 1.12–2.21) and E lesion (HR, 6.71; 95% CI, 1.06–42.7) were independent risk factors for renal outcome.ConclusionsEndocapillary proliferation is significantly associated with renal outcome in adult patients with HSPN, including those receiving immunosuppressive therapy. Other Oxford classification lesions, JHC, and ISKDC classification were not associated with renal outcome.

Significance of glomerular fibrinogen deposition in children with Henoch-Sch\xf6nlein purpura nephritis

BackgroundHenoch-Schönlein purpura nephritis (HSPN) is the most common pediatric secondary glomerular disease. This study aimed to investigate the significance of glomerular fibrinogen (Fib) deposition in children with HSPN.MethodsEighty-two patients with HSPN were enrolled retrospectively at the Children’s Hospital of Soochow University from January 2015 to March 2017. Patients were divided into groups according to the presence or absence and intensity of glomerular Fib deposits, and clinical and pathological features were compared among the groups.ResultsGlomerular Fib deposition was observed in 64 children (78.05%), including 1 Fib± case (1.22%), 23 Fib+ cases (28.05%), 37 Fib++ cases (45.12%), and 3 Fib+++ cases (3.66%). Significantly different levels of high-sensitivity C-reactive protein (hs-CRP), D-dimer (DD), proportions of CD19 + CD23+ cells and urine microalbumin:creatinine ratios (UMA/Cr) were noted among the different Fib deposition groups (no, mild and severe). Pairwise comparison in multiple groups revealed significantly increased hs-CRP, proportion of CD19 + CD23+ cells and UMA/Cr in the severe deposition group compared with the mild and no deposition groups, and remarkably increased DD levels were noted in the severe and mild deposition groups compared with the no deposition group. The degree of glomerular Fib deposition was positively correlated with the degree of glomerular IgA deposition, and the incidence of glomerular IgG deposition in the severe deposition group was increased compared with the no deposition group.ConclusionHSPN children with glomerular Fib deposition, especially those with severe Fib deposition, exhibit more severely disordered immunologic function, inflammatory reactions and hypercoagulability; glomerular damage in these patients may also be more severe.

Clinicopathological features of pediatric renal biopsies in the plateau regions of China.

ObjectiveThis study aimed to analyze the clinicopathological features of pediatric renal biopsies from plateau regions of China.MethodsClinicopathological features of pediatric renal biopsies were compared between plateau and non-plateau regions in patients who were admitted to West China Second University Hospital, Sichuan University between April 2001 and March 2017. Patients were children younger than 18 years.ResultsThe proportion of primary glomerular disease in the plateau group was lower than that in the non-plateau group (45.56% vs 62.09%, respectively). In the plateau group, IgA nephropathy (IgAN) was the major primary glomerulonephritis (GN) pathology. IgAN accounted for 36.54% and 21.63% of GN cases with nephrotic syndrome and hematuria, respectively. Henoch-Schönlein purpura nephritis was the most common secondary GN in both groups. The proportion of hepatitis B virus-associated GN was higher and that of lupus nephritis was lower in the plateau group than in the non-plateau group.ConclusionsThere are differences in renal pathological types between children in plateau regions and those in non-plateau regions. Among children in plateau regions, IgAN and Henoch-Schönlein purpura nephritis were the most common kidney diseases.

Urinary fibrin/fibrinogen degradation products measured using an anti-fibrinogen antibody predict orthostatic proteinuria.

The aim of this study was to assess the diagnostic value of urinary fibrin/fibrinogen degradation products (uFDP) measured using an anti-fibrinogen antibody in patients with orthostatic proteinuria (OP), and their use in differentiating between OP and glomerulonephritis (GN). uFDP were measured using first urine in the morning (supine) and non-first urine during a hospital visit (upright) and then normalized to urine creatinine (uFDP/Cr, ng/mgCr). We compared (i) OP patients (n = 16); (ii)those in remission from nephrotic syndrome (NS, n = 14) and from GN (IgA nephropathy [IgAN], n = 14; Henoch-Schönlein purpura nephritis [HSPN], n = 12); and (iii) those with active GN (IgAN, n = 12; HSPN, n = 19). The uFDP/Cr ratio increased from supine to upright urine in patients with OP (P < 0.001), but decreased in one case. uFDP were excreted in supine urine in 94% of OP patients, with no excretion in NS remission patients or in 92% of GN remission patients (P < 0.001 for both). uFDP/Cr in supine urine was similar between the OP and active GN patients (P = 0.40), whereas proteinuria in supine urine was in the normal range in all OP patients, but was significantly higher in upright urine in the OP patients (P < 0.001). In upright urine, urinary protein/creatinine ratio was significantly lower in patients with OP than in those with active GN (P = 0.005). A uFDP/Cr ratio cut-off of 1,108ng/mgCr in upright urine correctly differentiated OP from active GN, with a sensitivity of 87.5% and a specificity of 100%. Comparison of uFDP levels in supine/upright urine can be reliable for diagnosing OP and for differentiating it from active GN.

Tripterygium glycosides in treatment of henoch-schonlein purpura nephritis: a systematic review of randomized controlled trials

To evaluate the clinical efficacy and safety of tripterygium glycosides (TG) in the treatment of henoch-schonlein purpura nephritis(HSPN). Seven English and Chinese databases (up to Nov. 9, 2017), were searched to collect the RCTs on TG for HSPN. Two researchers independently screened the literature according to inclusion criteria and exclusion criteria, extracted data, and evaluated the quality of the literature. After completion, cross-checking was performed and Meta-analysis was performed using RevMan 5.3 software. At the same time, different outcomes of the interventions were analyzed subgroupically. A total of 46 RCTs were included, with 1 659 in the experimental group and 1 596 in the control group. All the clinical studies showed a low quality. In terms of complete remission rate, the group with TG performed better than the group with conventional therapy or GC（RR=1.82，95%CI[1.39，2.39];RR=2.03，95%CI[1.37，2.99]），the group with TG+GC performed better than the group with GC（RR=1.46，95%CI[1.32，1.60]），and the group with CTX+GC performed better than the group with TG+GC（RR=0.35，95%CI[0.16，0.75]）. In terms of total effective rate, the group with TG performed better than the group with conventional therapy or GC（RR=1.44，95%CI[1.19,1.74];RR=1.30，95%CI[1.16，1.46]），the group with TG+GC performed better than the group with GC（RR=1.27，95%CI[1.21，1.34]），and the group with CTX+GC performed better than the group with TG+GC（RR=0.60，95%CI[0.43，0.85]）. No significant difference was found between the group with TG+GC and LEF+GC（RR=0.68，95%CI[0.30，1.53]）. In terms of urinary protein, urine occult blood negative time，the group with TG performed better than the group with conventional therapy（MD=-9.00，95% CI[-11.99，-6.01];MD=-12.00，95%CI[-16.13，-7.87]），the group with TG+GC performed better than the group with GC（MD=-8.86，95%CI[-10.08，-7.64];MD=-16.24，95%CI[-23.80，-8.67]）. In terms of recurrence rate, the group with TG+GC was lower than the group with GC（RR=0.13，95%CI[0.06，0.25]）, but there were no significant difference between the group with TG and conventional therapy（RR=0.43，95%CI[0.15，1.19]）. In adverse reactions, the common adverse effects of TG were gastrointestinal discomfort, liver damage and leucopenia. TG for the treatment of HSPN can improve clinical efficacy, reduce recurrence, and the adverse reactions are relatively safe. Due to the generally low methodological quality of the included studies, which affected the accuracy and reliability of the result. Therefore, more high-quality, large samples and multi-center randomized controlled trials are necessary for further evidence.

The Spectrum of Biopsy-Proven Glomerular Diseases among Children in China: A National, Cross-Sectional Survey.

High-quality epidemiologic data on the spectrum of biopsy-proven glomerular diseases among children are limited. This study aimed to determine the profile of and temporal change in biopsy-proven pediatric glomerular diseases in China. We previously conducted a nationwide kidney biopsy survey including 71,151 patients over an 11-year period from January 2004 to December 2014. A total of 7962 children younger than 18 years old from 115 hospitals across China with biopsy-proven glomerular diseases were included in this study. The demographic and clinical variables were extracted from referral records and pathology reports. The composition of pediatric glomerular diseases and clinicopathologic correlations in different sexes, age groups, and regions were assessed. The changing patterns of common glomerulopathies over the study period were examined. Nephrotic syndrome (50%) was the most frequent indication for kidney biopsy in children. Minimal change disease was the most common primary glomerular disease (29%) followed by IgA nephropathy (17%). Henoch-Schonlein purpura nephritis (13%) and lupus nephritis (9%) were the most common secondary glomerular diseases. The proportion of minimal change disease was significant higher in boys (38%) than in girls (13%), whereas lupus nephritis was more prevalent in girls (20%) than in boys (3%). Purpura nephritis (23%) was the major pathologic pattern in younger children (0-12 years old), whereas minimal change disease (33%) was the most common glomerulopathy in adolescents (13-18 years old). The clinicopathologic correlations were slightly different between sexes and age groups. We observed increases in the proportions of minimal change disease, purpura nephritis, and membranous nephropathy over the study period that were contemporaneous with a fall in the proportion of FSGS. The spectrum of glomerular diseases among children varied across sexes, age groups, and regions and changed substantially from 2004 to 2014 in China.

Toll-Like Receptor 3 Signaling Contributes to Regional Neutrophil Recruitment in Cultured Human Glomerular Endothelial Cells

Background: Given the importance of neutrophil recruitment in the pathogenesis of glomerulonephritis (GN), the representative neutrophil chemoattractant C-X-C motif chemokine 1 (CXCL1)/GROα and the adhesion molecule E-selectin in glomerular endothelial cells (GECs) play a pivotal role in the development of GN. Endothelial Toll-like receptor 3 (TLR3) is thought to be involved in the inflammatory response via innate immunity. However, the role of endothelial TLR3 signaling in the expression of neutrophil chemoattractants and adhesion molecules remains to be elucidated. Thus, we aimed to examine this issue. Methods: We treated normal human GECs with polyinosinic-polycytidylic acid (poly IC), an authentic double-stranded RNA, and analyzed the expressions of CXCL1 and E-selectin using quantitative real-time reverse transcription-polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. To further elucidate the poly IC-induced signaling pathway, we subjected the cells to RNA interference against TLR3, interferon (IFN)-β, nuclear factor (NF)-κB p65, and IFN regulatory factor (IRF) 3. We also used immunofluorescence to examine the endothelial expression of CXCL1 in biopsy specimens from patients with crescentic and non-crescentic purpura nephritis (PN). Results: We found that the activation of TLR3 induced the endothelial expression of CXCL1 and E-selectin, and that this involved TLR3, ­NF-κB, IRF3, and IFN-β. Intense endothelial CXCL1 expression was observed in biopsy specimens from patients with crescentic PN. Conclusion: These findings support a role for glomerular antiviral innate immunity in the pathogenesis of GN. Intervention of glomerular TLR3 signaling may therefore be a suitable therapeutic strategy for treating GN in the future.