Respiratory failure and macrophage activation syndrome as an onset of systemic lupus erythematosus: A case report

BACKGROUND Macrophage activation syndrome(MAS)is defined as a specific secondary hemophagocytic lymphohistiocytosis that refers particularly to those triggered by autoimmune diseases.MAS is a rare and highly lethal complication of systemic lupus erythematosus(SLE),which can be associated with,or mimic,disease flare.However,the data regarding the clinical course,management and outcome of SLE with MAS is limited,especially in adults.Lack of clinical recognition of the disease often leads to poor prognosis.CASE SUMMARY We report a 36-year-old Chinese woman without relevant past medical history who was admitted to hospital with a 6-d history of jaundice and a high fever of 39.4°C lasting one day.Abdominal magnetic resonance imaging excluded obstructive jaundice,no infection was identified and empiric superior antibiotic treatment(meropenem)showed no clinical improvement.However,newly emerged pancytopenia and respiratory failure endangered the patient’s life.Autoimmune work-up finally led to the diagnosis of SLE,which initially presented as MAS and manifested respiratory failure,although neither bone marrow biopsy nor lymph node biopsy showed hemophagocytosis.To our knowledge,such a scenario has never been reported in detail before.The patient had a favorable reaction to combination treatment with corticosteroid and cyclosporine A and has been in clinical remission during the 1-year follow up period.CONCLUSION Respiratory failure and MAS can be an onset of SLE.Early diagnosis and appropriate treatment are extremely important for a better prognosis.

Decreased Number of CD14+TLR4+ Monocytes and Their Impaired Cytokine Responses to Lipopolysaccharide in Patients with Chronic Kidney Disease

This study aimed to examine the number of circulating Toll-like receptor 4（TLR4） ＋ CD14＋ monocytes in patients with different stages of chronic kidney disease（CKD）, their responses to lipopolysaccharide（LPS）, and to explore the potential association of the number of TLR4＋CD14＋ monocytes with clinical laboratory measures. The numbers of TLR4＋CD14＋, LPS-stimulated TNF-？＋CD14＋ and interleukin（IL）-6＋CD14＋ monocytes were determined by flow cytometry in 9 patients with stage 3 CKD, 11 with stage 4 CKD, 16 with stage 5 CKD, and 19 healthy controls（HCs）. Their laboratory tests were performed by routine methods and the potential association among these measures was analyzed by Pearson＇s correlation analysis. The numbers of CD14＋, CD14＋TLR4＋, LPSstimulated TNF-？＋CD14＋ and IL-6＋CD14＋ monocytes in patients with CKD were significantly less than those of HCs（all P〈0.05）, and were negatively associated with patient disease severity. The number of CD14＋TLR4＋ monocytes was positively correlated with estimated glomerular filtration rate（e GFR, P〈0.001） and the levels of hematocrit（P〈0.01）, but negatively correlated with the levels of blood urine nitrogen, serum creatinine, and C-reactive protein（P〈0.001 for all）, in the CKD patients. Our data indicate that significant reduction in the number of TLR4＋ monocytes and their impaired responses to LPS may be associated with the progression of CKD in Chinese patients.

Sofosbuvir/Ribavirin therapy for patients experiencing failure of ombitasvir/paritaprevir/ritonavir + ribavirin therapy: Two cases report and review of literature

BACKGROUND The effectiveness of sofosbuvir/ribavirin(SOF/RBV) combination therapy,which is one of the 1 st-choice therapeutic options for patients with hepatitis C virus(HCV) genotype 2(HCV-G2) in Japan according to the most recent version of the Japan Society of Hepatology guideline, for patients who experienced failure of the ombitasvir/paritaprevir/ritonavir plus ribavirin(OBV/PTV/r+RBV) combination therapy, which was another option for patients with HCV-G2, is unknown.CASE SUMMARY We evaluated the effects of SOF/RBV combination therapy in two patients with genotype 2 a who could not achieve a sustained virological response(SVR) by OBV/PTV/r+RBV combination therapy. One patient was complicated with VogtKoyanagi-Harada(VKH) disease. Resistance-associated variations before SOF/RBV combination therapy were not detected in two patients. Both patients had an SVR at 12 wk after the treatment(SVR12). Regarding adverse events(AEs), itching, chill, a dull feeling in the throat and cough as well as increase of alanine transaminase level were shown in one patient, while a headache and deterioration of light aversion probably due to the recurrence of VKH disease were shown in the other patients. In addition, the latter patient developed arthralgia and morning stiffness approximately 7 wk after the therapy and turned out to be diagnosed with rheumatoid arthralgia.CONCLUSION SOF/RBV therapy might be effective for patients experiencing failure of OBV/PTV/r+RBV therapy, but caution should be taken regarding the AEs.

Down-regulation of Risa improves podocyte injury by enhancing autophagy in diabetic nephropathy

Background: LncRNA AK044604(regulator of insulin sensitivity and autophagy, Risa) and autophagy-related factors Sirt1 and GSK3β play important roles in diabetic nephropathy(DN). In this study, we sought to explore the effect of Risa on Sirt1/GSK3β-induced podocyte injury.Methods: Diabetic db/db mice received Risa-inhibition adeno-associated virus(AAV) via tail vein injection, and intraperitoneal injection of lithium chloride(LiCl). Blood, urine, and kidney tissue samples were collected and analyzed at different time points. Immortalized mouse podocyte cells(MPCs) were cultured and treated with Risa-inhibition lentivirus(LV), EX-527, and LiCl. MPCs were collected under different stimulations as noted. The effects of Risa on podocyte autophagy were examined by qRT-PCR, Western blotting analysis, transmission electron microscopy,Periodic Acid-Schiff staining, and immunofluorescence staining.Results: Risa and activated GSK3β were overexpressed, but Sirt1 was downregulated in DN mice and high glucosetreated MPCs(P<0.001, db/m vs. db/db, NG or HM vs. HG), which was correlated with poor prognosis. Risa overexpression attenuated Sirt1-mediated downstream autophagy levels and aggravated podocyte injury by inhibiting the expression of Sirt1(P<0.001, db/m vs. db/db, NG or HM vs. HG). In contrast, Risa suppression enhanced Sirt1-induced autophagy and attenuated podocyte injury, which could be abrogated by EX-527(P<0.001, db/db+Risa-AAV vs. db/db, HG+Risa-LV vs. HG). Furthermore, LiCl treatment could restore GSK3β-mediated autophagy of podocytes(P<0.001, db/db+LiCl vs. db/db, HG+LiCl vs. HG), suggesting that Risa overexpression aggravated podocyte injury by decreasing autophagy.Conclusions: Risa could inhibit autophagy by regulating the Sirt1/GSK3β axis, thereby aggravating podocyte injury in DN. Risa may serve as a therapeutic target for the treatment of DN.

Chinese family care patterns of childhood rheumatic diseases:A cluster analysis

Objectives:The purpose is to distinguish family care(FC)patterns of childhood rheumatic diseases in Chinese families and to determine the predictors of FC patterns.Methods:This secondary analysis contained two cross-section surveys with a convenient sample of totally 398 caregivers who have a child with rheumatic diseases from four pediatric hospitals.Caregivers were required to completed Family Management Measure questionnaire.Cluster analysis was used to distinguish patterns and multinomial logistic regression analysis was used to find predictors.Results:Four patterns were identified:the normal-perspective and collaborative(28.4%),the effortless and contradictory(24.6%),the chaotic and strenuous(18.3%),and the confident and concerning(28.7%).Disease category(x2=21.23,P=0.002),geographic location(x2=8.41,P=0,038),maternal educational level(x2=12.69,P=0.048)and family monthly income(x2=33.21,P<0.001)predicted different patterns.Conclusions:FC patterns were different among families.Disease-related and family-related factors were vital predictors to distinguish patterns consistent with the Family Management Style Framework.The result assisted that clinicians recognize FC patterns and predictors effectively to provide tailored advice in time.

Impact of the antiproliferative agent ciclopirox olamine treatment on stem cells proteome

AIM:To investigate the proteome changes of stem cells due to ciclopirox olamine (CPX) treatment compared to control and retinoic acid treated cells. METHODS:Stem cells (SCs) are cells, which have the ability to continuously divide and differentiate into various other kinds of cells. Murine embryonic stem cells (ESCs) and multipotent adult germline stem cells (maG-SCs) were treated with CPX, which has been shown to have an antiproliferative effect on stem cells, and compared to stem cells treated with retinoic acid (RA),which is known to have a differentiating effect on stem cells. Classical proteomic techniques like 2-D gel electrophoresis and differential in-gel electrophoresis (DIGE) were used to generate 2D protein maps from stem cells treated with RA or CPX as well as from non-treated stem cells. The resulting 2D gels were scanned and the digitalized images were collated with the help of Delta 2D software. The differentially expressed proteins were analyzed by a MALDI-TOF-TOF mass spectrometer, and the identified proteins were investigated and categorized using bioinformatics. RESULTS:Treatment of stem cells with CPX, a synthetic antifungal clinically used to treat superficial mycoses, resulted in an antiproliferative effect in vitro, without impairment of pluripotency. To understand the mechanisms induced by CPX treatments which results in arrest of cell cycle without any marked effect on pluripotency, a comparative proteomics study was conducted. The obtained data revealed that the CPX impact on cell proliferation was accompanied with a significant alteration in stem cell proteome. By peptide mass fingerprinting and tandem mass spectrometry combined with searches of protein sequence databases, a set of 316 proteins was identified, corresponding to a library of 125 non-redundant proteins. With proteomic analysis of ESCs and maGSCs treated with CPX and RA, we could identify more than 90 single proteins, which were differently expressed in both cell lines. We could highlight, that CPX treatment of stem cells, with subsequent proliferation inhibition, resulted in an alteration of the expression of 56 proteins compared to nontreated cells, and 54 proteins compared to RA treated cells. Bioinformatics analysis of the regulated proteins demonstrated their involvement in various biological processes. To our interest, a number of proteins have potential roles in the regulation of cell proliferation either directly or indirectly. Furthermore the classification of the altered polypeptides according to their main known/postulated functions revealed that the majority of these proteins are involved in molecular functions like nucleotide binding and metal ion binding, and biological processes like nucleotide biosynthetic processes, gene expression, embryonic development, regulation of transcription, cell cycle processes, RNA and mRNA processing. Proteins, which are involved in nucleotide biosynthetic process and proteolysis, were downregulated in CPX treated cells compared to control, as well as in RA treated cells, which may explain the cell cycle arrest. Moreover, proteins which were involved in cell death, positive regulation of biosynthetic process, response to organic substance, glycolysis, anti-apoptosis, and phosphorylation were downregulated in RA treated cells compared to control and CPX treated cells. CONCLUSION:The CPX treatment of SCs results in downregulation of nucleotide binding proteins and leads to cell cycle stop without impairment of pluripotency.

IL-17 induces autoantibody overproduction and peripheral blood mononuclear cell overexpression of IL-6 in lupus nephritis patients

To investigate the role of IL-17 in the overproduction of autoantibodies and IL-6 overexpression by peripheral blood mononuclear cells (PBMC) of lupus nephritis (LN) patients Methods Fifteen consecutively hospitalized LN patients were selected as subjects and 15 healthy adults as normal controls PBMC were obtained by Ficoll density gradient centrifugation IgG, anti-dsDNA antibody and IL-6 protein levels were assessed using enzyme-linked immunosorbent assays (ELISA) on the supernatant of cul tured PBMC of LN patients or normal controls IL-6 mRNA levels in PBMC were measured using reverse transcription-polymerase chain reaction (RT-PCR) Results In medium culture, IgG, anti-dsDNA and IL-6 protein levels of the supernatant of PBMC from LN patients were significantly higher than those from normal controls (1492 1±73 2 ng/ml vs 636 7±51 9 ng/ml for IgG, 306 6±53 7 IU/ml vs 95 8±11 6 IU/ml for anti-dsDNA and 50 92±15 92 ng/ml vs 1 77±0 73 ng/ml for IL-6, all P<0 001) In LN patients, IgG, anti-dsDNA and IL-6 protein levels were higher in the supernatants of PBMC in the IL-17-stimulated culture than the medium culture, but in normal controls, only the IL-6 protein levels were significantly higher The increase in IgG, anti-dsDNA and IL-6 protein levels induced by IL-17 was dose-dependent and could be completely blocked by IL-17 monoclonal antibody mIgG 28 and partially blocked by dexamethasone Similarly, IL-6 mRNA overexpression of PBMC in LN patients or normal controls induced by IL-17 was both dose- and time-dependent During medium culture, IL-6 mRNA levels in LN patients were significantly higher than those in normal controls (1 80±0 11 vs 0 36±0 07) During stimulation with IL-17, IL-6 mRNA levels in LN patients were higher than those in normal controls (3 21±0 24 vs 1 30±0 14, P<0 05) and also significantly higher when comparing the stimulated culture with the medium culture either in LN patients or normal control Conclusions IL-17 may play an important role in the pathogenesis of LN through the induction of IgG, anti-dsDNA overproduction and IL-6 overexpression of PBMC in LN patients

Usefulness of mizoribine administration in children with frequently relapsing nephrotic syndrome, and the relationship between pharmacokinetic parameters and efficacy: a multicenter prospective cohort study in China

Background Mizoribine (MZR) is an immunosuppressant used to treat adult nephropathy.There is little experience with the drug in treating Chinese children with frequently relapsing nephrotic syndrome (FRNS).We investigated the efficacy and safety for treating MZR with FRNS.Furthermore,the relationship between efficacy and serum concentration was investigated.Methods A prospective multicenter observational 12-month study was performed for evaluating the usefulness of MZR with FRNS.Serum MZR concentration was measured,and the relationships between pharmacokinetic parameters (Cmax,AUC),number of relapses,and urinary protein were evaluated.Results Eighty-two pediatric patients from four hospitals were treated with MZR and prednisone.MZR treatment significantly reduced the number of relapses and steroid doses.A correlation between pharmacokinetic parameters and relapses was observed,which fits well with the sigmoidal Emax model.Even in the relationship between pharmacokinetic parameters and urinary proteins,it was recognized that there was a threshold in the pharmacokinetic parameters for the therapeutic effect similar to the results obtained with the sigmoidal Emax model.Eleven patients (13.4%) experienced mild adverse events.Conclusions MZR therapy was effective in reducing the number of relapses and steroid doses.No severe adverse reactions were observed.Therapeutically effective serum concentrations were estimated to be Cmax > about 2 μg/mL or AUC > about 10 lag h/mL.MZR and steroid treatment were effective and safe for pediatric FRNS.

Efficacy and Safety of Niaoduqing Particles for Delaying Moderate-to-severe Renal Dysfunction： A Randomized, Double-blind, Placebo-controlled, Multicenter Clinical Study

Background： Chronic kidney disease （CKD） with moderate-to-severe renal dysfunction usually exhibits an irreversible course, and available treatments for delaying the progression to end-stage renal disease are limited. This study aimed to assess the efficacy and safety of the traditional Chinese medicine, Niaoduqing particles, for delaying renal dysfunction in patients with stage 3b-4 CKD.Methods： The present study was a prospective, randomized, double-blind, placebo-controlled, naulticentcr clinical trial. Frorn May 2013 to December 2013,300 CKD patients with an estimated glomerular filtration rate （eGFR） between 20 and 45 ml ＂rain ~＂ 1.73 m 2, aged 18-70 years were recruited from 22 hospitals in 11 Chinese provinces. Patients were randomized in a 1：1 ratio to either a test group, which was administered Niaoduqing particles 5 g thrice daily and 10 g before bedtime for 24 weeks, or a control group, which was administered a placebo using the same methods. The primary endpoints were changes in baseline serum creatinine （Scr） and eGFR after completion of treatment. The primary endpoints were analyzed using Student＇s t-test or Wilcoxon＇s rank-sum test. The present study reported results based on an intention-to-treat （ITT） analysis. Results： A total of 292 participants underwent the ITT analysis. At 24 weeks, the median （interquartile range） change in Scr was 1.1 （-13.0-24.1） and 11.7 （-2.6-42.9） p, mol/L for the test and control groups, respectively （Z = 2.642, P = 0.008）, and the median change in eGFR was -0.2 （-4.3-2.7） and -2.2 （-5.7-0.8） ml.min-1·1.73 m-2, respectively （Z = -2.408, P = 0.016）. There were no significant differences in adverse events between the groups. Conclusions： Niaoduqing particles safely and effectively delayed CKD progression in patients with stage 3b-4 CKD. This traditional Chinese medicine may be a promising alternative medication for patients with moderate-to-severe renal dysfunction.

Identification of a novel COL4A5 mutation in the proband initially diagnosed as Ig AN from a Chinese family with X-linked Alport syndrome

Alport syndrome(AS) is a hereditary progressive nephropathy characterized by hematuria, ultrastructural lesions of the glomerular basement membrane, ocular lesions and sensorineural hearing loss. Germline mutations of COL4 A5 are associated with X-linked AS with an extreme phenotypic heterogeneity. Here, we investigated a Chinese family with Alport syndrome. The proband was a 9-year-old boy with hematuria and proteinuria. Based on the test results of renal biopsy and immunofluorescence,the proband was initially diagnosed as Ig A nephropathy and the treatment was recommended accordingly. Meanwhile, we found that the treatment outcome was poor. Therefore, for proper clinical diagnosis and appropriate treatment, targeted exome-based next-generation sequencing has been undertaken. We identified a novel hemizygous single nucleotide deletion c.1902 del A in COL4 A5 gene. Segregation analysis identified that this novel mutation is co-segregated among the affected family members but absent in unaffected family members. The clinical diagnosis of the proband was revised as AS accompanied by Ig A nephropathy,which has been rarely reported. Our findings demonstrated the significance of the application of Genetic screening, expanded the mutation spectrum of COL4 A5 associated AS patients with atypical renal phenotypes and provided a good lesson to be learned from our detour during the diagnosis.

Safety,Effectiveness,and Manipulability of Peritoneal Dialysis Machines Made in China:A Randomized,Crossover, Multicenter Clinical Study

Background: Automated peritoneal dialysis (APD) can cater to individual needs, provide treatment while asleep, take into account the adequacy of dialysis, and improve the quality of life. Currently, independent research and development of APD machines made in China are more conducive to patients. A randomized, multicenter, crossover study was conducted by comparing an APD machine made in China with an imported machine. The safety, effectiveness, and manipulability of the two machines were compared. Methods: Two hundred and sixty patients who underwent peritoneal dialysis (PD) on a regular basis in 18 centers between August 2015 and February 2016 were included. The inclusion criteria include age ≥18 years and PD ≥30 days. The exclusion criteria were as follows: hemodialysis; exit site or tunnel infection; and peritonitis ≤30 days. The patients were randomly divided into Group A, who were first treated with a FM machine made in China, then changed to an imported machine; and Group B, who were treated using the reverse sequence. APD treatment was performed with 10 L/10 h and 5 cycles of exchange. After 72 h, the daily peritoneal Kt/V, the accuracy of the injection rate, accuracy of the injection temperature, safety, and manipulability of the machine were assessed. Noninferiority test was conducted between the two groups. Results: The daily peritoneal Kt/V in the APD machine made in China and the imported APD machine were 0.17 (0.14, 0.25) and 0.16 (0.13, 0.23), respectively. There was no significant difference between the groups (Z = 0.15, P = 0.703). The lower limit of the daily Kt/V difference between the two groups was 0.0069, which was greater than the noninferiority value of -0.07 in this study. The accuracy of the injection rate and injection temperature was 89.7% and 91.5%, respectively, in the domestic APD machine, which were both slightly better than the accuracy rates of 84.0% and 86.8% in the imported APD machine (89.7% vs. 84.0%, P = 0.2466; 91.5% vs. 86.8%, P = 0.0954). Therefore, the APD machine made in China was not inferior to the imported APD machine. The fuselage of the imported APD machine was space?saving, while the APD machine made in China was superior with respect to body mobility, man?machine dialog operation, alarm control, and patient information recognition. Conclusions: The FM machine made in China was not inferior to the imported APD machine. In addition, the FM machine made in China had better operability.

Efficacy and safety of Shenyankangfu Tablet,a Chinese patent medicine,for primary glomerulonephritis:A multicenter randomized controlled trial

Background:Shenyankangfu Tablet(SYKFT)is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease.Objective:This trial compared the efficacy and safety of SYKFT,for the control of proteinuria in primary glomerulonephritis patients,against the standard drug,losartan potassium.Design,setting,participants and intervention:This was a multicenter,double-blind,randomized,controlled clinical trial.Primary glomerulonephritis patients,aged 18-70 years,with blood pressure≤140/90 mmHg,estimated glomerular filtration rate(eGFR)>45 mL/min per 1.73 ㎡,and 24-hour proteinuria level of 0.5-3.0 g,were recruited in 41 hospitals across 19 provinces in China and were randomly divided into five groups:SYKFT,losartan potassium 50 mg or 100 mg,SYKFT plus losartan potassium 50 mg or 100 mg.Main outcome measu res:The primary outcome was change in the 24-hour proteinuria level,after 48 weeks of treatment.Results:A total of 735 participants were enrolled.The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78%±2.56%(P=0.006)more than that in the losartan 50 mg group,which was 0.51%±2.54%(P=1.000)less than that in the losartan 100 mg group.Compared with the losartan potassium 50 mg group,the SYKFT plus losartan potassium 50 mg group had a 13.39%±2.49%(P<0.001)greater reduction in urine protein level.Compared with the losartan potassium 100 mg group,the SYKFT plus losartan potassium 100 mg group had a 9.77%±2.52%(P=0.001)greater reduction in urine protein.With a superiority threshold of 15%,neither was statistically significant.eGFR,serum creatinine and serum albumin from the baseline did not change statistically significant.The average change in TCM syndrome score between the patients who took SYKFT(-3.00[-6.00,-2.00])and who did not take SYKFT(-2.00[-5.00,0])was statistically significant(P=0.003).No obvious adverse reactions were observed in any group.Conclusion:SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients,with no change in the rate of decrease in the eGFR.SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone.Trial registration number:NCT02063100 on ClinicalTrials.gov.

Paraneoplastic focal segmental glomerulosclerosis associated with gastrointestinal stromal tumor with cutaneous metastasis: A case report

BACKGROUND Gastrointestinal stromal tumor(GIST)with cutaneous metastasis is very rare.As a result,cutaneous GISTs have not been well characterized.Focal segmental glomerulosclerosis(FSGS)is also a rare symptom among paraneoplastic nephritic syndromes(PNS).CASE SUMMARY In this case report,we describe a patient with cutaneous metastatic GIST accompanied by nephrotic syndrome occurring as a malignancy-associated PNS,for whom symptomatic treatment was ineffective,but clinical remission was achieved after surgery.Moreover,the patient has a missense mutation in NPHP4,which can explain the occurrences of GIST and FSGS in this patient and indicates that the association is not random.CONCLUSION This is the first reported case of a GIST with cutaneous metastasis accompanied by nephrotic syndrome manifesting as a PNS.

Treatment of STING-associated vasculopathy with onset in infancy

To the Editor:Gain-of-function mutations in TMEM173,which encodes the protein stimulator of interferon(IFN)genes(STING),can reportedly cause an autoinflammatory syndrome termed STING-associated vasculopathy with onset in infancy(SAVI).1-3 SAVI is characterized by cutaneous necrotic lesions,growth failure,systemic inflammation,and interstitial lung disease.1,4 Therapeutic management is challenging and difficult:steroids are only partially effective,and patients respond poorly to immunosuppressants.

Risk factors for renal outcomes in children with antineutrophil cytoplasmic antibody-associated vasculitis:a nationwide retrospective study in China

Background Pediatric antineutrophil cytoplasmic antibody-associated vasculitis(AAV)is a life-threatening systemic vasculitis featured by liability to renal involvement.However,there are few studies on the risk factors and predictive models for renal outcomes of AAV in children.Methods Data from 179 AAV children in multiple centers between January 2012 and March 2020 were collected retrospectively.The risk factors and predictive model of end-stage renal disease(ESRD)in AAV were explored.Results Renal involvement was the most typical manifestation(95.5%),and the crescent was the predominant pathological lesion(84.9%).The estimated glomerular filtration rate(eGFR)was evaluated in 114 patients,of whom 59.6%developed ESRD,and the median time to ESRD was 3.20 months.The eGFR[P=0.006,odds ratio(OR)=0.955,95%confidence interval(CI)=0.924–0.987]and the percentages of global glomerulosclerosis(pGGS;P=0.018,OR=1.060,95%CI=1.010–1.112)were independent risk factors for ESRD of renal biopsy.Based on the pGGS and eGFR at renal biopsy,we developed three risk grades of ESRD and one predictive model.The Kaplan‒Meier curve indicated that renal outcomes were significantly different in different risk grades(P<0.001).Compared with serum creatinine at baseline,the predictive model had higher accuracy(0.86 versus 0.58,P<0.001)and a lower coefficient of variation(0.07 versus 0.92)in external validation.Conclusions Renal involvement is the most common manifestation of pediatric AAV in China,of which more than half deteriorates into ESRD.The predictive model based on eGFR at renal biopsy and the pGGS may be stable and accurate in speculating the risk of ESRD in AAV children.

Effects of Niaoduqing Particles(尿毒清颗粒)on Delaying Progression of Renal Dysfunction:A Post-trial,Open-Label,Follow-up Study

Objective: To follow up the participants of the randomized clinical trial "Efficacy and Safety of Niaoduqing Particles(尿毒清颗粒) for Delaying Moderate-to-Severe Renal Dysfunction", and assess the long-term effects of Niaoduqing Particles on delaying the progression of renal dysfunction. Methods: Participants, who had previously been randomly assigned to receive Niaoduqing Particles or placebo for 24 weeks(146 cases in each group), were invited to follow-up and all were administered Niaoduqing Particles 5 g thrice daily and 10 g before bedtime for 24 weeks. The primary endpoints were changes in baseline serum creatinine(Scr) and estimated glomerular filtration rate(e GFR) after completion of the open-label treatment period. Results: After the double-blind period, the median(interquartile range) changes in Scr were 1.1(–13.0–24.1) and 11.7(–2.6–42.9) μmol/L for the Niaoduqing Particle and placebo groups, respectively(P=0.008), and the median changes in e GFRs were –0.2(–4.3–2.7) and –2.21(–5.7–0.8) mL·min^(-1)·1.73 m^(-2), respectively(P=0.016). There were significant differences in the double-blind period changes in renal function between groups. After the open-label period, the median changes in Scr were 9.0(–10.0–41.9) and 17.5(–6.0–50.0) μmol/L for the Niaoduqing Particle and placebo groups according to baseline grouping, respectively(P=0.214), and the median changes in eGFRs were –2.3(–6.4–1.9) and –3.7(–7.5–1.1) mL·min^(-1)·1.73 m^(-2), respectively(P=0.134). There were no statistical differences in the open-label period changes in renal function between groups. The eGFR reduction of participants who accepted Niaoduqing Particle treatment for 48 weeks was projected to 2.5 m L·min^(-1)·1.73 m(-2) per year. Conclusions: Niaoduqing Particles appear to have long-term efficacy for patients with moderate-to-severe renal dysfunction. Although there was no statistical difference, the early use of Niaoduqing Paticles seems to ameliorate the worsening of renal function.

Efficacy of rituximab therapy in children with refractory nephrotic syndrome:a prospective observational study in Shanghai

Background:Idiopathic nephrotic syndrome is the most common glomerular disease in children.This study was undertaken to observe the efficacy and side-effects of rituximab(RTX)in treating children with different types of refractory primary nephrotic syndrome.Methods:Twelve patients with steroid dependent nephrotic syndrome(SDNS),frequently relapsing nephritic syndrome(FRNS),and steroid resistant nephrotic syndrome(SRNS)were enrolled in our study.There were obvious drug side-effects,and proteinuria remained difficult to control.RTX was administered at a dose of 375 mg/m2 body surface area,once or twice weekly.Results:The male to female ratio was 3:1,and the onset age was 1.6–8.9 years.There were 9 patients with steroid sensitive nephrotic syndrome(SDNS or FRNS),and 3 patients with SRNS.There were 7 patients with minimal change disease(MCD),3 patients with focal segmental glomerular sclerosis(FSGS),1 with focal proliferative glomerulonephritis,and 1 without renal biopsy.The total effective treatment rate of RTX was 91.67%,and for 77.78%of the patients,steroid dosage could be reduced.Six months before and after RTX infusion,the mean steroid dosage was significantly decreased(P=0.014)and the recurrence number was significantly reduced(P<0.001).The results were better in MCD patients than in FSGS patients(P=0.045).There was no significant difference between FRNS/SDNS and SRNS patients(P=0.175).During RTX administration,3 patients developed skin rashes,1 developed hypotension,and 1 developed a fever.One patient experienced a persistent decrease in serum immunoglobulin level but without serious infection.Conclusion:RTX was effective in the treatment of refractory nephrotic syndrome,and it could significantly reduce the use of steroid and immunosuppressants.

Anti-cyclic citrullinated peptide antibody predicts the development of rheumatoid arthritis in patients with undifferentiated arthritis

Background:Clinical outcomes of undifferentiated arthritis(UA)are diverse,and only 40%of patients with UA develop rheumatoid arthritis(RA)after 3 years.Discovering predictive markers at disease onset for further intervention is critical.Therefore,our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development.Methods:We performed a prospective,multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals.Clinical and serological parameters were obtained at recruitment.Follow-up was undertaken in all patients every 12 weeks for 2 years.Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression.Results:A total of 234 patients were recruited in this study,and 17(7.3%)patients failed to follow up during the study.Among the 217 patients who completed the study,83(38.2%)patients went into remission.UA patients who developed RA had a higher rheumatoid factor(RF)-positivity(42.9%vs.16.8%,χ^2=8.228,P=0.008),anti-cyclic citrullinated peptide(CCP)antibodypositivity(66.7%vs.10.7%,χ^2=43.897,P<0.001),and double-positivity rate of RF and anti-CCP antibody(38.1%vs.4.1%,χ^2=32.131,P<0.001)than those who did not.Anti-CCP antibody but not RF was an independent predictor for RA development(hazard ratio 18.017,95%confidence interval:5.803–55.938;P<0.001).Conclusion:As an independent predictor of RA,anti-CCP antibody should be tested at disease onset in all patients with UA.

Significance of Sacroiliac Joint Aerocele in Diagnosis of Ankylosing Spondylitis

To explore the significance of sacroiliac joint aerocele in the diagnosis of ankylosing spondylitis, the data of 196 patients with ankylosing spondylitis (AS) were collected during December of 2008 to May of 2009. And 50 patients with osteoarthritis (OA), 15 patients with sclerosing osteitis (SO) and 47 patients with sacroiliac joint tumors were investigated as the control groups. The feature of sacroiliac joint aerocele in computed tomography (CT) images was observed carefully. In AS group there were 130 patients (66.3%) diagnosed as AS according to CT results, and 32 of them (24.6%) were observed with aerocele within sacroiliac joint cavity, majority of whom were earlier AS patients with slight bone destruction. Other 66 patients were diagnosed as early AS according to magnetic resonance imaging (MRI) and ultrasonography. CT examination showed that the 66 patients did not have apparent bone destruction, of whom, 26 (39.4%) patients had aerocele within sacroiliac joint cavity. Among the control groups of 15 (15/50, 30.0%) patients with OA, 5 (5/15, 33.3%) patients with SO were observed sacroiliac joint aerocele. The 47 patients with sacroiliac joint tumors were observed with bone or cartilage destruction, but without signs of sacroiliac joint aerocele. The sacroiliac joint aerocele in CT images of AS patients usually appeared as spots, streaks, small or larger round blocks, and it often happened in patients with earlier stage of diseases. Sacroiliac joint aerocele may be useful to early diagnosis of AS.