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

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World Journal of Pediatrics 2024年第5期20卷 506-516页

作者： Li-Wen Tan Jun-Li Wan Chun-Hua Zhu Hong Xu Zheng-Kun Xia Li-Zhi Chen Xiao-Chuan Wu Fang Wang Xiao-Rong Liu Cheng-Guang Zhao Xiao-Zhong Li Jian-Hua Mao Xiao-Wen Wang Wen-Yan Huang Yu-Hong Li Jian-Jiang Zhang Shi-Pin Feng Jun Yang Jiao-Jiao Liu Chun-Lin Gao Li-Ping Rong Lan-Jun Shuai Ke Xu He-Jia Zhang Qiu Li Ai-Hua Zhang Mo Wang Department of Nephrology Children’s Hospital of Chongqing Medical UniversityZhongshan 2nd Rd.136Chongqing400014China Ministry of Education Key Laboratory of Child Development and Disorders National Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChildren’s Hospital of Chongqing Medical UniversityChongqingChina Chongqing Key Laboratory of Pediatrics Children’s Hospital of Chongqing Medical UniversityChongqingChina Department of Nephrology Children’s Hospital of Nanjing Medical University72 Guangzhou RoadNanjing210008China Department of Nephrology Children’s Hospital of Fudan UniversityNational Paediatric Medical Center of ChinaShanghaiChina Department of Pediatrics Jinling HospitalNanjing Medical UniversityNanjingChina Department of Pediatrics Jinling HospitalThe First School of Clinical MedicineSouthern Medical UniversityNanjingChina Department of Pediatrics Jinling HospitalMedical School of Nanjing UniversityNanjingChina Department of Pediatric Nephrology and Rheumatology The First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouChina Department of Pediatrics The Second Xiangya Hospital of Central South UniversityChangshaChina Department of Pediatrics Peking University First HospitalBeijingChina Department of Nephrology Beijing Children’s HospitalCapital Medical UniversityBeijing100045China National Center for Children’s Health BeijingChina Department of Pediatrics Shengjing Hospital of China Medical UniversityShenyangChina Department of Nephrology and Immunology Children’s Hospital of Soochow UniversitySuzhouChina Department of Nephrology Children HospitalZhejiang University School of MedicineHangzhouChina Department of Nephrology Wuhan Children’s Hospital(Wuhan Maternal and Child Healthcare Hospital)Tongji Medical CollegeHuazhong University of Science&TechnologyWuhanChina Department of Nephrology and Rheumatology Shanghai Children’s HospitalSchool

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.

关键词： Antineutrophil cytoplasmic antibody End-stage renal disease glomerulonephritis Pediatric nephrology Vasculitis

Immunoglobulin A glomerulonephropathy:A review

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World Journal of Clinical Cases 2024年第8期12卷 1388-1394页

作者： Mohamad El Labban Salim Surani Department of Internal Medicine Mayo Cliic Health SystemMankatoMN 56001United States Department of Medicine&Pharmacology Texas A&M UniversityCollege StationTX 77843United State

In this editorial,we comment on the article by Meng et al published in the World Journal of Clinical Cases.We comprehensively review immunoglobulin A nephro-pathy(IgAN),including epidemiology,clinical presentation,diagnosis,and management.IgAN,also known as Berger's disease,is the most frequent type of primary glomerulonephritis(GN)globally.It is mostly found among the Asian population.The presentation can be variable,from microscopic hematuria to a rapidly progressive GN.Around 50%of patients present with single or recurring episodes of gross hematuria.An upper respiratory infection and tonsillitis often precede these episodes.Around 30%of patients present microscopic hematuria with or without proteinuria,usually detected on routine examination.The diagnosis relies on having a renal biopsy for pathology and immunofluorescence microscopy.We focus on risk stratification and management of IgAN.We provide a review of all the landmark studies to date.According to the 2021 KDIGO(kidney disease:Improving Global Outcomes)guidelines,patients with non-variant form IgAN are first treated conservatively for three to six months.This approach consists of adequate blood pressure control,reduction of proteinuria with renin-angiotensin system blockade,treatment of dyslipidemia,and lifestyle modifications(weight loss,exercise,smoking cessation,and dietary sodium restrictions).Following three to six months of conservative therapy,patients are further classified as high or low risk for disease progression.High-risk patients have proteinuria≥1 g/d or<1 g/d with significant microscopic hematuria and active inflammation on kidney biopsy.Some experts consider proteinuria≥2 g/d to be very high risk.Patients with high and very high-risk profiles are treated with immunosuppressive therapy.A proteinuria level of<1 g/d and stable/im-proved renal function indicates a good treatment response for patients on immu-nosuppressive therapy.

关键词： Immunoglobulin A nephropathy glomerulonephritis Nephritic syndrome Angiotensin-converting enzyme inhibitor Angiotensin receptor blocker Systemic steroids Mycophenolate mofetil

Successful rescue of disseminated Nocardia infection with multiple abscesses in a patient with membranous nephropathy after cardiopulmonary resuscitation:A three-year follow-up

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Journal of Biomedical Research 2024年第2期38卷 189-194,I0019,I0020页

作者： Yili Xu Hanyang Qian Wen Qian Li Dong Weiying Liu Yan Zhu Yaning Mei Yi Xu Ling Wang Yi Xia Xu Qi Huanping Mei Xueqiang Xu Huijuan Mao Changying Xing Ningning Wang Department of Nephrology the First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingJiangsu 210029China Department of Nephrology Nanjing Tongren HospitalNanjingJiangsu 211102China Department of Image the First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingJiangsu 210029China Department of Infectious Disease the First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingJiangsu 210029China Department of Nephrology the Second Hospital of NanjingNanjingJiangsu 210029China Department of Microorganism the First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingJiangsu 210029China Department of Hematology the First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingJiangsu 210029China Department of Rheumatology and Immunology the First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingJiangsu 210029China

Nocardiosis manifests as an opportunistic infection,primarily affecting individuals who are immunocompromised and susceptible to the infection.We present a case study of one patient with nephrotic syndrome and membranous nephropathy,who underwent treatment with prednisone and cyclosporine in 2016.In early 2017,the patient was diagnosed with a"fungal infection"and discontinued the use of cyclosporine.After one month of anti-infection therapy,a cranial magnetic resonance imaging scan showed multiple abscesses in the right temporal region.The diagnosis of nocardiosis was confirmed based on the presence of metastatic abscess masses,multiple lung and brain lesions,and a positive culture of Nocardia in the drainage.We changed the anti-infection therapy to a combination of trimethoprim-sulfamethoxazole(TMP-SMX),minocycline,and voriconazole.However,the patient experienced a sudden cardiac arrest and subsequently recovered after cardiopulmonary resuscitation.During the five-month follow-up period following the discharge,the patient displayed an enhanced nutritional status and stable renal function.The focal infection ultimately resolved during the subsequent three years.Neuro-infection caused by Nocardia should be considered in immunocompromised patients,and TMP-SMX is the preferred initial therapy;however,because of the high mortality rate,a long-term combination therapy with imipenem,cefotaxime,amikacin,and TMP-SMX is suggested.

关键词： Nocardia infection glomerulonephritis membranous nephrology cardiopulmonary resuscitation

Protective effect of modified Huangqi Chifeng decoction(加味黄芪赤风汤)on immunoglobulin A nephropathy through toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-kappa B signaling pathway

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Journal of Traditional Chinese Medicine 2024年第2期44卷 324-333页

作者： LI Liusheng ZHAO Mingming CHANG Meiying SI Yuan ZHAO Jinning YANG Bin ZHANG Yu Department of Oncology Beijing Hospital of Integrated Traditional Chinese and Western MedicineBeijing 100039China Department of Nephropathy Xiyuan HospitalChina Academy of Chinese Medical SciencesBeijing 100091China Xin-Huangpu Joint Innovation Institute of Chinese Medicine Guangzhou 510070China Department of Pathology Xiyuan Hospital China Academy of Chinese Medical SciencesBeijing 100091China Department of Experimental Research Center Xiyuan HospitalChina Academy of Chinese Medical SciencesBeijing 100091China

OBJECTIVE:To examine the nephroprotective mechanism of modified Huangqi Chifeng decoction(加味黄芪赤风汤,MHCD)in immunoglobulin A nephropathy(IgAN)rats.METHODS:To establish the IgAN rat model,the bovine serum albumin,lipopolysaccharide,and carbon tetrachloride 4 method was employed.The rats were then randomly assigned to the control,model,telmisartan,and high-,medium-,and low-dose MHCD groups,and were administered the respective treatments via intragastric administration for 8 weeks.The levels of 24-h urinary protein,serum creatinine(CRE),and blood urea nitrogen(BUN)were measured in each group.Pathological alterations were detected.IgA deposition was visualized through the use of immunofluorescence staining.The ultrastructure of the kidney was observed using a transmission electron microscope.The expression levels of interleukin-6(IL-6),monocyte chemoattractant protein-1(MCP-1),and transforming growth factor-β1(TGF-β1)were examined by immunohistochemistry and quantitative polymerase chain reaction.Levels of toll-like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),and nuclear factor-kappa B(NF-κB)P65,were examined by immunohistochemistry,Western blotting,and quantitative polymerase chain reaction.RESULTS:The 24-h urine protein level in each group increased significantly at week 6,and worsen from then on.But this process can be reversed by treatments of telmisartan,and high-,medium-,and low-dose of MHCD,and these treatments did not affect renal function.Telmisartan,and high-,and medium-dose of MHCD reduced IgA deposition.Renal histopathology demonstrated the protective effect of high-,medium-,and low-dose of MHCD against kidney injury.The expression levels of MCP-1,IL-6,and TGF-β1 in kidney tissues were downregulated by low,medium and high doses of MHCD treatment.Additionally,treatment of low,medium and high doses of MHCD decreased the protein and mRNA levels of TLR4,MyD88,and NF-κB.CONCLUSIONS:MHCD exerted nephroprotective effects on IgAN rats,and MHCD regulated the expressions of key targets in TLR4/MyD88/NF-

关键词： glomerulonephritis IGA toll-like receptor 4 myeloid differentiation factor 88 NF-kappa B signal transduction inflammation renal fibrosis modified Huangqi Chifeng decoction

Abrogation of immune complex glomerulonephritis by native carboxypeptidase and pharmacological antagonism of the C5a receptor

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Cellular & Molecular Immunology 2016年第5期13卷 651-657页

作者： Jessy J. Alexander Lee D. Chaves Anthony Chang Shruti Dighe Alexander Jacob Richard J. Quigg Division of Nephrology Department of Medicine University at Buffalo School of Medicine and Health Sciences Buffalo NY USA Department of Pathology The University of Chicago Chicago IL USA Correspondence: Dr Jessy J. Alexander Division of Nephrology State University of New York at Buffalo Clinical and Translational Research Center 875 Ellicott Street 8-022 Buffalo NY 14203 USA

Activation of complement generates C5a which leads to signaling through C5aR 1. This is tightly controlled, including by the plasma proteins factor H （FH） and carboxypeptidase N. Here we studied a chronic serum sickness （CSS） model of glomerulonephritis （GN） in which there is an active humoral immune response, formation of glomerular immune complexes （ICs）, and resulting glomerular inflammation. The antibody response, glomerular IC deposition, the degree of GN, and consequent renal functional insufficiency in CSS were all worse in FH-/- mice compared to wild-type FH＋/＋ animals. This was ameliorated in the former by giving a C5aR1 antagonist for the final 3 weeks of the 5-week protocol. In contrast, blocking CP-mediated inactivation of C5a increased these disease measures. Thus, complement regulation by both plasma FH and CP to limit the quantity of active C5a is important in conditions where the humoral immune response is directed to a continuously present foreign antigen. Signaling through C5aR1 enhances the humoral immune response as well as the inflammatory response to ICs that have formed in glomeruli. Both effects are relevant even after disease has begun. Thus, pharmacological targeting of C5a in IC-mediated GN has potential clinical relevance.

关键词： C5a carboxypeptidase N factor H glomerulonephritis

Cryoglobulinemic vasculitis and glomerulonephritis: concerns in clinical practice

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Chinese Medical Journal 2019年第14期132卷 1723-1732页

作者： Yi-Pu Chen Hong Cheng Hong-Liang Rui Hong-Rui Dong Division of Nephrology Beijing Anzhen HospitalCapital Medical UniversityBeijing 100029China

Objective:Cryoglobulinemia often causes systemic vasculitis,thereby damaging to skin and internal organs including kidneys,even life-threatening.This review aimed to introduce the advances in understanding,detection,and treatment of this disease in recent years,with a particular concern to clinical practice.Data sources:All the data in this review were from the English or Chinese literature in the PubMed and China National Knowledge Infrastructure databases as of March 2019.Study selection:This review selected important original articles,meaningful reviews,and some reports on cryoglobulinemia published in recent years and in history,as well as the guidelines for treatment of underlying diseases which lead to cryoglobulinemia.Results:Diagnosis of cryoglobulinemia relies on serum cryoglobulin test,in which to ensure that the blood sample temperature is not less than 37℃ in the entire pre-analysis phase is the key to avoid false negative results.Cryoglobulinemic vasculitis (Cryo Vas),including cryoglobulinemic glomerulonephritis (Cryo GN),usually occurs in types Ⅱ and Ⅲ mixed cryoglobulinemia,and can also be seen in type Ⅰ cryoglobulinemia caused by monoclonal IgG3 or IgG1.Skin purpura,positive serum rheumatoid factor,and decreased serum levels of C4 and C3 are important clues for prompting types Ⅱ and Ⅲ Cryo Vas.Renal biopsy is an important means for diagnosis of Cryo GN,while membranous proliferative GN is the most common pathological type of Cryo GN.In recent years,great advances have been made in the treatment of Cryo Vas and its underlying diseases,and this review has briefly introduced these advances.Conclusions:Laboratory examinations of serum cryoglobulins urgently need standardization.The recent advances in the diagnosis and treatment of Cryo Vas and GN need to be popularized among the clinicians in related disciplines.

关键词： Cryoglobulin Vasculitis glomerulonephritis Monoclonal immunoglobulin Hepatitis C virus Autoimmune disease

Relationship between genotypes and clinical manifestation, pathology, and cccDNA in Chinese children with hepatitis B virus-associated glomerulonephritis

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世界儿科杂志:英文版 2016年第3期12卷 347-352页

作者： Yong-Hong Sun Xiao-Yan Lei Yi-Pa Sai Jun-Hui Chen Yuan-Chun Sun Xia Gao Department of Pediatrics People's Hospital of Gansu ProvinceLanzhouGansuChina

Background:Hepatitis B virus-associated glomerulonephritis(HBV-GN)is one of the extrahepatic manifestations after HBV infection,which would cause great clinical harm to people.The present study was undertaken to investigate the HBV-GN genotypes and its clinical relevance in Chinese children.Methods:A total of 41 HBV-infected children diagnosed with HBV-GN were enrolled in the study.All patients underwent liver and kidney biopsy.The genotypes and cccDNA were detected in their serum samples to analyze the relationship between HBV genotypes and clinical characteristics,cccDNA,and pathology.Results:Among the 41 children with HBV-GN,29(70.7%)had genotype C,10(24.4%)had genotype B,2(4.9%)had genotype B/C,and none of them had genotype non-B/C.Most children had genotypes B or C;moreover,the genotype C was the most frequent one.The incidence of hematuria and albuminuria,reduction in complement C3,increase in serum alanine aminotransferase levels and renal insufficiency in the children with genotype C were signifi cantly higher than those in the children with genotype B(P0.05).The frequency of HBV cccDNA positive in the genotype C group was significantly higher than that in the genotype B group(72.4%vs.30.0%,P0.05).Conclusion:Genotype C was the most frequent genotype in the described group of patients with HBV-GN,and the liver and kidney damage indicators were more likely to occur in patients with genotype C.

关键词： cccDNA genotypes glomerulonephritis hepatitis B virus pathology

Crescentic glomerulonephritis in children:a single centre experience

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世界儿科杂志:英文版 2016年第2期12卷 225-230页

作者： Sare GülfemÖzlü AysunÇaltık Özlem Aydoğ Mehmet Bülbül Gülay Demircin EvrimÇakıcı Nilüfer Arda AyşeÖner Department of Pediatric Nephrology Dr Sami Ulus Childrens and Maternity HospitalAnkaraTurkey Department of Pathology Sami Ulus Childrens and Maternity HospitalAnkaraTurkey

Background:Crescentic glomerulonephritis(CsGN)is characterized by crescents in 50%or more of glomeruli and clinically by a sudden and progressive decline in renal function.Methods:We evaluated the etiology,clinical features,prognostic factors and long-term outcome of CsGN.Between January 2000 and December 2010,45 children(26 girls,19 boys)with biopsy-proven CsGN(>50%crescents)were investigated retrospectively.Results:The mean age of the patients was 130.86±33.77 months.The mean duration of symptoms prior to diagnosis was 26±12 days(4-40 days).Most of the children had hypertension(62.2%),macroscopic hematuria(73.3%),oligoanuria(44.4%),edema(51.1%)and purpuric rash(40%)at presentation.The final clinical status of the patients was complete remission(n=21),partial remission(n=5)or chronic kidney disease(n=19).Adverse outcomes were significantly associated with a long duration between the onset of symptoms and treatment(P=0.038),the presence of oligoanuria(P=0.006),a severe decreased glomerular filtration rate(GFR75%)(P=0.03),and the ratio of fi brous crescents(P=0.015).Conclusion:The outcome of CsGN in children continues to be poor,and it should be treated as a renal emergency.

关键词： glomerulonephritis renal biopsy renal failure

Exploring the Protective Effect of the Ethanolic Extract of Rosa laevigata Michx.Fruit on Rats with Mesangial Proliferative glomerulonephritis Based on NLRP3 Inflammasome Pathway

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Proceedings of Anticancer Research 2023年第1期7卷 41-46页

作者： Juan Ji Zhaoyu Bi Ling Tian Jing Li Xing Fan Limin Zhang Song Li Department of Nephrology Affiliated Hospital of Hebei UniversityBaoding 071000Hebei ProvinceChina Department of Urology Affiliated Hospital of Hebei UniversityBaoding 071000Hebei ProvinceChina

Objective:To investigate the effect of the ethanolic extract of Rosa laevigata Michx.fruit on rats with mesangial proliferative glomerulonephritis based on the NLRP3 inflammasome pathway.Methods:Thirty Wistar rats were divided into three groups,a blank control group,a diabetic nephropathy(DN)model group,and an ethanolic extract intervention group,according to the random number table method,with 10 rats in each group.One day before the experiment,basic feeding was initiated for all the rats;the changes in activity and weight of each group of rats were observed and recorded after 7 d,and a rat model of renal function injury was established after 1 d.Results:Compared with the control group,the model group had significantly higher kidney/body ratio,24 h urine protein,serum creatinine(SCr),blood urea nitrogen(BUN),glomerular mesangial cell(GMC)count,and extracellular matrix(ECM)positive area ratio(Pglomerulonephritis and renal fibrosis.

关键词： Ethanolic extract of Rosa laevigata Michx.fruit glomerulonephritis NLRP3