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Relationship between serum C3/C4 ratio and prognosis of immunoglobulin A nephropathy based on propensity score matching

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Chinese Medical Journal 2020年第6期133卷 631-637页

作者： Yan Zhang Shu-Wei Duan Pu chen Zhong Yin Yong Wang Guang-Yan Cai xiang-mei chen Department of Nephrology Chinese People's Liberation Army General HospitalChinese People's Liberation Army Institute of NephrologyState Key Laboratory of Kidney DiseasesNational Clinical Research Center for Kidney DiseasesBeijing Key Laboratory of Kidney Disease ResearchBeijing 100853China

Background:Aberrant activation of the complement system plays an important role in the pathogenesis and development of immunoglobulin A nephropathy(IgAN).The relationship between serum complement and the clinical-histopathological features and outcomes of IgAN is controversial.This retrospective study aimed to examine the relationship between the complement 3/4(C3/C4)ratio and the clinicopathologic changes and prognosis of patients with IgAN.Methods:A total of 397 patients with primary IgAN from January 2007 to December 2012 at the Chinese People's Liberation Army General Hospital were included in this study.The correlation test and Chi-square test or one-way analysis of variance test were performed to evaluate the relationship between the C3/C4 ratio and other clinical-pathological factors.Propensity score matching and a multivariate Cox regression model were used to calculate the risk factors of renal outcome.Results:The median follow-up period was 75 months.During the follow-up period,62 patients(15.6%)developed into the endstage renal disease(ESRD).The C3/C4 ratio at baseline was associated with the level of serum creatinine(SCr),24 h urinary protein excretion(24 h Upre),global glomerular sclerosis,and tubulointerstitial lesion.The level of SCr and 24 h Upre and the degree of chronic kidney injury were statistically different among groups defined by different C3/C4 ratio levels.The survival rates of patients among groups with different C3/C4 ratio levels were different.After propensity score matching,eighty-eight pairs of patients were successfully matched,and the C3/C4 ratio was an influencing factor for the patients5 outcome(hazard ratio 0.587,95%confidence interval 0.329-0.880).Patients with a C3/C4 ratio<3.6 had a poorer outcome compared with the others(P=0.002).Conclusions:IgAN patients with decreased C3/C4 ratio displayed significantly more severe clinical symptoms and chronic renal injury than patients with higher ratios.A low C3/C4 ratio could be a risk factor for patients developing to ESRD.

关键词： Complement Serum C3/C4 Immunoglobulin A nephropathy Prognosis

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Single-cell RNA sequencing data suggest a role for angiotensin-converting enzyme 2 in kidney impairment in patients infected with 2019-novel coronavirus

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Chinese Medical Journal 2020年第9期133卷 1129-1131页

作者： Yi-Yao Deng Ying Zheng Guang-Yan Cai xiang-mei chen Quan Hong Department of Nephrology Chinese People’s Liberation Army General HospitalChinese People’s Liberation Army Institute of NephrologyState Key Laboratory of Kidney DiseasesNational Clinical Research Center for Kidney DiseasesBeijing Key Laboratory of Kidney DiseasesBeijing 100039China

The World Health Organization has recently declared the 2019-novel coronavirus(2019-nCoV)a global public health emergency.Huang et al[1]reported acute kidney injury(AKI)in 7%of the 41 patients infected with 2019-nCoV,this value was even higher(up to 31%)among intensive-care patients.Furthermore,Li et al[2]reported that plasma creatinine levels increased in 11 of 59 patients with 2019-nCoV infection,suggesting that kidney function was probably impaired when the disease progressed.Guan et al[3]reported that plasma creatinine level increased in 4.3%of severely diseased patients.2019-nCoV is a highly contagious pathogen that predominantly causes pneumonic symptoms.Although respiratory failure has been associated with the highest mortality,the lung was not the only organ involved.Hoffmann et al[4]reported that 2019-nCoV and severe acute respiratory syndrome-associated coronavirus(SARS-CoV)share a common receptor angiotensin-converting enzyme 2(ACE2)that is required to enter target cells,and cellular protease transmembrane protease serine 2(TMPRSS2)can cleave and activate the spike protein of 2019-nCoV for membrane fusion.We investigated whether ACE2 and TMPRSS2 were expressed in kidney cells using precisiontechnology single-cell RNA sequencing.

关键词： ACE2 patients kidney

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Progress of small ubiquitin-related modifiers in kidney diseases

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Chinese Medical Journal 2019年第4期132卷 466-473页

作者： Ou Li Qian Ma Fei Li Guang-Yan Cai xiang-mei chen Quan Hong Department of Nephrology Chinese PLA General HospitalChinese PLA Institute of NephrologyState Key Laboratory of Kidney DiseasesNational Clinical Research Center for Kidney DiseasesBeijing Key Laboratory of Kidney DiseasesBeijing 100853China.

Objective: Small ubiquitin-related modifiers (SUMOs) are a group of post-translational modification proteins extensively expressed in eukaryotes. Abnormal SUMOylation can lead to the development of various diseases. This article summarizes the progress on research of the role of SUMOs in various types of kidney diseases to further increase the understanding of the regulatory functions of SUMOylation in the pathogenesis of kidney diseases. Data sources: This review was based on articles published in the PubMed databases up to January 2018, using the keywords including "SUMOs," "SUMOylation," and "kidney diseases." Study selection: Original articles and critical reviews about SUMOs and kidney disease were selected for this review. A total of 50 studies were in English. Results: SUMO participates in the activation of NF-κB inflammatory signaling pathway, playing a central regulatory role in the inflammation and progression of DN, and the secretion of various chemokines in AKI. SUMO involves in the regulation of TG2 and Nrf2 antioxidant stress, affecting renal tubular injury in AKI. SUMO affects the MAPK/ERK pathway, regulating intracellular signal transduction, modulating the transcription and expression of effector molecules in DN. SUMO contributes to the TGF-β/Smad pathway, leading to fibrosis of the kidney. The conjugate combination of SUMO and p53 regulates cell proliferation and apoptosis, and participates in the regulation of tumorigenesis. In addition, SUMOylation of MITF modulates renal tumors secondary to melanoma, Similarly, SUMOylation of tumor suppressor gene VHL regulates the occurrence of renal cell carcinoma in VHL syndrome. Conclusions: Tissue injury, inflammatory responses, fibrosis, apoptosis, and tumor proliferation in kidney diseases all involve SUMOs. Further research of the substrate SUMOylation and regulatory mechanisms of SUMO in kidney diseases will improve and develop new treatment measures and strategies targeting kidney diseases.

关键词： Small ubiquitin-related modifiers SUMOylation Kidney diseases

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Embryonic Stem Cells-loaded Gelatin Microcryogels Slow Progression of Chronic Kidney Disease

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Chinese Medical Journal 2016年第4期129卷 392-398页

作者： Xiao-Dong Geng Wei Zheng Cong-mei Wu Shu-Qiang Wang Quan Hong Guang-Yan Cai xiang-mei chen Di Wu Department of Nephrology Chinese People's Liberation Army General Hospital Chinese People's Liberation Army Institute of Nephrology State Key Laboratory of Kidney Diseases National Clinical Research Center for Kidney Diseases Beijing Key Laboratory of Kidney Disease Beijing 100853 China Department of Biotechnology School of Chemistry and Life Science Changchun University of Technology Changchun Jilin 130012 China

Background： Chronic kidney disease （CKD） has become a public health problem.New interventions to slow or prevent disease progression are urgently needed.In this setting, cell therapies associated with regenerative effects are attracting increasing interest.We evaluated the effect of embryonic stem cells （ESCs） on the progression of CKD.Methods： Adult male Sprague-Dawley rats were subjected to 5/6 nephrectomy.We used pedicled greater omentum flaps packing ESC-loaded gelatin microcryogets （GMs） on the 5/6 nephrectomized kidney.The viability of ESCs within the GMs was detected using in vio two-photon fluorescence confocal imaging.Rats were sacrificed after 12 weeks.Renal injury was evaluated using serum creatinine, urea nitrogen, 24 h protein, renal pathology, and tubular injury score results.Structural damage was evaluated by periodic acid-Schiff and Masson trichrome staining.Results： In vitro, ESCs could be automatically loaded into the GMs.Uniform cell distribution, good cell attachment, and viability were achieved from day 1 to 7 in vitro.After 12 weeks, in the pedicled greater omentum flaps packing ESC-loaded GMs on 5/6 nephrectomized rats group, the plasma urea nitrogen levels were 26% lower than in the right nephrectomy group, glomerulosclerosis index was 62% lower and tubular injury index was 40% lower than in the 5/6 nephrectomized rats group without GMs.Conclusions： In a rat model of established CKD, we demonstrated that the pedicled greater omentum flaps packing ESC-loaded GMs on the 5/6 nephrectomized kidney have a long-lasting therapeutic rescue function, as shown by the decreased progression of CKD and reduced glomerular injury.

关键词： Chronic Renal Insufficiency Embryonic Stem Cells Gelatin Microcryogels Regenerative Medicine

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Clinical Analysis of a Hypokalemic Salt-losing Tubulopathy Case

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Chinese Medical Journal 2016年第5期129卷 601-603页

作者： Wei Zheng Quan Hong Xue-Guang Zhang Xiao-Dong Geng Guang-Yan Cai xiang-mei chen Di Wu Department of Nephrology Chinese People's Liberation Army General Hospital Chinese People's Liberation Army Institute of Nephrology State Key Laboratory of Kidney Diseases National Clinical Research Center for Kidney Diseases Beijing Key Laboratory of Kidney Disease Beijing 100853 China

Hypokalemia is among the most common electrolyte disorders in clinical practice and severe condition is life-threatening and has received extensive attention in clinical practice. Genetic diagnosis remains the gold standard for the diagnosis and identification of hereditary renal tubular diseases. Below is the report of genotyping and diagnosis of a case of secondary Gitelman syndrome （GS） based on next-generation sequencing.

关键词： Diagnosis Gene Screening Hypokalemia

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Association between age-related kidney function and vascular subclinical state in a healthy Chinese population

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Chinese Medical Journal 2021年第19期134卷 2376-2378页

作者： Nan Wang Xiao-Juan Bai Lu-Lu Han Wen Han Xue-Feng Sun xiang-mei chen Department of Gerontology and Geriatrics Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhaiGuangdong 519099China Department of Gerontology and Geriatrics Shengjing Hospital of China Medical UniversityShenyangLiaoning 110004China Department of Kidney General Hospital of Chinese People's Liberation ArmyBeijing 100853China

To the Editor:Aging is associated with kidney dysfunction and an increased risk of cardiovascular disease.The connection between the cardiovascular system and kidney function is apparent,even in the early stage of renal insufficiency.Cystatin C(CYSC),one of the cystatin superfamily that is expressed in all the nucleated cells,was considered to be one of the best indicators for evaluating renal function.[1]CYSC is a potent inhibitor of cathepsin B(CTSB),which is strictly regulated by CYSC in extracellular matrix remodeling.Imbalances between CYSC and CTSB are connected with atherosclerosis(AS),coronary heart disease,and chronic kidney disease with aging-related phenotypes.Our previous study confirmed that serum CTSB levels were associated with age and decreased cardiovascular-renal functions in healthy adults,[2]suggesting that CTSB exhibits heightened sensitivity to changes in cardiovascular and glomerular function.The present investigation,underlining the role of synthetic and degradative pathways in the aging process,emphasizes that cardio-renal interaction with aging could depend partly on differential expression of some genes leading to an imbalance of functional proteins.In this study,we analyzed the association between renal function,measured by CYSC and estimated glomerular filtration rate(eGFR),and vascular parameters in a healthy Chinese population.

关键词： kidney function. cardiovascular

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A non-invasive diagnostic model of immunoglobulin A nephropathy and serological markers for evaluating disease severity

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Chinese Medical Journal 2019年第6期132卷 647-652页

作者： Qiu-Xia Han Yong Wang Han-Yu Zhu Dong Zhang Jing Gao Zhang-Suo Liu Guang-Yan Cai xiang-mei chen Department of Nephrology The First Affiliated Hospital of Zhengzhou University Research Institute of Nephrology in Zhengzhou University Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province Zhengzhou Henan 450052 China Department of Nephrology Chinese People's Liberation Army General Hospital Chinese People's Liberation Army Institute of Nephrology State Key Laboratory of Kidney Diseases National Clinical Research Center for Kidney Diseases Beijing Key Laboratory of Kidney Diseases Beijing 100853 China Department of Clinical Biochemistry Chinese People's Liberation Army General Hospital Beijing 100853 China

Background: Immunoglobulin A nephropathy (IgAN) is the most common pathological type of glomerular disease. Kidney biopsy, the gold standard for IgAN diagnosis, has not been routinely applied in hospitals worldwide due to its invasion nature. Thus, we aim to establish a non-invasive diagnostic model and determine markers to evaluate disease severity by analyzing the serological parameters and pathological stages of patients with IgAN. Methods: A total of 272 biopsy-diagnosed IgAN inpatients and 518 non-IgA nephropathy inpatients from the Department of Nephrology of Chinese People's Liberation Army General Hospital were recruited for this study. Routine blood examination, blood coagulation testing, immunoglobulin-complement testing, and clinical biochemistry testing were conducted and pathological stages were analyzed according to Lee grading system. The serological parameters and pathological stages were analyzed. The receiver operating characteristic (ROC) analysis was performed to estimate the diagnostic value of the clinical factors. Logistic regression was used to establish the diagnostic model. Results: There were 15 significantly different serological parameters between the IgAN and non-IgAN groups (all P< 0.05). The ROC analysis was performed to measure the diagnostic value for IgAN of these parameters and the results showed that the area under the ROC curve (AUC) of total protein (TP), total cholesterol (TC), fibrinogen (FIB), D-dimer (D2), immunoglobulin A (IgA), and immunoglobulin G (IgG) were more than 0.70. The AUC of the "TC + FIB + D2 + IgA + age" combination was 0.86, with a sensitivity of 85.98% and a specificity of 73.85%. Pathological grades of Ⅰ,Ⅱ,Ⅲ,Ⅳ, and Ⅴ accounted for 2.21 %, 17.65%, 62.50%, 11.76%, and 5.88%, respectively, with grade Ⅲ being the most prevalent. The levels of urea nitrogen (UN)(13.57土 5.95 vs. 6.06 土 3.63, 5.92 + 2.97, 5.41 ± 1.73, and 8.41 ±3.72μmol/L, respectively) and creatinine (Cr)(292.19± 162.21 vs. 80.42±24.75, 103.79±72.72, 96.41 ±33.79, and 163.04±47.51 μmol/L, res

关键词： Immunoglobulin A nephropathy Noninvasive Diagnostic model Severity

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Association between ventricular repolarization variables and cardiac diastolic function: A cross-sectional study of a healthy Chinese population

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World Journal of Clinical Cases 2019年第8期7卷 940-950页

作者： Zhi-Dan Li Xiao-Juan Bai Lu-Lu Han Wen Han Xue-Feng Sun xiang-mei chen Department of Gerontology and Geriatrics Shengjing Hospital of China Medical University Department of Kidney General Hospital of Chinese People's Liberation Army

BACKGROUND Diastolic electromechanical couple, a well-described phenomenon in symptomatic heart failure, has not been well studied in healthy people. We hypothesized that ventricular repolarization variables, such as the QT interval,Tpeak-to-Tend(Tpe) interval and Tpe/QT ratio, are associated with cardiac diastolic function in the healthy Chinese population.AIM To assess the relationship between ventricular repolarization variables and cardiac diastolic function in apparently healthy Chinese individuals.METHODS This was a community-based cross-sectional study conducted in Shenyang,China. A total of 414 healthy subjects aged 35-91 years were enrolled. All subjects underwent standard 12-lead electrocardiography(ECG) and comprehensive echocardiography. ECG enabled the measurement of QT and Tpe intervals and Tpe/QT ratio. echocardiographic parameters, such as the ratio of mitral early diastolic inflow velocity(E) and late diastolic inflow velocity(A), E-wave deceleration time, left atrial volume(LAV) and LAV index, were measured to assess diastolic function. E/A < 0.75 was considered to indicate reduced diastolic function. ECG and echocardiography results were analyzed separately and in a blinded fashion. Correlation and regression analyses were applied to determine associations.RESULTS Ventricular repolarization variables, such as the QTc interval(393.59 ± 26.74 vs403.86 ± 33.56; P < 0.001), Tpe interval(72.68 ± 12.41 vs 77.26 ± 17.86; P < 0.01),Tpec interval(76.36 ± 13.53 vs 83.32 ± 21.25; P < 0.001) and Tpe/QT ratio(0.19 ±0.03 vs 0.20 ± 0.04; P < 0.01), were significantly different between the normal diastolic function group and the reduced diastolic function group. Significant associations were found between repolarization variables and diastolic function.After adjusting for all other possible confounders, the QTc and Tpe_c intervals were significantly associated with the E/A ratio(P = 0.008; P = 0.010). In men, the QTc interval was associated with abnormal diastolic function, and compared to the third QTc tertil

关键词： QT interval Tpeak-to-Tend interval Diastolic dysfunction Ventricular repolarization Electrocardiography

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Potential Value of Datura stramonium Agglutinin-recognized Glycopatterns in Urinary Protein on Differential Diagnosis of Diabetic Nephropathy and Nondiabetic Renal Disease

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Chinese Medical Journal 2018年第2期131卷 180-187页

作者： Xiao-Li Yang Han-Jie Yu Han-Yu Zhu Ying Zheng Qiu-Xia Han Guang-Yan Cai xiang-mei chen 'Department of Nephrology Chinese People's Liberation Army General Hospital Chinese People's Liberation Army Institute of NephrologyState Key Laboratory of Kidney Diseases (2011DAVO0088) National Clinical Research Center for Kidney Diseases Beijing Key Laboratory of Kidney Diseases Beijing 100853 China Laboratory for Functional Glycomics College of I'ifeSciences Northwest University Xi'an Shaanxi 710069 China Department of Nephrology The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan 450052 China

Background： Diabetic nephropathy （DN） is the most common and serious microvascular complication of diabetes. To date, the gold standard for identifying DN and nondiabetic renal disease （NDRD） is a renal biopsy; however, there is currently no reliable diagnostic marker to identify DN and NDRD in a noninvasive manner. This study aimed to investigate the different glycopatterns in urine specimens of DN patients and NDRD patients for a differential diagnosis. Methods： In total, 19 DN patients and 18 NDRD patients who underwent renal biopsies between March 2015 and March 2016 at the Chinese People＇s Liberation Army General Hospital were enrolled in this study. A lectin microarray was used to investigate the glycopatterns in the urinary protein of the 37 patients. Ratio analysis and one-way analysis of variance were used to screen altered glycopatterns. Then, the altered glycopatterns between the DN and NDRD groups were verified by a urinary protein microarray among another 32 patients （15 with DN and 17 with NDRD）, and receiver operating characteristic （ROC） curve analysis was used to determine the diagnostic value of the altered glycopatterns in differentiating DN and NDRD. Finally, lectin blotting was used to evaluate the altered glycosylation in protein level. Results： The result of lectin microarrays revealed that the relative abundance of the （13-1,4）-linked N-acetyI-D-glucosamine （GlcNAc） recognized by lectin Datura stramonium agglutinin （DSA） was significantly higher in urinary protein in DN patients than that in NDRD patients （fold change 〉1.50, P 〈 0.001）. Subsequently, the results of urinary protein microarrays were consistent with lectin microarrays （P 〈 0.05）. Furthermore, the ROC curve showed that glycopatterns could effectively distinguish DN from NDRD patients （area under the ROC curve = 0.94, P 〈 0.001）. DSA lectin blotting showed that glycoproteins, with a molecular weight of approximately 50,000, demonstrated a difference in urine samples between DN patients and NDRD patients. Conclusions： The relati

关键词： Diabetic Nephropathy： Glycopattern NondiabeticRenal Disease, Urinary Protein

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Diagnosis of Kaposi sarcoma by a modified fine needle aspiration method combing cell block in Chinese patients with human immunodeficiency virus/acquired immunodeficiency syndrome

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Chinese Medical Journal 2020年第23期133卷 2894-2896页

作者： Lei Sun Liang Zhang Kun Yang Jia-Min chen xiang-mei chen Man Li Xin-Gang Zhou Zhi-Yuan Ma Li-Ming Qi Peng Wang Department of Pathology Beijing Ditan HospitalCaptial Medical UniversityBeijing 100015China

To the Editor:Kaposi’s sarcoma(KS),a low-grade vascular tumor,is one of the most common neoplasms reported in patients with acquired immunodeficiency syndrome(AIDS).Based on epidemiological and clinical characteristics,four types of KS have been reported:classic KS,endemic KS(in equatorial Africa),AIDS-associated KS(AIDS-KS),and iatrogenic KS.Clinically,the presentation of KS can be variable with dark or brown macules,plaques,or nodules that may bleed or,ulcerate on the skin and mucous membranes.Besides,the lymph nodes and some visceral organs can also be involved in more advanced stages of the disease.

关键词： Kaposi immunodeficiency needle neoplasms organs

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