Publications by authors named "Huijie Xiao"

44 Publications

Factors predicting the recovery from acute kidney injury in children with primary nephrotic syndrome.

Clin Exp Nephrol 2021 May 15. Epub 2021 May 15.

Department of Pediatrics, Peking University First Hospital, No.1 Xi An Men Da Jie, Beijing, China.

Background: The prognosis of acute kidney injury (AKI) varies in children with nephrotic syndrome (NS), data on factors predicting the recovery and recurrence of AKI in children with NS are limited. This study aimed to explore the possible factors predicting the recovery from and recurrence of AKI in children with primary NS.

Methods: Children with primary NS complicated with AKI from 1993 to 2017 in a single centre were reviewed retrospectively. The clinical pictures and possible factors predicting the recovery from and recurrence of AKI in children with primary NS were investigated.

Results: Sixty-eight episodes of AKI in 59 children with NS were analysed: 88.2% of AKI recovered within 3 months, and 2.9% of AKI did not recover after 3 months. Survival analysis revealed that leucocyturia is significantly related to the AKI recovery time (P = 0.001), and children with leucocyturia [22 (4, 79) days] recovered significantly slower than did children without leucocyturia [12.0 (2, 39) days]. Renal tubular and interstitial injury were prominent in children with leucocyturia, and 11.9% of children with index AKI experienced the recurrence of AKI.

Conclusions: Most episodes of AKI that occurred in children with NS recovered completely. Leucocyturia is a significant factor predicting the recovery time of AKI.
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http://dx.doi.org/10.1007/s10157-021-02074-zDOI Listing
May 2021

Therapeutic Mechanism and Effect of Camptothecin on Dextran Sodium Sulfate-Induced Ulcerative Colitis in Mice.

J Immunol Res 2021 24;2021:5556659. Epub 2021 Apr 24.

Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China.

Camptothecin (CPT) is a cytotoxic quinoline alkaloid isolated from the bark and branches of the Chinese tree . CPT inhibits topoisomerase I. It possesses various antitumor activities and is mainly used in the treatment of colon, ovarian, liver, and bone cancers as well as leukemia. CPT inhibits the expressions of inflammatory genes and can prevent death from chronic inflammation. Therefore, we investigated the effect of CPT treatment in ulcerative colitis (UC) using DSS-induced UC mouse model; after that, we explored its potential mechanisms. Here, we found that CPT exerted protection on DSS-induced UC in rats. In addition, the administration prominently reduced the disease activity index as well as colon length of the model rats and remarkably reduced the inflammatory cytokines. Further, CPT significantly reduced several vital proinflammatory proteins in LPS-induced RAW264.7 cells. In summary, our findings demonstrate that CPT is hopefully to act as a therapeutic agent for UC.
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http://dx.doi.org/10.1155/2021/5556659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093050PMC
April 2021

LAMB2 novel variant c.2885-9 C>A affects RNA splicing in a minigene assay.

Mol Genet Genomic Med 2021 May 13:e1704. Epub 2021 May 13.

Department of Pediatrics, Peking University First Hospital, Beijing, China.

Background: Both Pierson syndrome (PS) and isolated nephrotic syndrome can be caused by LAMB2 biallelic pathogenic variants. Only 15 causative splicing variants in the LAMB2 gene have been reported. However, the pathogenicity of most of these variants has not been verified, which may lead to incorrect interpretation of the functional consequence of these variants.

Methods: Using high-throughput DNA sequencing and Sanger sequencing, we detected variants in a female with clinically suspected PS. A minigene splicing assay was performed to assess the effect of LAMB2 intron 20 c.2885-9C>A on RNA splicing. We also performed the immunohistochemical analysis of laminin beta-2 in kidney tissues.

Results: Two novel LAMB2 heteroallelic variants were found: a paternally inherited variant c.2885-9C>A in intron 20 and a maternally inherited variant c. 3658C>T (p. (Gln1220Ter)). In vitro minigene assay showed that the variant c.2885-9C>A caused erroneous integration of a 7 bp sequence into intron 20. Immunohistochemical analysis revealed the absence of glomerular expression of laminin beta-2, the protein encoded by LAMB2.

Conclusion: We demonstrated the impact of a novel LAMB2 intronic variant on RNA splicing using the minigene assay firstly. Our results extend the mutational spectrum of LAMB2.
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http://dx.doi.org/10.1002/mgg3.1704DOI Listing
May 2021

Sap flow of Amorpha fruticosa: implications of water use strategy in a semiarid system with secondary salinization.

Sci Rep 2020 08 11;10(1):13504. Epub 2020 Aug 11.

College of Soil and Water Conservation, Beijing Forestry University, Beijing, 100083, People's Republic of China.

A. fruticosa (Amorpha fruticosa L.) is widely used for revegetation in semiarid lands that undergo secondary salinization. Understanding A. fruticosa plants response to soil water and salt stress is essential for water irrigation management and proper revegetation practices. In this study, we measured sap flow, stomatal conductance, meteorological and soil characteristics in an A. fruticosa community that recently experienced secondary salinization in northwestern China. Results of our study showed that daytime and nocturnal sap flows averaged 804.37 g·cm·day and 46.06 g·cm·day, respectively, during the growing season. Within individual days, the highest sap flow appeared around noon local time and followed a similar pattern of photosynthetically active radiation (PAR). Despite the significant effect of meteorological factors on the characteristics of sap flow, our study highlighted that the sap flow of A. fruticosa is strongly regulated by the availability of soil relative extractable water (REW). The daytime sap flow, which is predominant compared to nocturnal sap flow, was strongly affected by PAR, air temperature and vapor-pressure deficit. With water stress in the top 40 cm of the soil (REW < 0.4), daytime sap flow displayed a strong relationship with soil water content (SWC) (positive) and soil electrical conductivity (EC) (negative) in the relatively shallow soil profile (up to 40 cm). For the nocturnal sap flow, our results suggest that in the absence of soil water stress (REW > 0.4), the nocturnal sap flow is mainly used to replenish the stem water content and sustain nocturnal transpiration. Under soil water stress, nocturnal sap flow is mainly used to replenish stem water content. The results of our study indicate that it is necessary to shorten the irrigation cycle during the primary growing period (May-July) of A. fruticosa. Moreover, in the absence of soil water stress (REW > 0.4), A. fruticosa can survive well in an saline environment with soil EC < 5 mS·cm.
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http://dx.doi.org/10.1038/s41598-020-70511-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419527PMC
August 2020

Value of electron microscopy in the pathological diagnosis of native kidney biopsies in children.

Pediatr Nephrol 2020 12 3;35(12):2285-2295. Epub 2020 Jul 3.

Laboratory of Electron Microscopy, Pathological Center, Peking University First Hospital, No. 8. Xishiku Street, Xi Cheng District, Beijing, 100034, China.

Background: Pediatric native kidney diseases are common worldwide. The pathological diagnosis of kidney lesions is crucial for clinical treatment and prognosis. The aim of the current study was therefore to evaluate the value of electron microscopy (EM) to the final diagnosis of native kidney biopsies in children.

Methods: A retrospective evaluation of 855 pediatric kidney biopsies obtained from the Department of Pediatrics in Peking University First Hospital between November 2010 and December 2017 was performed to assess the contribution of EM to the final diagnosis.

Results: The role of EM in the final diagnosis was determined to be crucial in 300 cases (35.1%), important in 280 cases (32.7%), and auxiliary in 275 cases (32.2%). EM is considered most valuable in a large percentage of glomerular diseases, mainly including minimal change disease, early-stage membranous nephropathy, postinfectious glomerulonephritis, Alport syndrome, thin basement membrane nephropathy, and thrombotic microangiopathy. EM also provided helpful diagnostic information in cases of focal segmental glomerulosclerosis, lupus nephritis, IgA nephropathy, and IgA vasculitis (Henoch-Schonlein purpura nephritis). Additionally, EM was crucial in 90.0% of cases of subtle pathological changes observed with light microscopy (LM) and immunofluorescence (IF) and in 69.3% of the IF-negative specimens. Patients with nephrotic syndrome or hematuria also benefit from ultrastructural examination.

Conclusions: The present study demonstrated the crucial or important role of EM in the diagnosis of a majority of native kidney biopsies in children. The application of EM should be integrated together with LM and IF as a routine method of assessing pediatric kidney specimens. Graphical abstract.
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http://dx.doi.org/10.1007/s00467-020-04681-6DOI Listing
December 2020

Phenotypic spectrum and antialbuminuric response to angiotensin converting enzyme inhibitor and angiotensin receptor blocker therapy in pediatric Dent disease.

Mol Genet Genomic Med 2020 08 3;8(8):e1306. Epub 2020 Jun 3.

Department of Pediatrics, Peking University First Hospital, Beijing, China.

Background: To characterize the phenotypic spectrum and assess the antialbuminuric response to angiotensin converting enzyme (ACE) inhibitor and/or angiotensin receptor blocker (ARB) therapy in a cohort of children with Dent disease.

Methods: The patients' clinical findings, renal biopsy results, genetic and follow-up data were analyzed retrospectively. Mutations in CLCN5 or OCRL were detected by next-generation sequencing or Sanger sequencing.

Results: Of 31 Dent disease boys, 24 carried CLCN5 and 7 carried OCRL mutations. Low molecular weight proteinuria and albuminuria were detected in all cases. Nephrotic-range proteinuria and severe albuminuria were identified in 52% and 62% of cases, respectively; by 7 years of age, 6 patients had hematuria and nephrotic-range proteinuria, and 7 patients had hematuria and moderate to severe albuminuria. In addition to disease-related renal features, patients with Dent-1 disease also presented with congenital cataract (1/9) and developmental delay (2/7). Seventeen of 31 patients underwent renal biopsy. Glomerular changes included mild glomerular lesions, mesangial proliferative glomerulonephritis and focal segmental glomerular sclerosis. Thirteen of the 31 patients had follow-up records and received ACE inhibitor and/or ARB treatment for more than 3 months. After a median 1.7 (range 0.3-8.5) years of treatment, a reduction in the urinary microalbumin-to-creatinine ratio was observed in 54% of children.

Conclusions: Hematuria with nephrotic-range proteinuria or moderate to severe albuminuria was common in Dent disease patients. Extrarenal manifestations were observed in Dent-1 patients, which extends the phenotypic spectrum. In addition, ACE inhibitors and ARBs are well tolerated, and they are partially effective in controlling albuminuria.
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http://dx.doi.org/10.1002/mgg3.1306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434612PMC
August 2020

Interpretation of Autosomal Recessive Kidney Diseases With "Presumed Homozygous" Pathogenic Variants Should Consider Technical Pitfalls.

Front Pediatr 2020 17;8:165. Epub 2020 Apr 17.

Department of Pediatrics, Peking University First Hospital, Beijing, China.

A false interpretation of homozygosity for pathogenic variants causing autosomal recessive disorders can lead to improper genetic counseling. The aim of this study was to demonstrate the underlying etiologies of presumed homozygous disease-causing variants harbored in six unrelated children with five different genetic renal diseases when the same variant was identified in a heterozygous state in only one of the two parents from each family using direct sequencing. Peripheral blood genomic DNA samples were extracted. Six short tandem repeats were used to verify the biological relationships between the probands and their parents. Quantitative PCR was performed to detect mutant exons with deletions. Single nucleotide polymorphism analysis and genotyping with polymorphic microsatellite markers were performed to identify uniparental disomy (UPD). Each proband and his/her parents had biological relationships. Patients 2, 4, and 6 were characterized by large deletions encompassing a missense/small deletion in , and , respectively. Patients 1 and 5 were caused by segmental UPD in and , respectively. In patient 6, maternal UPD, mosaicism in paternal sperm or variant in could not be ruled out. When a variant analysis report shows that a patient of non-consanguineous parents has a pathogenic presumed homozygous variant, we should remember the need to assess real homozygosity for the variant, and a segregation analysis of the variants within the parental DNAs and comprehensive molecular tests to evaluate the potential molecular etiologies, such as a point variant and an overlapping exon deletion, UPD, germline mosaicism and variant, are crucial.
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http://dx.doi.org/10.3389/fped.2020.00165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180205PMC
April 2020

Endoplasmic Reticulum Stress Activation in Alport Syndrome Varies Between Genotype and Cell Type.

Front Genet 2020 10;11:36. Epub 2020 Feb 10.

Department of Pediatrics, Peking University First Hospital, Beijing, China.

Alport syndrome is a hereditary progressive chronic kidney disease caused by mutations in type IV collagen genes . X-linked Alport syndrome (XLAS) is caused by mutations in the gene and is the most common form of Alport syndrome. A strong correlation between the type of mutation and the age developing end-stage renal disease in male patients has been found. Mutation to the α (IV) chain causes retention of the protein to the endoplasmic reticulum lumen, which causes endoplasmic reticulum stress (ERS) and subsequent exertion of deleterious intracellular effects through the activation of ERS. The exact time point that mutant type IV collagen α chain exerts its deleterious effects remains elusive. In this study, we explored the relationship between the genotype and cell type in ERS activation. We obtained skin fibroblasts from Alport syndrome patients with different mutation categories [i.e., a missense mutation (c.4298G > T, p.Gly1433Val) in exon 47, a splicing mutation (c.1949-1G > A) in intron 25 and an insertion (c.573_c.574insG, p. Pro193Alafs*23) in exon 10], and then reprogrammed these fibroblasts into induced pluripotent stem cells (iPSCs). Interestingly, no significant dysregulation of ERS pathway markers was observed for the three mutant iPSCs; however, significant activation of ERS in mutant fibroblasts was observed. In addition, we found that the activation levels of some ERS markers in fibroblasts varied among the three mutation types. Mutant proteins were demonstrated to have different effects on cells at different stages of ontogenesis, providing a theoretical basis for choosing the timing of intervention. The observed differences in activation of ERS by the mutant fibroblasts may contribute to the intracellular molecular mechanisms that describe the correlation between genotype and clinical features in XLAS.
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http://dx.doi.org/10.3389/fgene.2020.00036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7025644PMC
February 2020

Corrigendum: Analysis of 14 Patients With Congenital Nephrotic Syndrome.

Front Pediatr 2019;7:471. Epub 2019 Nov 13.

Department of Pediatrics, Peking University First Hospital, Beijing, China.

[This corrects the article DOI: 10.3389/fped.2019.00341.].
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http://dx.doi.org/10.3389/fped.2019.00471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6864410PMC
November 2019

M-phase phosphoprotein 8 promotes gastric cancer growth and metastasis via p53/Bcl-2 and EMT-related signaling pathways.

J Cell Biochem 2020 03 6;121(3):2330-2342. Epub 2019 Nov 6.

Department of Cancer Center, First Hospital of Jilin University, Changchun, China.

Background: The main issue of this study is to demonstrate whether M-phase phosphoprotein 8 (MPP8) affect gastric tumor growth and metastasis.

Methods: Retrospective study was proceeded in 280 patients' surgical specimens with different disease stages. Loss-of-function assays, including 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide, flow cytometry, and transwell assays were performed to evaluate the biological function of MPP8 in gastric cancer cells. Apoptosis and metastasis relative biomarkers were measured by quantitative real-time polymerase chain reaction and Western blot analysis.

Results: Compared with normal adjacent tissues, obviously elevated MPP8 expression was found in gastric cancer tissues. Elevated MPP8 expression was associated with male sex (vs female sex), intermediate differentiation (vs poorly differentiated cancer), and later stage (vs earlier stage). Furthermore, MPP8 overexpression in tumor tissues was marginally associated with a poor prognosis, with a significant relationship between MPP8 overexpression and prognosis among patients with poorly differentiated gastric cancer. Inhibition of MPP8 in these cells significantly suppressed proliferation and colony formation, promoted apoptosis, and repressed invasion. Furthermore, silencing of MPP8 remarkably increased apoptosis-related proteins (p53, Bax, and PARP) expression, but downregulated Bcl-2 expression. Silencing of MPP8 also decreased the expression of metastasis pathway-related proteins (N-cadherin and vimentin), and as well as the levels of anti-oncogene ZEB1, MET, and KRAS mRNA.

Conclusion: Our findings demonstrated that MPP8 might be an oncogene by positively regulating gastric cancer cell function through the p53/Bcl-2 and epithelial to mesenchymal transition-related signaling pathways.
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http://dx.doi.org/10.1002/jcb.29456DOI Listing
March 2020

Analysis of 14 Patients With Congenital Nephrotic Syndrome.

Front Pediatr 2019 13;7:341. Epub 2019 Aug 13.

Department of Pediatrics, Peking University First Hospital, Beijing, China.

From January 1995 to June 2018, 14 patients with congenital nephrotic syndrome (CNS) were diagnosed in the Department of Pediatrics, Peking University First Hospital. The clinical data were retrospectively studied. Eight patients underwent genetic testing; 7 of them had mutations (primary CNS), and 1 did not have a mutation. Of the 7 patients with mutations, 6 died, and 1 had proteinuria. Of the 14 patients, 8 had cytomegalovirus (CMV) infection, and anti-CMV therapy was administered to 7 of them. The other patient was hospitalized in critically ill condition and died before anti-CMV therapy administration. Of the 7 patients who were administered anti-CMV therapy, proteinuria disappeared in 2 patients; 2 patients died; 2 patients were lost to follow up; and 1 patient still had 3+ proteinuria. Three patients had both mutations and CMV infection. After anti-CMV therapy, proteinuria was resolved in 1 patient but relapsed to 3+ proteinuria due to a new infection. The other 2 patients died. Of 14 patients, only 1 patient underwent renal biopsy, with results showing mesangial proliferative glomerulonephritis pathology, negative CMV inclusion body, and CMV-DNA. In this study, genetic defect could play a primary role in CNS, and CMV could play a secondary role. Primary CNS with mutations has a poor prognosis. Primary CNS might be accompanied by CMV infection that responds poorly to antiviral treatment. Secondary CNS caused by CMV infection may be cured with antiviral therapy. However, genetic analysis is necessary to exclude genetic defects.
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http://dx.doi.org/10.3389/fped.2019.00341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700319PMC
August 2019

Diverse phenotypes in children with PAX2-related disorder.

Mol Genet Genomic Med 2019 06 6;7(6):e701. Epub 2019 May 6.

Department of Pediatrics, Peking University First Hospital, Beijing, China.

Background: The aim of this study was to analyze the diverse phenotypes of children with PAX2-related disorder so as to improve our understanding of this disease.

Methods: The clinical data of ten children with PAX2 mutations, detected by targeted region capture sequencing or whole-exome sequencing, were retrospectively analyzed. Family members of index cases were verified by Sanger sequencing and family segregation analysis was performed.

Results: The age of first symptom of 10 unrelated children (six girls and four boys) was 6.4 (ranged from postnatal day to 14.8) years old. Proteinuria, abnormal renal function, and structure were found in all patients. Renal hypoplasia and renal cysts were found in 10 of 10 and five of 10 cases, respectively. Three patients progressed to chronic kidney disease stage 5 and the onset age of end-stage renal disease was 9.8-16.4 years old. PAX2-related ocular abnormalities were found in five of seven cases and three patients were observed to have more than one ocular findings involved. In addition to diverse renal and ocular findings, new phenotypes including congenital ventricular septal defect, skeletal deformity (fourth metatarsal microsomia), ovarian teratoma, and relatively rare extrarenal manifestations such as growth retardation, gout, and microcephaly were also found. Three novel mutations were reported for the first time. De novo mutations occurred in all patients who were carried out segregation analysis. Patients with the same mutation had different manifestations. PAX2-related disorder showed remarkable clinical variability and phenotypic heterogeneity.

Conclusion: We firstly reported skeletal deformity (fourth metatarsal microsomia), ovarian teratoma, and congenital ventricular septal defect as new phenotypes of PAX2-related disorder which enlarged the phenotypic spectrum. Gout was firstly reported as the onset symptom of PAX2-related disorder. The diagnosis of PAX2-related disorder should be considered without family history due to a much higher percentage of De novo mutations.
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http://dx.doi.org/10.1002/mgg3.701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6565600PMC
June 2019

Effect of heterozygous pathogenic COL4A3 or COL4A4 variants on patients with X-linked Alport syndrome.

Mol Genet Genomic Med 2019 05 18;7(5):e647. Epub 2019 Mar 18.

Department of Pediatrics, Peking University First Hospital, Beijing, China.

Background: Alport syndrome is an inherited renal disease caused by mutations in COL4A3, COL4A4, or COL4A5 genes. Coexisting mutations in either two of the three genes in Alport patients have been reported recently. However, the effect of heterozygous mutations in COL4A3 or COL4A4 genes in X-linked Alport syndrome (XLAS) patients is unclear.

Methods: Using targeted next-generation sequencing, six unrelated Chinese children were identified to have a combination of a pathogenic variant in COL4A5 and a heterozygous mutation in COL4A3 or COL4A4. They were three males and three females. Another three XLAS males each with only one pathogenic variant in COL4A5 were included. The clinical data were analyzed and compared between the males in two groups (group 1, males with a pathogenic variant in COL4A5 and a heterozygous pathogenic variant in COL4A3 or COL4A4; group 2, males with only one pathogenic variant in COL4A5).

Results: Patients with XLAS who also had heterozygous pathogenic COL4A3 or COL4A4 variants accounted for 1% of Alport syndrome. In this study, three children showed coexisting pathogenic variants in COL4A5 and COL4A3. Two children showed pathogenic variants in COL4A5 and COL4A4. One child had pathogenic variants in the three COL4A3-5 genes, in which the pathogenic variant in COL4A5 was de novo and the pathogenic variants in COL4A4 and COL4A3 were inherited independently (in trans). The site and type of mutations in COL4A5 were similar between the two groups. It was revealed that males in group 1 presented more severe proteinuria than males in group 2 (p < 0.05).

Conclusion: The present study provides further evidence for complicated genotype in Alport syndrome. For the first time, we reported a case with three pathogenic variants in COL4A5, COL4A3, and COL4A4 genes. Moreover, we found that heterozygous pathogenic COL4A3 or COL4A4 variants are likely to make XLAS disease more serious.
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http://dx.doi.org/10.1002/mgg3.647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503168PMC
May 2019

Population pharmacokinetics and dosage optimization of tacrolimus in pediatric patients with nephrotic syndrome
.

Int J Clin Pharmacol Ther 2019 Mar;57(3):125-134

Objectives: The aims of this study were to investigate the population pharmacokinetic (PPK) characteristics of tacrolimus in Chinese children with nephrotic syndrome and to apply it in clinical practice.

Materials And Methods: A total of 137 concentrations from 61 patients were collected from routine therapeutic drug monitoring data between 2011 and 2018. Population modeling was performed with the nonlinear mixed-effects model (NONMEM) program, using a one-compartment model with first-order absorption and elimination. The mean population estimate values of clearance (CL/F) and volume of distribution (V/F) were determined. Common demographic and clinical variables were tested for their influence on these parameters. External validation was conducted, and Monte Carlo simulation, based on the final model, was carried out to determine optimal dosage regimen.

Results: Age and body weight were the covariates that displayed a significant influence on CL/F and V/F according to the final regression model. Goodness-of-fit plots, bootstrap outcomes, and external validation confirmed the relatively good stability and prediction capability of the model. The interindividual variability of CL/F was 31.10%, and the residual variability was 0.91 ng/mL. Mean prediction error (MPE, %) and Mean absolute prediction error (MAPE, %) were 10.3% and 16.6%, respectively. Monte Carlo simulation based on the final model was carried out to determine optimal dosage regimen.

Conclusion: A PPK model of tacrolimus in children with nephrotic syndrome was developed. Age and bodyweight could partly explain the interindividual variability in the CL/F and V/F of tacrolimus. The final model could be used to accurately predict tacrolimus individual pharmacokinetic parameters and assist in dosage optimization.
.
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http://dx.doi.org/10.5414/CP203355DOI Listing
March 2019

Urinary epidermal growth factor as a prognostic marker for the progression of Alport syndrome in children.

Pediatr Nephrol 2018 10 11;33(10):1731-1739. Epub 2018 Jun 11.

Department of Pediatrics, Peking University First Hospital, No.1 Xi An Men Da Jie, Beijing, 100034, People's Republic of China.

Background: Alport syndrome is a rare hereditary kidney disease manifested with progressive renal failure. Considerable variation exists in terms of disease progression among patients with Alport syndrome. Identification of patients at high risk of rapid progression remains an unmet need. Urinary epidermal growth factor (uEGF) has been shown to be independently associated with risk of progression to adverse kidney outcome in multiple independent adult chronic kidney disease (CKD) cohorts. In this study, we aim to assess if uEGF is associated with kidney impairment and its prognostic value for children with Alport syndrome.

Methods: One hundred and seventeen pediatric patients with Alport syndrome and 146 healthy children (3-18 years old) were included in this study. uEGF was measured in duplicates in baseline urine samples using ELISA (R&D) and concentration was normalized by urine creatinine (uEGF/Cr). In patients with longitudinal follow-up data (n = 38), progression was defined as deteriorated kidney function (CKD stage increase) during follow-up period (follow-up length is about 31 months in average). The association of baseline uEGF/Cr level with estimated glomerular filtration rate (eGFR) slope and Alport syndrome patients' progression to a more advanced CKD stage during the follow-up period was used to evaluate the prognostic value of the marker.

Results: We found that uEGF/creatinine (uEGF/Cr) decreases with age in pediatric patients with Alport syndrome with a significantly faster rate than in healthy children of the same age group. uEGF/Cr is significantly correlated with eGFR (r = 0.75, p < 0.001), after adjustment for age. In 38 patients with longitudinal follow-up, we observed a significant correlation between uEGF/Cr and eGFR slope (r = 0.58, p < 0.001). Patients with lower uEGF/Cr level were at increased risk of progression to a higher CKD stage. uEGF/Cr was able to distinguish progressors from non-progressors with an AUC of 0.88, versus 0.77 by eGFR and 0.81 by 24-h urinary protein (24-h UP).

Conclusions: Our study suggests that uEGF/Cr is a promising biomarker for accelerated kidney function decline in pediatric patients with Alport syndrome. It may help to identify patients at high risk of progression for targeted clinical care and improve the patients' stratification in interventional trials.
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http://dx.doi.org/10.1007/s00467-018-3988-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6132884PMC
October 2018

The ratio of urinary α1-microglobulin to microalbumin can be used as a diagnostic criterion for tubuloproteinuria.

Intractable Rare Dis Res 2018 Feb;7(1):46-50

Department of Pediatric, Peking University First Hospital, Beijing, China.

Low-molecular-weight proteinuria is one of the characteristic clinical manifestations of renal tubular and interstitial diseases. Low-molecular-weight proteinuria is defined as excessive urinary loss of α1-microglobulin, β2-microglobulin, or other low-molecular-weight plasma proteins. The current study examined the ratio of urinary α1-microglobulin to microalbumin in 24 Chinese pediatric patients with renal tubular and interstitial diseases, including 10 patients with Dent disease, 2 patients with Lowe syndrome, 6 patients with acute tubulointerstitial nephritis (ATIN), 4 patients with acute tubulointerstitial nephritis with uveitis syndrome (TINU), and 2 patients with nephronophthisis (NPHP). Patients with steroid-sensitive nephrotic syndrome, IgA nephropathy, Henoch-Schonlein purpura nephritis, or lupus nephritis served as control groups. In all of the patients with tubular and interstitial disease, urinary α1-microglobin increased 10-300-fold above the upper limit of the normal range, the ratio of urinary α1-microglobulin to microalbumin was greater than 1, and the percentage of low-molecular-weight plasma proteins (LMWP) in urine was greater than 50% according to urine protein electrophoresis. There was close correlation between the ratio of urinary α1-microglobulin to microalbumin and the percentage of LMWP in urine according to urine protein electrophoresis ( = 0.797, = 0.000). We suggested firstly that the ratio of urinary α1-microglobulin to microalbumin, greater than 1, can be used as a diagnostic criterion for tubuloproteinuria.
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http://dx.doi.org/10.5582/irdr.2017.01079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5849625PMC
February 2018

Steroid-resistant nephrotic syndrome caused by co-inheritance of mutations at and genes in two Chinese siblings.

Intractable Rare Dis Res 2017 Nov;6(4):299-303

Department of Pediatric, Peking University First Hospital, Beijing, China.

Hereditary nephrotic syndrome often presents with steroid-resistance and onset within the first year of life. Mutations in genes highly expressed in podocytes have been found in two thirds of these patients, especially and among at least 29 genetic causes that have been discovered. We reported two siblings with steroid-resistant nephrotic syndrome caused by co-inheritance of mutations at (c.1339G>A, p.E447K) and (c.748G>C, p.D250H) genes. The siblings presented with steroid-resistant nephrotic syndrome and pathological lesions of focal segmental glomerulosclerosis (FSGS), while the elder sister also developed hypertension, renal failure and cardiac dysfunction.
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http://dx.doi.org/10.5582/irdr.2017.01037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5735285PMC
November 2017

Value of the Oxford classification of IgA nephropathy in children with Henoch-Schönlein purpura nephritis.

J Nephrol 2018 04 28;31(2):279-286. Epub 2017 Nov 28.

Biostatistics department, University of Michigan, 1415 Washington Heights, Ann Arbor, MI, 48109, USA.

Background: The widely used International Study of Kidney Disease in Children (ISKDC) classification for Henoch-Schönlein purpura nephritis (HSPN) does not completely correlate with the clinical presentation and long-term prognosis of this disease. Primary IgA nephropathy (IgAN) and HSPN share common features; thus, the Oxford classification of IgAN might be useful in predicting the long-term outcomes of HSPN. However, its value has not been confirmed in children with HSPN.

Methods: We selected children with HSPN diagnosed between 2003 and 2015, and reclassified their renal biopsies according to the Oxford classification scoring system. The primary outcome was impaired renal function, and remission of proteinuria and clinical remission were secondary outcomes.

Results: We included 104 patients (58 males, 46 females) with a median age of 10 (4-17) years. Mesangial hypercellularity (M1) was strongly associated with proteinuria, and tubular atrophy/interstitial fibrosis (T1&2) and C2 (with crescents in > 25% of glomeruli) were associated with reduced estimated glomerular filtration rate (eGFR) at the time of biopsy. Patients with M1, endocapillary proliferation (E1), segmental glomerulosclerosis (S1), and crescents (C1&2) were more likely to have been treated with high-dose methylprednisolone. At univariate time-dependent analyses, S1 was strongly associated with the primary outcome (p = 0.025), whereas T1&2 was significantly negatively associated with proteinuria remission (p = 0.035) and clinical remission (p = 0.038).

Conclusions: Our findings suggest that the Oxford classification is valid for children with HSPN. S and T lesions, which are ignored in the ISKDC classification, can be used to assess renal outcomes of HSPN, and such assessments are not affected by currently available treatments. The value of M, E and C lesions in predicting response to therapy and renal outcome warrants further study.
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http://dx.doi.org/10.1007/s40620-017-0457-zDOI Listing
April 2018

Dent disease: Same mutation but different phenotypes in two brothers in China.

Intractable Rare Dis Res 2017 May;6(2):114-118

Department of Pediatric, Peking University First Hospital, Beijing, China.

Dent disease is an X-linked recessive proximal tubular disorder that affects mostly male patients in childhood or early adult life, caused by mutations in (Dent disease 1) or (Dent disease 2) genes, respectively. It presents mainly with hypercalciuria, low-molecular-weight proteinuria, nephrocalcinosis and progressive renal failure. We report here the same mutation but different phenotypes in two Chinese brothers, and speculate on the possible reasons for the variability of the genotype-phenotype correlations.
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http://dx.doi.org/10.5582/irdr.2017.01019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451742PMC
May 2017

Diagnosis and treatment of Dent disease in 10 Chinese boys.

Intractable Rare Dis Res 2017 Feb;6(1):41-45

Department of Pediatric, Peking University First Hospital, Beijing, China.

Dent disease is a rare X-linked recessive proximal tubular disorder that affects mostly male patients in childhood or early adult life. Dent disease is clinically characterized by the presence of low molecular weight proteinuria (LMWP), hypercalciuria, medullary nephrocalcinosis, nephrolithiasis, and progressive renal failure. The clinical features, diagnosis, and treatment of Dent disease were examined in 10 Chinese boys. All 10 childhood cases of Dent disease in China presented with tubular proteinuria in the nephrotic range and hypercalciuria. The ratio of α1-microglobulinuria to microalbuminuria, if close to or above 1, can be used as a diagnostic criterion for tubuloproteinuria. Lotensin was ineffective at treating proteinuria while dihydrochlorothiazide reduced urine calcium excretion.
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http://dx.doi.org/10.5582/irdr.2016.01088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5359351PMC
February 2017

G protein subunit α q regulates gastric cancer growth via the p53/p21 and MEK/ERK pathways.

Oncol Rep 2017 Apr 13;37(4):1998-2006. Epub 2017 Mar 13.

Cancer Center, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.

Genetic alterations in G protein subunit α q (GNAQ) have been reported in numerous types of human cancer. However, the role of GNAQ in human gastric cancer (GC) has not been explored. In the present study, we found that GNAQ was highly expressed in GC patient samples and GNAQ expression was related to patient age, GC differentiation status and adjuvant therapy, as determined by immunohistochemical assay. Lentivirus delivery of short hairpin RNA (shRNA) targeting GNAQ was used to explore the function of GNAQ in GC cells. Silencing of GNAQ markedly suppressed proliferation and colony formation in GC cells, and arrested the cell cycle at the S phase. Mechanistic analysis revealed that knockdown of GNAQ significantly increased the expression of p53 and p21, and decreased cyclin A and p-CDK2 protein expression. Moreover, the phosphorylation of ERK and MEK was also decreased after knockdown of GNAQ as determined by western blotting assay. Overall, our results suggest that GNAQ plays a critical role in regulating GC cell growth and survival via canonical oncogenic signaling pathways including MAPK and p53, and therefore serves as a promising new therapeutic target in GC.
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http://dx.doi.org/10.3892/or.2017.5500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5367349PMC
April 2017

Spectrum of mutations in Chinese children with steroid-resistant nephrotic syndrome.

Pediatr Nephrol 2017 Jul 15;32(7):1181-1192. Epub 2017 Feb 15.

Division of Nephrology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Enders 561, Boston, MA, 02115, USA.

Background: The aim of this study was to elucidate whether genetic screening test results of pediatric patients with steroid-resistant nephrotic syndrome (SRNS) vary with ethnicity.

Methods: Using high-throughput DNA sequencing, 28 nephrotic syndrome-related genes were analyzed in 110 chil-dren affected by SRNS and 10 children with isolated proteinuria enrolled by 5 centers in China (67 boys, 53 girls). Their age at disease onset ranged from 1 day to 208 months (median, 48.8 months). Patients were excluded if their age at onset of disease was over 18 years or if they were diagnosed as having Alport syndrome.

Results: A genetic etiology was identified in 28.3% of our cohort and the likelihood of establishing a genetic diagnosis decreased as the age at onset of nephrotic syndrome increased. The most common mutated genes were ADCK4 (6.67%), NPHS1 (5.83%), WT1 (5.83%), and NPHS2 (3.33%), and the difference in the frequencies of ADCK4 and NPHS2 mutations between this study and a study on monogenic causes of SRNS in the largest international cohort of 1,783 different families was significant. A case of congenital nephrotic syndrome was attributed to a homozygous missense mutation in ADCK4, and a de novo missense mutation in TRPC6 was detected in a case of infantile nephrotic syndrome.

Conclusions: Our results showed that, in the first and the largest multicenter cohort of Chinese pediatric SRNS reported to date, ADCK4 is the most common causative gene, whereas there is a low prevalence of NPHS2 mutations. Our data indicated that the genetic testing results for pediatric SRNS patients vary with different ethnicities, and this information will help to improve management of the disease in clinical practice.
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http://dx.doi.org/10.1007/s00467-017-3590-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478193PMC
July 2017

Mutations in TTC21B cause different phenotypes in two childhood cases in China.

Nephrology (Carlton) 2018 Apr;23(4):371-376

Department of Pediatric, Peking University First Hospital, Beijing, China.

Aim: The TTC21B gene is now known as causative of nephronophthisis-related ciliopathies (NPHP-RC). We reported two Chinese paediatric cases with end-stage renal disease and other phenotypes caused by the TTC21B gene mutations.

Methods: The clinical features of Chinese paediatric cases with NPHP-RC were summarized. Mutation analysis of the TTC21B gene was performed using next-generation sequencing.

Results: The two cases both had nephrotic proteinuria, renal failure, hypertension and abnormal liver function (or hepatic fibrosis). One case also presented situs inversus and short phalanges. They developed end-stage renal disease (ESRD) at 1 year old and 8 years old, respectively, when renal pathology both showed focal segmental glomerular sclerosis (FSGS) with tubulointerstitial lesions including interstitial fibrosis and atrophic tubules. Three novel disease-causing TTC21B mutations were identified. One case carried homozygous mutation c.2211 + 3A > G, while the other case carried compound heterozygous mutations c.1552 T > C (p.C518R) and c.1456dupA (p.R486KfsX22).

Conclusion: Mutations in TTC21B cause a range of ciliopathy phenotypes in humans. We identified 3 novel TTC21B mutations in two Chinese paediatric cases that both presented end-stage renal disease and other different features. This is the first TTC21B mutations ever reported in China.
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http://dx.doi.org/10.1111/nep.13008DOI Listing
April 2018

LAMB2 mutation with different phenotypes in China
.

Clin Nephrol 2017 Jan;87 (2017)(1):33-38

Background: Mutations of the LAMB2 gene mainly cause Pierson syndrome (OMIM) #609049), characterized by congenital nephrotic syndrome (CNS) and complex ocular involvements with microcoria as the most prominent clinical feature. However, the phenotypic spectrum of LAMB2-associated disorders is broader, isolated congenital or infantile nephrotic syndrome can also be seen. The aim of this study was to explore the phenotypes of different LAMB2 mutations in China.

Methods: LAMB2 mutations were analyzed in three Chinese childhood steroid-resistant nephrotic syndrome cases, two of them with ocular abnormalities.

Results: LAMB2 mutations were confirmed in all the three cases, two presented with Pierson syndrome, while one presented with isolated infantile steroid-resistant nephrotic syndrome.

Conclusions: The phenotypes caused by LAMB2 mutation were variable, mainly Pierson syndrome, as well as isolated nephrotic syndrome without ocular involvement. Mutational analysis of LAMB2 should be considered in all steroid-resistant nephrotic syndrome patients, with or without any ocular abnormalities.
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http://dx.doi.org/10.5414/CN108979DOI Listing
January 2017

Dent's disease complicated by nephrotic syndrome: A case report.

Intractable Rare Dis Res 2016 Nov;5(4):297-300

Pediatrics, Peking University First Hospital, Beijing, China.

Dent's disease is an X-linked recessive proximal tubular disorder that mostly affects male patients in childhood or early adult life. The condition is caused by mutations in the (Dent disease 1) or (Dent disease 2) genes located on chromosome Xp11.22 and Xq25, respectively. In most male patients, proteinuria is subnephrotic but may reach nephrotic levels. Here, we report the first case of Dent's disease complicated by nephrotic syndrome. Dent's disease should be considered in the differential diagnosis of nephrotic syndrome, and especially in male patients with early onset of nephrotic syndrome. A urinary α1-microglobulin/albumin ratio > 1 may provide the first clue to a tubulopathy.
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http://dx.doi.org/10.5582/irdr.2016.01058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116868PMC
November 2016

Adjuvant treatment combining cellular immunotherapy with chemotherapy improves the clinical outcome of patients with stage II/III gastric cancer.

Cancer Med 2017 01 27;6(1):45-53. Epub 2016 Oct 27.

Cancer Center, the First Hospital of Jilin University, Changchun, China.

Postsurgical relapse remains a common issue for resectable gastric cancer (GC). Here, we investigated the efficacy and safety of an adjuvant treatment combining chemotherapy with cellular immunotherapy (CIT) using autologous natural killer cells, γδT cells, and cytokine-induced killer cells in the treatment of stage II/III GC. A pilot prospective cohort study was conducted in 169 patients with stage II/III GC who had undergone gastrectomy with D2 lymph node dissection. Patients were assigned into two groups according to the patient choice of treatment, including chemotherapy alone (chemo) or chemotherapy combined with CIT (chemo/CIT). Disease-free survival (DFS), overall survival (OS), and adverse events were evaluated. Univariate and multivariate Cox models were used to analyze the impact of chemo/CIT on DFS and OS. Kaplan-Meier analysis with the log-rank test was used to compare the clinical outcome between two groups. Three-year DFS rate was 60.6% and 74.7% (P = 0.036) and 3-year OS rate was 64.9% and 83% (P = 0.051) for the chemo and chemo/CIT group, respectively. TNM stage and chemo/CIT were independent prognostic factors for both DFS (for TNM stage, P < 0.001, hazard ratio [HR]: 5.599, 95% confidence interval [CI]: 2.791-11.232; for chemo/CIT, P = 0.013, HR: 0.478, 95% CI: 0.266-0.858) and OS (for TNM stage, P < 0.001, HR: 6.559, 95% CI: 2.903-14.817; for chemo/CIT, P = 0.04, HR: 0.506, 95% CI: 0.264-0.970). In subgroup analysis, 3-year DFS and OS rates of patients with stage III GC in the chemo/CIT group were significantly higher than those in the chemo group (38.4% vs. 57.1%, P = 0.038; and 45.9% vs. 76%, P = 0.06, respectively), while there was no significant difference between the two groups in patients with stage II GC. Only 15.9% of patients (10/63) in the chemo/CIT group had mild and manageable fever (grades 1 and 2), while no other side effects were observed. The adjuvant treatment combining chemotherapy with cellular immunotherapy is well tolerated and significantly improves the clinical outcome of patients with stage II/III GC, when compared with chemotherapy alone, therefore warrants further attention in treatment for relapsed GC after tumor resection.
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http://dx.doi.org/10.1002/cam4.942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5269688PMC
January 2017

[Clinical and genetic features of X-linked Alport syndrome in men positive for the collagen Ⅳ α5 chain in epidermal basement membrane].

Zhonghua Er Ke Za Zhi 2016 Jan;54(1):61-4

Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.

Objective: To analyze the clinical and genetic features of X-linked Alport syndrome (XLAS) in men positive for the collagen α5(Ⅳ) chain in epidermal basement membrane.

Method: This was a retrospective study. Totally 725 families were diagnosed as Alport syndrome in Department of Pediatrics of Peking University First Hospital during January 1998 to December 2014, among them 450 patients were males with XLAS. Patients who met both of the following two criteria were included in this study. (1)Patients underwent α5(Ⅳ) chain staining in the epidermal basement membrane. (2)Mutations in COL4A5 gene were detected.Mann-Whitney test and χ(2) test were used.

Result: Totally 140 males with XLAS were included in this study, 18 cases were α5 (Ⅳ)-positive and 122 cases were α5 (Ⅳ)-negative. The two groups of patients were compared, the median age at analysis was 11.0 vs. 7.2 years (Z = -1.839, P = 0.066), the 24-hour urine protein was 1.50 vs. 0.57 g/d (Z = -1.212, P = 0.226), the rate of hearing loss was 28% vs. 53% (χ(2) = 3.619, P = 0.067), the number of patients progressed to end stage renal disease (ESRD) was 4 vs. 12 (χ(2) =2.377, P = 0.128), the median age of ESRD was 31.0 vs. 16.6 years (Z = -2.554, P = 0.011), the rate of missense mutations in COL4A5 gene was 67% vs. 52% (χ(2) = 1.424, P = 0.313).

Conclusion: Compared the two groups of patients with positive and negative staining for the collagen Ⅳ α5 chain in epidermal basement membrane, there was no significant difference in the proteinuria level, the rate of hearing loss and genotype of COL4A5 gene. But the patients with positive staining progressed to ESRD significantly later than the patients with negative staining.
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http://dx.doi.org/10.3760/cma.j.issn.0578-1310.2016.01.014DOI Listing
January 2016

[Progress in diagnosis and treatment of tubular interstitial nephritis-uveitis syndrome].

Zhonghua Er Ke Za Zhi 2015 Sep;53(9):714-6

Email:

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September 2015

[Retrospective study of primary IgA nephropathy with crescent formation and/or rapidly progressive glomerulonephritis in children].

Zhonghua Er Ke Za Zhi 2015 Sep;53(9):670-5

Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.

Objective: IgA nephropathy is the most common type of glomerulonephritis in the world. Its clinical and pathological manifestations vary. A few of the patients with IgA nephropathy present with rapidly progressive glomerulonephritis (RPGN) and/or crescent formation. Their conditions are serious and acute, but there are few reports on their characteristics, treatment and outcome. This study aimed to analyze the clinicalopathological features, treatment and prognosis of primary IgA nephropathy in children, to provide a reference for clinical diagnosis and treatment.

Method: A retrospective study was conducted in children with primary IgA nephropathy with crescent formation and/or rapidly progressive glomerulonephritis admitted to our department from 2000 to 2014. The patients meeting the inclusion and exclusion criteria were included. Patients were divided into RPGN group and non-RPGN group according to the clinical manifestations, crescent formation group and non-crescent group, crescentic IgA nephropathy group and non-crescentic IgA nephropathy group according to renal biopsy. Their clinical manifestations and pathological features, treatment and prognosis were compared.

Result: A total of 265 patients were recruited, 10 patients (3.8%) had RPGN, 151 patients (57.0%) had crescent formation, 19 cases (7.2%) showed crescentic IgA nephropathy.Compared with non-RPGN group, RPGN group showed more gross hematuria, higher serum creatinine, lower creatinine clearance correction at biopsy and follow-up, and more crescentic IgA nephropathy (P<0.05). The percent of patients who received methylprednisolone pulse and blood purification therapy in RPGN group is higher than that of non-RPGN group (P<0.05). Compared with non-crescent group, crescent formation group showed more gross hematuria at biopsy and follow-up, higher serum creatinine at biopsy, lower creatinine clearance correction, more 24-hour urinary protein at biopsy and higher serum creatinine at follow-up (P<0.05). The percentage of patients received more methylprednisolone pulse, oral steroids, cyclophosphamide pulse in crescent formation group was higher than that of non-crescent group (P<0.05). Compared with non-crescentic IgA nephropathy group, crescentic IgA nephropathy group showed more RPGN percent, higher serum creatinine, more 24-hour urinary protein at biopsy (P<0.05). The percentage of patients who received more methylprednisolone pulse and blood purification therapy in crescentic IgA nephropathy group was more than non-crescentic IgA nephropathy group (P<0.05). At follow-up, 20.0% of the patients with RPGN and crescent nephritis returned to normal renal function and the percent of crescent glomerulonephritis but not RPGN was 71.4%, RPGN but not crescent glomerulonephritis was 80.0%, crescent formation but not crescent nephritis was 87.5%.

Conclusion: In primary IgA nephropathy with crescent formation and/or rapidly progressive glomerulonephritis, the patients with both RPGN and crescentic IgA nephropathy showed the worst clinical manifestations, its prognosis was worst while the patients with crescent formation showed the mildest clinical manifestations and best prognosis.
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September 2015

Long-term treatment by ACE inhibitors and angiotensin receptor blockers in children with Alport syndrome.

Pediatr Nephrol 2016 Jan 7;31(1):67-72. Epub 2015 Aug 7.

Department of Pediatrics, Peking University First Hospital, No. 1, Xi An Men Da Jie, Beijing, 100034, People's Republic of China.

Background: The aim of this study was to analyze the long-term efficacy and safety of angiotensin-converting enzyme inhibitor (ACEi) and ACEi + angiotensin receptor blocker (ARB) treatments in a cohort of children with Alport syndrome (AS).

Methods: This was a respective review of 79 Chinese children with AS who received ACEi alone or combined ACEi + ARB therapy.

Results: The mean age of the pediatric patients with AS at onset of treatment was 8.6 ± 4.1 (range 1.5-16.3) years. The mean duration of follow-up was 2.5 ± 1.8 (range 0.5-7.8) years. For analysis, we separated the children into three groups according to proteinuria level before treatment, namely, <25, 25-50, and ≥50 mg/kg/day, respectively; after 1 year of treatment the proteinuria had decreased from 11.0 to 9.7 mg/kg/day, from 34.6 to 15.2 mg/kg/day, and from 73.0 to 50.0 mg/kg/day in each group, respectively. Proteinuria decreased significantly during the first 2 years of treatment and was stable from the third to fifth years of treatment. There was no statistically significant difference in the antiproteinuric effect of the ACEi and ACEi + ARB treatments in patients with severe or less severe mutations after 1 year of therapy. Five children stopped the ACEi + ARB treatment due to a decline in creatinine clearance.

Conclusion: Our findings demonstrate that early and long-term ACEi and ARB treatments in children with AS is efficient and well tolerated. The antiproteinuric effect of ACEi and ARB is of equal value in children with severe and less severe mutations in the COL4An gene.
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http://dx.doi.org/10.1007/s00467-015-3184-5DOI Listing
January 2016