Objective:To screen bile acid-related characteristic genes in IgA nephropathy (IgAN) based on the feature gene selection algorithm in the machine learning method, aiming to exploring the molecular biological mechanisms and biomarkers of IgAN.Methods:The gene expression data and sample grouping information of GSE93798, GSE116626 and GSE35487 were downloaded from the Gene Expression Omnibus (GEO). Bile acid-related gene sequences were obtained from the Molecular Signatures Database (MSigDB). R language was used to identify differentially expressed genes between IgAN samples and healthy control samples. Candidate genes were obtained by intersecting differentially expressed genes and bile acid-related genes. The least absolute shrinkage and selection operator (LASSO) algorithm in machine learning was used to screen the feature genes in the candidate genes as biomarkers, and the feature genes in the training set and validation set were analyzed by the rate of change index. Receiver operating characteristic curve (ROC) method was used to evaluate the diagnostic value of identified bile acid related characteristic genes for IgAN. Gene set enrichment analysis (GSEA) was used to analyze the Spearman correlation between the characteristic genes and all other genes and their related metabolic pathways. The expression of disease-characteristic genes in the kidney tissues of IgAN rats was validated by real-time PCR.Results:Gene expression information from kidney tissue samples of 20 IgAN cases and 22 healthy controls were obtained from GEO database. A total of 204 bile acid-related genes including 24 pathways were obtained from MSigDB. The results of gene differential expression analysis showed that 333 genes in the kidney tissues of IgAN patients were differentially expressed compared with those of healthy controls, including 102 up-regulated genes and 231 down-regulated genes, among which 12 differentially expressed genes were related to bile acid genes, as follows: NR1H4,SLC23A1, ALDH8A1, FABP1, ALB, SLC27A2, DIO1, CYP8B1, BBOX1, PIPOX, AKR1C1 and SLC10A2. Five characteristic genes ( NR1H4, SLC23A1, FABP1, ALB and AKR1C1) were screened by LASSO regression algorithm.ROC analysis results showed that in GSE93798 cohort genes, the AUC of NR1H4, SLC23A1, FABP1 and ALB genes with differential expression was >0.95 respectively in diagnosing IgAN, and that of AKR1C1 genes with differential expression was >0.85 in diagnosing IgAN. The gene expression data of SLC23A1 in GSE35487 cohort was missing. ROC analysis results of other four genes showed that the AUC of differential expression of ALB gene for IgAN was >0.95 respectively, that of NR1H4 gene was >0.70, and that of both FABP1 and AKR1C1 gene was >0.60. In the GSE116626 cohort genes, the AUC of five disease characteristic genes ( NR1H4, SLC23A1, FABP1, ALB, AKR1C1) for diagnosing IgAN was >0.60, respectively. These results suggested that 5 characteristic genes have certain distinguishing ability between IgAN group and control group. GSEA results were displayed that the characteristic genes were related to butyric acid metabolism, propionic acid metabolism, arginine and proline metabolism, valine leucine and isoleucine degradation, fatty acid metabolism, etc. These results suggested that five characteristic genes might be related to IgAN through the above metabolic mechanisms. The verification results of five bile acid characteristic genes in the rat model of IgAN in the kidney tissue showed that the expressions of four genes, NR1H4, SLC23A1, FABP1 and ALB, were higher than those of the control group, and there was no statistical significance in the expression of AKR1C1 gene between the two groups. Conclusions:The expression of bile acid-related characteristic genes is abnormal in the kidney tissue of IgAN patients. Four bile acid-related differentially expressed genes, NR1H4, SLC23A1, FABP1 and ALB, are expected to be biomarkers for non-invasive diagnosis and therapeutic targets .

Objective:To screen bile acid-related characteristic genes in IgA nephropathy (IgAN) based on the feature gene selection algorithm in the machine learning method, aiming to exploring the molecular biological mechanisms and biomarkers of IgAN.Methods:The gene expression data and sample grouping information of GSE93798, GSE116626 and GSE35487 were downloaded from the Gene Expression Omnibus (GEO). Bile acid-related gene sequences were obtained from the Molecular Signatures Database (MSigDB). R language was used to identify differentially expressed genes between IgAN samples and healthy control samples. Candidate genes were obtained by intersecting differentially expressed genes and bile acid-related genes. The least absolute shrinkage and selection operator (LASSO) algorithm in machine learning was used to screen the feature genes in the candidate genes as biomarkers, and the feature genes in the training set and validation set were analyzed by the rate of change index. Receiver operating characteristic curve (ROC) method was used to evaluate the diagnostic value of identified bile acid related characteristic genes for IgAN. Gene set enrichment analysis (GSEA) was used to analyze the Spearman correlation between the characteristic genes and all other genes and their related metabolic pathways. The expression of disease-characteristic genes in the kidney tissues of IgAN rats was validated by real-time PCR.Results:Gene expression information from kidney tissue samples of 20 IgAN cases and 22 healthy controls were obtained from GEO database. A total of 204 bile acid-related genes including 24 pathways were obtained from MSigDB. The results of gene differential expression analysis showed that 333 genes in the kidney tissues of IgAN patients were differentially expressed compared with those of healthy controls, including 102 up-regulated genes and 231 down-regulated genes, among which 12 differentially expressed genes were related to bile acid genes, as follows: NR1H4,SLC23A1, ALDH8A1, FABP1, ALB, SLC27A2, DIO1, CYP8B1, BBOX1, PIPOX, AKR1C1 and SLC10A2. Five characteristic genes ( NR1H4, SLC23A1, FABP1, ALB and AKR1C1) were screened by LASSO regression algorithm.ROC analysis results showed that in GSE93798 cohort genes, the AUC of NR1H4, SLC23A1, FABP1 and ALB genes with differential expression was >0.95 respectively in diagnosing IgAN, and that of AKR1C1 genes with differential expression was >0.85 in diagnosing IgAN. The gene expression data of SLC23A1 in GSE35487 cohort was missing. ROC analysis results of other four genes showed that the AUC of differential expression of ALB gene for IgAN was >0.95 respectively, that of NR1H4 gene was >0.70, and that of both FABP1 and AKR1C1 gene was >0.60. In the GSE116626 cohort genes, the AUC of five disease characteristic genes ( NR1H4, SLC23A1, FABP1, ALB, AKR1C1) for diagnosing IgAN was >0.60, respectively. These results suggested that 5 characteristic genes have certain distinguishing ability between IgAN group and control group. GSEA results were displayed that the characteristic genes were related to butyric acid metabolism, propionic acid metabolism, arginine and proline metabolism, valine leucine and isoleucine degradation, fatty acid metabolism, etc. These results suggested that five characteristic genes might be related to IgAN through the above metabolic mechanisms. The verification results of five bile acid characteristic genes in the rat model of IgAN in the kidney tissue showed that the expressions of four genes, NR1H4, SLC23A1, FABP1 and ALB, were higher than those of the control group, and there was no statistical significance in the expression of AKR1C1 gene between the two groups. Conclusions:The expression of bile acid-related characteristic genes is abnormal in the kidney tissue of IgAN patients. Four bile acid-related differentially expressed genes, NR1H4, SLC23A1, FABP1 and ALB, are expected to be biomarkers for non-invasive diagnosis and therapeutic targets .

Objective To investigate the clinicopathological characteristics of idiopathic membranous nephropathy (IMN) in elderly patients.Methods Clinicopatholigical data of 400 patients with IMN identified by renal biopsy from January 2006 to December 2016 were analyzed retrospectively.The patients were divided into three groups:the young (≤44 years old),the middle-aged (45-59 years old) and the elderly (≥60 years old),and the clinicopathological characteristics were compared among three groups.Results The average age of the elderly group was (64.9 ± 4.3) years,the elderly group had worse renal function than the young group (F =784.60,P =0.000) and the middle-aged group [estimated glomerular filtration rate (eGFR) were (91.1 ± 25.9) 、(119.8 ± 37.0) and (102.5 ± 33.2) ml · min-1 · 1.73 m-2,F =21.74,P =0.000].The incidence of hypertension was higher in the elderly group than the other two groups [40.0％ (32/80) vs.19.6％ (30/153) and 22.2％ (37/167),x2 =12.76,P =0.003].The incidence of MN with ischemic nephropathy and tubulointerstitial lesion in the elderly group was higher than in the young group[15.0％ (12/80) vs.5.8％ (9/153),x2 =5.31,P =0.021].Conclusion The elderly patients with IMN are likely to be complicated with hypertension,ischemic nephropathy and tubulointerstitial lesions indicating poorer prognosis,so more attention should be paid to the early diagnosis and treatment of these comorbidities.

Kidney damage is common in patients with diabetes mellitus (DM).However,whether the type of kidney damage can be reliably diagnosed using clinical data alone remains unclear.Predictive factors for diabetic nephropathy (DN) outcomes are also poorly understood.In this study,the clinical manifestations of 111 cases of biopsy-proven DN were described,and the clinical and pathological parameters of patients with different DN outcomes were compared.Results showed that long DM duration (＞ 10 years in 32.4％ of patients),severe proteinuria (62.2％),and renal dysfunction (estimated glomerular filtration rate [eGFR] ＜ 60 mL/(min-1.73 m2)) (52.3％) did not accurately indicate whether the condition of these patients progressed to DN.Hematuria (48.6％) failed to specify either DN or nondiabetic renal disease.Diabetic retinopathy (78.4％) was a crucial complication in patients with DN.Kaplan-Meier analysis revealed that the renal survival of 53 patients who were diagnosed with DN and were followed up was not significantly associated with glomerular classification (P ＞ 0.05).Cox's regression analysis demonstrated that renal survival time was significantly influenced by sex (β=1.394,P =0.038),hematuria (β =0.036,P =0.029),and eGFR (β =-0.039,P =0.002) but was not significantly affected by age,24 h urinary protein excretion,or glomerular classification (P ＞ 0.05).In conclusion,the clinical characteristics of DN vary,and renal biopsy is necessary to determine renal damage patterns.Sex,hematuria,and the eGFR may affect DN outcomes,whereas the glomerular classification may not.

Objective To investigate the different expressions of plasma M type phospholipase A2 receptor antibody and IgG subtypes deposition of kidney tissues in idiopathic membranous nephropathy and hepatitis B virus-associated membranous nephropa-thy,and to evaluate the significance of plasma M type phospholipase A2 receptor antibody and IgG subtypes in diagnosis of hepatitis B virus-associated membranous nephropathy.Methods Plasma samples were obtained from patients with idiopathic membranous nephropathy,hepatitis B virus-associated membranous nephropathy and minimal change disease,respectively,before immunosup-pressive therapy.Concentration of plasma M type phospholipase A2 receptor antibody was detected by sandwich ELISA and concen-tration of IgG subtypes were measured by immunofluorescence.Results Concentration of plasma M type phospholipase A2 receptor antibody was (15.4±7.2)μg/mL in idiopathic membranous nephropathy group,higher than that in the hepatitis B virus-associated membranous nephropathy group (10.3±5.7)μg/mL (P <0.01),between idiopathic membranous nephropathy group and hepatitis B virus-associated membranous nephropathy group.There was no distinct difference of IgG subtypes deposition in glomerlar capil-lary wall.Conclusion There is obvious clinical significance of concentration of plasma M type phospholipase A2 receptor antibody in differential diagnosis of idiopathic membranous nephropathy and hepatitis B virus-associated membranous nephropathy,while no distinct significance of IgG subtypes deposition.

Objective To analyze clinical and pathologic features of a rare vascular amyloid deposits of amyloid nephropathy ( VADAN) in 6 patients, so as to improve its diagnosis and treatment. Methods All patients received immunopathology, microscopy and electron microscopy examination, and amyloid types were analyzed. Results There were 3 males and 3 females with ages ranging from 52 to 73 years. Two patients suffered from multiple myeloma. Majority patients had slight albuminuria and hematuria. One patient combined with minimal change glomerular disease presented nephrotic syndrome. One patient combined with IgA nephropathy had albuminuria and hematuria. And one patient had myeloma cast nephropathy with acute renal failure. Kidney biopsy proved amyloid deposits along interlobular arterial wall only in all 6 patients. Two cases secondary from multiple myeloma were κ amyloid, and the rests were λ amyloid. Conclusions VADAN is a rare type of amyloid nephropathy. Its clinical manifestation is different from common amyloid nephropathy. Kidney biopsy will benefit its differential diagnosis.

ObjectiveTo investigate the clinicopathological characteristics of non-diabetic renal diseases (NDRD) in the patients with diabetes mellitus.MethodsClinicopatholigical data of 202 patients with diabetes mellitus and NDRD identified by renal biopsy from January 1st,2003 to December 31st,2010 were analyzed retrospectively.All the patients were divided into three groups:the young (≤35 years old),the middle-aged (36-59 years old) and the elder (≥60 years old).Clinicopathological characteristics were compared among 3 groups.ResultsIn the young group (n=33),42.4％ of patients presented as chronic glomerulonephritic syndrome,while 36.4％ as IgA nephropathy for pathology.In the middle-aged group(n=136),35.3％ of patients presented as chronic glomerulonephritic syndrome,27.2％ as nephritic syndrome,17.6％ as chronic renal failure,14.7％ as latent glomerulonephritis,and 5.1％ as acute renal failure,while42.6％ as IgA nephropathy for pathology.In the elder group(n=33),30.3％ of patients presented as nephritic syndrome,30.3％ as chronic renal failure,while 27.3％ as membranous nephropathy for pathology.ConclusionsIn clinical manifestation,young patients are mainly chronic glomerulonephritic syndrome,middle-aged patients are diversified,and elder patients are mainly nephritic syndrome andchronicrenalfailure. Inpathology, youngandmiddle-agedpatientsaremainlyIgA nephropathy,and elder patients are mainly membranous nephropathy.

SUMMARY A 15-year-old boy was admitted with nephritic and nephrotic syndrome,renal dysfunction and decreased serum C3,who suffered from varicella for two months.His renal histopathology revealed endocapillary proliferative glomerulonephritis with podocytes proliferation and severe tubular injury by light microscopy.Direct immunofluorescence showed global granular deposition of IgG,IgA,IgM,C3,Clq and fibrinogen in mesangium and along glomerular capillary wall.Electron microscopic examination showed electron-dense deposits in multiple sites of glomeruli.Furthermore,specific serum IgM antibodies against varicella-zoster virus (VZV) were detected.VZV antigen and mRNA were demonstrated in glomerular and tubular epithelial cells by immunohistochemical staining and in-situ hybridization.Virus particles and virus inclusions were identified by electron microscopy and special staining ( Methylene Blue and Eosion staining or Mann staining).The patient also experienced epileptic episodes and his brain MRI and electroenephalogram indicated herpes encephalitis with secondary epilepsy.Therefore,the diagnosis of VZV-associated glomerulonephritis and encephalitis was established.This is the first case of VZV-associated glomerulonephritis with renal histooathological evidence using in situ hybridization technique.

Objective To investigate the impact of metabolic syndrome(MS)on clinicopathology of IgA nephropathy(IgAN). Methods A total of 118 IgAN patients complicated with MS were enrolled in the study as IgAN-MS group. Then 118 IgAN patients of same age arrange without MS were randomly selected as IgAN-non-MS group.A comparative analysis of clinical and pathological data between these two groups was performed. Results The urine protein, serum creatinine, body mass index, mean arterial pressure, serum triglyceride, fasting blood glucose and serum uric acid in IgAN-MS group were all significantly higher than those in IgAN-non-MS group(P<0.05 or P<0.01). The serum HDL-C level in IgAN-MS group was significantly lower than that in IgAN-non-MS group(P<0.01). The percentages of patient with hypertension, abnormal glucose metabolism or abnormal lipid metabolism in IgAN-MS group were also significantly higher than those in IgAN-non-MS group(P <0.01). The glomerular and tubulointerstitial pathological changes in IgAN-MS group were significantly more severe than those in IgAN-non-MS group(P<0.01). There were significantly positive correlations between MS and urinary protein quantity, serum creatinine level, and glomerular damage index or tubulointerstitial damage index(P<0.01)by Spearman rank correlation analysis. Conclusion MS may be an important risk factor of IgAN progression.

Objective To introduce a case of varicella.zoster virus(VZV)-related glomerulonephritis and encephalitis. Methods The clinical data and renal pathology were analyzed.Associated literatures were reviewed. Results A 15 years old male patient presented nephritic syndrome,nephrotic syndrome and renal dysfunction with reduced serum complement C3 level from the 5th day after he suffered from varicella.The pathological diagnosis of his kidney tissue was endocapillary proliferative glomerulonephritis with podocyte proliferation and severe renal tubular injury by light microscopy.Immunofluorescent and electron microscopic examinations showed "full-house"staining and granular electron-dense deposits in multiple sites.respectively. Furthermore.virus-like particles or/and inclusions could also be seen by electron microscopy and Mann staining light microscopy.Positive varicella-zoster virus (VZV) specific lgM antibody was detected by serum virological test.VZV antigen and RNA transcript were found in glomerular and tubular cells by immunohistochemical staining and in situ hybridization of renal tissues,respectively. The patient had epileptic episodes for many times in his disease course and his brain MRI and electroencephalogram findings accorded with viml encephalitis with secondary epilepsy.So,the diagnosis of VZV-related glomerulonephritis and encephalitis was established. Conclusion This is the first report of VZV-related glomerulonephritis and encephalitis confirmed by serum virology and tissue virology.