Study on improvement effects and mechanism of rhein on immunoglobulin A nephropathy / 中国药房

OBJECTIVE To study the improvement effects and mechanism of rhein on immunoglobulin A nephropathy （IgAN） model rat based on signal transducer and activator of transcription 3 （STAT3） signaling pathway. METHODS Rats were randomly divided into normal control group， IgAN model group and rhein treatment group， with 10 rats in each group. IgAN model group and rhein treatment group were given combination of bovine serum albumin+lipopolysaccharide+carbon tetrachloride to induce IgAN model. Since the 7th week， rhein treatment group rats were intragastrically given relevant medicine， and normal control group and model group rats were given equal amount of normal saline intragastrically， for consecutive 4 weeks. After the last administration， the count of urine sediment erythrocyte， 24 h-urine total protein （UTP）， the levels of immunoglobulin A （IgA） in serum and secretory immunoglobulin A （sIgA） in intestinal mucosa were detected. The pathological changes of Peyer’s patch in renal cortex and intestinal mucosa and IgA deposition in renal cortex were observed. The expressions of interleukin-17 （IL-17）， IL- 6 and transforming growth factor β （TGF-β） in Peyer’s patch of intestinal mucosa in rats were detected. The expressions of STAT3 and related orphan receptor γt （RORγt） mRNA in Peyer’s patch were detected. The expressions of p-STAT3 and RORγt proteins in Peyer’s patch were detected. RESULTS Compared with normal control group， the count of urine sediment erythrocyte， 24 h-UTP， the levels of IgA in serum and sIgA in intestinal mucosa were increased significantly in IgAN model group （P＜0.01）； enlarged renal corpuscles， dilated renal sacs， obvious intratubular mesangial hyperplasia and fibrosis were observed in renal cortex； the volume and germinal center of Peyer’s patch in intestinal mucosa increased； IgA deposition of renal cortex zxyylxk20220103） was obvious； the expressions of IL-17， IL-6 and TGF-β in Peyer’s patch， mRNA expressions of STAT3 and RORγt， protein expressions of p-STAT3 and RORγt were increased significantly （P＜0.01）. Compared with IgAN model group，above indexes were decreased significantly in rhein treatment group （P＜0.01）， pathological damage of renal cortex was improved， the volume of Peyer’s patch and germinal center of intestinal mucosa were reduced， and IgA deposition in renal cortex was weakened. CONCLUSIONS Rhein can improve IgAN model rats， the mechanism of which may be associated with inhibiting STAT3 signaling pathway and regulating immune function of Peyer’s patch in intestinal mucosa.

Central Retinal Vein Occlusion as a Presenting Feature Caused by Hypertensive Crisis Secondary to IgA Nephropathy

We present a case of Ischemic Central retinal vein occlusion (CRVO) caused by hypertension secondary to renal failure in IgA nephropathy. A 17 year old male came with chief complaints of sudden painless diminution of vision in RE since 15 days. On examination the Right eye showed multiple superficial retinal haemorrhages in all 4 quadrents with dilated veins and cystoid macular edema suggestive of CRVO and Left eye showed superficial flame shaped haemorrhage suggestive of grade 3 hypertensive changes.

Mechanism of Modified Shengjiangsan in Treatment of IgA Nephropathy Based on Network Pharmacology， Molecular Docking， and Experimental Verification / 中国实验方剂学杂志

ObjectiveTo preliminarily predict the active components， targets， and signaling pathways of modified Shengjiangsan in the treatment of immunoglobulin A nephropathy （IgAN） based on network pharmacology， and to explore its underlying mechanism through molecular docking and experimental verification on animals. MethodThe active ingredients and related targets of modified Shengjiangsan were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP）， UniProt， SwissTargetPrediction， and literature review. IgAN-related targets were obtained from GeneCards and Online Mendelian Inheritance in Man （OMIM）. Cytoscape 3.9.0 was used to construct the regulation network of the related targets of Shengjiangsan and IgAN， and the protein-protein interaction （PPI） network was plotted by STRING. The common genes were analyzed for gene ontology （GO） functional annotation and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment by Metascape. Key targets and main active ingredients were selected for molecular docking by AutoDockTools 1.5.6. The experimental model of IgAN was induced by bovine serum albumin（BSA， ig） combined with lipopolysaccharide （LPS， iv） and the complex of CCl4 and castor oil （sc） in rats. The model rats were treated with modified Shengjiangsan and benazepril hydrochloride for four weeks. The rats were sacrificed after drug administration. The levels of transforming growth factor-β1 （TGF-β1） and interleukin-6 （IL-6） in the serum and kidney tissues were detected by enzyme-linked immunosorbent assay（ELISA）， immunohistochemistry， Real-time quantitative polymerase chain reaction （Real-time PCR）， and Western blot. ResultA total of 105 active ingredients were obtained according to oral bioavailability（OB）， drug-likeness（DL）， and literature screening. There were 124 common genes and 59 core targets. Neurotrophic tyrosine receptor kinase 1 （NTRK1）， cullin-3 （CUL3）， tumor protein 53 （TP53）， epidermal growth factor receptor （EGFR）， exportin 1 （XPO1）， and other targets might be closely related to IgAN. As predicted by KEGG enrichment analysis， the treatment of IgAN with modified Shengjiangsan mainly involved the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， nuclear transcription factor-kappa B （NF-κB） signaling pathway， and cytokine-cytokine receptor interaction signaling pathway. As revealed by molecular docking， the main active ingredients in modified Shengjiangsan showed stable binding activities with NTRK1， CUL3， TP53， EGFR， and XPO1 in the core targets， indicating that it presumedly regulated inflammatory responses by affecting NTRK1， CUL3， TP53， EGFR， and XPO1 target proteins. The results of experimental verification on animals showed that the expression levels of cytokines TGF-β1 and IL-6 in the serum and kidney tissues of IgAN rats were significantly decreased by modified Shengjiangsan， suggesting that Shengjiangsan might inhibit excessive fibrosis， and inflammatory and immune responses by regulating signaling pathways such as cytokine-cytokine receptor interaction， PI3K/Akt， and NF-κB. ConclusionModified Shengjiangsan may treat IgAN through multiple targets and pathways. Its mechanism may be related to the inhibition of excessive fibrosis， and inflammatory and immune responses by affecting the expression of NTRK1， CUL3， TP53， EGFR， and XPO1 and the regulation of the cytokine-cytokine receptor interaction， PI3K/Akt， NF-κB， and other signaling pathways.

Efficacy and safety of adding mizoribine to standard treatment in patients with immunoglobulin A nephropathy: A randomized controlled trial

BACKGROUND: Mizoribine (MZR) is an immunosuppressive drug used in Japan for treating patients with lupus nephritis and nephrotic syndrome and has been also reportedly effective in patients with immunoglobulin A (IgA) nephropathy. However, to date, few randomized control studies of MZR are performed in patients with IgA nephropathy. Therefore, this prospective, open-label, randomized, controlled trial aimed to investigate the efficacy and safety of adding MZR to standard treatment in these patients, and was conducted between April 1, 2009, and March 31, 2016, as a multicenter study. METHODS: Patients were randomly assigned (1:1) to receiving standard treatment plus MZR (MZR group) or standard treatment (control group). MZR was administered orally at a dose of 150 mg once daily for 12 months. RESULTS: Primary outcomes were the percentage reduction in urinary protein excretion from baseline and the rate of patients with hematuria disappearance 36 months after study initiation. Secondary outcomes were the rate of patients with proteinuria disappearance, clinical remission rate, absolute changes in estimated glomerular filtration rate from baseline, and the change in daily dose of prednisolone. Forty-two patients were randomly assigned to MZR (n = 21) and control groups (n = 21). Nine patients in MZR group and 15 patients in the control group completed the study. No significant differences were observed between the two groups with respect to primary and secondary outcomes. CONCLUSION: The addition of MZR to standard treatment has no beneficial effect on reducing urinary protein excretion and hematuria when treating patients with IgA nephropathy.

Clinical efficacy and safety of leflunomide combined with prednisone in the treatment of immunoglobulin A nephropathy / 中国基层医药

Objective To explore the clinical efficacy and safety of leflunomide combined with prednisone in the treatment of immunoglobulin A nephropathy.Methods 80 patients with IgA nephropathy were chosen and randomly divided into two groups,40 cases in each group.The control group was orally given prednisone(initial dose 1 mg · kg-1 · d-1),after 2 months of treatment 5mg/2 weeks reduction,and 10mg/d as maintenance therapy,while the observation group was treated with 20mg/d leflunomide treatment based on the treatment of control group.All the two groups had 3 months as a course of treatment.Before treatment and after treatment,the 24h urinary protein,serum albumin,serum creatinine,glomerular filtration rate,cholesterol,triglycerides,cystatin C levels and urinary vascular cell adhesion molecule-1 after treatment (urinary VCAM-1) and interleukin-18 (IL-8) in the two groups were recorded and compared,as well as the clinical efficacy and adverse reactions.Results The total effective rate in the observation group was 92.5％,which was significantly higher than 75.0％ in the control group (x2 =4.501,P ＜ 0.05).After treatment,the serum creatinine,serum albumin,cholesterol,triglycerides,cystatin C,24h urine protein,glomerular filtration rate and urinary VCAM-1,IL-8 in the two groups were all significantly improved (t ≥ 1.945,all P ＜ 0.05).After treatment,the cholesterol and triglycerides in the two groups had no significant differences (t =0.322,1.307,all P ＞ 0.05).After treatment,in the observation group,the serum creatinine,cystatin C,24h urinary protein excretion,VCAM-1 and IL-8 in urine were significantly lower than those in the control group,while serum albumin and glomerular filtration rate were significantly higher (t ≥2.632,all P ＜ 0.05).In the observation group,the total effective rate of Ⅳ,Ⅴ grade by Lee classification were significantly higher (x2 =4.269,4.600,all P ＜ 0.05).And in the two groups,the total effective rate of Ⅰ,Ⅱ grade by Lee classification had no statistically significant differences(x2 =0.000,0.000,all P ＞0.05).In the observation group,the incidence rate of adverse reaction was 10.0％,that in the control group was 8.6％,there was no statistically significant difference between the two groups (x2 =0.157,P ＞ 0.05).Conclusion Leflunomide combined with prednisone in the treatment of IgA nephropathy has better clinical efficacy and higher safety,its mechanism may be associated with decreased urinary VCAM-1 and serum IL-18 levels.

Complement System and Immunoglobulin A Nephropathy / 中国医科大学学报

Although immunoglobulin A (IgA) nephropathy (IgAN) is considered as an immune-mediated inflammatory disease,the pathogenesis and mechanisms associated with its progression have not been completely understood.To date,the potential pathogenesis of IgAN is thought to be a possible increase of galactose-deficient IgA1,followed by binding to antiglycan antibodies to form immune complexes,which are deposited in the glomerular mesangium and lead to the activation of complement pathways and initiation of immune-mediated inflammation.Activation of alternative and lectin complement pathways,complement components,and complement regulatory proteins play important roles in the pathogenesis and progression of IgAN.Complement components and complement regulatory factors in the renal tissue,urine,and serum samples are considered to be useful predictive biomarkers to evaluate the activation of the complement system and determine the prognosis of IgAN.The application of novel techniques such as the genome-wide association study would promote further research to determine the role and mechanisms of action of the complement system,whereby it could be used as a new therapeutic target for the management of IgAN.

Progress of microRNA-21 in kidney diseases / 国际儿科学杂志

MicroRNA(miRNA) is a class of small noncoding RNA molecules that regulate gene expression by functioning as a post-transcriptional regulatory factor basing on pairing with target mRNA,leading to mRNA cleavage or translation repression,and playing an important role in several fundamental biological and pathological processes.Consequently,nearly every biological process is related to miRNA.MicroRNA-21 is a typical miRNA,which has been found in recent years.It has been shown to participate in the development and prognosis of the pathogenesis of acute kidney injury,IgA nephropathy,renal cell carcinoma and other renal disea ses.Therefore,microRNA-21 may be a new target for the treatment of these diseases in the future.This paper reviews the correlative literature and research development regarding the roles of microRNA-21 in kidney disease,and providing references for diagnosis and treatment of kidney disease in the future.

Plasma endocan level and prognosis of immunoglobulin A nephropathy

BACKGROUND: Endocan, previously called endothelial cell–specific molecule-1, is a soluble proteoglycan that is secreted from vascular endothelial cells. Elevated plasma endocan levels were shown to be associated with poor cardiovascular outcomes in patients with chronic kidney disease (CKD). We investigated the clinical relevance of plasma and urine endocan levels in patients with immunoglobulin A nephropathy (IgAN). METHODS: Sixty-four patients with IgAN and 20 healthy controls were enrolled in this study. Plasma and urine endocan levels were measured. Clinical parameters, pathologic grades, and renal outcomes were compared among subgroups with different plasma and urine endocan levels. RESULTS: Both plasma and urine endocan levels were significantly higher in patients with IgAN than in controls. Elevated serum phosphorus and C-reactive protein were independent determinants for plasma endocan, and elevated C-reactive protein was also an independent determinant for urine endocan levels in multivariate analysis. Plasma endocan level was not significantly different across CKD stages, but patients with higher plasma endocan levels showed adverse renal outcome. Urine endocan levels were also elevated in patients with poor renal function. Cox proportional hazard models showed that high plasma endocan was an independent risk factor for CKD progression after adjusting for the well-known predictors of outcome in patients with IgAN. CONCLUSION: This study suggested that plasma endocan might be useful as a prognostic factor in patients with IgAN.

The correlation between human leukocyte antigens-A, B, DRB1 high-resolution alleles and chronic renal failure caused by immunoglobulin-a nephropathy / 中华器官移植杂志

Objective To investigate the correlation between human leukocyte antigens-A,-B,-DRB1 (HLA-A,-B,-DRB1) high resolution alleles and chronic renal failure (CRF) caused by immunoglobulin-a nephropathy (IgAN).Method The polymerase chain reaction-sequence-based typing (PCR-SBT) method was used to investigate the genotypes of HLA-A,-B and-DRB1 high-resolution alleles in 191 cases of CRF caused by IgAN (experimental group) and 503 healthy blood donors (control group).The alleles frequencies between two groups were compared and the association between CRF caused by IgAN and the polyrnorphism of HLA was analyzed.Result (1) There were 25 alleles at A locus,48 alleles at B locus and 32 alleles at DRB1 locus in experimental group.(2) The genetic frequency of HLAA * 2901 [Pc =0.033,OR =10.738,95％ CI (1.193,96.691)],HLA DRB1 * 1106 [Pc =0.0001,OR =0.969,95％ CI (0.944,0.994)],HLA-DRB1 * 1202[Pc =0.002,OR =1.859,95％ CI (1.259,2.745)],HLA-DRB1 * 1401 [Pc =0.021,OR =0.984,95％ CI (0.967,0.998)],HLA-DRB1 * 1602[Pc=0.015,OR=1.915,95％ CI (1.157,3.17)] in experimental group was higher than in control group (P＜0.05).Conclusion There is susceptibility association of HLA-A * 2901,HLA-DRB1 * 1106,HLA-DRE * 1202,HLA-DRB1 * 1401,HLA-DRB1 * 1602 with CRF caused by IgAN.It is concluded that there is a close genetic and immunological correlation between HLA alleles and the pathogenesis of CRF caused by IgAN.

Progress of Toll-like receptors and the pathogenesis of IgA nephropathy / 国际儿科学杂志

Immunoglobulin A nephropathy (IgAN),characterized pathologically by deposition of IgA complexes in the glomerular mesangium,is the most common form of primary glomerulo-nephritis in children and adolescents and is considered to be one of the important cause of end-stage renal failure.Abnormal immune factors become the research hotspot in recent years,but the specific pathogenesis has not yet been fully elucidated.Toll-like receptors are a family of receptors,which have been evolutionarily conserved to recognize pathogen-associated molecular patterns.Toll-like receptors do not only play an important role in activation of innate immune,but also regulate acquired immune,which is a bridge connecting the natural immune and acquired immune.Studies have shown that Toll-like receptors plays an important role in the process of occurrence and development of IgAN.This paper reviews its biological characteristics and the pathogenesis of IgA nephropathy.

Significado de la ubicación de los depósitos de igA (mesangio capilares versus mesangiales puros) en la nefropatía igA y su asociación con las variables morfológicas de la clasificación de Oxford y varios datos demográficos / Significance of igA deposits location (mesangiocapillary versus pure mesangial) in igA nephropathy and its association with morphologic variables of Oxford classification and various demographic data

Introducción: La nefropatía IgA se caracteriza por la presencia de depósitos glomerulares con predominio de IgA. Dentro de la descripción de la nefropatía IgA, existe una variación en la ubicación de los depósitos de inmunoglobulina A, desde el área mesangial hasta las paredes capilares. Objetivo: El objetivo de este estudio es determinar la posible correlación entre la ubicación de los depósitos de IgA y las variables morfológicas de la clasificación de Oxford (MEST, por sus siglas en inglés). Proliferación (hipercelularidad) mesangial (M) y endocapilar (E), glomeruloesclerosis(S) y atrofia tubular y fibrosis intersticial (T), y diversos datos clínicos de pacientes con nefropatía por inmunoglobulina. Métodos: El diagnóstico patológico de la nefropatía IgA requiere la demostración de depósitos inmunes con predominio de IgA con un patrón mesangial o mesangiocapilar a través de la microscopia por inmunofluorescencia (IF por su sigla en ingles). Los depósitos inmunes fueron semicuantificados con grados de fluorescencia de 0 a 3 cruces (+). La definición de la nefropatía por IgA requiere la presencia de depósitos de IgA difusos y globales con ≥ 2 + de fluorescencia y la ausencia de depósitos de C I q. Todas las biopsias renales realizadas entre julio del 2009 y julio de 2012, fueron enviadas a nuestro laboratorio de patología renal para analizarlas. Ninguno de los pacientes fue tratado antes de habérsele realizado la biopsia. Las biopsias con menos de 8 glomérulos fueron excluidas del estudio. Ninguno de los pacientes recibió un diagnóstico de nefropatía IgA, si había antecedentes de enfermedad vascular del colágeno o cirrosis hepática en los cuestionarios clínicos, los análisis de laboratorio o en el historial médico obtenidos al ingresar a los pacientes para realizarles la biopsia renal. Resultados: Un total de 114 biopsias fueron incluidas en el estudio. La edad media de los pacientes fue de 37,7 ± 13,6 años. Los pacientes se dividieron en dos grupos: depósitos puros mesangiales y depósitos mesangiocapilares. El número medio de glomérulos obtenidos por biopsia fue de 14,8 ± 7,2. El nivel medio de la proteinuria fue de 1742 ± 1324 mg /día (mediana = 1500 mg /día). En todas las biopsias, el número mediode glomérulos totalmente esclerosados fue de 2,4 ± 2,9 (mediana =1 glomérulo). Asimismo, la media del nivel de creatinina sérica fue de 1,6 ± 1,5 /dl (mediana = 1,2 mg / dl). En este estudio, el 10,5 por ciento de las biopsias renales tenían depósito de IgA mesangiocapilares. No se encontró ninguna asociación significativa entre la proporción de glomérulos totalmente esclerosados, la proliferación extracapilar, el porcentaje de fibrosis peri-glomerular, el engrosamiento de la cápsula de Bowman, el porcentaje de fibrosis intersticial, la proliferación mesangial de cualquier grado, o el ensanchamiento mesangial con depósitos mesangiales puros o depósitos mesangiocapilares (p≤ 0,05). No hubo ninguna asociación significativa entre la edad, la creatinina sérica y los niveles de proteinuria con depósitos mesangiales puros o mesangiocapilares (p≥0,05). Entre las cuatro variables morfológicas de la clasificación MEST de Oxford, únicamente la variable E (proliferación endocapilar) tuvo asociación significativa con depósitos mesangiocapilares (p=0,04) Conclusiones: La asociación entre depósitos mesangiocapilares IgA y la proliferación endocapilar puede implicar una mayor gravedad de la enfermedad por nefropatía IgA. Por lo tanto, se recomienda que la ubicación y la intensidad de los depósitos de IgA se incluyan de forma sistemática en los informes de biopsia renal.

Introduction: IgA nephropathy is characterized by the presence of IgA-dominant glomerular deposits. Within this description, there is variation in the location of this immunoglobulin, from mesangial area to capillary walls. Objectives: The aim of this study is to determine the potential correlation between the location of IgA deposits and morphologic variables of Oxford classification (MEST) and various clinical data of patients with immunoglobulin A nephropathy (IgAN). Results: A total of 114 biopsies were enrolled to the study. Mean age of patients was 37.7 ± 13.6 years. Patients were divided into two groups of pure mesagnial and mesangiocapillary deposits. In this study 10.5 percent of renal biopsies had mesangial-capillary IgA deposits. There was not significant association of proportion of totally sclerosed glomeruli, extracapillary, proliferation, percentage of peri-glomerular fibrosis, thickening of the Bowman’s capsule, perent of interstitial fibrosis, mesangial proliferation in any degree and mesangial widening with pure mesangial or mesangial- capillary deposits (p>0.05).There was not significant association of age, serum creatinine and levels of proteinuria with pure mesangial or mesangiocapillary deposits (p>0.05).Among four morphologic variables of Oxford classification only E variable (endocapillary proliferation) had significant association with mesangiocapillary deposits (P=0.04). Conclusion: The association of mesangiocapillary IgA deposits with endocapillary proliferation may imply the severity of the disease. We recommend that the location and intensity of IgA is routinely included in the renal biopsy report.

Clinical manifestations of IgA nephropathy combined with thin glomerular basement membrane nephropathy in children

BACKGROUND: Immunoglobulin A nephropathy (IgAN) and thin glomerular basement membrane nephropathy (TBMN) are the most common causes of persistent hematuria during childhood. The objective of this study is to determine the difference in clinicl features and laboratory findings between pediatric patients with IgA deposited TBMN and IgAN alone. METHODS: Between January 2000 and March 2009, 95 children were diagnosed with IgAN by renal biopsy. Clinical features and laboratory findings of patients with isolated IgAN and with IgAN plus TBMN were compared; the children diagnosed with IgAN were compared to 127 children who had been diagnosed with TBMN alone during the same period. RESULTS: There were 71 (74.7%) of a total 95 patients that were diagnosed with isolated IgAN (Group 1); in 24 (25.3%) of the 95 patients IgAN was combined with TBMN (Group 2). There was marked difference in the gender distribution between Group 2 and isolated TBMN patients. The degree of proteinuria and pathologic severity was higher in Group 1 compared with Group 2. Gross hematuria was present in both groups. There were no distinguishing features in the other laboratory parameters. CONCLUSION: Patients with both IgAN and TBMN seem to have similar clinical features to patients with isolated IgAN; however, the latter tend to have better pathologic and laboratory findings, compared to the patients with IgAN alone.

Hyperuricemia as a marker for progression of immunoglobulin A nephropathy

BACKGROUND: The variable clinical and histopathological manifestations of immunoglobulin A nephropathy (IgAN) make it difficult to predict disease progression. A recent study showed that hyperuricemia, a condition common in hypertension and vascular disease, may contribute to renal dysfunction and histological changes including renal arteriosclerosis, tubular atrophy, and interstitial fibrosis. Herein, we investigated the clinical significance of uric acid level at the time of biopsy, as a marker of IgAN progression. METHODS: We included 193 patients with biopsy-proven IgAN. Renal disease progression was defined as serum creatinine elevation above 1.2mg/dL or over 20% elevation from baseline. Hyperuricemia was defined as a serum uric acid level > or =7.3mg/dL in men and > or =5.3mg/dL in women, which were 1 standard deviation above the mean value in the normal subjects. RESULTS: The hyperuricemia group (n=50) had higher blood pressure, body mass index, and serum creatinine, and a greater amount of proteinuria and a lower glomerular filtration rate than the nonhyperuricemia group (n=143). Hyperuricemia increased the risk of IgAN progression (odds ratio, 4.53; 95% confidence interval, 1.31-15.66). The disease progression group (n=26) had a greater frequency of hyperuricemia, hypertension, and nephrotic range proteinuria than the nonprogression group (n=119). The renal survival analysis showed that the hyperuricemia group had a higher rate of IgAN disease progression. CONCLUSION: Hyperuricemia at the time of diagnosis is an important marker for IgAN progression.

A proton nuclear magnetic resonance-based metabonomics study of metabolic profiling in immunoglobulin a nephropathy

OBJECTIVES: Immunoglobulin A nephropathy is the most common cause of chronic renal failure among primary glomerulonephritis patients. The ability to diagnose immunoglobulin A nephropathy remains poor. However, renal biopsy is an inconvenient, invasive, and painful examination, and no reliable biomarkers have been developed for use in routine patient evaluations. The aims of the present study were to identify immunoglobulin A nephropathy patients, to identify useful biomarkers of immunoglobulin A nephropathy and to establish a human immunoglobulin A nephropathy metabolic profile. METHODS: Serum samples were collected from immunoglobulin A nephropathy patients who were not using immunosuppressants. A pilot study was undertaken to determine disease-specific metabolite biomarker profiles in three groups: healthy controls (N = 23), low-risk patients in whom immunoglobulin A nephropathy was confirmed as grades I-II by renal biopsy (N = 23), and high-risk patients with nephropathies of grades IV-V (N = 12). Serum samples were analyzed using proton nuclear magnetic resonance spectroscopy and by applying multivariate pattern recognition analysis for disease classification. RESULTS: Compared with the healthy controls, both the low-risk and high-risk patients had higher levels of phenylalanine, myo-Inositol, lactate, L6 lipids ( = CH-CH2-CH = O), L5 lipids (-CH2-C = O), and L3 lipids (-CH2-CH2-C = O) as well as lower levels of β -glucose, α-glucose, valine, tyrosine, phosphocholine, lysine, isoleucine, glycerolphosphocholine, glycine, glutamine, glutamate, alanine, acetate, 3-hydroxybutyrate, and 1-methylhistidine. CONCLUSIONS: These metabolites investigated in this study may serve as potential biomarkers of immunoglobulin A nephropathy. Point scoring of pattern recognition analysis was able to distinguish immunoglobulin A nephropathy patients from healthy controls. However, there were no obvious differences between the low-risk and high-risk groups in our research. These results offer new, sensitive and specific, noninvasive approaches that may be of great benefit to immunoglobulin A nephropathy patients by enabling earlier diagnosis.

15-Deoxy-Delta(12,14)-Prostaglandin J2 and Proinflammatory Cytokines in IgA Nephropathy / 대한신장학회지

PURPOSE: This study was performed to demonstrate a correlation among urinary 15d-PGJ2, proinflammatory cytokines (i.e. IL-23, IL-6, and TGF-beta1), and CRP, and to determinate the contributors to prognostic score and proteinuria in IgAN patients. METHODS: Fifty-four patients with biopsy-proven IgAN were enrolled. For comparison with IgAN, five MCD patients were also enrolled. Immunohistochemical staining for PPAR-gamma in kidney tissue and measurements of urinary IL-6, IL-23, TGF-beta1, 15d-PGJ2 and serum CRP were performed RESULTS: There was no difference according to PPAR-gamma staining. 15d-PGJ2 was negatively correlated with urinary IL-23, TGF-beta1, and CRP. Among proinflammatory cytokines and CRP, there were positive relationships with each other except for IL-23 and CRP. TGF-beta1 in the group having proteinuria more than 3 g/day was statistically higher than that in the sole hematuria group. However, in multivariate regression analysis, not a single relation was found between TGF-beta1 and proteinuria. Prognostic score was correlated with IL-6, IL-23, TGF-beta1, CRP, 15d-PGJ2, and 24hr proteinuria. 24hr proteinuria was correlated with IL-6 and 15d-PGJ2. In multivariate regression analysis, CRP, 15d-PGJ2, and 24hr proteinuria contributed to prognostic score, and only 15d-PGJ2 contributed to 24hr proteinuria. Last, urinary 15d-PGJ2 in IgAN was higher than that in MCD. CONCLUSION: Endogenous 15d-PGJ2 was associated with inflammation and might be considered as a material which could delay the damage of kidney in IgAN. In the future, larger cohort and long-term follow-up studies are needed to demonstrate the role of 15d-PGJ2 as prognostic indicator or marker of kidney damage.

Relationship between Clinical and Histological Features in Children with Immunoglobulin A Nephropathy / 实用儿科临床杂志

Objective To explore the relationship between clinical and histological features in children with immunoglobulin A(IgA) nephropathy(IgAN).Method Twenty-one children with IgAN were classified by clinical features,histological and immunological changes.The relationships among them were analyzed.Results IgAN occurred in boys more than girls with the ratio of 2.5∶1.Clinical feature manifested by asymptomatic hematuria(66.7%),hematuria with proteinuria(19.1%),nephrotic syndrome(4.7%),nephritic syndrome(9.5%).The grade Ⅲ(Hass M.classification) in pathological changes was commonly seen with more combined immunoglobulin deposit.Conclusions The incidence of IgAN increased followed by more renal biopsies in asymptomatic hematuria and proteinuria.Clinical features varied and involved all the kinds of glomerulonephritis.There are some relations between clinical and pathological features.Asymptomatic hematuria presented with mild histological changes achieved better outcome.The more proteinuria is always with more severity of histological changes,which should be diagnosed and treated early.

Comparison of Clinical Pathology in Children with Immunoglobulin A Nephropathy and Henoch - Schonlein Purpura Nephritis / 实用儿科临床杂志

Objective To explore the relationship of immunoglobulin A(IgA) nephropathy (IgAN) and Henoch - Schonlein purpura nephritis(HSPN) in children by making comparison in the aspects of clinical symptoms, laboratory tests and renal pathology. Methods Process the data of 69 cases of HSPN and 33 cases of IgAN respectively in clinical symptoms' frequency, indices of urinalysis and blood cell count, protein quantity in urine of 24 hours, serum level of immunoglobulins, C3 and C4, as well as renal pathologic results. Results In IgAN group, the incidence of male was higher than that of female, respiratory tract infections usually occur as prodrome. Macroscopic hematuria was the most prominent clinical feature, while rash, joint pain, abdominal symptoms seldom happened. Level of hemoglobin in IgAN group was decreased significantly. There were no significant differences in edema, hypertension, proteinuria degree, level of plasm albumin, level of serum IgA, IgG, IgM, IgE, C3 and C4, as well as the features of renal pathologic changes between IgAN and HSPN.Conclusions IgAN and HSPN have similar features in clinical symptoms,level of immunoglobulins and complements and renal pathology. But it is still under discussion whether they are different stages of the same disease.

The Effectiveness of the Serum IgA Level in Diagnosing IgA Nephropathy / 대한신장학회잡지

BACKGROUND: Immunoglogulin A(IgA) nephropathy is the most common primary glomerular disease throughout the world. 30-50% of patients with IgA nephropathy(IgAN) have high serum IgA concentrations. However, we do not know if the degree of elevation in IgA level increases the likelihood of having IgAN. Neither do we know if the IgA level has any association with pathological findings of IgAN. METHODS: We analyzed the relationships between IgAN and the levels of serum IgA which has been a routine part of the study in all patients with glomerulonephritis in our institution for the last 4 years. We reviewed 270 patients in whom the pathological diagnosis and the results of their IgA levels were both available. RESULTS: Of 80 patients who were IgA nephropathy, 26 patients(32.5%) had higher than normal cut- off value of serum IgA(385 mg/dL). In contrast, 8.9 % of patients with other types of glomerulonephropathies showed the values above normal(p<0.0001). The risk ratio for an increase of one unit of the IgA level was 1.0025(logistic regression, p=0.0043), which was increased to 1.0079 when patients with low complement levels were excluded from the analysis. The data were also analyzed according to the immunofluorescence microscopic findings of IgAN, which were found to have no significant correlation with IgA concentrations. CONCLUSION: The IgA level is a risk factor for IgAN throughout the whole range. However, it does not correlate with the IgA deposition in the renal tissue. We believe that this study will help understanding the interpretation of IgA levels in patients with IgAN.

Lymphocyte Subpopulations in Patients with Minimal Change Disease and IgA Nephropathy / 대한신장학회잡지

The pathogenetic mechanisms of minimal change disease and immunoglobulin A nephropathy remain uncertain, but recently various reports have reported the important role of the immunological aspect in the pathogenesis of glomerular injury. To assess the abnormalities of immunoregulatory system in these glomerular disease, the percentages of lymphocyte subpopulations in peripheral blood were studied in 24 cases of minimal change disease and 28 of immunoglobulin A nephropathy diagnosed by renal biopsy. The results were as follows: 1) CD4/CD8 ratio of the minimal change disease was significantly increased, compared with normal controls and immunoglobulin A nephropathy(P<0.05). 2) No significant difference in T helper cell and T suppressor cell was found between steroid response group and steroid non-response group in minimal change disease. 3) No significant difference in lymphocyte subpopulation was found between group with nephrotic range of proteinuria and group without nephrotic range of proteinuria in minimal change disease. 4) The discrepancies in lymphocyte subpopulations was not observed between group with infection and group without infection in immunoglobulin A nephropathy. 5) The pathologic grade (criteria of WHO) did not demonstrate a significant difference in lymphocyte subpopulation in immunoglobulin A nephropathy. In conclusion, these results suggest that the dysregulation of cell-mediated immunologic system is involved in the pathogenesis of minimal change disease and immunoglobulin A nephropathy, and some differences of immunoregulatory abnormalities between minimal change disease and immunoglobulin A nephropathy exist. But in this study the change in lymphocyte subpopulation does not anticipate the clinical course and prognosis of minimal change disease and immunoglobulin A nephropathy.

A PRELIMINARY PATHOLOGICAL STUDY OF IgA NEPHROPATHY-LIGHT-AND ELECTRON MICROSCOPIC OBSERVATION / 解放军医学杂志

In this study, renal biopsy specimens from 150 cases of IgA nephropathy were studied with light-and electron microscopically. Histological lesions from minimal change to diffuse mesangial proliferation were observed. According to the degree of the renal lesions, the 150 cases were divided into 6 subtypes. Proliferation of mesangial matrix was found to be the striking ultrastructural alteration, which often appeared as focal segmental or global proliferation of mesangial cells, as well as marked increase in mesangial matrix. Electron-dense deposits were largely localized in mesangial matrix and in suben dothelial regions. However, no positive correlation could be seen between the number of the deposits and the degree of the lesions.