Expression of vitamin D receptor in renal tissue of lupus nephritis and its association with renal injury activity

Lupus ◽  
2019 ◽  
Vol 28 (3) ◽  
pp. 290-294 ◽  
Author(s):  
J Sun ◽  
S Zhang ◽  
J S Liu ◽  
M Gui ◽  
H Zhang
Keyword(s):  
Vitamin D ◽  
Lupus Nephritis ◽  
Vitamin D Receptor ◽  
Activity Index ◽  
Renal Tissue ◽  
Renal Pathology ◽  
Renal Tumors ◽  
Control Group ◽  
Systemic Lupus ◽  
Chronicity Index

Objective Vitamin D receptor (VDR) has potent anti-inflammatory activities. VDR gene polymorphism has been linked with systemic lupus erythematosus (SLE). However, its expression in the kidney has not been evaluated. This study aimed to investigate the relationship between VDR expression and renal pathology as well as clinical manifestations in lupus nephritis (LN). Methods A total of 20 renal biopsy specimens from 35 patients with LN were classified according to the International Society of Nephrology/Renal Pathology Society 2003 LN-type standards pathological type, and the activity index and chronicity index were determined. Five normal renal tissue samples were obtained from surrounding areas distal to nephronophthisis or renal tumors (>2 cm). The expression of VDR was assessed by immunohistochemistry. The relationships between VDR expression and histological injury index, proteinuria and Systemic Lupus International Collaborating Clinics (SLICC) renal activity scores were analyzed. Results As compared to the control group, the expression of VDR in the LN group was lower ( p < 0.001) and negatively correlated with activity index (r = –0.548, p = 0.012) but not with chronicity index (r = –0.277, p = 0.236). The expression of VDR in renal tissue was also associated with SLICC renal activity scores (r = –0.470, p = 0.037). Conclusion The down-regulation of VDR expression in renal tissues of LN patients was negatively correlated with renal activity and injury severity.

scholarly journals MO076REGULATION OF DIFFERENTIAL CELLULAR RESPONSE TO OXIDATIVE STIMULI IN SYSTEMIC LUPUS ERYTHEMATOSUS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Corina-Daniela Ene ◽  
Mircea Penescu ◽  
Simona Roxana Georgescu ◽  
Mircea Tampa ◽  
Ilinca Nicolae
Keyword(s):  
Oxidative Stress ◽  
Lupus Nephritis ◽  
Disease Activity ◽  
Cellular Response ◽  
Oxidative Dna Damage ◽  
Molecular Mechanisms ◽  
Activity Index ◽  
Group Versus ◽  
Control Group ◽  
Systemic Lupus

Abstract Background and Aims Interaction of reactive oxygen species (ROS) with lipids, proteins, nucleic acids and hydro carbonates promotes acute and chronic tissue damage, mediates immunomodulation and triggers autoimmunity in systemic lupus erythematous (SLE) patients. The aim of the study was to determine the pathophysiological mechanisms of the oxidative stress-related damage and molecular mechanisms to counteract oxidative stimuli in lupus nephritis. Method Our study included 82 volunteers with SLE: 38 SLE volunteers with lupus nephritis (LN group) and 44 SLE volunteers without renal impairment (non-LN group) and a control group of 40 healthy volunteers. LN was diagnosed by histological exam (optic microscopy, electronic microscopy and immunofluorescence). Disease activity was measured by systemic SLE disease activity index (SLEDAI), urinary protein/creatinine ration, anti-dsDNA, C3, C4 and urinary β2-microglobulin. In the present paper, we evaluated in serum: Results We detected high lipid peroxidation, elevated oxidative DNA damage, excess accumulation of reactive carbonylic compounds, important oxidation of carbohydrates, disulphide bonds formation and high nitrotyrosination with statistically significant differences between groups, when compared LN and non-LN groups with control group. When compared LN and non-LN groups, our results showed: 3-Nitrotyrosine levels, the decrease of total and native serum thiols, pentosidine levels, sRAGE level and OGG1 activity correlated with disease activity markers in both LN and non-LN groups, while AGE correlated with disease activity only in non-LN group. Conclusion The cellular response to oxidative stimuli in SLE is concreted in the amplification of oxidative degradation of lipids, proteins, nucleic acid, hydro carbonates and in alteration of endogenous strategies for suppression /modulating oxidative stress. The defective DNA repair mechanism via OGG1 and the reduced regulatory effect of sRAGE in activation AGE-RAGE axis in LN group versus non-LN could explain alteration of renal architecture and development of renal injury.

scholarly journals Comparison of the 2018 and 2003 International Society of Nephrology/Renal Pathology Society classification in terms of renal prognosis in patients of lupus nephritis: a retrospective cohort study

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Ryosuke Umeda ◽  
Soshiro Ogata ◽  
Shigeo Hara ◽  
Kazuo Takahashi ◽  
Daijo Inaguma ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Renal Biopsy ◽  
International Society ◽  
Activity Index ◽  
Renal Pathology ◽  
Renal Outcome ◽  
Rank Test ◽  
Class Iii ◽  
Renal Prognosis ◽  
Chronicity Index

Abstract Background Although the 2018 revised International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification was proposed recently, until now, no reports have been made comparing the association of renal prognosis between the 2018 revised ISN/RPS classification and the 2003 ISN/RPS classification. The present study aimed to assess the usefulness, especially of activity and chronicity assessment, of the 2018 revised ISN/RPS classification for lupus nephritis (LN) in terms of renal prognosis compared to the classification in 2003. Methods We retrospectively collected medical records of 170 LN patients from the database of renal biopsy at Fujita Health University from January 2003 to April 2019. Each renal biopsy specimen was reevaluated according to both the 2003 ISN/RPS classification and the 2018 revised ISN/RPS classification. Renal endpoint was defined as a 30% decline of estimated glomerular filtration rate (eGFR). Results A total of 129 patients were class III/IV±V (class III, 44 patients; class IV, 35 patients; class III/IV+V, 50 patients). The mean age was 42 years, 88% were female, and the median observation period was 50.5 months. Renal prognosis was significantly different among the classes and significantly poor in the patients with higher modified National Institute of Health (mNIH) chronicity index (C index, ≥ 4) by a log-rank test (p = 0.05 and p = 0.02, respectively). By Cox proportional hazard models, only the C index was significantly associated with renal outcome (hazard ratio 1.32, 95% CI 1.11–1.56, p ≤ 0.01), while the classes, the 2003 activity and chronicity subdivision, and the mNIH activity index had no significant association with renal outcome. Each component of the C index was significantly associated with renal outcome in different models. Conclusion This study demonstrates that the 2018 revised ISN/RPS classification was more useful in terms of association with renal prognosis compared to the 2003 ISN/RPS classification.

scholarly journals Comparison of 2018 and 2003 International Society of Nephrology/Renal Pathology Society classification in terms of renal prognosis in patients of lupus nephritis: a retrospective cohort study.

2020 ◽  
Author(s):  
Ryosuke Umeda ◽  
Soshiro Ogata ◽  
Shigeo Hara ◽  
Kazuo Takahashi ◽  
Daijo Inaguma ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Renal Biopsy ◽  
International Society ◽  
Activity Index ◽  
Renal Pathology ◽  
Renal Outcome ◽  
Rank Test ◽  
Class Iii ◽  
Renal Prognosis ◽  
Chronicity Index

Abstract Background: Although 2018 revised ISN/RPS classification was proposed recently, until now, no reports have been made comparing the association of renal prognosis between 2018 revised ISN/RPS classification and 2003 ISN/RPS classification. The present study aimed to assess the usefulness, especially of activity and chronicity assessment, of the 2018 revised International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification for lupus nephritis (LN) in terms of renal prognosis compared to the classification in 2003.Methods: We retrospectively collected medical records of 170 LN patients from the database of renal biopsy in Fujita Health University from January 2003 to April 2019. Each renal biopsy specimen was reevaluated according to both the 2003 ISN/RPS classification and the 2018 revised ISN/RPS classification. Renal endpoint was defined as 30% decline of estimated glomerular filtration rate (eGFR). Results: A total 129 patients were class III/IV±V (class III, 44 patients; class IV, 35 patients; class III/IV+V, 50 patients). Mean age was 42 years, 88% were female, and median observation period was 50.5 months. Renal prognosis was significantly different among the classes, and significantly poor in the patients with higher modified National Institute of Health (mNIH) Chronicity index (C index, ≥4) by a log-rank test (p=0.05, p=0.02 respectively). By Cox proportional hazard models, only C index was significantly associated with renal outcome (Hazard Ratio; 1.32, 95% CI; 1.11-1.56, p≤0.01), while the classes, the 2003 activity and chronicity subdivision, and mNIH activity index had no significant association with renal outcome. Each component of C index was significantly associated with renal outcome in different models. Conclusion: This study demonstrates that the 2018 revised ISN/RPS classification was more useful in terms of association with renal prognosis compared to the 2003 ISN/RPS classification

THE CLINICAL, LABORATORY MANIFESTATIONS AND HISTOPATHOLOGY IN NEPHROTIC PATIENTS WITH LUPUS NEPHRITIS

2018 ◽  
pp. 52-58
Author(s):  
Le Thuan Nguyen ◽  
Bui Bao Hoang
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Clinical Laboratory ◽  
Activity Index ◽  
Clinical Manifestations ◽  
Systemic Lupus ◽  
Cross Sectional ◽  
Organ Systems ◽  
Tubulointerstitial Lesions

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organ systems. The kidney appears to be the most commonly affected organ, especially nephrotic is a serious kidney injury. The clinical, laboratory manifestations and histopathology are very useful for diagnosis, provide the means of predicting prognosis and guiding therapy in nephrotic patients with lupus nephritis. Methods: Descriptive cross-sectional study of nephrotic patients with lupus treated in the Department of Nephrology Trung Vuong Hospital and Cho Ray Hospital between May/2014 and May/2017. Renal histopathological lesions were classified according to International Society of Nephrology/Renal Pathology Society - ISN/RPS ’s 2003. The clinical, laboratory manifestations and histopathological features were described. Results: Of 32 LN with nephritic range proteinuria cases studied, 93.7% were women. The 3 most common clinical manifestations were edema (93.8%), hypertension (96.8%) and pallor (68.9%), musculoskeletal manifestions (46.9%), malar rash (40.6%). There was significant rise in laboratory and immunological manifestions with hematuria (78.1%), Hb < 12g/dL (93.5%), increased Cholesterol (100%), and Triglycerid (87.5%), Creatinine > 1.4 mg/dL (87.5%), increased BUN 71.9%, ANA (+) 93.8%, Anti Ds DNA(+) 96.9%, low C3: 96.9%, low C4: 84.4%. The most various and severe features were noted in class IV with active tubulointerstitial lesions and high activity index. Conclusion: Lupus nephritis with nephrotic range proteinuria has the more severity of histopathological feature and the more severity of the more systemic organ involvements and laboratory disorders were noted. Key words: Systemic lupus, erythematosus (SLE) lupus nepphritis, clinical

Impact of markers of endothelial injury and hypercoagulability on systemic lupus erythematosus

Lupus ◽  
2020 ◽  
Vol 29 (2) ◽  
pp. 182-190
Author(s):  
W Batista Cicarini ◽  
R C Figueiredo Duarte ◽  
K Silvestre Ferreira ◽  
C de Mello Gomes Loures ◽  
R Vargas Consoli ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Disease Activity Index ◽  
Endothelial Injury ◽  
Control Group ◽  
Systemic Lupus ◽  
Low Concentrations ◽  
The Relationship

We have explored the relationship between possible hemostatic changes and clinical manifestation of the systemic lupus erythematosus (SLE) as a function of greater or lesser disease activity according to Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) criteria. Endothelial injury and hypercoagulability were investigated in patients with SLE by measuring thrombomodulin (TM), D-dimer (DDi) and thrombin generation (TG) potential. A total of 90 participants were distributed into three groups: 1) women with SLE presenting with low disease activity (laSLE) (SLEDAI-2K ≤ 4), 2) women with SLE presenting with moderate to high disease activity (mhaSLE) (SLEDAI-2K > 4), and 3) a control group comprising healthy women. Levels of TM and DDi were higher both in the laSLE and mhaSLE groups compared to controls and in mhaSLE compared to the laSLE group. With respect to TG assay, lagtime and endogen thrombin potential, low concentrations of tissue factor provided the best results for discrimination among groups. Analysis of these data allow us to conclude that TM, DDi and TG are potentially useful markers for discriminating patients with very active from those with lower active disease. Higher SLE activity may cause endothelial injury, resulting in higher TG and consequently a hypercoagulability state underlying the picture of thrombosis common in this inflammatory disease.

scholarly journals Effect of vitamin D supplementation on disease activity (SLEDAI) and fatigue in Systemic Lupus Erythematosus patients with hipovitamin D: An Open Clinical Trial

2018 ◽  
Vol 8 (2) ◽  
Author(s):  
Achmad Rifa’i ◽  
Handono Kalim ◽  
Kusworini Kusworini ◽  
Cesarius Singgih Wahono
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Clinical Trial ◽  
Vitamin D ◽  
Placebo Group ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Vitamin D Supplementation ◽  
Control Group ◽  
Systemic Lupus ◽  
Significant Difference

Background : Low level of vitamin D impact the disease activity and the degree of fatigue in SLE patients. This study aims to determine the effect of vitamin D supplementation on disease activity and fatigue condition in Systemic Lupus Erythematosus (SLE) patients with hipovitamin D.Methods: We performed an open clinical trial. Subjects were randomized into two different groups (supplementation or placebo) using simple random sampling. The treatment group got vitamin D3 softgel/ cholecalciferol 1200 IU/day or 30 mg/day, while the control group gotplacebo for 3 months. SLEDAI scores and FSS scores were calculated at pre and posttreatment.Results: There were 20 subjectsfor supplementation group and 19 subjects in the placebo group. From this study, before and after treatment, we found a significant difference of mean level of vitamin D in supplementation group (p=0.000), and no significant difference inpatients with placebo (p=0.427). Moreover, from the SLEDAI score analysis, observed a significant difference bothin the supplemented group (p=0.000) and the placebo group (p=0.006). FSS scores significantly different in the supplemented group (p=0.000). Incorrelation test,there was a negative correlation (r=-0763) between vitamin D level and disease activity (SLEDAI), and both showing stastistical significance between thepre supplementation (p=0.000) and post supplementation (r=-0846; p=0.000). Similarly to theFSS scores, there was a meaningfulnegative correlation (r=-0.931, p=0.000) between the level of vitamin D with FSS scores pre and post supplementation (r=-0.911; p= 0.000). Furthermore, there was a significant correlation between disease activity (SLEDAI) pre supplementation with fatigue condition pre supplementation (r=0.846; p = 0.000) and postsupplementation (r=0.913; p= 0.000).Conclusion: The supplementation of vitamin D 1200 IU per day in patients with SLE improve disease activity and degree of fatigue. Keywords: vitamin D, disease activity, fatigue, SLE

scholarly journals THE ASSOCIATION OF AРAI-POLYMORPHISM OF VITAMIN D RECEPTOR GENE (VDR) WITH DEVELOPMENT OF GENERALIZED PARODONTITIS IN UKRAINIAN POPULATION

2019 ◽  
Vol 72 (7) ◽  
pp. 1253-1257
Author(s):  
Ilia G. Fomenko ◽  
Viktoriia Yu. Harbuzova ◽  
Olha A. Obukhova ◽  
Vladislav V. Pohmura ◽  
Inna A. Plakhtiienko ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Receptor Gene ◽  
Smoking Habit ◽  
Binary Logistic Regression ◽  
Control Group ◽  
Vitamin D Receptor Gene ◽  
Vdr Gene ◽  
Comparison Groups ◽  
Relationship Of

Introduction: At present, it is believed that the genetic component is important in the pathogenesis of periodontitis. One of the candidate genes that are of major importance in the development of the disease is the vitamin D receptor gene (VDR). The association of its genetic polymorphisms, in particular Apal, with periodontitis in different populations of the world is proved. The aim: To study the association of the Apal-polymorphism VDR gene with the development of generalized periodontitis in the Ukrainian population. Materials and methods: Patient genotypes were determined by polymerase chain reaction with subsequent analysis of restriction fragment length (PCR-RFLP) from buccal epithelium 116 patients with generalized periodontitis (GP) and 67 individuals of control group. Statistical analysis was performed by using SPSS-17,0 program. Results: As a result of the performed studies, it was shown that in the group of patients with GP, the ratio of homozygous for the main allele (a/a), heterozygote (a/A) and homozygote for the minor allele (A/A) was 26 (22,4%), 62 (53,4%), 28 (24,2%), and in control group – 25 (37,3%), 27 (40,3%), 15 (22,4%), respectively. The distribution of genotypes in the comparison groups was not statistically significant (P = 0,084). By the method of binary logistic regression in the framework of the additive inheritance model (a/A vs a/a), a reliable relationship of the genotype with the Apal-polymorphism of the VDR gene was established with the development of generalized periodontitis (Р=0,029). It was shown that in heterozygotes (a/A) the risk of GP in 2,208 (95% CI = 1,084-4,496) times is higher than in homozygotes of the main allele (a/a). After adjusting for age, sex, smoking habit, BMI, the reliability of these results was maintained (P = 0,030). Conclusions: The ApaI-polymorphism of the VDR gene is associated with the development of generalized periodontitis in the Ukrainian population.

scholarly journals Vitamin D receptor expression in SLE peripheral blood CD4+T cells is associated with disease activity and cell apoptosis

2021 ◽  
Author(s):  
Ying Zhang ◽  
Lingying Niu ◽  
Fan Wang ◽  
Xiaojun Tang ◽  
Chun Wang ◽  
...  
Keyword(s):  
Vitamin D ◽  
T Cells ◽  
Disease Activity ◽  
Vitamin D Receptor ◽  
Cell Apoptosis ◽  
Cd4 T Cells ◽  
Activity Index ◽  
Receptor Expression ◽  
Th2 Cells ◽  
Tfh Cells

ABSTRACT Objectives Systemic lupus erythematosus (SLE) is characterised by accumulated cell apoptosis. Vitamin D receptor (VDR) has immunomodulatory effect and potent anti-apoptosis activities. The aim of this study was to examine the correlation between CD4+T cells VDR expression, cell apoptosis, and disease activity in patients with SLE. Methods Forty-five SLE patients were recruited and 50 healthy individuals served as controls. The expression of VDR in CD4+T cells and their subsets were determined by flow cytometry. The correlations between VDR expression and cell apoptosis or disease parameters in SLE patients were analysed. Results VDR expression in CD4+T cells and their subsets were upregulated in SLE patients, especially in help T (Th)1, regulatory T (Treg), and follicular helper T (Tfh) cells. Frequency of VDR-positive CD4+T cells was positively associated with SLE disease activity index (SLEDAI)-2K values and inversely correlated with serum C3 concentration. The frequency of VDR-positive CD4+T cells, Th1 cells, Th2 cells, Th17 cells, Treg cells, and Tfh cells was positively correlated with cells apoptosis. Conclusion VDR expression in CD4+T cells and their subsets were increased in SLE. VDR expression was positively associated with disease activity and cell apoptosis in SLE patients.

scholarly journals Change of Renal Gallium Uptake Correlated with Change of Inflammation Activity in Renal Pathology in Lupus Nephritis Patients

2021 ◽  
Vol 10 (20) ◽  
pp. 4654
Author(s):  
Tsu-Yi Hsieh ◽  
Yi-Ching Lin ◽  
Wei-Ting Hung ◽  
Yi-Ming Chen ◽  
Mei-Chin Wen ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Left Kidney ◽  
Renal Pathology ◽  
Class Iii ◽  
Stage Renal Disease ◽  
End Stage ◽  
Active Inflammation ◽  
Histological Results

Background: Lupus nephritis (LN) often lead to end-stage renal disease in systemic lupus erythematosus patients. This study aimed to investigate the clinical application of renal gallium-67 scans for determining renal histological parameters in LN patients. Methods: Between 2006 and 2018, 237 biopsy-proven and 35 repeat biopsies LN patients who underwent renal gallium scans before or after biopsy were included for analysis. The classification and scoring of LN were assessed according to the International Society of Nephrology/Renal Pathology Society. A delayed 48-h gallium scan was performed and interpreted by semiquantitative methods using left kidney/spine (K/S) ratio. The renal histological results were compared with gallium uptake. Results: Out of 237 participants, 180 (76%) had proliferative LN. Baseline gallium left K/S ratio was significantly higher in class IV LN as compared to class III (median (interquartile range, IQR): 1.16 (1.0–1.3), 0.95 (0.9–1.1), respectively, p < 0.001). Furthermore, changes in gallium uptake between two biopsies were positively correlated with changes activity index (r = 0.357, p = 0.035), endocapillary hypercellularity (r = 0.385, p = 0.032), and neutrophils infiltration (r = 0.390, p = 0.030) in renal pathology. Conclusions: Renal gallium uptake is associated with active inflammation in LN. Changes in renal gallium uptake positively correlated with changes in activity index in renal pathology.

scholarly journals Analysis of Vitamin D Receptor Gene Polymorphism in Chronic Periodontitis among Saudi Population

2021 ◽  
Vol 2 (01) ◽  
pp. 12-16
Author(s):  
Fathy M. Elfasakhany ◽  
Omaima N. Al-Qahtani ◽  
Asmaa M. Badri ◽  
Hala A. Abuelela
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Receptor Gene ◽  
Equilibrium Analysis ◽  
Plaque Index ◽  
Control Group ◽  
Saudi Population ◽  
Bleeding On Probing ◽  
Probing Depth ◽  
The Mean

Abstract Objective Genetic and environmental factors have important roles in the development of periodontitis. We aimed to assess the relation of vitamin D receptor (VDR) ApaI and TaqI polymorphisms and the susceptibility of periodontitis in Saudi population in Makkah region. Materials and Methods In total, 86 unrelated patients with moderate-to-severe periodontitis and 86 controls were enrolled in this study. Evaluation of the periodontal state was performed by using plaque index, bleeding on probing, probing depth, and attachment loss. Extraction of genomic DNA from peripheral blood and genotyping of VDR gene ApaI G/T (rs7975232) and TaqI T/C (rs731236) polymorphisms were performed by utilizing polymerase chain reaction and restriction digestion. Results There were statistically significant differences between both groups regarding the mean bleeding on probing, mean probing depth, mean plaque index, and the mean attachment level (p < 0.001) indicating that the matching based on the investigated groups was adequate. The examined populations were in Hardy-Weinberg equilibrium. Analysis of the genotype and allele frequencies of both VDR ApaI and TaqI single nucleotide polymorphisms revealed that they were statistically indifferent between the control group and the periodontitis subjects (p> 0.05). Conclusion These results suggested that VDR ApaI and TaqI polymorphisms might not be related to the susceptibility of periodontal disease in the Saudi subjects in Makkah region.

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