FC 091URINARY CCL5 MRNA, A POTENTIAL BIOMARKER FOR PROGRESSION OF TYPE 2 DIABETIC NEPHROPATHY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Songtao Feng ◽  
Yueming Gao ◽  
Jingyuan Cao ◽  
Di Yin ◽  
Linli Lv ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Mrna Expression ◽  
Quantitative Pcr ◽  
Protein Level ◽  
Cox Regression ◽  
Urinary Protein ◽  
Hub Genes ◽  
Urinary Protein Level ◽  
Gene Modules

Abstract Background and Aims In recent years, it has been found that targeted mRNA detection of sediment cells in urine can be used as novel biomarkers for the diagnosis of diabetic nephropathy (DN). However, its value in predicting the progression of DN is not clear. The purpose of this study is to seek for urinary mRNA markers that evaluate the prognosis of DN through systems biological screening, clinical verification and prospective studies. Method GEO database and “Nephroseq” platform were searched, and the transcriptome data of DN glomeruli and tubules and their clinical information were obtained. Weighted gene co-expression network analysis (WGCNA) combined with gene ontology (GO) annotation and KEGG pathway enrichment analysis were used to screen the hub genes negatively related to eGFR, and the hub genes were used as candidate markers for mRNA detection in urine sediment in DN patients. A total of 91 patients with DN diagnosed by renal biopsy were included, and 60 patients with type 2 diabetes and 61 healthy people were selected as the control groups. The mRNA expression of candidate molecules was detected by Taqman probe quantitative PCR, and the correlation between mRNA expression and eGFR and urinary protein levels were analyzed. Patients with DN were followed up for a median time of 21 months, and the primary end point was defied as end stage renal disease or eGFR decreasing by more than 50%. Multivariate Cox regression was used to evaluate the value of mRNA in predicting DN progression. Results GSE30528 and GSE30529 datasets were selected for analysis, including mRNA expression data of 9 cases of DN and 13 cases of normal glomeruli; and 10 cases of DN and 12 cases of normal tubules respectively. The clinical data of the patients in this study, including gender, race, age and eGFR, were searched on the Nephroseq platform. The gene modules negatively related to eGFR were screened by WGCNA. GO and KEGG analysis showed that the main function of the gene modules in both datasets were related to the activation of inflammatory cells and chemokines pathway. Through the screening of hub genes and the comparison of expression levels, CCL5, CXCL1, CXCL6 and CXCL12 were finally obtained as candidate genes. Quantitative PCR showed that the levels of CCL5 and CXCL1 was significantly increased in DN group, CCL5 was negatively correlated with eGFR and positively correlated with urinary protein level, while CXCL1 was negatively correlated with eGFR, but had no significant correlation with urinary protein level. Multivariate Cox regression showed that eGFR, urinary protein level, degree of renal fibrosis and urinary CCL5 were independent risk factors of primary end point. Conclusion The activation of chemokine signal pathway in renal tissue is involved in the progression of DN. Urinary CCL5 mRNA can independently predict the prognosis of DN and may be served as a novel biomarker for the progression of DN.

scholarly journals Association between Sarcopenia and Renal Function in Patients with Diabetes: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Satoshi Ida ◽  
Ryutaro Kaneko ◽  
Kanako Imataka ◽  
Kazuya Murata
Keyword(s):  
Renal Function ◽  
Protein Level ◽  
Observational Studies ◽  
Meta Analysis ◽  
Albumin Level ◽  
Urinary Albumin ◽  
Urinary Protein ◽  
Urinary Protein Level ◽  
Patients With Diabetes ◽  
Meta Analyses

Previous studies involving patients with diabetes have indicated that sarcopenia is related to renal function. The objective of the present study was to investigate the association between sarcopenia and urinary albumin level, urinary protein level, and estimated glomerular filtration rate (eGFR) in patients with diabetes. A meta-analysis of observational studies was conducted. A literature search was performed using MEDLINE, Cochrane Controlled Trials Registry, and ClinicalTrials.gov. Data were extracted from studies investigating the association between sarcopenia and urinary albumin level, urinary protein level, and eGFR and by calculating odds ratio (OR) and 95% confidence intervals (CIs). Statistical analysis was performed using a random-effects model to calculate pooled OR and 95% CI. Six studies (2662 patients) that met the criteria were included in the meta-analysis. Sarcopenia was significantly associated with urinary albumin level with a pooled OR of 2.11 (95% CI, 1.55–2.88; P<0.001). The pooled ORs of the associations between sarcopenia and urinary protein level and decreased eGFR were 1.82 (95% CI, 1.13–2.92; P=0.01) and 3.75 (95% CI, 1.24–11.41), respectively. Sarcopenia was significantly associated with urinary albumin level, urinary protein level, and decreased eGFR. However, further investigations are needed, including meta-analyses with a larger number of studies.

scholarly journals Circulating Fibroblast Growth Factor 21 Levels Predict Progressive Kidney Disease in Subjects With Type 2 Diabetes and Normoalbuminuria

2015 ◽  
Vol 100 (4) ◽  
pp. 1368-1375 ◽  
Author(s):  
C. H. Lee ◽  
E. Y. L. Hui ◽  
Y. C. Woo ◽  
C. Y. Yeung ◽  
W. S. Chow ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Diabetic Nephropathy ◽  
Cox Regression ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Baseline Serum ◽  
Cox Regression Analysis ◽  
Egfr Decline

Background: Elevated fibroblast growth factor 21 (FGF21) levels have been suggested, from cross-sectional studies, as an indicator of subclinical diabetic nephropathy. We investigated whether serum FGF21 was predictive of the development of diabetic nephropathy. Method: Baseline serum FGF21 levels were measured in 1136 Chinese type 2 diabetic subjects recruited from the Hong Kong West Diabetes Registry. The role of serum FGF21 in predicting decline in estimated glomerular filtration rate (eGFR) over a median follow-up of 4 years was analyzed using Cox regression analysis. Results: At baseline, serum FGF21 levels increased progressively with eGFR category (P for trend &lt;.001). Among 1071 subjects with baseline eGFR ≥ 30 mL/min/1.73 m2, serum FGF21 levels were significantly higher in those with eGFR decline during follow-up (n = 171) than those without decline (n = 900) (P &lt; .001). In multivariable Cox regression analysis, baseline serum FGF21 was independently associated with eGFR decline (hazard ratio, 1.21; 95% confidence interval [CI], 1.01–1.43; P = .036), even after adjustment for baseline eGFR. In a subgroup of 559 subjects with baseline eGFR ≥60 mL/min/1.73 m2 and normoalbuminuria, serum FGF21 level remained an independent predictor of eGFR decline (hazard ratio, 1.36; 95% CI, 1.06–1.76; P = .016). Integrated discrimination improvement (IDI) suggested that the inclusion of baseline serum FGF21 significantly improved the prediction of eGFR decline (IDI, 1%; 95% CI, 0.1–3.0; P = .013) in this subgroup, but not in the initial cohort involving all subjects. Conclusions: Elevated serum FGF21 levels may be a useful biomarker for predicting kidney disease progression, especially in the early stages of diabetic nephropathy.

scholarly journals Interpretation of 24-Hour Urinary Protein Level for Diagnosis of Nephrotic Syndrome in Marked Hypoalbuminemia

2021 ◽  
Author(s):  
Raghvendra Narayan ◽  
Shivani Singh
Keyword(s):  
Nephrotic Syndrome ◽  
Serum Albumin ◽  
Protein Level ◽  
Urinary Protein ◽  
Mantoux Test ◽  
Laboratory Methods ◽  
X Ray ◽  
Urinary Protein Level ◽  
Chest X Ray ◽  
Nephrotic Range Proteinuria

Nephrotic syndrome is a common renal problem in childhood and is characterised by generalised oedema, massive proteinuria, hypoalbuminemia and hyperlipidemia. There are various laboratory methods to quantify proteinuria. Among them 24-hour urinary protein estimation is considered a gold standard for diagnosis of nephrotic syndrome. Nephrotic range proteinuria is considered when 24-hour urinary protein is more than 40 mg/m2/hr. There is scarce literature available regarding the changes in quantitative proteinuria when there is marked hypoalbuminemia (serum albumin less than 2.5 gm/dL). This series is about three patients of nephrotic syndrome (6 yers old male, 4 years old male and 5 years old male), having marked hypoalbuminemia and their 24-hour urinary protein level resulted into non-nephrotic range. All the patients underwent relevant physical, clinical examinations and laboratory blood and urine investigations(Haemoglobin, Mantoux test, chest x-ray, urine routine, urine culture and sensitivity, lipid profile, serum albumin and 24 hour urinary protein). All the cases were managed with Prednisolone and diuretics like Furosemide and were followed up till the subside of proteinuria and oedema conditions.

scholarly journals Henoch-Schönlein Nephritis Manifesting with Purpura 15 years after Diagnosis of IgA Nephropathy

2019 ◽  
Vol 2019 ◽  
pp. 1-3
Author(s):  
Hideaki Yamabe ◽  
Mitsuaki Kaizuka ◽  
Satoru Tsunoda ◽  
Tasuku Nagasawa ◽  
Kazuo Nomura ◽  
...  
Keyword(s):  
Abdominal Pain ◽  
Iga Nephropathy ◽  
Protein Level ◽  
Immunoglobulin A ◽  
Urinary Protein ◽  
Screening Tests ◽  
Iga Vasculitis ◽  
Protein Levels ◽  
Urinary Protein Level ◽  
Urinary Abnormalities

Henoch-Schönlein nephritis or immunoglobulin A (IgA) vasculitis is characterized by purpura, arthralgia, abdominal pain, and glomerulonephritis with glomerular IgA deposition. Notably, the presence of purpura is essential to diagnose this disease. We report the case of a patient in whom proteinuria and haematuria were detected during screening tests and he was diagnosed with IgA nephropathy at 20 years of age. Corticosteroids were administered for 7 years and were subsequently tapered. At 35 years of age, he noticed purpura on his lower extremities and was diagnosed with anaphylactoid purpura. Following the appearance of purpura, urinalysis revealed an increase in urinary protein levels from 0.7 g/g creatinine (Cr) to 1.4 g/gCr, and his serum Cr levels increased from 1.1 mg/dL to 1.35 mg/dL. Two months later purpura subsided, and his urinary protein level and serum Cr level were restored to the former levels. Although the cause remains unknown, an interval may occasionally be observed between the appearance of purpura and urinary abnormalities. However, to our knowledge to date, a 15-year interval is the longest interval, in such cases, reported in the literature.

P0971IDENTIFICATION OF HUB GENES ASSOCIATED WITH THE DEPOSITION OF EXTRACELLULAR MATRIX AND SPECIFIC FOR DIABETIC NEPHROPATHY BY WEIGHTED GENE CO-EXPRESSION NETWORK ANALYSIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Songtao Feng ◽  
Linli Lv ◽  
Gao Yueming ◽  
Cao Jingyuan ◽  
Di Yin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Diabetic Nephropathy ◽  
Network Analysis ◽  
Expression Level ◽  
Hub Genes ◽  
Hub Gene ◽  
Gene Screening ◽  
Gene Modules ◽  
Geo Database

Abstract Background and Aims Diabetic nephropathy (DN) and its most severe manifestation, end-stage renal disease (ESRD), remains one of the leading causes of reduced lifespan in people with diabetes. Identifying novel molecules that are involved in the pathogenesis of DN has both diagnostic and therapeutic implications. The gene co-expression network analysis (WGCNA) algorithm represents a novel systems biology approach that provide the approach of association between gene modules and clinical traits to find the module involvement into the certain phenotypic trait. The goal of this study was to identify hub genes and their roles in DN from the aspect of whole gene transcripts analysis. Method Various types of chronic kidney diseases (CKD), including DN, microarray-based mRNA gene expression data, listed in the Gene Expression Omnibus (GEO) database, were analyzed. Next, we constructed a weighted gene co-expression network and identified modules distinguishing DN from normal or other types of CKD by WGCNA. Functional annotations of the genes in modules specialized for DN were analyzed by Gene Ontology (GO) enrichment analysis. Through protein-protein interaction (PPI) analysis and hub gene screening, the hub genes specific for DN were obtained. Furthermore, we drew ROC curves to determine the diagnosis and differential diagnosis value to DN of hub genes. Finally, another study of microarray in the GEO database was selected to verify the expression level of hub genes and in the “Nephroseq” database, the correlation between the gene expression level and eGFR was analyzed. Results “GSE99339”, glomerular tissue microarray in 187 patients with a total of 10947 genes, was selected for analysis. After excluding the inappropriate cases, a total of 179 specimens were analyzed, including 14 cases of DN, 22 cases of focal segmental glomerulosclerosis (FSGS), 15 cases of hypertensive nephropathy (HT), 26 cases of IgA nephropathy (IgAN), 13 cases of minimal change disease (MCD), 21 cases of membranous nephropathy (MGN), 23 cases of rapidly progressive glomerulonephritis (RPGN), 30 cases of lupus nephritis (LN) and 14 cases of kidney tissue adjacent to tumor. Co-expression network analysis by WGCNA identified 23 distinct gene modules of the total 10947 genes and revealed “MEsaddlegreen” module was strongly correlated with DN (r=0,54), but not with other groups. GO functional annotation showed that these 64 genes in the “MEsaddlegreen” module mainly enriched in the deposition of extracellular matrix, which represents the specific and diagnostic pathophysiological process of DN. Further PPI and hub gene screening analysis revealed that LUM, ELN, FBLN1, MMP2, FBLN5 and FMOD can be served as hub genes, which had been proved to play an important role in the deposition of extracellular matrix. Furthermore, we found that the expression of hub genes was the highest in DN group and for the diagnosis value of DN by each gene, the area under the ROC curve is about 0.75∼0.95. The external verification of another study showed that compared with the normal control group, the expression of these hub genes was the highest in the DN group, and their expression level was negatively correlated with eGFR. Conclusion Using WGCNA and further bioinformatics approach, we identified six hub genes that appear to be identical to DN development. As such, they may represent potential diagnostic biomarkers as well as therapeutic targets with clinical utility.

scholarly journals Identification of Hub Genes Associated With Clinical Characteristics and Potential Therapy of Diabetic Nephropathy by Bioinformatics Analysis.

2020 ◽  
Author(s):  
Si Xu ◽  
Sha Wu ◽  
Min Yang ◽  
Xiaoning Li
Keyword(s):  
Extracellular Matrix ◽  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Bioinformatic Analysis ◽  
Molecular Therapy ◽  
Akt Signaling Pathway ◽  
Targeted Molecular Therapy ◽  
Hub Genes ◽  
Diagnostic Biomarkers ◽  
Gene Modules

Abstract Background: To provide molecular markers and potential targeted molecular therapy for diabetic nephropathy by screening hubgenes based on bioinformatic analysis. Results: We found 91 differentially expressed genes (DEGs) between diabetic nephropathy tissues and normal kidney tissues. Majority DEGs were significantly enriched in the extracellular matrix structural constituent, collagen-containing extracellular matrix. KEGG pathway analysis showed that most of DEGs participated in PI3K-Akt signaling pathway, AGE-RAGE signaling pathway in diabetic complications. Five high relevant sub-networks and the top 16 genes according to 12 topological algorithms were screened out and also five co-expressed gene modules were identified by WGCNA. Eventually, 5 hub genes were identified by taking the intersection which might be involved in the progression of DN. And 11 microRNAs were associated with related genes in WebGestalt. Conclusions: We identified five hub genes, namely COL1A2, COL6A3, COL15A1, CLU and LUM, and their related microRNAs(especially miR29 and miR196), which might be used as diagnostic biomarkers and therapeutic targets for diabetic nephropathy.

scholarly journals Correlational study of interleukin-6 with albuminuria in type 2 diabetes mellitus

2019 ◽  
Vol 7 (7) ◽  
pp. 2754
Author(s):  
Ganga Prasad Vaishya ◽  
Granth Kumar ◽  
Vijayavarman V. ◽  
Sanjeev Kumar Pandey ◽  
Arun Kumar ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Interleukin 6 ◽  
Chronic Kidney Failure ◽  
Urinary Protein ◽  
Low Grade ◽  
Cross Sectional ◽  
Mediators Of Inflammation ◽  
Diabetes Patients

Background: Individuals with type 2 diabetes display features of low-grade inflammation. Mediators of inflammation such as IL-6 have been proposed to be involved in the events causing as well as progression of diabetes. Diabetic nephropathy is one of the commonest causes of chronic kidney failure throughout the world. Although diabetic nephropathy is traditionally considered a non-immune disease, accumulating evidence now indicates that immunologic and inflammatory mechanisms play a significant role in its development and progression.Methods: This cross sectional study was conducted in the department of medicine, UPUMS, Saifai. The study was conducted from June 2018 to February 2019. A total of 80 type 2 diabetes patients were included in the study. After informed consent, patients were recruited. FBS, PPBS, HbA1C, 24 Hrs Urinary protein and interleukin-6 levels were measured. The data was analysed using SPSS 23. Pearson co relation co efficient was determined between IL -6, HbA1c and Urinary protein.Result: A total of 80 type 2 diabetes patients were studied. The study subjects were divided into 3 groups based on the urinary protein level into normo-albuminuria, Micro- albuminuria and macro- albuminuria. FBS, PPBS, HBA1c, 24 Hrs Urinary protein and Interleukin – 6 were significantly associated with proteinuria (p<0.001). Urinary protein was positively correlated with IL-6 (R2=0.57, p<0.01). The blood glucose was positively correlated with IL-6 (R2=0.413, p-0.01).Conclusion: Raised IL-6 levels in diabetics revealed the presence of inflammation. Our study showed positive correlation between IL-6, HBA1c and Urinary protein.

scholarly journals Urinary mRNA expression of ACE and ACE2 in human type 2 diabetic nephropathy

Diabetologia ◽  
2008 ◽  
Vol 51 (6) ◽  
pp. 1062-1067 ◽  
Author(s):  
G. Wang ◽  
F. M.-M. Lai ◽  
K.-B. Lai ◽  
K.-M. Chow ◽  
C.-H. B. Kwan ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Mrna Expression ◽  
Human Type ◽  
Type 2 Diabetic

P0504FACTORS ASSOCIATED WITH THE LONG-TERM RENAL OUTCOME OF IDIOPATHIC FOCAL SEGMENTAL GLOMERULOSCLEROSIS WITH NEPHROTIC SYNDROME

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
HIROAKI TANAKA ◽  
Takayuki Fujii ◽  
JUNYA KOSHIZAKA ◽  
NOBUAKI YAMAUCHI ◽  
MAYU MORIMOTO ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Protein Level ◽  
Roc Analysis ◽  
Hazard Analysis ◽  
Urinary Protein ◽  
Renal Outcome ◽  
Urinary Protein Level ◽  
Renal Prognosis ◽  
The Mean

Abstract Background and Aims In the treatment of idiopathic focal segmental glomerulosclerosis (FSGS) with nephrotic syndrome, the remission of proteinuria is considered to be an important goal. The partial remission of proteinuria improves renal survival, whereas it may progressively reduce the renal function. A study searched for a novel partial remission more accurately reflecting the long-term renal outcome. The goal of proteinuria reduction for improving the renal prognosis remains to be clarified. We examined factors associated with the long-term renal outcome of idiopathic FSGS. Method Of 148 patients with FSGS diagnosed based on kidney biopsy between 1981 and 2018, a retrospective cohort study was conducted involving 33 who had undergone immunosuppressive therapy for nephrotic syndrome, and had been followed-up for ≥1 year, excluding those with secondary FSGS. We examined the renal prognosis, regarding a 50% decrease in the estimated glomerular filtration rate (eGFR) as an outcome. We calculated the rate of decrease in the urinary protein level 4 and 8 months after the start of treatment, and estimated the rate of decrease associated with renal hypofunction using ROC analysis. Based on the results of ROC analysis, Cox’s proportional hazard analysis was performed using factors contributing to renal hypofunction as covariates. Results Concerning the background of the 33 patients, the mean follow-up period was 11.4 years, and there were 24 males. The mean age was 49.8 years, and the mean blood pressure was 100.5 mmHg. The mean urinary protein level, albumin (Alb) level, eGFR, and total cholesterol (TCho) level were 7.4 g/day, 2.1 g/dL, 44.3 mL/min/1.73 m2, and 369 mg/dL, respectively. Corticosteroid therapy was selected in 21 patients, whereas it was combined with steroid pulse therapy in 12. The daily dose of prednisolone was 37.3 mg. On ROC analysis, the rate of decrease in the urinary protein level after 4 months was 83.1% (AUC: 0.74, sensitivity: 0.80, specificity: 0.74), and that after 8 months was 85.7% (AUC: 0.78, sensitivity: 0.90, specificity: 0.65). Cox’s proportional hazard analysis, in which the data were adjusted with the sex, blood pressure, urinary protein level at the start of treatment, Alb level, eGFR, and treatment methods, showed that the rate of decrease in the urinary protein level after 4 months was significantly correlated with renal hypofunction: after 4 months: hazard ratio, 0.19 (95%CI: 0.04-0.77); p=0.0202; after 8 months: hazard ratio, 0.34 (95%CI: 0.05-1.37); p=0.1359. Conclusion In the treatment of idiopathic FSGS with nephrotic syndrome, the rate of decrease in the urinary protein level 4 months after the start of treatment was correlated with the long-term renal outcome.

scholarly journals The effect of common uromodulin variants on urinary protein level and gene transcription

2013 ◽  
Vol 84 (2) ◽  
pp. 410-411 ◽  
Author(s):  
Luca Rampoldi ◽  
Anna Köttgen ◽  
Olivier Devuyst
Keyword(s):  
Gene Transcription ◽  
Protein Level ◽  
Urinary Protein ◽  
Urinary Protein Level
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