In Diabetic Kidney Disease Urinary Exosomes Better Represent Kidney Specific Protein Alterations Than Whole Urine

2015 ◽  
Vol 42 (6) ◽  
pp. 418-424 ◽  
Author(s):  
Krishnamurthy P. Gudehithlu ◽  
Ignacio Garcia-Gomez ◽  
Jane Vernik ◽  
Carolyn Brecklin ◽  
Mark Kraus ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Structural Changes ◽  
Sandwich Elisa ◽  
Kidney Tissue ◽  
Protein Markers ◽  
Gelatinase Activity ◽  
Diabetic Kidney ◽  
Urinary Exosomes ◽  
Whole Urine

Background: Predicting or diagnosing underlying kidney disease by analyzing whole urine remains the mainstay of nephrology practice. However, whole urine is a poor compartment to assess many structural changes in the kidney because whole urine contains only a few proteins derived from the kidney itself. Urinary exosomes, on the other hand, which are derived from the kidney, contain proteins secreted by the kidney. We experimentally tested the hypothesis that ‘urinary exosomes more faithfully represent changes in the kidney tissue than whole urine'. A direct comparison between whole urine and urine exosomal levels of two chosen kidney disease markers, gelatinase and ceruloplasmin, was carried out on diabetic kidney disease patients. Methods: Urinary exosomes were separated from whole urine by sequential centrifugation including ultra-centrifugation. Gelatinase activity was measured using fluorosceinated gelatin as the substrate, and ceruloplasmin was measured by sandwich ELISA. A few kidney specimens from patients biopsied for atypical features were histochemically stained for validation of the biochemical results. Results: We found that changes in both, gelatinase (decreased activity) and ceruloplasmin (increased levels), in the urinary exosomes of diabetic kidney patients were in agreement with the alterations of these two proteins in the kidney tissue. In contrast, the levels of these two proteins in whole urine were highly variable and did not correlate with levels in the diabetic kidney tissue. Conclusion: In conclusion, these results confirmed our hypothesis that protein markers in urinary exosomes better reflected the underlying protein changes in the kidney than in whole urine samples.

scholarly journals Extracellular vesicle-derived AEBP1 mRNA as a novel candidate biomarker for diabetic kidney disease

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yiying Tao ◽  
Xing Wei ◽  
Yue Yue ◽  
Jiaxin Wang ◽  
Jianzhong Li ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Kidney Tissue ◽  
Extracellular Vesicle ◽  
Clinical Parameter ◽  
Diagnostic Efficacy ◽  
Diabetic Kidney ◽  
Efficacy Assessment ◽  
Novel Biomarkers ◽  
And Control

Abstract Background A novel and improved methodology is still required for the diagnosis of diabetic kidney disease (DKD). The aim of the present study was to identify novel biomarkers using extracellular vesicle (EV)-derived mRNA based on kidney tissue microarray data. Methods Candidate genes were identified by intersecting the differentially expressed genes (DEGs) and eGFR-correlated genes using the GEO datasets GSE30528 and GSE96804, followed by clinical parameter correlation and diagnostic efficacy assessment. Results Fifteen intersecting genes, including 8 positively correlated genes, B3GALT2, CDH10, MIR3916, NELL1, OCLM, PRKAR2B, TREM1 and USP46, and 7 negatively correlated genes, AEBP1, CDH6, HSD17B2, LUM, MS4A4A, PTN and RASSF9, were confirmed. The expression level assessment results revealed significantly increased levels of AEBP1 in DKD-derived EVs compared to those in T2DM and control EVs. Correlation analysis revealed that AEBP1 levels were positively correlated with Cr, 24-h urine protein and serum CYC and negatively correlated with eGFR and LDL, and good diagnostic efficacy for DKD was also found using AEBP1 levels to differentiate DKD patients from T2DM patients or controls. Conclusions Our results confirmed that the AEBP1 level from plasma EVs could differentiate DKD patients from T2DM patients and control subjects and was a good indication of the function of multiple critical clinical parameters. The AEBP1 level of EVs may serve as a novel and efficacious biomarker for DKD diagnosis.

MO636THE ROLE OF DIFFUSION-WEIGHTED MRI AND APPARENT DIFFUSION COEFFICIENT IN ASSESSMENT OF DIABETIC KIDNEY DISEASE: PRELIMINARY EXPERIENCE STUDY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Mohamed Taha
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Structural Changes ◽  
University Hospital ◽  
Poor Correlation ◽  
Diabetic Patients ◽  
Healthy Controls ◽  
Adc Value ◽  
Diabetic Kidney ◽  
Adc Values

Abstract Background and Aims Diabetic kidney disease is the most common cause of ESRD. There is poor correlation between the degree of renal fibrosis and current screening markers. A noninvasive imaging technique is needed to assess the degree of structural changes in the kidney. Method Forty adult diabetic patients with chronic kidney disease as well as 20 age- and sex-matched adult healthy controls were recruited from Nephrology Department of our University Hospital. All patients underwent renal MR-DWI and ADC mapping on a 1.5-T scanner (Philips Achieva) using phased array body coil. Results Among the studied 40 diabetic patients, five groups of patients were resulted 8 patients for each and the ADC values were inversely correlated with advancement in renal parenchymal affection, ie, in late stages of the disease the ADC values were lower than in early stages. The mean ADC values of renal parenchyma in patients with diabetic kidney disease were considerably lower than that of healthy controls with normal renal function (2.1± 0.3x10− 3 mm2/s vs 2.4± 0.1x10− 3 mm2/s with p< 0.001). Conclusion ADC value is a possible noninvasive technique in evaluating the stage of renal dysfunction with assessment of disease progression.

scholarly journals Cerebral Structural Changes in Diabetic Kidney Disease: African American–Diabetes Heart Study MIND

Diabetes Care ◽  
2014 ◽  
Vol 38 (2) ◽  
pp. 206-212 ◽  
Author(s):  
Kaycee M. Sink ◽  
Jasmin Divers ◽  
Christopher T. Whitlow ◽  
Nicholette D. Palmer ◽  
S. Carrie Smith ◽  
...  
Keyword(s):  
African American ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Structural Changes ◽  
Diabetic Kidney ◽  
Heart Study ◽  
Diabetes Heart Study

scholarly journals FcER1: A Novel Molecule Implicated in the Progression of Human Diabetic Kidney Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Swastika Sur ◽  
Mark Nguyen ◽  
Patrick Boada ◽  
Tara K. Sigdel ◽  
Hans Sollinger ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Target Genes ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Rational Drug Design ◽  
Transcriptional Analysis ◽  
Peripheral Blood Mononuclear ◽  
Tissue Samples ◽  
Diabetic Kidney

Diabetic kidney disease (DKD) is a key microvascular complication of diabetes, with few therapies for targeting renal disease pathogenesis and progression. We performed transcriptional and protein studies on 103 unique blood and kidney tissue samples from patients with and without diabetes to understand the pathophysiology of DKD injury and its progression. The study was based on the use of 3 unique patient cohorts: peripheral blood mononuclear cell (PBMC) transcriptional studies were conducted on 30 patients with DKD with advancing kidney injury; Gene Expression Omnibus (GEO) data was downloaded, containing transcriptional measures from 51 microdissected glomerulous from patients with DKD. Additionally, 12 independent kidney tissue sections from patients with or without DKD were used for validation of target genes in diabetic kidney injury by kidney tissue immunohistochemistry and immunofluorescence. PBMC DKD transcriptional analysis, identified 853 genes (p < 0.05) with increasing expression with progression of albuminuria and kidney injury in patients with diabetes. GEO data was downloaded, normalized, and analyzed for significantly changed genes. Of the 325 significantly up regulated genes in DKD glomerulous (p < 0.05), 28 overlapped in PBMC and diabetic kidney, with perturbed FcER1 signaling as a significantly enriched canonical pathway. FcER1 was validated to be significantly increased in advanced DKD, where it was also seen to be specifically co-expressed in the kidney biopsy with tissue mast cells. In conclusion, we demonstrate how leveraging public and private human transcriptional datasets can discover and validate innate immunity and inflammation as key mechanistic pathways in DKD progression, and uncover FcER1 as a putative new DKD target for rational drug design.

scholarly journals The potential effects of dietary flavones on diabetic nephropathy; a review of mechanisms

2020 ◽  
Vol 9 (2) ◽  
pp. e09-e09
Author(s):  
Lida Menati ◽  
Amirhosein Meisami ◽  
Mitra Zarebavani
Keyword(s):  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Kidney Tissue ◽  
Experimental Models ◽  
Antioxidant Systems ◽  
Protective Effects ◽  
Diabetic Kidney ◽  
Natural Agents ◽  
Patients With Diabetes

Diabetes as a chronic metabolic disorder affects the worldwide population with high incidence of morbidity and mortality. Different complications such as nephropathy, neuropathy, ocular diseases, and cardiovascular disease are common in patients with diabetes that threaten the patient’s lifestyle. Diabetic nephropathy (DN) usually is related to some major structural alterations in the kidney which characterized by generation of toxic reactive oxygen species (ROS) or inhibition of antioxidant systems in kidney tissue. Different natural agents have been introduced to be used as a complementary treatment to prevent diabetic kidney disease. Flavones (apigenin, luteolin, nobiletin and chrysin) as a subgroup of flavonoids are natural occurring substances which have several pharmacological activates, including antioxidant, antiapoptotic, anti-inflammatory, and anti-tumor efficacy. Recent evidence indicated that flavones may be effective for prevention and treatment of diabetes complications in experimental models. The present study was designed to review the relationship between flavones administration and diabetes and diabetic kidney disease by focusing on the possible molecular pathway. The findings indicate that flavones have protective effects against diabetic kidney disease by modulation of different pathways related to oxidative stress, inflammation, and apoptosis in animal models. Therefore, more clinical investigations are suggested to be conducted to find the protective effects of flavones in patients with diabetes.

scholarly journals Identification of VCAN as Hub Gene for Diabetic Kidney Disease Immune Injury Using Integrated Bioinformatics Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Qiannan Xu ◽  
Binjue Li ◽  
Yucheng Wang ◽  
Cuili Wang ◽  
Shi Feng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Expression Profiles ◽  
Kidney Tissue ◽  
Gene Expression Profiles ◽  
Online Database ◽  
Hub Gene ◽  
Diabetic Kidney ◽  
Immune Injury

Background: Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease in China. Tubular injury contributes to the progression of DKD. Our study was conducted to explore the differential gene expression profiles between kidneys from patients with DKD and kidney living donors (LDs).Methods: In total, seven DKD and eighteen LD gene expression profiles from the GSE104954 dataset were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were analyzed in R with the limma package. DEGs were uploaded to the g:Profiler online database to explore the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Ingenuity pathway analysis (IPA) was carried out using online IPA software. Weighted gene co-expression network analysis (WGCNA) was performed using the WGCNA R package. By integrating DEGs and genes from the top 1 phenotype-gene associated module, we determined the hub gene. We next tested the hub gene, VCAN, in the GSE30122 dataset. We also validated the versican levels in human kidney tissues, explored immune cell type enrichment using an online database xCell, and investigated the correlation between cell types and VCAN expression.Results: A total of 563 DEGs was identified. A large number of pathways were involved in the immune response process according to the results of GO, KEGG, and IPA. Using WGCNA, we selected the lightcyan module in which genes showed the strongest correlation with the phenotype and smallest P-value. We also identified VCAN as a hub gene by integrating DEG analysis and WGCNA. Versican expression was upregulated in human diabetic kidney tissue. Moreover, versican was speculated to play a role in immune injury according to the enrichment of functions and signaling pathways. VCAN transcript levels correlate with the assembly of immune cells in the kidney.Conclusion: Immune processes played an essential role in DKD tubulointerstitium injury. The hub gene VCAN contributed to this process.

scholarly journals Use of Contrast-Enhanced Ultrasound to Study Relationship between Serum Uric Acid and Renal Microvascular Perfusion in Diabetic Kidney Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Ling Wang ◽  
Jia-Fen Cheng ◽  
Li-Ping Sun ◽  
Ya-Xiang Song ◽  
Le-Hang Guo ◽  
...  
Keyword(s):  
Uric Acid ◽  
Kidney Disease ◽  
Serum Uric Acid ◽  
Diabetic Kidney Disease ◽  
Microvascular Perfusion ◽  
Renal Ultrasound ◽  
Contrast Enhanced Ultrasound ◽  
Protein Markers ◽  
Diabetic Kidney ◽  
Contrast Enhanced

Purpose.To investigate the relationship between uric acid and renal microvascular perfusion in diabetic kidney disease (DKD) using contrast-enhanced ultrasound (CEUS) method.Materials and Methods.79 DKD patients and 26 healthy volunteers were enrolled. Renal function and urine protein markers were tested. DKD patients were subdivided into two groups including a normal serum uric acid (SUA) group and a high SUA group. Contrast-enhanced ultrasound (CEUS) was performed, and low acoustic power contrast-specific imaging was used for quantitative analysis.Results.Normal controls (NCs) had the highest levels of AUC, AUC1, and AUC2. Compared to the normal SUA DKD group, high SUA DKD patients had significantly higher IMAX, AUC, and AUC1 (P<0.05). DKD patients with low urinary uric acid (UUA) excretion had significantly higher AUC2 compared to DKD patients with normal UUA (P<0.05).Conclusion.Hyperuricemia in DKD patients was associated with a renal ultrasound image suggestive of microvascular hyperperfusion. The CEUS parameter AUC1 holds promise as an indicator for renal microvascular hyperperfusion, while AUC2 might be a useful indicator of declining glomerular filtration rate in DKD patients with decreased excretion of uric acid.

Systems Medicine Derived Biomarkers to Assess How Canagliflozin Delays Progression of Diabetic Kidney Disease

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1126-P
Author(s):  
HIDDO LAMBERS. HEERSPINK ◽  
PAUL PERCO ◽  
JOHANNES LEIERER ◽  
MICHAEL K. HANSEN ◽  
ANDREAS HEINZEL ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Systems Medicine ◽  
Diabetic Kidney

Factors Related to the High Prevalence of Diabetic Kidney Disease in Ecuador-Update for Health Policy Makers

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 526-P
Author(s):  
MARIANA E. GUADALUPE ◽  
GRACIELA B. ALVAREZ CONDO ◽  
FANNY E. VERA LORENTI ◽  
BETTY J. PAZMIÑO GOMEZ ◽  
EDGAR I. RODAS NEIRA ◽  
...  
Keyword(s):  
Health Policy ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Policy Makers ◽  
Diabetic Kidney ◽  
High Prevalence

Albuminuria Is More Closely Associated with Vascular Endothelial Function than eGFR in Type 2 Diabetes with Diabetic Kidney Disease

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 443-P
Author(s):  
YOSHINORI KAKUTANI ◽  
MASANORI EMOTO ◽  
YUKO YAMAZAKI ◽  
KOKA MOTOYAMA ◽  
TOMOAKI MORIOKA ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Kidney Disease ◽  
Endothelial Function ◽  
Diabetic Kidney Disease ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
Diabetic Kidney
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