scholarly journals Integrative Informatics Analysis of Transcriptome and Identification of Interacted Genes in the Glomeruli and Tubules in CKD

2021 ◽  
Vol 7 ◽  
Author(s):  
Lingyun Liu ◽  
Fuzhe Ma ◽  
Yuanyuan Hao ◽  
Zhengzi Yi ◽  
Xiaoxia Yu ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Complex Disease ◽  
Meta Analysis ◽  
Cell Assembly ◽  
Secreted Protein ◽  
Glomerular Injury ◽  
Ckd Progression ◽  
Protein Levels ◽  
Proliferation And Apoptosis

Chronic kidney disease (CKD) is a complex disease in which the renal function is compromised chronically. Many studies have indicated the crosstalk between the tubule and the glomerulus in CKD progression. However, our understanding of the interaction of tubular and glomerular injury remains incomplete. In this study, we applied a meta-analysis approach on the transcriptome of the tubules and glomeruli of CKD patients to identify differentially expressed genes (DEGs) signature. Functional analysis of pathways and Gene Ontology found that tubular DEGs were mainly involved in cell assembly and remodeling, glomerular DEGs in cell proliferation and apoptosis, and overlapping DEGs mainly in immune response. Correlation analysis was performed to identify the associated DEGs in the tubules and glomeruli. Secreted protein comparison and verification experiments indicated that WFDC2 from the tubule could downregulate PEX19 mRNA and protein levels at the glomeruli in diabetic kidney disease (DKD). This study revealed the distinctive pathways of the tubules and glomeruli and identified interacted genes during CKD progression.

scholarly journals Sexual dimorphism in the progression of type 2 diabetic kidney disease in T2DN rats

2021 ◽  
Author(s):  
Denisha R Spires ◽  
Oleg Palygin ◽  
Vladislav Levchenko ◽  
Elena Isaeva ◽  
Christine A. Klemens ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Disease Risk ◽  
Plasma Cholesterol ◽  
Cardiovascular Disease Risk ◽  
Glomerular Injury ◽  
Diabetic Kidney ◽  
Age Related

Diabetic kidney disease (DKD) is a common complication of diabetes, which frequently leads to end-stage renal failure and increases cardiovascular disease risk. Hyperglycemia promotes renal pathologies such as glomerulosclerosis, tubular hypertrophy, microalbuminuria, and a decline in glomerular filtration rate. Importantly, recent clinical data have demonstrated distinct sexual dimorphism in the pathogenesis of DKD in people with diabetes, which impacts both severity- and age-related risk factors. This study aimed to define sexual dimorphism and renal function in a non-obese type 2 diabetes model with the spontaneous development of advanced diabetic nephropathy (T2DN rats). T2DN rats at 12- and over 48-weeks old were used to define disease progression and kidney injury development. We found impaired glucose tolerance and glomerular hyperfiltration in T2DN rats to compare with non-diabetic Wistar control. The T2DN rat displays a significant sexual dimorphism in insulin resistance, plasma cholesterol, renal and glomerular injury, urinary nephrin shedding, and albumin handling. Our results indicate that both male and female T2DN rats developed non-obese type 2 DKD phenotype, where the females had significant protection from the development of severe forms of DKD. Our findings provide further evidence for the T2DN rat strain's effectiveness for studying the multiple facets of DKD.

scholarly journals Urinary Markers of Glomerular Injury in Diabetic Nephropathy

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Abraham Cohen-Bucay ◽  
Gautham Viswanathan
Keyword(s):  
Renal Failure ◽  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Current Literature ◽  
Cardiovascular Events ◽  
Diabetic Kidney Disease ◽  
Glomerular Injury ◽  
Diabetic Kidney ◽  
Urinary Markers

Diabetic nephropathy, the leading cause of renal failure worldwide, affects approximately one-third of all people with diabetes. Microalbuminuria is considered the first sign and the best predictor of progression to renal failure and cardiovascular events. However, albuminuria has several limitations. Therefore, earlier, more sensitive and specific biomarkers with greater predictability are needed. The aim of this paper is to discuss the current literature on biomarkers of glomerular injury that have been implicated in diabetic kidney disease.

scholarly journals Urinary chemokine C-X-C motif ligand 16 and endostatin as predictors of tubulointerstitial fibrosis in patients with advanced diabetic kidney disease

2019 ◽  
Author(s):  
Yu Ho Lee ◽  
Ki Pyo Kim ◽  
Sun-Hwa Park ◽  
Dong-Jin Kim ◽  
Yang-Gyun Kim ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Interstitial Fibrosis ◽  
Renal Outcome ◽  
Enzyme Linked Immunosorbent Assay ◽  
Glomerular Injury ◽  
Tubular Atrophy ◽  
Diabetic Kidney ◽  
Cytokines And Chemokines ◽  
Pathologic Features

Abstract Background Interstitial fibrosis and tubular atrophy (IFTA) is a well-recognized risk factor for poor renal outcome in patients with diabetic kidney disease (DKD). However, a noninvasive biomarker for IFTA is currently lacking. The purpose of this study was to identify urinary markers of IFTA and to determine their clinical relevance as predictors of renal prognosis. Methods Seventy patients with biopsy-proven isolated DKD were enrolled in this study. We measured multiple urinary inflammatory cytokines and chemokines by multiplex enzyme-linked immunosorbent assay in these patients and evaluated their association with various pathologic features and renal outcomes. Results Patients enrolled in this study exhibited advanced DKD at the time of renal biopsy, characterized by moderate to severe renal dysfunction [mean estimated glomerular filtration rate (eGFR) 36.1 mL/min/1.73 m2] and heavy proteinuria (mean urinary protein:creatinine ratio 7.8 g/g creatinine). Clinicopathologic analysis revealed that higher IFTA scores were associated with worse baseline eGFR (P < 0.001) and poor renal outcome (P = 0.002), whereas glomerular injury scores were not. Among measured urinary inflammatory markers, C-X-C motif ligand 16 (CXCL16) and endostatin showed strong correlations with IFTA scores (P = 0.001 and P < 0.001, respectively), and patients with higher levels of urinary CXCL16 and/or endostatin experienced significantly rapid renal progression compared with other patients (P < 0.001). Finally, increased urinary CXCL16 and endostatin were independent risk factors for poor renal outcome after multivariate adjustments (95% confidence interval 1.070–3.455, P = 0.029). Conclusions Urinary CXCL16 and endostatin could reflect the degree of IFTA and serve as biomarkers of renal outcome in patients with advanced DKD.

scholarly journals SUN-311 NF-KAPPA B ACTIVATION PROMOTES GLOMERULAR INJURY AND INFLAMMATION IN LONG-TERM EXPERIMENTAL DIABETIC KIDNEY DISEASE

2019 ◽  
Vol 4 (7) ◽  
pp. S289
Author(s):  
O. FORESTO-NETO ◽  
A.H. Albino ◽  
S.C.A. Arias ◽  
V.D. Faustino ◽  
F.F.F. Zambom ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Glomerular Injury ◽  
Nf Kappa B ◽  
Diabetic Kidney

scholarly journals Antioxidant agents for delaying diabetic kidney disease progression: A systematic review and meta-analysis

PLoS ONE ◽  
2017 ◽  
Vol 12 (6) ◽  
pp. e0178699 ◽  
Author(s):  
Davide Bolignano ◽  
Valeria Cernaro ◽  
Guido Gembillo ◽  
Rossella Baggetta ◽  
Michele Buemi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Kidney Disease ◽  
Disease Progression ◽  
Diabetic Kidney Disease ◽  
Meta Analysis ◽  
Diabetic Kidney ◽  
Antioxidant Agents ◽  
Kidney Disease Progression

scholarly journals Genetic and Biological Effects of ICAM-1 E469K Polymorphism in Diabetic Kidney Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Xiuli Zhang ◽  
Norhashimah Abu Seman ◽  
Henrik Falhammar ◽  
Kerstin Brismar ◽  
Harvest F. Gu
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Complex Disease ◽  
Biological Effects ◽  
Association Studies ◽  
Genetic Effects ◽  
Protein Crystal ◽  
Intercellular Adhesion Molecule ◽  
Protein Marker ◽  
Diabetic Kidney

Diabetic kidney disease (DKD) is a complex disease, in which local inflammatory stress results from both metabolic and hemodynamic derangements. Intercellular adhesion molecule 1 (ICAM-1) is an acute-phase protein marker of inflammation. In the recent years, clinical observations have reported that increased serum/plasma ICAM-1 levels are positively correlated with albuminuria in the patients with type 1 (T1D) and type 2 diabetes (T2D). Genetic association studies have demonstrated that genetic polymorphisms, including SNP rs5498 (E469K, G/A), in the ICAM1 gene is associated with DKD. rs5498 is a nonsynonymous SNP and caused by substitution between E (Glu) and K (Lys) for ICAM-1 protein. In this review, we first summarized the genetic effects of ICAM1 E469K polymorphism in DKD and then demonstrated the possible changes of ICAM-1 protein crystal structures according to the genotypes of this polymorphism. Finally, we discussed the genetic effects of the ICAM1 E469K polymorphism and the biological role of increased circulating ICAM-1 protein and its formation changes in DKD.

scholarly journals -866G/A and Ins/Del polymorphisms in the UCP2 gene and diabetic kidney disease: case-control study and meta-analysis

2020 ◽  
Vol 43 (2) ◽  
Author(s):  
Cristine Dieter ◽  
Taís Silveira Assmann ◽  
Natália Emerim Lemos ◽  
Eloísa Toscan Massignam ◽  
Bianca Marmontel de Souza ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Case Control Study ◽  
Meta Analysis ◽  
Case Control ◽  
Diabetic Kidney ◽  
Ucp2 Gene ◽  
Disease Case ◽  
Control Study

scholarly journals The Association between Obstructive Sleep Apnea on Diabetic Kidney Disease: A Systematic Review and Meta-Analysis

SLEEP ◽  
2016 ◽  
Vol 39 (2) ◽  
pp. 301-308 ◽  
Author(s):  
Wen Bun Leong ◽  
Ferozkhan Jadhakhan ◽  
Shahrad Taheri ◽  
G. Neil Thomas ◽  
Peymané Adab
Keyword(s):  
Systematic Review ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Meta Analysis ◽  
Diabetic Kidney ◽  
Obstructive Sleep

scholarly journals A hyaluronan synthesis inhibitor delays progression of diabetic kidney disease in a mouse experimental model

Kidney360 ◽  
2021 ◽  
pp. 10.34067/KID.0004642020
Author(s):  
Guillermo Selman ◽  
Laisel Martinez ◽  
Andrea Lightle ◽  
Alejandra Aguilar ◽  
Daniel Woltmann ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Plasma Glucose ◽  
Diabetic Kidney Disease ◽  
Control Diet ◽  
Experimental Period ◽  
Glomerular Injury ◽  
Synthesis Inhibitor ◽  
Diabetic Kidney ◽  
Injury Index ◽  
And Control

Background: The role of hyaluronan (HA) in the development and progression of diabetic kidney disease (DKD), as well as the precise mechanisms and consequences of HA involvement in this pathology are still to be clarified. Methods: In this study, we assayed the effects of the HA synthesis inhibitor 4-methylumbelliferone (4-MU) on the development of DKD. Diabetic type 2 model mice (eNOS-/- C57BLKS/Jdb) were fed artificial diets containing 5% 4-MU or not for 9 weeks. Plasma glucose, glomerular filtration rate (GFR), albumin to creatinine ratio (ACR), and biomarkers of kidney function and systemic inflammation were measured at baseline and after treatment. Diabetic nephropathy was further characterized in treated and control mice by histopathology. Results: Treated animals consumed a daily dose of approximately 6.2 g of 4-MU per kg of body weight. At the end of the experimental period, the 4-MU supplemented diet resulted in a significant decrease in non-fasting plasma glucose (516 [interquartile range 378-1170] vs. 1149 [875.8-1287] mg/dL, P=0.050) and a trend toward lower HA kidney content (5.6 ± 1.5 vs. 8.8 ± 3.1 ng/mg of kidney weight, P=0.070) compared to the control diet, respectively. Diabetic animals treated with 4-MU showed significantly higher GFR and lower urine ACR and plasma cystatin C levels than diabetic controls. Independent histological assessment of DKD also demonstrated a significant decrease in mesangial expansion score and glomerular injury index in 4-MU-treated mice compared to controls. Plasma glucose showed a strong correlation with kidney HA levels (r=0.66, P=0.0098). Both total hyaluronan (r=0.76, P=0.0071) and low-molecular-weight hyaluronan content (r=0.64, P=0.036) in the kidneys correlated with urine ACR in mice. Conclusion: These results show that the hyaluronan synthesis inhibitor 4-MU effectively slowed the progression of DKD and constitutes a potential new therapeutic approach to treat DKD.

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