Animal Models and Renal Biomarkers of Diabetic Nephropathy

2020 ◽  
pp. 521-551
Author(s):  
Laura Pérez-López ◽  
Mauro Boronat ◽  
Carlos Melián ◽  
Yeray Brito-Casillas ◽  
Ana M. Wägner
Keyword(s):  
Diabetic Nephropathy ◽  
Animal Models ◽  
Renal Biomarkers

scholarly journals Recent Advances in Animal Models of Diabetic Nephropathy

2014 ◽  
Vol 126 (4) ◽  
pp. 191-195 ◽  
Author(s):  
Boris Betz ◽  
Bryan R. Conway
Keyword(s):  
Diabetic Nephropathy ◽  
Animal Models ◽  
Recent Advances

scholarly journals Wnt6 regulates epithelial cell differentiation and is dysregulated in renal fibrosis

2016 ◽  
Vol 311 (1) ◽  
pp. F35-F45 ◽  
Author(s):  
Hayley Beaton ◽  
Darrell Andrews ◽  
Martin Parsons ◽  
Mary Murphy ◽  
Andrew Gaffney ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Epithelial Cell ◽  
Animal Models ◽  
Epithelial Cells ◽  
Renal Fibrosis ◽  
Critical Role ◽  
Functional Characterization ◽  
Nuclear Accumulation ◽  
Tubular Injury ◽  
Renal Epithelial Cells

Diabetic nephropathy is the most common microvascular complication of diabetes mellitus, manifesting as mesangial expansion, glomerular basement membrane thickening, glomerular sclerosis, and progressive tubulointerstitial fibrosis leading to end-stage renal disease. Here we describe the functional characterization of Wnt6, whose expression is progressively lost in diabetic nephropathy and animal models of acute tubular injury and renal fibrosis. We have shown prominent Wnt6 and frizzled 7 (FzD7) expression in the mesonephros of the developing mouse kidney, suggesting a role for Wnt6 in epithelialization. Importantly, TCF/Lef reporter activity is also prominent in the mesonephros. Analysis of Wnt family members in human renal biopsies identified differential expression of Wnt6, correlating with severity of the disease. In animal models of tubular injury and fibrosis, loss of Wnt6 was evident. Wnt6 signals through the canonical pathway in renal epithelial cells as evidenced by increased phosphorylation of GSK3β (Ser9), nuclear accumulation of β-catenin and increased TCF/Lef transcriptional activity. FzD7 was identified as a putative receptor of Wnt6. In vitro Wnt6 expression leads to de novo tubulogenesis in renal epithelial cells grown in three-dimensional culture. Importantly, Wnt6 rescued epithelial cell dedifferentiation in response to transforming growth factor-β (TGF-β); Wnt6 reversed TGF-β-mediated increases in vimentin and loss of epithelial phenotype. Wnt6 inhibited TGF-β-mediated p65-NF-κB nuclear translocation, highlighting cross talk between the two pathways. The critical role of NF-κB in the regulation of vimentin expression was confirmed in both p65−/−and IKKα/β−/−embryonic fibroblasts. We propose that Wnt6 is involved in epithelialization and loss of Wnt6 expression contributes to the pathogenesis of renal fibrosis.

Murine Models of Diabetic Nephropathy

2012 ◽  
Vol 120 (04) ◽  
pp. 191-193 ◽  
Author(s):  
V. Peters ◽  
C. Schmitt
Keyword(s):  
Diabetic Nephropathy ◽  
Animal Models ◽  
Mouse Models ◽  
Critical Analysis ◽  
Disease Process ◽  
Diabetic Animal ◽  
Renal Diseases ◽  
Murine Models ◽  
Renal Changes ◽  
End Stage

AbstractDiabetic nephropathy is the leading cause of end stage renal diseases worldwide. Even though several diabetic animal models exist, not a single one develops renal changes sufficiently reflecting those seen in humans. This review provides an overview on mouse models presenting with various features of diabetic nephropathy. The critical analysis and comparison of existing mouse models substantially enhances our understanding of the disease process and should provide a guide for choosing the most suitable mouse model for the investigation of diabetic nephropathy.

Value of the intrarenal arterial resistivity indices and different renal biomarkers for early identification of diabetic nephropathy in type 1 diabetic patients

2016 ◽  
Vol 29 (3) ◽  
Author(s):  
Soha Abd El Dayem ◽  
Abo El magd El Bohy ◽  
Amal El Shehaby
Keyword(s):  
Diabetic Nephropathy ◽  
Early Detection ◽  
Glycosylated Hemoglobin ◽  
Diabetic Patients ◽  
Creatinine Ratio ◽  
Fatty Acid Binding ◽  
Albumin Creatinine Ratio ◽  
Renal Biomarkers ◽  
Type 1 Diabetic Patients

AbstractThe aim of this study was to compare resistivity index (RI) in type 1 diabetic patients and normal controls and to evaluate whether high RI is associated with different biomarkers of diabetic nephropathy (DN) as early detection of DN offers the best chance of delaying or possibly preventing progression to end-stage renal disease.The study included 62 type 1 diabetic patients and 30 healthy volunteers of the same age and sex. Blood samples were taken for assessment of glycosylated hemoglobin, lipid profile and urine samples were taken for assessment of albumin/creatinine ratio, neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid binding protein (L-FABP) and kidney injury molecule-1 (Kim-1). Forty-five diabetic patients and 30 controls had a renal Doppler ultrasonography. t-Test or Mann Whitney U-test for independent variables, Pearson’s or Spearman correlation analysis were used.The mean age of diabetic patients was 16.3±1.5 years, and mean duration of diabetes was 9.4±2.9 years. RI, albumin/creatinine ratio, NGAL, Kim-1 and L-FABP were significantly higher in diabetics than in controls. RI, NGAL, Kim-1, and L-FABP were significantly higher in microalbuminuric compared to normoalbuminuric diabetics. In normoalbuminuric diabetics, RI, NGAL, Kim-1 and L-FABP were significantly higher compared to controls. The study revealed significant positive correlation between the RI in diabetics and both KIM-1 and albumin/creatinine ratio.Increased RI and renal biomarkers in diabetics are early sensitive specific markers of DN, even preceded the development of microalbuminuria, denoting that they can be used as an early and sensitive markers for early detection of DN.

scholarly journals Prediction Value of Serum NGAL in the Diagnosis and Prognosis of Experimental Acute and Chronic Kidney Injuries

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 981
Author(s):  
Weida Wang ◽  
Zhaojun Li ◽  
Yuanyuan Chen ◽  
Haijie Wu ◽  
Sen Zhang ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Animal Models ◽  
Early Diagnosis ◽  
Kidney Injury ◽  
Disease Models ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Diagnosis And Prognosis ◽  
Lps Challenge ◽  
Immune Mediated

Sensitive and accurate serum biomarkers for monitoring acute and chronic kidney disease progression are more convenient and can better evaluate drug efficiency in pharmacological research. Neutrophil Gelatinase-associated Lipocalin (NGAL) is considered a hopeful early biomarker of acute kidney injury (AKI), but its utility in early prediction and prognosis of diabetic nephropathy (DN) and immune-mediated glomerulonephritis is still not clear. Moreover, detailed prognosis studies of NGAL in AKI are lacking, and most studies use a urine source. In the current study, through two experimental AKI and two chronic kidney injury animal models, serum NGAL (sNGAL) prediction values on diagnosis and prognosis of kidney injuries in animal disease models have been investigated thoroughly. Four experimental kidney disease models include cisplatin-induced and lipopolysaccharide (LPS)-induced AKI, streptozocin-induced diabetic nephropathy (DN), and cationized-bovine serum albumin (c-BSA)-induced membranous nephropathy (MN), respectively. The sNGAL concentration was measured at different stages of kidney injury (KI) in each experimental model, and receiver operating characteristic (ROC) analyses were performed to investigate the diagnosis efficiency of sNGAL for KI. Western blot and immunohistochemistry were used to measure the protein levels in the kidneys, and pathological analysis was used as the gold standard to confirm KI. Results suggest that sNGAL can predict early diagnosis of cisplatin-induced AKI accurately but is less powerful in later stages compared to blood urea nitrogen (BUN) and serum creatinine (Scr). sNGAL is sensitive but lacks specificity to evaluate early kidney injury for LPS-induced AKI under low-dosage LPS challenge. sNGAL is not an efficient biomarker for early diagnosis of STZ-induced DN, but sNGAL is an efficient predictor for the early diagnosis and prognosis of immune-mediated MN. In conclusion, application of sNGAL as a kidney injury biomarker to determine the diagnosis and prognosis in pharmacological studies is dependent on experimental animal models.

scholarly journals Rodent animal models: from mild to advanced stages of diabetic nephropathy

2014 ◽  
Vol 22 (5) ◽  
pp. 279-293 ◽  
Author(s):  
Manpreet Kaur ◽  
Onkar Bedi ◽  
Shilpi Sachdeva ◽  
B. V. K. Krishna Reddy ◽  
Puneet Kumar
Keyword(s):  
Diabetic Nephropathy ◽  
Animal Models ◽  
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