scholarly journals New Experimental Models of Diabetic Nephropathy in Mice Models of Type 2 Diabetes: Efforts to Replicate Human Nephropathy

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
María José Soler ◽  
Marta Riera ◽  
Daniel Batlle
Keyword(s):  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Substantial Effect ◽  
Experimental Models ◽  
Characteristic Features ◽  
Stage Renal Disease ◽  
End Stage ◽  
Glomerular Tuft ◽  
Human Nephropathy

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. The use of experimental models of DN has provided valuable information regarding many aspects of DN, including pathophysiology, progression, implicated genes, and new therapeutic strategies. A large number of mouse models of diabetes have been identified and their kidney disease was characterized to various degrees. Most experimental models of type 2 DN are helpful in studying early stages of DN, but these models have not been able to reproduce the characteristic features of more advanced DN in humans such as nodules in the glomerular tuft or glomerulosclerosis. The generation of new experimental models of DN created by crossing, knockdown, or knockin of genes continues to provide improved tools for studying DN. These models provide an opportunity to search for new mechanisms involving the development of DN, but their shortcomings should be recognized as well. Moreover, it is important to recognize that the genetic background has a substantial effect on the susceptibility to diabetes and kidney disease development in the various models of diabetes.

scholarly journals Revisiting Experimental Models of Diabetic Nephropathy

2020 ◽  
Vol 21 (10) ◽  
pp. 3587
Author(s):  
Anna Giralt-López ◽  
Mireia Molina-Van den Bosch ◽  
Ander Vergara ◽  
Clara García-Carro ◽  
Daniel Seron ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Experimental Models ◽  
Diabetic Patients ◽  
Rodent Models ◽  
Basement Membrane Thickening ◽  
Matrix Expansion ◽  
Risk Biomarkers ◽  
Stage Renal Disease ◽  
End Stage

Diabetes prevalence is constantly increasing and, nowadays, it affects more than 350 million people worldwide. Therefore, the prevalence of diabetic nephropathy (DN) has also increased, becoming the main cause of end-stage renal disease (ESRD) in the developed world. DN is characterized by albuminuria, a decline in glomerular filtration rate (GFR), hypertension, mesangial matrix expansion, glomerular basement membrane thickening, and tubulointerstitial fibrosis. The therapeutic advances in the last years have been able to modify and delay the natural course of diabetic kidney disease (DKD). Nevertheless, there is still an urgent need to characterize the pathways that are involved in DN, identify risk biomarkers and prevent kidney failure in diabetic patients. Rodent models provide valuable information regarding how DN is set and its progression through time. Despite the utility of these models, kidney disease progression depends on the diabetes induction method and susceptibility to diabetes of each experimental strain. The classical DN murine models (Streptozotocin-induced, Akita, or obese type 2 models) do not develop all of the typical DN features. For this reason, many models have been crossed to a susceptible genetic background. Knockout and transgenic strains have also been created to generate more robust models. In this review, we will focus on the description of the new DN rodent models and, additionally, we will provide an overview of the available methods for renal phenotyping.

scholarly journals The Severity of Diabetic Retinopathy Is an Independent Factor for the Progression of Diabetic Nephropathy

2020 ◽  
Vol 10 (1) ◽  
pp. 3
Author(s):  
Shi-Chue Hsing ◽  
Chia-Cheng Lee ◽  
Chin Lin ◽  
Jiann-Torng Chen ◽  
Yi-Hao Chen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Kidney Disease ◽  
Renal Disease ◽  
Disease Progression ◽  
Renal Disease Progression ◽  
Hazard Ratios ◽  
Stage Renal Disease ◽  
End Stage

(1) Background: It has rarely been studied whether the severity of diabetic retinopathy (DR) could influence renal disease progression in end-stage renal disease (ESRD) and chronic kidney disease (CKD) in patients with type 2 diabetes. The aim of this study was to evaluate renal disease progression in ESRD and CKD according to DR severity in patients with type 2 diabetes. (2) Methods: We included 1329 patients and divided the cohort into two end-points. The first was to trace the incidence of ESRD in all enrolled participants and the other was to follow their progression to CKD. (3) Results: Significantly higher crude hazard ratios (HRs) of ESRD incidence in all enrolled participants were noted, and this ratio increased in a stepwise fashion. However, after adjustment, DR severity was not associated with ESRD events. Therefore, a subgroup of 841 patients without CKD was enrolled to track their progression to CKD. Compared with no diabetic retinopathy, the progression of CKD increased in a stepwise fashion, from mild nonproliferative diabetic retinopathy (NPDR) to moderate NPDR, to severe NPDR and to proliferative diabetic retinopathy (PDR), both in the crude and adjusted models. (4) Conclusions: The severity of retinopathy appeared to be associated with renal lesions and the development of CKD. Our findings suggest that the severity of DR is a risk factor for progression to CKD. Therefore, diabetic retinopathy is useful for prognosticating the clinical course of diabetic kidney disease.

Diabetic kidney disease in thedb/dbmouse

2003 ◽  
Vol 284 (6) ◽  
pp. F1138-F1144 ◽  
Author(s):  
Kumar Sharma ◽  
Peter McCue ◽  
Stephen R. Dunn
Keyword(s):  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Mouse Model ◽  
Renal Disease ◽  
Mouse Models ◽  
Diabetic Kidney Disease ◽  
Diabetic Kidney ◽  
Matrix Expansion ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy is increasing in incidence and is now the number one cause of end-stage renal disease in the industrialized world. To gain insight into the genetic susceptibility and pathophysiology of diabetic nephropathy, an appropriate mouse model of diabetic nephropathy would be critical. A large number of mouse models of diabetes have been identified and their kidney disease characterized to various degrees. Perhaps the best characterized and most intensively investigated model is the db/ db mouse. Because this model appears to exhibit the most consistent and robust increase in albuminuria and mesangial matrix expansion, it has been used as a model of progressive diabetic renal disease. In this review, we present the findings from various studies on the renal pathology of the db/ db mouse model of diabetes in the context of human diabetic nephropathy. Furthermore, we discuss shortfalls of assessing functional renal disease in mouse models of diabetic kidney disease.

scholarly journals Greater variability in lipid measurements associated with kidney diseases in patients with type 2 diabetes mellitus in a 10-year diabetes cohort study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eric Yuk Fai Wan ◽  
Esther Yee Tak Yu ◽  
Weng Yee Chin ◽  
Christie Sze Ting Lau ◽  
Anna Hoi Ying Mok ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hazard Ratio ◽  
Lipoprotein Cholesterol ◽  
Low Density Lipoprotein Cholesterol ◽  
Cholesterol Ratio ◽  
Stage Renal Disease ◽  
End Stage

AbstractThis study aimed to evaluate the associations between variability of lipid parameters and the risk of kidney disease in patients with type 2 diabetes mellitus. Low-density lipoprotein-cholesterol, total cholesterol to high-density lipoprotein-cholesterol ratio and triglyceride were specifically addressed in this study. This retrospective cohort study included 105,552 patients aged 45–84 with type 2 diabetes mellitus and normal kidney function who were managed under Hong Kong public primary care clinics during 2008–2012. Those with kidney disease (estimated glomerular filtration rate < 60 mL/min/1.73 m2 or urine albumin to creatinine ratio ≥ 3 mg/mmol) were excluded. Variabilities of low-density lipoprotein-cholesterol, total cholesterol to high-density lipoprotein-cholesterol ratio and triglyceride were determined using the standard deviation of the respective parameter obtained from a mixed effects model to minimize regression dilution bias. The associations between lipid variability and renal outcomes including incident kidney disease, renal function decline defined as ≥ 30% reduction in estimated glomerular filtration rate since baseline, and end-stage renal disease (estimated glomerular filtration rate < 15 mL/min/1.73 m2) were evaluated by multivariable Cox regression. After a median follow-up of 66.5 months (0.5 million person-years in total), 49,653 kidney disease, 29,358 renal function decline, and 1765 end-stage renal disease cases were recorded. Positive linear associations between low-density lipoprotein-cholesterol and total cholesterol to high-density lipoprotein-cholesterol ratio variabilities and the risk of all renal outcomes were demonstrated. However, no association between triglyceride variability and any outcome was found. Each mmol/L increase in low-density lipoprotein-cholesterol variability was associated with 20% (Hazard ratio 1.20 [95% CI 1.15–1.25]), 38% (Hazard ratio 1.37 [95% CI 1.30–1.45]), and 108% (Hazard ratio 2.08 [95% CI 1.74–2.50]) higher risk in incident kidney disease, renal function decline and end-stage renal disease respectively. Similarly, each unit increase in total cholesterol to high-density lipoprotein-cholesterol ratio variability was associated with 35% (Hazard ratio 1.15 [95% CI 1.10–1.20]), 33% (Hazard ratio 1.33 [95% CI 1.26–1.40]), and 75% (Hazard ratio 1.75 [95% CI 1.46–2.09]) heightened risk in incident kidney disease, renal function decline and end-stage renal disease respectively. Cholesterol variability may potentially be a useful predictor of kidney diseases in patients with type 2 diabetes mellitus. Attention should be drawn to cholesterol variability when managing diabetic patients and further research is warranted to investigate the modifiable risk factors for lipid variability.

Podocalyxin as an early marker predicting diabetic nephropathy and its correlation with stages of diabetic nephropathy in type two diabetic patients

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Salah El-Din A Shelbaya ◽  
Hanan M Ali ◽  
Rana H Ibrahim ◽  
Nourhan Safwat Sawirs
Keyword(s):  
Diabetic Nephropathy ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Control Group ◽  
Diabetic Patients ◽  
Type 2 Dm ◽  
Stage Renal Disease ◽  
End Stage ◽  
Positive Significant Correlation

Abstract Background Nephropathy, a major complication of diabetes, is the leading cause of end-stage renal disease. Early identification of nephropathy in diabetes patients is crucial because it creates opportunity for preventing the incidence of DN and/or even slows down the process of end-stage renal disease attributed to diabetes. Human podocytes (Pods) have been demonstrated to be functionally and structurally injured in the natural history of diabetic nephropathy. Aim of the Work To evaluate the possible association between the urinary podocalyxin levels and severity and grade of diabetic nephropathy and to use urinary podocalyxin as a non-invasive marker for early stage of diabetic nephropathy in type 2 DM. Patients and Methods We collected 60 known clinically and biochemically type 2 diabetic patients.20 diabetic patients with no evidence of diabetic nephropathy, 20 patients diagnosed as diabetic nephropathy in microalbuminuria stages and 20 patients diagnosed as diabetic nephropathy in macroalbuminuria stages from Ain Shams University hospitals between April and December 2018 and 20 apparently healthy volunteers will included as a control group. Results Urinary PCX was significantly higher in patients group compared to control group. Urinary PCX was significantly higher in microalbuminuric group than in normoalbuminuric group and higher in macroalbuminuric group than in microalbuminuric group. There was a positive significant correlation between FBS, 2HrPP, HBA1C and urinary PCX. There was a positive significant correlation between s.create and urinary PCX. There was a positive significant correlation between ACR and urinary PCX. Conclusion Urinary podocalyxin seems to be beneficial as an early marker for early stages of diabetic nephropathy in type 2 DM patients.

scholarly journals Arg913Gln variation of SLC12A3 gene is associated with diabetic nephropathy in type 2 diabetes and Gitelman syndrome: a systematic review

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Eduardo De la Cruz-Cano ◽  
Cristina del C. Jiménez-González ◽  
Vicente Morales-García ◽  
Conny Pineda-Pérez ◽  
Juan G. Tejas-Juárez ◽  
...  
Keyword(s):  
Systematic Review ◽  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Gitelman Syndrome ◽  
Slc12a3 Gene ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background Diabetic nephropathy is a global common cause of chronic kidney disease and end-stage renal disease. A lot of research has been conducted in biomedical sciences, which has enhanced understanding of the pathophysiology of diabetic nephropathy and has expanded the potential available therapies. An increasing number of evidence suggests that genetic alterations play a major role in development and progression of diabetic nephropathy. This systematic review was focused on searching an association between Arg913Gln variation in SLC12A3 gene with diabetic nephropathy in individuals with Type 2 Diabetes and Gitelman Syndrome. Methods An extensive systematic review of the literature was completed using PubMed, EBSCO and Cochrane Library, from their inception to January 2018. The PRISMA guidelines were followed and the search strategy ensured that all possible studies were identified to compile the review. Inclusion criteria for this review were: 1) Studies that analyzed the SLC12A3 gene in individuals with Type 2 Diabetes and Gitelman Syndrome. 2) Use of at least one analysis investigating the association between the Arg913Gln variation of SLC12A3 gene with diabetic nephropathy. 3) Use of a case–control or follow-up design. 4) Investigation of type 2 diabetes mellitus in individuals with Gitelman’s syndrome, with a history of diabetic nephropathy. Results The included studies comprised 2106 individuals with diabetic nephropathy. This review shows a significant genetic association in most studies in the Arg913Gln variation of SLC12A3 gene with the diabetic nephropathy, pointing out that the mutations of this gene could be a key predictor of end-stage renal disease. Conclusions The results showed in this systematic review contribute to better understanding of the association between the Arg913Gln variation of SLC12A3 gene with the pathogenesis of diabetic nephropathy in individuals with T2DM and GS.

scholarly journals Significance of Metformin Use in Diabetic Kidney Disease

2020 ◽  
Vol 21 (12) ◽  
pp. 4239 ◽  
Author(s):  
Daiji Kawanami ◽  
Yuichi Takashi ◽  
Makito Tanabe
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Experimental Studies ◽  
Glucose Lowering ◽  
Diabetic Kidney ◽  
First Line Therapy ◽  
Stage Renal Disease ◽  
End Stage ◽  
Pharmacologic Actions

Metformin is a glucose-lowering agent that is used as a first-line therapy for type 2 diabetes (T2D). Based on its various pharmacologic actions, the renoprotective effects of metformin have been extensively studied. A series of experimental studies demonstrated that metformin attenuates diabetic kidney disease (DKD) by suppressing renal inflammation, oxidative stress and fibrosis. In clinical studies, metformin use has been shown to be associated with reduced rates of mortality, cardiovascular disease and progression to end-stage renal disease (ESRD) in T2D patients with chronic kidney disease (CKD). However, metformin should be administered with caution to patients with CKD because it may increase the risk of lactic acidosis. In this review article, we summarize our current understanding of the safety and efficacy of metformin for DKD.

scholarly journals Tiaolipiwei Acupuncture Reduces Albuminuria by Alleviating Podocyte Lesions in a Rat Model of Diabetic Nephropathy

2018 ◽  
Vol 2018 ◽  
pp. 1-10
Author(s):  
Zhilong Zhang ◽  
Xinju Li ◽  
Liang Liu ◽  
Jiya Sun ◽  
Xu Wang ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Rat Model ◽  
Morphological Changes ◽  
Renal Tissue ◽  
Transmission Electron ◽  
End Of Treatment ◽  
Stage Renal Disease ◽  
End Stage ◽  
Protein Serum

Background. Diabetic nephropathy is a common and serious complication of diabetes and a major cause of end-stage renal disease. Tiaolipiwei acupuncture is a safe treatment approach that may be effective for lowering albuminuria in diabetic nephropathy. Yet, the exact mechanisms of this therapeutic effect are unclear. Methods. A rodent model of type 2 diabetic nephropathy (T2DN) was induced by a high-fat diet combined with low-dose streptozotocin. T2DN rats were treated with Tiaolipiwei acupuncture (ACU) for 4, 8, or 12 weeks. At the end of treatment, urinary and blood samples were collected for analysis. Transmission electron microscopy was used to observe morphological changes, and protein expression levels of nephrin, CD2AP, podocalyxin, and desmin were quantified in renal tissue. Results. Compared to the T2DN groups, the T2DN + ACU groups showed significant improvements in 24-hour urinary protein, serum urea, cholesterol, and triglycerides at all time points. ACU treatment also improved the density of slit diaphragms. Simultaneously, ACU promoted the renal expression of nephrin, CD2AP, and podocalyxin and decreased the expression of desmin. Conclusion. Our study suggests that Tiaolipiwei acupuncture ameliorates podocyte lesions to reduce albuminuria and prevent the progression of T2DN in a rat model.

scholarly journals Optimal Early Diagnosis and Monitoring of Diabetic Kidney Disease in Type 2 Diabetes Mellitus: Addressing the Barriers to Albuminuria Testing

2021 ◽  
Vol 12 ◽  
pp. 215013272110036
Author(s):  
Elena A. Christofides ◽  
Niraj Desai
Keyword(s):  
Type 2 Diabetes ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Urine Albumin ◽  
Increased Risk ◽  
Ckd Stage ◽  
Stage Renal Disease ◽  
End Stage ◽  
Kidney Health

Chronic kidney disease (CKD) in patients with type 2 diabetes (T2D) is associated with increased risk of end-stage renal disease (ESRD) and cardiovascular disease (CVD). Urine albumin-to-creatinine ratio (UACR) is a sensitive and early indicator of kidney damage, which should be used routinely to accurately assess CKD stage and monitor kidney health. However, this test currently is performed in only a minority of patients with T2D. Here, we review the importance of albuminuria testing and current barriers that hinder patient access to UACR testing and describe solutions to such testing in a community clinical setting.

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