scholarly journals Epigenetics of Diabetic Nephropathy: From Biology to Therapeutics

2020 ◽  
pp. 48-57
Author(s):  
Keith Al-Hasani ◽  
Ishant Khurana ◽  
Theresa Farhat ◽  
Assaad Eid ◽  
Assam El-Osta
Keyword(s):  
Diabetic Nephropathy ◽  
End Stage Renal Disease ◽  
Kidney Development ◽  
Kidney Cells ◽  
Epigenetic Mechanisms ◽  
Stage Renal Disease ◽  
End Stage ◽  
Diseased Kidney

Diabetic nephropathy (DN) is a lethal microvascular complication associated with Type 1 and Type 2 diabetes mellitus, and is the leading single cause of end-stage renal disease. Although genetic influences are important, epigenetic mechanisms have been implicated in several aspects of the disease. The current therapeutic methods to treat DN are limited to slowing disease progression without repair and regeneration of the damaged nephrons. Replacing dying or diseased kidney cells with new nephrons is an attractive strategy. This review considers the genetic and epigenetic control of nephrogenesis, together with the epigenetic mechanisms that accompany kidney development and recent advances in induced reprogramming and kidney cell regeneration in the context of DN.

Diabetic nephropathy

2011 ◽  
pp. 1935-1946 ◽  
Author(s):  
Janaka Karalliedde ◽  
Giancarlo Janaka
Keyword(s):  
Cardiovascular Disease ◽  
Diabetic Retinopathy ◽  
Diabetic Nephropathy ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Albumin Excretion ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy is classically defined as a rise in urinary albumin excretion rate (UAER), often associated with an increase in blood pressure, with concomitant retinopathy but without evidence of other causes of renal disease (1). It is characterized by a progressive decline in glomerular filtration rate (GFR), eventually resulting in end-stage renal disease. Diabetic nephropathy occurs in approximately 30–35% of type 1 and type 2 patients and tends to cluster in families. These families also show a predisposition to cardiovascular disease and hypertension—and, hypertension, or a predisposition to it, appears a major determinant of diabetic renal disease. These data taken together clearly suggest an individual susceptibility to this complication. The phases of diabetic nephropathy based on urine albumin excretion status and GFR are shown in Table 13.5.3.1 (2). Histological changes of diabetic glomerulopathy are present in over 95% of patients with type 1 diabetes and albuminuria (UAER >300 mg/day) and in approximately 85% of type 2 diabetic patients who develop albuminuria with concomitant diabetic retinopathy (1, 2). In the absence of diabetic retinopathy nearly 30% of patients with type 2 diabetes and proteinuria have nondiabetic renal lesions (1). The all-cause mortality in patients with diabetic nephropathy is nearly 20–40 times higher than that in patients without nephropathy. In recent years it has become apparent that renal disease and cardiovascular disease are closely related and diabetic nephropathy is acknowledged as an independent and powerful risk factor for cardiovascular disease (3). Many patients with diabetes and renal impairment die from a cardiovascular disease event before they progress to end-stage renal disease. Diabetic nephropathy is the most common cause of end-stage renal disease worldwide and represent about 30–40% of all patients receiving renal replacement therapy in the Western World.

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 Urinary Adiponectin Is an Independent Predictor of Progression to End-Stage Renal Disease in Patients With Type 1 Diabetes and Diabetic Nephropathy

Diabetes Care ◽  
2015 ◽  
Vol 38 (5) ◽  
pp. 883-890 ◽  
Author(s):  
Nicolae M. Panduru ◽  
Markku Saraheimo ◽  
Carol Forsblom ◽  
Lena M. Thorn ◽  
Daniel Gordin ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Diabetic Nephropathy ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Independent Predictor ◽  
Stage Renal Disease ◽  
End Stage

scholarly journals Urinary complement proteins and risk of end-stage renal disease: quantitative urinary proteomics in patients with type 2 diabetes and biopsy-proven diabetic nephropathy

2021 ◽  
Author(s):  
L. Zhao ◽  
Y. Zhang ◽  
F. Liu ◽  
H. Yang ◽  
Y. Zhong ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Renal Outcome ◽  
Complement Proteins ◽  
Stage Renal Disease ◽  
End Stage ◽  
Egfr Decline

Abstract Purpose To investigate the association between urinary complement proteins and renal outcome in biopsy-proven diabetic nephropathy (DN). Methods Untargeted proteomic and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analyses and targeted proteomic analysis using parallel reaction-monitoring (PRM)-mass spectrometry was performed to determine the abundance of urinary complement proteins in healthy controls, type 2 diabetes mellitus (T2DM) patients, and patients with T2DM and biopsy-proven DN. The abundance of each urinary complement protein was individually included in Cox proportional hazards models for predicting progression to end-stage renal disease (ESRD). Results Untargeted proteomic and functional analysis using the KEGG showed that differentially expressed urinary proteins were primarily associated with the complement and coagulation cascades. Subsequent urinary complement proteins quantification using PRM showed that urinary abundances of C3, C9, and complement factor H (CFAH) correlated negatively with annual estimated glomerular filtration rate (eGFR) decline, while urinary abundances of C5, decay-accelerating factor (DAF), and CD59 correlated positively with annual rate of eGFR decline. Furthermore, higher urinary abundance of CFAH and lower urinary abundance of DAF were independently associated with greater risk of progression to ESRD. Urinary abundance of CFAH and DAF had a larger area under the curve (AUC) than that of eGFR, proteinuria, or any pathological parameter. Moreover, the model that included CFAH or DAF had a larger AUC than that with only clinical or pathological parameters. Conclusion Urinary abundance of complement proteins was significantly associated with ESRD in patients with T2DM and biopsy-proven DN, indicating that therapeutically targeting the complement pathway may alleviate progression of DN.

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