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Medicine Mar 2023Diabetic kidney disease is the leading cause of chronic kidney disease and end-stage renal disease. The pathogenesis and risk factors for the development of diabetic... (Review)
Review
Diabetic kidney disease is the leading cause of chronic kidney disease and end-stage renal disease. The pathogenesis and risk factors for the development of diabetic kidney disease are complex and multifaceted, resulting in glomerular hypertrophy, tubulointerstitial inflammation, and fibrosis. The clinical staging progresses over 5 stages from early hyperfiltration to overt nephropathy. Primary prevention like glycaemic control, control of blood pressure, treatment of dyslipidemia and lifestyle modifications have shown promising benefits. Despite widespread research, very few drugs are available to retard disease progression. More literature and research are needed to fill these lacunae. We carried out a literature search focusing on newer updates in diabetic kidney disease pathophysiology, diagnosis and management using a PubMed search through the National library of medicine using keywords "Diabetic kidney disease," and "Diabetic nephropathy" till the year 2022. We have summarized the relevant information from those articles.
Topics: Humans; Diabetic Nephropathies; Kidney Failure, Chronic; Blood Pressure; Risk Factors; Diabetes Mellitus
PubMed: 37000108
DOI: 10.1097/MD.0000000000033366 -
Oxidative Medicine and Cellular... 2019Diabetic nephropathy is the leading cause of chronic kidney disease (CKD) in western countries. Notably, it has a rapidly rising prevalence in China. The patients,... (Review)
Review
Diabetic nephropathy is the leading cause of chronic kidney disease (CKD) in western countries. Notably, it has a rapidly rising prevalence in China. The patients, commonly complicated with cardiovascular diseases and neurologic disorders, are at high risk to progress into end-stage renal disease (ESRD) and death. However, the pathogenic mechanisms of diabetic nephropathy have not been determined. Cellular senescence, which recently has gained broad attention, is thought to be an important player in the onset and development of diabetic nephropathy. In this issue, we generally review the mechanisms of cellular senescence in diabetic nephropathy, which involve telomere attrition, DNA damage, epigenetic alterations, mitochondrial dysfunction, loss of Klotho, Wnt/-catenin signaling activation, persistent inflammation, and accumulation of uremic toxins. Moreover, we highlight the potential therapeutic targets of cellular senescence in diabetic nephropathy and provide important clues for clinical strategies.
Topics: Animals; Cellular Senescence; DNA Damage; Diabetic Nephropathies; Epigenesis, Genetic; Humans; Mitophagy; Signal Transduction
PubMed: 31687085
DOI: 10.1155/2019/7495629 -
American Journal of Physiology. Renal... Jun 2003Diabetic 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... (Review)
Review
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.
Topics: Albuminuria; Animals; Blood Pressure; Diabetes Mellitus; Diabetic Nephropathies; Fluorescent Antibody Technique; Glomerular Mesangium; Hypertrophy; Kidney; Kidney Function Tests; Kidney Glomerulus; Mice
PubMed: 12736165
DOI: 10.1152/ajprenal.00315.2002 -
Frontiers in Endocrinology 2022Diabetic nephropathy (DN) is regarded as the leading cause of end-stage renal disease worldwide and lacks novel therapeutic targets. To screen and verify special...
Diabetic nephropathy (DN) is regarded as the leading cause of end-stage renal disease worldwide and lacks novel therapeutic targets. To screen and verify special biomarkers for glomerular injury in patients with DN, fifteen datasets were retrieved from the Gene Expression Omnibus (GEO) database, correspondingly divided into training and testing cohorts and then merged. Using the limma package, 140 differentially expressed genes (DEGs) were screened out between 81 glomerular DN samples and 41 normal ones from the training cohort. With the help of the ConsensusClusterPlus and WGCNA packages, the 81 glomerular DN samples were distinctly divided into two subclusters, and two highly associated modules were identified. By using machine learning algorithms (LASSO, RF, and SVM-RFE) and the Venn diagram, two overlapping genes (PRKAR2B and TGFBI) were finally determined as potential biomarkers, which were further validated in external testing datasets and the HFD/STZ-induced mouse models. Based on the biomarkers, the diagnostic model was developed with reliable predictive ability for diabetic glomerular injury. Enrichment analyses indicated the apparent abnormal immune status in patients with DN, and the two biomarkers played an important role in the immune microenvironment. The identified biomarkers demonstrated a meaningful correlation between the immune cells' infiltration and renal function. In conclusion, two robust genes were identified as diagnostic biomarkers and may serve as potential targets for therapeutics of DN, which were closely associated with multiple immune cells.
Topics: Algorithms; Animals; Biomarkers; Diabetes Mellitus; Diabetic Nephropathies; Humans; Machine Learning; Mice
PubMed: 35663304
DOI: 10.3389/fendo.2022.876960 -
Diabetes Care Mar 2005
Review
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Diabetic Nephropathies; Disease Models, Animal; Humans
PubMed: 15735220
DOI: 10.2337/diacare.28.3.745 -
Journal of Diabetes Research 2016
Topics: Animals; Biomarkers; Diabetic Nephropathies; Drugs, Chinese Herbal; Fibrosis; Genetic Predisposition to Disease; Hemodynamics; Humans; Inflammation; Mice; Proteinuria; Systems Biology
PubMed: 26881250
DOI: 10.1155/2016/5241549 -
Frontiers in Endocrinology 2022
Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Humans
PubMed: 36120444
DOI: 10.3389/fendo.2022.1011665 -
Frontiers in Endocrinology 2024Diabetic retinopathy (DR) and diabetic nephropathy (DN), are major microvascular complications of diabetes. DR is an important predictor of DN, but the relationship...
CONTEXT
Diabetic retinopathy (DR) and diabetic nephropathy (DN), are major microvascular complications of diabetes. DR is an important predictor of DN, but the relationship between the severity of DR and the pathological severity of diabetic glomerulopathy remains unclear.
OBJECTIVE
To investigate the relationship between severity of diabetic retinopathy (DR) and histological changes and clinical indicators of diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM).
METHODS
Patients with T2DM (n=272) who underwent a renal biopsy were eligible. Severity of DR was classified as non-diabetic retinopathy, non-proliferative retinopathy, and proliferative retinopathy (PDR). Relationship between DN and DR and the diagnostic efficacy of DR for DN were explored.
RESULTS
DN had a higher prevalence of DR (86.4%) and DR was more severe. The sensitivity and specificity of DR in DN were 86.4% and 78.8%, while PDR was 26.4% and 98.5%, respectively. In DN patients, the severity of glomerular lesions (p=0.001) and prevalence of KW nodules (p<0.001) significantly increased with increasing severity of DR. The presence of KW nodules, lower hemoglobin levels, and younger age were independent risk factors associated with more severe DR in patients with DN.
CONCLUSION
DR was a good predictor of DN. In DN patients, the severity of DR was associated with glomerular injury, and presence of KW nodules, lower hemoglobin levels and younger age were independent risk factors associated with more severe DR.
TRIAL REGISTRATION
ClinicalTrails.gov, NCT03865914.
Topics: Humans; Diabetic Nephropathies; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Risk Factors; Hemoglobins
PubMed: 38344659
DOI: 10.3389/fendo.2024.1292412 -
Frontiers in Endocrinology 2023Diabetic nephropathy (DN) is a serious microvascular consequence of diabetes mellitus (DM), posing an encumbrance to public health worldwide. Control over the onset and... (Review)
Review
Diabetic nephropathy (DN) is a serious microvascular consequence of diabetes mellitus (DM), posing an encumbrance to public health worldwide. Control over the onset and progress of DN depend heavily on early detection and effective treatment. DN is a major contributor to end-stage renal disease, and a complete cure is yet to be achieved with currently available options. Though some therapeutic molecules have exhibited promise in treating DN complications, their poor solubility profile, low bioavailability, poor permeation, high therapeutic dose and associated toxicity, and low patient compliance apprehend their clinical usefulness. Recent research has indicated nano-systems as potential theranostic platforms displaying futuristic promise in the diagnosis and treatment of DN. Early and accurate diagnosis, site-specific delivery and retention by virtue of ligand conjugation, and improved pharmacokinetic profile are amongst the major advantages of nano-platforms, defining their superiority. Thus, the emergence of nanoparticles has offered fresh approaches to the possible diagnostic and therapeutic strategies regarding DN. The present review corroborates an updated overview of different types of nanocarriers regarding potential approaches for the diagnosis and therapy of DN.
Topics: Humans; Diabetic Nephropathies; Nanomedicine; Kidney Failure, Chronic; Glomerular Filtration Rate; Precision Medicine; Diabetes Mellitus
PubMed: 38027185
DOI: 10.3389/fendo.2023.1236686 -
Journal of Diabetes Research 2017
Topics: Albuminuria; Diabetic Nephropathies; Humans
PubMed: 29201920
DOI: 10.1155/2017/2379432