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Diabetes/metabolism Research and Reviews Feb 2017Diabetic nephropathy constitutes a devastating complication in patients with type 1 diabetes mellitus, and its diagnosis is traditionally based on microalbuminuria. The... (Review)
Review
Diabetic nephropathy constitutes a devastating complication in patients with type 1 diabetes mellitus, and its diagnosis is traditionally based on microalbuminuria. The aim of this review is to update through the medical literature the suggested early natural course of diabetic nephropathy, the theories behind the pathways of its pathogenesis, and its diagnosis. Poor glycemic control, dyslipidemia, smoking, advanced glycation end products, and environmental and genetic clues play an important role in the development of diabetic nephropathy. Microalbuminuria has been traditionally considered as a primary early marker of microvascular complication unraveling the risk for progress to the advanced stages of chronic kidney disease, but because of our inability to make an early diagnosis of diabetic nephropathy in young patients as well as nonalbuminuric diabetic nephropathy, recently, other additional markers of renal injury like serum and urinary neutrophil gelatinase-associated lipocalin, chitinase-3-like protein 1, cystatin C, and plasma growth differentiation factor 15 have been proposed to unmask early renal dysfunction, even before microalbuminuria supervenes. Copyright © 2016 John Wiley & Sons, Ltd.
Topics: Biomarkers; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Humans
PubMed: 27457509
DOI: 10.1002/dmrr.2841 -
Pharmacology & Therapeutics Jan 2023Diabetic nephropathy is one of the most common complications in diabetes. It has been shown to be the leading cause of end-stage renal disease. However, due to their... (Review)
Review
Diabetic nephropathy is one of the most common complications in diabetes. It has been shown to be the leading cause of end-stage renal disease. However, due to their complex pathological mechanisms, effective therapeutic drugs other than angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), which have been used for 20 years, have not been developed so far. Recent studies have shown that diabetic nephropathy is characterized by multiple signalling pathways and multiple targets, including inflammation, apoptosis, pyroptosis, autophagy, oxidative stress, endoplasmic reticulum stress and their interactions. It definitely exacerbates the difficulty of therapy, but at the same time it also brings out the chance for natural products treatment. In the most recent two decades, a large number of natural products have displayed their potential in preclinical studies and a few compounds are under invetigation in clinical trials. Hence, many compounds targeting these singals have been emerged as a comprehensive blueprint for treating strategy of diabetic nephropathy. This review focuses on the cellular and molecular mechanisms of natural prouducts that alleviate this condition, including preclinical studies and clinical trials, which will provide new insights into the treatment of diabetic nephropathy and suggest novel ideas for new drug development.
Topics: Humans; Diabetic Nephropathies; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Diabetes Mellitus
PubMed: 36427568
DOI: 10.1016/j.pharmthera.2022.108314 -
Biomedicine & Pharmacotherapy =... Dec 2022Diabetic nephropathy (DN) is the leading cause of end‑stage renal disease. Although Ginkgo biloba extract has a protective effect on DN, the protective effect and...
Diabetic nephropathy (DN) is the leading cause of end‑stage renal disease. Although Ginkgo biloba extract has a protective effect on DN, the protective effect and mechanism of its active ingredient Ginkgolide B (GB) on DN remain unclear. The aim of the present study was to investigate whether GB improves DN via alleviating oxidative stress and ferroptosis by inhibiting GPX4 ubiquitination in PA-G-induced mouse podocytes and DN mice. The study in vitro showed that GB effectively reduced serum total cholesterol, triglyceride concentrations and lipid accumulation in PA-G-induced MPC5 cells. In addition, GB promoted the expression of ferroptosis markers GPX4 and FTH1, while inhibited the expression of TfR1, fibrosis markers α-SMA and Collagen α1, as well as intracellular iron content and ROS levels. Interference of GPX4 expression with siRNA counteracted the effect of GB. And GB inhibited GPX4 ubiquitination in a dose-dependent manner. In vivo the experimental results showed that GB effectively reduced hyperglycemia, serum total cholesterol and triglyceride concentrations, reduced urinary albumin excretion and the number of renal lipid droplets, and improved changes in renal structure in DN mice. GB inhibited the expression of ferroptosis marker TfR1 and fibrosis markers α-SMA and Collagen α1, while promoted the expression of ferroptosis markers GPX4 and FTH1. In conclusion, the results suggested that GB may improve DN via protecting the kidney from ferroptosis and oxidative stress damage by inhibiting the ubiquitination of GPX4. These findings suggested that GB, a natural medicine, may be an effective therapeutic option for DN.
Topics: Mice; Animals; Ferroptosis; Diabetic Nephropathies; Phospholipid Hydroperoxide Glutathione Peroxidase; Oxidative Stress; Ubiquitination; Fibrosis; Triglycerides; Cholesterol; Diabetes Mellitus
PubMed: 36411664
DOI: 10.1016/j.biopha.2022.113953 -
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 -
Frontiers in Endocrinology 2022With the development of economy, the living standard of people all over the world has been greatly improved, and the incidence of diabetes is also increasing. Many...
BACKGROUND
With the development of economy, the living standard of people all over the world has been greatly improved, and the incidence of diabetes is also increasing. Many people with diabetes also develop other complications that reduce their quality of life. Diabetic nephropathy is a common complication of type2 diabetes. Understanding the related factors of diabetic nephropathy is greatly significant to control the occurrence of diabetic nephropathy and improve patient's life quality.
DATA AND METHODS
Data were collected from 2009 to 2018 in NHANES. Curve fitting graph was performed to investigate the association between globulin (GLB) and diabetic nephropathy(DN). Four logistic regression models were conducted to control the potential confounding factors. Subgroup analysis was carried out to assess the stability of results.
RESULTS
GLB was positively correlated with the occurrence of DN after controlling for potential confounders. Higher GLB was associated with an increased risk of diabetic nephropathy [odds ratio(OR), 1.10; 95% confidence interval (CI), 1.07-1.13, < 0.001].
CONCLUSIONS
In this cross-sectional study, GLB was significant positively correlated with the occurrence of DN in patients with type2 diabetes mellitus.
Topics: Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Globulins; Humans; Nutrition Surveys; Quality of Life
PubMed: 35898464
DOI: 10.3389/fendo.2022.890273 -
Medicine Oct 2023Diabetic nephropathy (DN) is a common and severe complication of diabetes mellitus and is the leading cause of chronic kidney disease (CKD) worldwide. Despite current... (Review)
Review
Diabetic nephropathy (DN) is a common and severe complication of diabetes mellitus and is the leading cause of chronic kidney disease (CKD) worldwide. Despite current treatments, many individuals with DN progress to end-stage renal disease (ESRD), requiring dialysis or kidney transplantation. The advancement in our understanding of the pathogenesis of diabetic nephropathy has led to the development of new prevention and treatment strategies. We comprehensively reviewed the literature on advances in the prevention and treatment of DN. We searched PubMed, Scopus, and Web of Science databases for articles published between 2000 and 2023, using keywords such as "diabetic nephropathy," "prevention," "treatment," and "recent advances." The recent advances in the prevention and treatment of DN include novel approaches targeting inflammation and fibrosis, such as inhibitors of the nuclear factor kappa-B (NF-kB) pathway, inhibitors of the transforming growth factor-beta (TGF-beta) pathway, and anti-inflammatory cytokines. Other promising strategies include stem cell therapy, gene therapy, and artificial intelligence-based approaches, such as predictive models based on machine learning algorithms that can identify individuals at high risk of developing DN and guide personalized treatment strategies. Combination therapies targeting multiple disease pathways may also offer the most significant potential for improving outcomes for individuals with DN. Overall, the recent advances in the prevention and treatment of DN represent promising avenues for future research and clinical development. Novel therapies targeting inflammation and fibrosis, stem cell and gene therapies, and artificial intelligence-based approaches all show great potential for improving outcomes for individuals with DN.
Topics: Humans; Diabetic Nephropathies; Artificial Intelligence; Renal Dialysis; Inflammation; Fibrosis; Kidney; Diabetes Mellitus
PubMed: 37800812
DOI: 10.1097/MD.0000000000035397 -
Frontiers in Endocrinology 2023A causal relationship concerning coffee intake and diabetic nephropathy (DN) is controversial. We conducted a Mendelian randomization study to assess the causal nature...
RATIONALE AND OBJECTIVE
A causal relationship concerning coffee intake and diabetic nephropathy (DN) is controversial. We conducted a Mendelian randomization study to assess the causal nature of these associations.
METHODS
40 independent single nucleotide polymorphisms (SNPs) associated with coffee intake were selected from the UK Biobank study. Summary-level data for diabetic nephropathy were obtained from publicly available genome-wide association studies (GWAS) and the FinnGen consortium. Inverse variance weighted (IVW), MR-Egger, and weighted median (WM) methods were used to examine a causal association. Sensitivity analyses included Cochran's Q test, the intercept of MR-Egger, MR-PRESSO, and the Outlier method. Leave-One-Out sensitivity analyses were also conducted to reduce the heterogeneity.
RESULTS
Our current study demonstrated positive associations of genetically predicted coffee intake with diabetic nephropathy (OR=1.939; = 0.045 and type 2 diabetes with renal complications (OR = 2.787, = 0.047). These findings were robust across several sensitivity analyses.
CONCLUSIONS
This study found a positive correlation between coffee consumption and the risk of diabetic nephropathy using genetic data. For a more accurate and trustworthy conclusion, subgroup analysis on coffee intake, including preparing method, variety of coffee, and quantity, is required.
Topics: Humans; Diabetic Nephropathies; Coffee; Diabetes Mellitus, Type 2; Genome-Wide Association Study; Mendelian Randomization Analysis
PubMed: 37469984
DOI: 10.3389/fendo.2023.1169933 -
Nature Reviews. Nephrology May 2017The development of type 1 and type 2 diabetes mellitus has a substantial negative impact on morbidity and mortality and is responsible for substantial individual and... (Review)
Review
The development of type 1 and type 2 diabetes mellitus has a substantial negative impact on morbidity and mortality and is responsible for substantial individual and socioeconomic costs worldwide. One of the most serious consequences of diabetes mellitus is the development of diabetic angiopathy, which manifests clinically as microvascular and macrovascular complications. One microvascular complication, diabetic nephropathy, is the most common cause of end-stage renal disease in developed countries. Although several available therapeutic interventions can delay the onset and progression of diabetic nephropathy, morbidity associated with this disease remains high and new therapeutic approaches are needed. In addition, not all patients with diabetes mellitus will develop diabetic nephropathy and thus new biomarkers are needed to identify individuals who will develop this life-threatening disease. An increasing body of evidence points toward a role of the complement system in the pathogenesis of diabetic nephropathy. For example, circulating levels of mannose-binding lectin (MBL), a pattern recognition molecule of the innate immune system, have emerged as a robust biomarker for the development and progression of this disease, and evidence suggests that MBL, H-ficolin, complement component C3 and the membrane attack complex might contribute to renal injury in the hyperglycaemic mileu. New approaches to modulate the complement system might lead to the development of new agents to prevent or slow the progression of diabetic nephropathy.
Topics: Complement Membrane Attack Complex; Complement System Proteins; Diabetic Nephropathies; Glycoproteins; Humans; Lectins; Mannose-Binding Lectin
PubMed: 28262777
DOI: 10.1038/nrneph.2017.31 -
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 -
Experimental and Clinical Endocrinology... Dec 2016
Topics: Diabetic Nephropathies; Humans; Hypertension
PubMed: 27280477
DOI: 10.1055/s-0036-1582341