Diabetic Nephropathy: Challenges in Pathogenesis, Diagnosis, and Treatment

BioMed Research International, Journal Year: 2021, Volume and Issue: 2021, P. 1 - 17

Published: July 8, 2021

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. Chronic hyperglycemia and high blood pressure are main risk factors for development DN. In general, screening microalbuminuria should be performed annually, starting 5 years after diagnosis in type 1 diabetes at annually thereafter 2 diabetes. Standard therapy glucose control using renin-angiotensin system blockade, targeting $\text{A}1\text{c}<7\%$ , <130/80 mmHg. Regression albuminuria remains an important therapeutic goal. However, there problems treatment nonproteinuric DN (NP-DN), which does not follow classic pattern fact, prevalence continues to increase, additional needed prevent or ameliorate condition. addition conventional therapies, vitamin D receptor activators, incretin-related drugs, therapies that target inflammation may also promising prevention progression. This review focuses on role oxidative stress pathogenesis DN, approaches NP-DN, current emerging interventions.

Language: Английский

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Early detection of diabetic nephropathy in patient with type 2 diabetes mellitus: A review of the literature

Diabetes and Vascular Disease Research, Journal Year: 2021, Volume and Issue: 18(6)

Published: Nov. 1, 2021

Type 2 diabetes mellitus is a pathology of heterogeneous etiology characterized by hyperglycemia resulting from lack insulin action, secretion, or both, and the population with predicted to be about 439 million worldwide 2030. Prolong has been related microvascular complications especially diabetic nephropathy. DN most common complication type mellitus, it leading cause end-stage renal disease worldwide. It crucial diagnose patients who are more sensible develop for better control process disease. Several factors mechanisms contribute development outcome Microalbuminuria an early marker use as routine screening, but damages may happening even without microalbuminuria. There several significant kidney damage biomarkers which helps in detection DN. An biomarker allow earlier diagnosis, treatment reduces prevalence slows progression. Therefore, this review focuses on laboratory that earlier, validation specific could potentially make possible treatment, retardation progression

Language: Английский

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Oxidative stress and inflammation in diabetic nephropathy: role of polyphenols

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: July 21, 2023

Diabetic nephropathy (DN) often leads to end-stage renal disease. Oxidative stress demonstrates a crucial act in the onset and progression of DN, which triggers various pathological processes while promoting activation inflammation forming vicious oxidative stress-inflammation cycle that induces podocyte injury, extracellular matrix accumulation, glomerulosclerosis, epithelial-mesenchymal transition, tubular atrophy, proteinuria. Conventional treatments for DN have limited efficacy. Polyphenols, as antioxidants, are widely used with multiple targets fewer adverse effects. This review reveals stress-associated led damage cells, including podocytes, endothelial mesangial epithelial cells. It potent antioxidant anti-inflammatory properties by targeting Nrf2, SIRT1, HMGB1, NF-κB, NLRP3 polyphenols, quercetin, resveratrol, curcumin, phenolic acid. However, there remains long way comprehensive understanding molecular mechanisms applications clinical therapy polyphenols.

Language: Английский

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Immune responses in diabetic nephropathy: Pathogenic mechanisms and therapeutic target

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 15, 2022

Diabetic nephropathy (DN) is a chronic, inflammatory disease affecting millions of diabetic patients worldwide. DN associated with proteinuria and progressive slowing glomerular filtration, which often leads to end-stage kidney diseases. Due the complexity this metabolic disorder lack clarity about its pathogenesis, it more difficult diagnose treat than other Recent studies have highlighted that immune system can inadvertently contribute pathogenesis. Cells involved in innate adaptive responses target due increased expression immune-related localization factors. Immune cells then activate pro-inflammatory response involving release autocrine paracrine factors, further amplify inflammation damage kidney. Consequently, strategies by targeting are currently under study. In light steady rise incidence, timely review summarizes latest findings role pathogenesis discusses promising preclinical clinical therapies.

Language: Английский

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Ubiquitin-Specific Proteases (USPs) and Metabolic Disorders

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3219 - 3219

Published: Feb. 6, 2023

Ubiquitination and deubiquitination are reversible processes that modify the characteristics of target proteins, including stability, intracellular localization, enzymatic activity. Ubiquitin-specific proteases (USPs) constitute largest deubiquitinating enzyme family. To date, accumulating evidence indicates several USPs positively negatively affect metabolic diseases. USP22 in pancreatic β-cells, USP2 adipose tissue macrophages, USP9X, 20, 33 myocytes, USP4, 7, 10, 18 hepatocytes, hypothalamus improve hyperglycemia, whereas USP19 adipocytes, USP21 USP2, 14, 20 hepatocytes promote hyperglycemia. In contrast, USP1, 5, 9X, 15, 22, 36, 48 modulate progression diabetic nephropathy, neuropathy, and/or retinopathy. ameliorates non-alcoholic fatty liver disease (NAFLD), while hepatic 11, 19, exacerbate it. The roles USP7 22 disorders controversial. 17, vascular cells postulated to be determinants atherosclerosis. Moreover, mutations

Language: Английский

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Flavonoids improve type 2 diabetes mellitus and its complications: a review

Frontiers in Nutrition, Journal Year: 2023, Volume and Issue: 10

Published: May 31, 2023

The prevalence of type 2 diabetes mellitus (T2DM) is increasing every year. Medications are currently the most common therapy for T2DM. However, these medications have certain adverse effects. In order to find safe and effective ways improve this disease, researchers discovered that some natural products can decrease blood sugar. Flavonoids one essential low molecular weight phenolic chemicals in plant world, which widely exist roots, stems, leaves, flowers, fruits. They possess a variety biological activities, including organ protection, hypoglycemic, lipid-lowering, anti-oxidative anti-inflammatory Some flavonoids ameliorate T2DM its complications through anti-oxidation, action, glucose lipid metabolism regulation, insulin resistance management, etc. Hence, review aims at demonstrating potential benefits complications. This laid foundation development novel hypoglycemic from flavonoids.

Language: Английский

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Emerging Role of Ferroptosis in Diabetic Kidney Disease: Molecular Mechanisms and Therapeutic Opportunities

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 19(9), P. 2678 - 2694

Published: Jan. 1, 2023

Diabetic kidney disease (DKD) is one of the most common and severe microvascular complications diabetes mellitus (DM), has become leading cause end-stage renal (ESRD) worldwide.Although exact pathogenic mechanism DKD still unclear, programmed cell death been demonstrated to participate in occurrence development diabetic injury, including ferroptosis.Ferroptosis, an iron-dependent form driven by lipid peroxidation, identified play a vital role therapeutic responses variety diseases, such as acute injury (AKI), carcinoma DKD.In past two years, ferroptosis well investigated patients animal models, but specific mechanisms effects have not fully revealed.Herein, we reviewed regulatory ferroptosis, summarized recent findings associated with involvement DKD, discussed potential promising target for treatment, thereby providing valuable reference basic study clinical therapy DKD.

Language: Английский

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Podocyte injury of diabetic nephropathy: Novel mechanism discovery and therapeutic prospects

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 168, P. 115670 - 115670

Published: Oct. 13, 2023

Diabetic nephropathy (DN) is a severe complication of diabetes mellitus, posing significant challenges in terms early prevention, clinical diagnosis, and treatment. Consequently, it has emerged as major contributor to end-stage renal disease. The glomerular filtration barrier, composed podocytes, endothelial cells, the basement membrane, plays vital role maintaining function. Disruptions podocyte function, including hypertrophy, shedding, reduced density, apoptosis, can impair integrity resulting elevated proteinuria, abnormal rate, increased creatinine levels. Hence, recent research increasingly focused on injury DN, with growing emphasis exploring therapeutic interventions targeting injury. Studies have revealed that factors such lipotoxicity, hemodynamic abnormalities, oxidative stress, mitochondrial dysfunction, impaired autophagy contribute This review aims summarize underlying mechanisms DN provide an overview current status regarding experimental drugs DN. findings presented herein may offer potential targets strategies for management associated

Language: Английский

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Mitochondrial oxidative damage reprograms lipid metabolism of renal tubular epithelial cells in the diabetic kidney

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: Jan. 11, 2024

Abstract The functional and structural changes in the proximal tubule play an important role occurrence development of diabetic kidney disease (DKD). Diabetes-induced metabolic changes, including lipid metabolism reprogramming, are reported to lead state tubular epithelial cells (TECs), among all disturbances metabolism, mitochondria serve as central regulators. Mitochondrial dysfunction, accompanied by increased production mitochondrial reactive oxygen species (mtROS), is considered one primary factors causing injury. Most studies have discussed how altered flux drives oxidative stress during DKD. In present study, we focused on targeting damage upstream factor abnormalities under conditions TECs. Using SS31, a tetrapeptide that protects cristae structure, demonstrated contributes TEC injury peroxidation caused accumulation. Mitochondria protected using SS31 significantly reversed decreased expression key enzymes regulators fatty acid oxidation (FAO), but had no obvious effect major glucose rate-limiting enzymes. facilitated renal Sphingosine-1-phosphate (S1P) deposition limited elevated Acer1, S1pr1 SPHK1 activity, Spns2 expression. These data suggest unbalanced droplet (LD) formulation, peroxidation, impaired FAO sphingolipid homeostasis An vitro study high drove cytosolic phospholipase A2 (cPLA2), which, turn, was responsible for LD generation S1P accumulation, HK-2 cells. A mitochondria-targeted antioxidant inhibited activation cPLA2f isoforms. Taken together, these findings identify mechanistic links between reprogrammed TECs, provide further evidence nephroprotective effects via influencing pathways.

Language: Английский

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Inflammation in diabetes complications: molecular mechanisms and therapeutic interventions

MedComm, Journal Year: 2024, Volume and Issue: 5(4)

Published: April 1, 2024

Abstract At present, diabetes mellitus (DM) has been one of the most endangering healthy diseases. Current therapies contain controlling high blood sugar, reducing risk factors like obesity, hypertension, and so on; however, DM patients inevitably eventually progress into different types complications, resulting in poor quality life. Unfortunately, clear etiology pathogenesis complications have not elucidated owing to intricate whole‐body systems. The immune system was responsible regulate homeostasis by triggering or resolving inflammatory response, indicating it may be necessary complications. In fact, previous studies shown inflammation plays multifunctional roles is attracting attention meaningful therapeutic strategy. To this end, review systematically concluded current over relationships susceptible (e.g., diabetic cardiomyopathy, retinopathy, peripheral neuropathy, nephropathy) inflammation, ranging from cell cytokines interaction pathomechanism organ injury. Besides, we also summarized various strategies improve target special remedies conventional lifestyle changes. This will offer a panoramic insight mechanisms an perspective discuss contemporary clinical interventions.

Language: Английский

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