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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Therapeutic Advances in Diabetic Nephropathy

Journal of Clinical Medicine, Journal Year: 2022, Volume and Issue: 11(2), P. 378 - 378

Published: Jan. 13, 2022

Diabetic kidney disease (DKD) is the most common cause of end-stage (ESKD) in United States. Risk factor modification, such as tight control blood glucose, management hypertension and hyperlipidemia, use renin-angiotensin-aldosterone system (RAAS) blockade have been proven to help delay progression DKD. In recent years, new therapeutics including sodium-glucose transport protein 2 (SGLT2) inhibitors, endothelin antagonists, glucagon like peptide-1 (GLP-1) agonists, mineralocorticoid receptor antagonists (MRA), provided additional treatment options for patients with This review discusses various available treat diabetic disease.

Language: Английский

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Diabetic Nephropathy: Significance of Determining Oxidative Stress and Opportunities for Antioxidant Therapies

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(15), P. 12378 - 12378

Published: Aug. 3, 2023

Diabetes mellitus (DM) belongs to the category of socially significant diseases with epidemic rates increases in prevalence. Diabetic nephropathy (DN) is a specific kind kidney damage that occurs 40% patients DM and considered serious complication DM. Most modern methods for treatments aimed at slowing down progression DN have side effects do not produce unambiguous positive results long term. This fact has encouraged researchers search additional or alternative treatment methods. Hyperglycemia negative effect on renal structures due number factors, including activation polyol hexosamine glucose metabolism pathways, renin-angiotensin-aldosterone sympathetic nervous systems, accumulation advanced glycation end products insulin resistance endothelial dysfunction tissues. The above mechanisms cause development oxidative stress (OS) reactions mitochondrial dysfunction, which turn contribute DN. Modern antioxidant therapies involve various phytochemicals (food antioxidants, resveratrol, curcumin, alpha-lipoic acid preparations, etc.), are widely used only diabetes but also other systemic diseases. It been suggested therapeutic approaches target source reactive oxygen species may certain advantages terms nephroprotection from OS. review describes significance studies OS biomarkers pathogenesis analyzes reducing intensity prevention

Language: Английский

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T cells and their products in diabetic kidney disease

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

Published: Jan. 26, 2023

Diabetic kidney disease (DKD) is the most common cause of end-stage renal and has gradually become a public health problem worldwide. DKD increasingly recognized as comprehensive inflammatory that largely regulated by T cells. Given pivotal role cells cells-producing cytokines in DKD, we summarized recent advances concerning progression type 2 diabetic nephropathy provided novel perspective immune-related factors diabetes. Specific emphasis placed on classification cells, process cell recruitment, function development damage, potential treatments therapeutic strategies involving

Language: Английский

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Osteopontin as a Biomarker in Chronic Kidney Disease

Biomedicines, Journal Year: 2023, Volume and Issue: 11(5), P. 1356 - 1356

Published: May 4, 2023

Osteopontin (OPN) is a ubiquitously expressed protein with wide range of physiological functions, including roles in bone mineralization, immune regulation, and wound healing. OPN has been implicated the pathogenesis several forms chronic kidney disease (CKD) where it promotes inflammation fibrosis regulates calcium phosphate metabolism. expression increased kidneys, blood, urine patients CKD, particularly those diabetic glomerulonephritis. The full-length cleaved by various proteases, thrombin, matrix metalloproteinase (MMP)-3, MMP-7, cathepsin-D, plasmin, producing N-terminal (ntOPN), which may have more detrimental effects CKD. Studies suggest that serve as biomarker while research needed to fully evaluate validate ntOPN CKD biomarkers, available evidence suggests they are promising candidates for further investigation. Targeting be potential treatment strategy. Several studies show inhibition or activity can attenuate injury improve function. In addition its on function, linked cardiovascular disease, major cause morbidity mortality

Language: Английский

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Pathomechanisms of Diabetic Kidney Disease

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(23), P. 7349 - 7349

Published: Nov. 27, 2023

The worldwide occurrence of diabetic kidney disease (DKD) is swiftly rising, primarily attributed to the growing population individuals affected by type 2 diabetes. This surge has been transformed into a substantial global concern, placing additional strain on healthcare systems already grappling with significant demands. pathogenesis DKD intricate, originating hyperglycemia, which triggers various mechanisms and pathways: metabolic, hemodynamic, inflammatory, fibrotic ultimately lead renal damage. Within each pathway, several mediators contribute development structural functional changes. Some these mediators, such as inflammatory cytokines, reactive oxygen species, transforming growth factor β are shared among different pathways, leading overlap interaction between them. While current treatment options for have shown advancement over previous strategies, their effectiveness remains somewhat constrained patients still experience residual risk progression. Therefore, comprehensive grasp molecular underlying onset progression imperative continued creation novel groundbreaking therapies this condition. In review, we discuss achievements in fundamental research, particular emphasis individual factors recent developments treatment.

Language: Английский

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Efficacy and safety of tripterygium glycosides combined with ACEI/ARB on diabetic nephropathy: a meta-analysis

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 17, 2025

This study aims to evaluate the efficacy and safety of tripterygium glycosides combined with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARBs) in treating Diabetic nephropathy provide high-level evidence support its standardized application. Literatures were retrieved from PubMed, Web Science, EMBASE, Cochrane Library, CNKI, Wanfang VIP databases, search time frame was defined as establishment April 2023. only included randomized controlled trials ACEI/ARB treatment diabetic nephropathy, final studies identified according inclusion exclusion criteria, meta-analysis data performed using RevMan 5.3 software. A total 44 RCTs 3537 DN patients study. Compared control group, significantly reducing 24 h-UTP (24 h urine protein) [SMD = -1.46, 95% CI (-1.70, -1.23), P < 0.00001], increasing effective rate [RR 1.23, (1.17,1.29), elevating serum albumin 0.85, (0.69, 1.02), improving creatinine -0.35, (-0.59, -0.11), 0.004], no difference BUN (blood urea nitrogen) -0.17, (-0.48,0.13), 0.27], adverse reactions higher than those group 1.96, 95%CI (1.43, 2.68), 0.0001]. showed that combination more alone. However, side effects especially liver function damage, which also suggested worth considering. Therefore, although provided a choice for clinical limited In future studies, we need further optimize reduce ensure

Language: Английский

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Kidney and Cardiovascular Outcomes Among Patients With CKD Receiving GLP-1 Receptor Agonists: A Systematic Review and Meta-Analysis of Randomized Trials

American Journal of Kidney Diseases, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve cardiac and kidney outcomes in patients with diabetes; however their efficacy individuals reduced estimated glomerular filtration rate (eGFR) is uncertain. This study evaluated the effects of GLP-1RAs on cardiovascular (CV) chronic disease (CKD). Systematic review meta-analysis randomized controlled trials (RCTs) reported through May 25, 2024. Adult participants RCTs baseline eGFR <60 mL/min/1.73 m2. including adults (≥18 years old) varying degrees function, CKD characterized by a less than 60 m2, that compared control treatments respect to composite outcome, all-cause mortality, or CV outcome. From among 212 screened studies, 12 involving included m2 were included. Two independent investigators extracted data. Pooled odds ratios (ORs) for outcome using random-effects models. Evidence certainty was assessed GRADE system. 17,996 RCT analyses. significantly associated risk (OR: 0.85 [95% CI 0.77-0.94]; p=0.001) low heterogeneity (I2<0.01%). also >30% decline 0.78, p=0.004), >40% 0.76, p=0.01), >50% 0.72, p<0.001). Risk mortality lower GLP-1RA group 0.77 0.60-0.98]; p=0.03), though there high (I2=71.6%). Composite use GLP-1R 0.86 0.74-0.99]; p=0.03; I2=40.3%). Sensitivity analyses restricted human GLP-1 backbone agents showed enhanced benefits. Inconsistent definitions, focus diabetic populations most potential publication bias. improved outcomes, survival enrolled an array clinical trials.

Language: Английский

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MicroRNA-10 negatively regulates inflammation in diabetic kidney via targeting activation of the NLRP3 inflammasome

Molecular Therapy, Journal Year: 2021, Volume and Issue: 29(7), P. 2308 - 2320

Published: March 18, 2021

NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome activation has emerged as a central mediator of kidney inflammation in diabetic disease (DKD). However, the mechanism underlying this DKD remains poorly defined. In study, we found that kidney-enriched microRNA-10a -10b (miR-10a/b), predominantly expressed podocytes tubular epithelial cells, were downregulated from mice patients with DKD. High glucose decreased miR-10a/b expression vitro an osmolarity-independent manner. functioned negative regulators through targeting 3′untranslated region mRNA, inhibiting assembly decreasing caspase-1-dependent release pro-inflammatory cytokines. Delivery into prevented renal inflammation, it reduced albuminuria streptozotocin (STZ)-treated mice, whereas knocking down increased activation. Restoration established ameliorated mitigated both db/db STZ-treated mice. These results suggest novel intervention strategy for by inflammasome.

Language: Английский

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Serum integrative omics reveals the landscape of human diabetic kidney disease

Molecular Metabolism, Journal Year: 2021, Volume and Issue: 54, P. 101367 - 101367

Published: Nov. 1, 2021

Diabetic kidney disease (DKD) is the most common microvascular complication of type 2 diabetes mellitus (2-DM). Currently, urine and biopsy specimens are major clinical resources for DKD diagnosis. Our study proposes to evaluate diagnostic value blood in monitoring onset distinguishing its status clinic.This recruited 1,513 participants including healthy adults patients diagnosed with 2-DM, early-stage (DKD-E), advanced-stage (DKD-A) from 4 independent medical centers. One discovery four testing cohorts were established. Sera collected subjected training proteomics large-scale metabolomics.Deep profiling serum proteomes metabolomes revealed several insights. First, that combination α2-macroglobulin, cathepsin D, CD324 could serve as a surrogate protein biomarker progression. Second, metabolomics demonstrated galactose metabolism glycerolipid disturbed metabolic pathways DKD, metabolite glycerol-3-galactoside be used an marker predict DKD. Third, integrating increased predictive stability accuracy status.Serum integrative omics provide stable accurate biomarkers early warning diagnosis provides rich open-access data resource optimizing management.

Language: Английский

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