A Synopsis of the Evidence for the Science and Clinical Management of Cardiovascular-Kidney-Metabolic (CKM) Syndrome: A Scientific Statement From the American Heart Association

Circulation, Год журнала: 2023, Номер 148(20), С. 1636 - 1664

Опубликована: Окт. 9, 2023

A growing appreciation of the pathophysiological interrelatedness metabolic risk factors such as obesity and diabetes, chronic kidney disease, cardiovascular disease has led to conceptualization cardiovascular-kidney-metabolic syndrome. The confluence within syndrome is strongly linked for adverse outcomes. In addition, there are unique management considerations individuals with established coexisting factors, or both. An extensive body literature supports our scientific understanding of, approach to, prevention However, critical gaps in knowledge related terms mechanisms development, heterogeneity clinical phenotypes, interplay between social determinants health biological accurate assessments incidence context competing risks. There also key limitations data supporting care syndrome, particularly early-life prevention, screening interdisciplinary models, optimal strategies lifestyle modification weight loss, targeting emerging cardioprotective kidney-protective therapies, patients both impact systematically assessing addressing health. This statement uses a crosswalk major guidelines, addition review literature, summarize evidence fundamental science, screening,

Язык: Английский

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Diabetic Nephropathy: Update on Pillars of Therapy Slowing Progression

Diabetes Care, Год журнала: 2023, Номер 46(9), С. 1574 - 1586

Опубликована: Авг. 25, 2023

Management of diabetic kidney disease (DKD) has evolved in parallel with our growing understanding the multiple interrelated pathophysiological mechanisms that involve hemodynamic, metabolic, and inflammatory pathways. These pathways others play a vital role initiation progression DKD. Since its initial discovery, blockade renin-angiotensin system remained cornerstone DKD management, leaving large component residual risk to be dealt with. The advent sodium-glucose cotransporter 2 inhibitors followed by nonsteroidal mineralocorticoid receptor antagonists and, some extent, glucagon-like peptide 1 agonists (GLP-1 RAs) ushered resounding paradigm shift supports pillared approach maximizing treatment reduce outcomes. This is like derived from heart failure treatment. mandates all agents have been shown clinical trials cardiovascular outcomes and/or mortality greater extent than single drug class alone should used combination. In this way, each focuses on specific aspect disease's pathophysiology. Thus, failure, β-blockers, sacubitril/valsartan, antagonist, diuretic are together. article, we review evolution pillar concept therapy as it applies discuss how based outcome evidence. We also exciting possibility GLP-1 RAs may an additional quest further slow diabetes.

Язык: Английский

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Identification and validation of immune and oxidative stress-related diagnostic markers for diabetic nephropathy by WGCNA and machine learning

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Фев. 22, 2023

Diabetic nephropathy (DN) is the primary cause of end-stage renal disease, but existing therapeutics are limited. Therefore, novel molecular pathways that contribute to DN therapy and diagnostics urgently needed.

Язык: Английский

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Efficacy and safety of aldosterone synthase inhibition with and without empagliflozin for chronic kidney disease: a randomised, controlled, phase 2 trial

The Lancet, Год журнала: 2023, Номер 403(10424), С. 379 - 390

Опубликована: Дек. 15, 2023

Язык: Английский

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Type 2 diabetes mellitus in adults: pathogenesis, prevention and therapy

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Окт. 2, 2024

Язык: Английский

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Effects of semaglutide with and without concomitant SGLT2 inhibitor use in participants with type 2 diabetes and chronic kidney disease in the FLOW trial

Nature Medicine, Год журнала: 2024, Номер 30(10), С. 2849 - 2856

Опубликована: Июнь 24, 2024

Abstract People with type 2 diabetes and chronic kidney disease have a high risk for failure cardiovascular (CV) complications. Glucagon-like peptide-1 receptor agonists sodium-glucose cotransporter-2 inhibitors (SGLT2i) independently reduce CV events. The effect of combining both is unclear. FLOW trial participants were stratified by baseline SGLT2i use ( N = 550) or no 2,983) randomized to semaglutide/placebo. primary outcome was composite failure, ≥50% estimated glomerular filtration rate reduction, death death. the 24% lower in all treated semaglutide versus placebo (95% confidence interval: 34%, 12%). occurred 41/277 (semaglutide) 38/273 (placebo) on at (hazard ratio 1.07; 95% 0.69, 1.67; P 0.755) 290/1,490 372/1,493 not taking 0.73; 0.63, 0.85; < 0.001; interaction 0.109). Three confirmatory secondary outcomes predefined. Treatment differences favoring total slope (ml min −1 /1.73 m /year) 0.75 (−0.01, 1.5) subgroup 1.25 (0.91, 1.58) non-SGLT2i subgroup, 0.237. Semaglutide benefits major events all-cause similar regardless 0.741 0.901, respectively). reducing consistent with/without use; power limited detect smaller but clinically relevant effects. ClinicalTrials.gov identifier: NCT03819153 .

Язык: Английский

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Oxidative Stress: A Culprit in the Progression of Diabetic Kidney Disease

Antioxidants, Год журнала: 2024, Номер 13(4), С. 455 - 455

Опубликована: Апрель 12, 2024

Diabetic kidney disease (DKD) is the principal culprit behind chronic (CKD), ultimately developing end-stage renal (ESRD) and necessitating costly dialysis or transplantation. The limited therapeutic efficiency among individuals with DKD a result of our finite understanding its pathogenesis. complex interactions between various factors. Oxidative stress fundamental factor that can establish link hyperglycemia vascular complications frequently encountered in diabetes, particularly DKD. It crucial to recognize essential integral role oxidative development diabetic complications, Hyperglycemia primary trigger an upsurge production reactive oxygen species (ROS), sparking stress. main endogenous sources ROS include mitochondrial production, NADPH oxidases (Nox), uncoupled endothelial nitric oxide synthase (eNOS), xanthine oxidase (XO), cytochrome P450 (CYP450), lipoxygenase. Under persistent high glucose levels, immune cells, complement system, advanced glycation end products (AGEs), protein kinase C (PKC), polyol pathway, hexosamine pathway are activated. Consequently, oxidant–antioxidant balance within body disrupted, which triggers series reactions downstream pathways, including phosphoinositide 3-kinase/protein B (PI3K/Akt), transforming growth beta/p38-mitogen-activated (TGF-β/p38-MAPK), nuclear kappa (NF-κB), adenosine monophosphate-activated (AMPK), Janus kinase/signal transducer activator transcription (JAK/STAT) signaling. might persist even if strict control achieved, be attributed epigenetic modifications. treatment remains unresolved issue. Therefore, reducing intriguing target. clinical trials have shown bardoxolone methyl, erythroid 2-related 2 (Nrf2) activator, blood glucose-lowering drugs, such as sodium-glucose cotransporter inhibitors, glucagon-like peptide-1 receptor agonists effectively slow down progression by Other antioxidants, vitamins, lipoic acid, Nox regulators, present promising option for In this review, we conduct thorough assessment both preclinical studies current findings from focus on targeted interventions aimed at manipulating these pathways. We aim provide comprehensive overview state research area identify key areas future exploration.

Язык: Английский

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Recent Advances in the Management of Diabetic Kidney Disease: Slowing Progression

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(6), С. 3086 - 3086

Опубликована: Март 7, 2024

Diabetic kidney disease (DKD) is a major cause of chronic (CKD), and it heightens the risk cardiovascular incidents. The pathogenesis DKD thought to involve hemodynamic, inflammatory, metabolic factors that converge on fibrotic pathway. Genetic predisposition unhealthy lifestyle practices both play significant role in development progression DKD. In spite recent emergence angiotensin receptors blockers (ARBs)/angiotensin converting enzyme inhibitor (ACEI), sodium-glucose cotransporter 2 (SGLT2) inhibitors, nonsteroidal mineralocorticoid antagonists (NS-MRAs), current therapies still fail effectively arrest Glucagon-like peptide 1 receptor agonists (GLP-1RAs), promising class agents, possess potential act as renal protectors, slowing Other including pentoxifylline (PTF), selonsertib, baricitinib hold great promise for due their anti-inflammatory antifibrotic properties. Multidisciplinary treatment, encompassing modifications drug therapy, can decelerate Based treatment heart failure, recommended use multiple drugs combination rather than single-use Unearthing mechanisms underlying urgent optimize management Inflammatory (including IL-1, MCP-1, MMP-9, CTGF, TNF-a TGF-β1), along with lncRNAs, not only serve diagnostic biomarkers, but also therapeutic targets. this review, we delve into We explore additional value combing these develop novel strategies. Drawing from understanding pathogenesis, propose HIF AGE epigenetic targets future.

Язык: Английский

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Diabetes and Renal Complications: An Overview on Pathophysiology, Biomarkers and Therapeutic Interventions

Biomedicines, Год журнала: 2024, Номер 12(5), С. 1098 - 1098

Опубликована: Май 15, 2024

Diabetic kidney disease (DKD) is a major microvascular complication of both type 1 and 2 diabetes. DKD characterised by injury to glomerular tubular compartments, leading dysfunction over time. It one the most common causes chronic (CKD) end-stage renal (ESRD). Persistent high blood glucose levels can damage small vessels in kidneys, impairing their ability filter waste fluids from effectively. Other factors like pressure (hypertension), genetics, lifestyle habits also contribute development progression DKD. The key features complications diabetes include morphological functional alterations glomeruli tubules mesangial expansion, glomerulosclerosis, homogenous thickening basement membrane (GBM), albuminuria, tubulointerstitial fibrosis progressive decline function. In advanced stages, may require treatments such as dialysis or transplant sustain life. Therefore, early detection proactive management its are crucial preventing preserving

Язык: Английский

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Cardiovascular and Kidney Risks in Individuals With Type 2 Diabetes: Contemporary Understanding With Greater Emphasis on Excess Adiposity

Diabetes Care, Год журнала: 2024, Номер 47(4), С. 531 - 543

Опубликована: Фев. 27, 2024

In high-income countries, rates of atherosclerotic complications in type 2 diabetes have declined markedly over time due to better management traditional risk factors including lipids, blood pressure, and glycemia levels. Population-wide reductions smoking also helped lower so reduce premature mortality diabetes. However, as excess adiposity is a stronger driver for heart failure (HF), obesity levels remained largely unchanged, HF risks not much may even be rising the increasing number people developing at younger ages. Excess weight an underrecognized factor chronic kidney disease (CKD). Based on evidence from range sources, we explain how must influencing most well before develops, particularly younger-onset diabetes, which linked greater adiposity. We review potential mechanisms linking CKD speculate some responsible pathways-e.g., hemodynamic, cellular overnutrition, inflammatory-could favorably influenced by intentional loss (via lifestyle or drugs). On basis available evidence, suggest that cardiorenal outcome benefits seen with sodium-glucose cotransporter inhibitors partially derive their interference these same pathways. note many other common (e.g., hepatic, joint disease, perhaps mental health) are variably adiposity, aggregated exposure has now increased All such observations need tackle earlier

Язык: Английский

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