Molecular mechanisms and therapeutic targets for diabetic kidney disease

Kidney International, Journal Year: 2022, Volume and Issue: 102(2), P. 248 - 260

Published: June 3, 2022

Diabetic kidney disease has a high global burden and substantially increases the risk of failure cardiovascular events. Despite treatment, there is substantial residual progression with existing therapies. Therefore, an urgent need to better understand molecular mechanisms driving diabetic help identify new therapies that slow reduce associated risks. initiated by diabetes-related disturbances in glucose metabolism, which then trigger other metabolic, hemodynamic, inflammatory, fibrotic processes contribute progression. This review summarizes evidence on drivers onset progression, focusing inflammatory mediators—factors are largely unaddressed as primary treatment targets for increasing supporting key roles pathophysiology disease. Results from recent clinical trials highlight promising drug therapies, well role dietary strategies, treating Chronic (CKD), characterized albuminuria, low estimated glomerular filtration rate (eGFR), or both,1GBD Kidney Disease CollaborationGlobal, regional, national chronic disease, 1990-2017: systematic analysis Global Burden Study 2017.Lancet. 2020; 395: 709-733Abstract Full Text PDF PubMed Scopus (1156) Google Scholar affect over 840 million people worldwide.2Jager K.J. Kovesdy C. Langham R. et al.A single number advocacy communication-worldwide more than 850 individuals have diseases.Kidney Int. 2019; 96: 1048-1050Abstract (DKD), damage due diabetes, leading attributable cause CKD, occurring approximately 40% type 2 diabetes (T2D) 30% those 1 (T1D).1GBD Scholar,3Alicic R.Z. Rooney M.T. Tuttle K.R. disease: challenges, progress, possibilities.Clin J Am Soc Nephrol. 2017; 12: 2032-2045Crossref (753) The DKD expected increase parallel rise prevalence,3Alicic projected nearly 50%, 537 783 people, next 24 years.4International Diabetes FederationIDF Atlas.10th ed. International Federation, 2021Google improve diagnosis management DKD, including target related (CV) risk.1GBD Mechanisms can be broadly classified fibrotic.3Alicic Scholar,5Pérez-Morales R.E. Del Pino M.D. Valdivielso J.M. al.Inflammation disease.Nephron. 143: 12-16Crossref (57) Scholar,6Mora-Fernández Domínguez-Pimentel V. de Fuentes M.M. al.Diabetic physiology therapeutics.J Physiol. 2014; 592: 3997-4012Crossref (99) In this review, current understanding drive pathogenesis presented basis advancing therapeutic interventions. Hyperglycemia induces hyperfiltration hypertension, hemodynamic long been recognized initiate propagate diabetes.3Alicic Glomerular exacerbated levels amino acids, example, after protein overfeeding, hormonal changes poor glycemic control, level glucagon.7Rhee C.M. Kalantar-Zadeh K. Novel approaches hypoglycemia burnt-out disease.Curr Opin Nephrol Hypertens. 2022; 31: 72-81Crossref (0) Scholar, 8Tuttle Bruton J.L. Effect insulin therapy renal response acids hypertrophy non-insulin-dependent diabetes.Kidney 1992; 42: 167-173Abstract 9Tuttle Perusek M.C. al.Effect strict control enlargement insulin-dependent mellitus.N Engl Med. 1991; 324: 1626-1632Crossref (142) 10Tuttle Puhlman M.E. Cooney S.K. Short R.A. Effects glucagon hemodynamics diabetes.Am Physiol Renal 2002; 282: F103-F112Crossref These circulating mediators primarily act perfusion through afferent arteriole dilation.3Alicic Scholar,8Tuttle addition, activation renin angiotensin system local hyperfiltration. Angiotensin II production within constricts efferent arteriole, thereby, contributes higher pressure. stimulates expression proinflammatory profibrotic via barotrauma also direct cellular effects.3Alicic Scholar,10Tuttle sodium-glucose cotransporter-2 (SGLT2) now another important modulator hemodynamics. It expressed luminal surface epithelial cells proximal convoluted tubule responsible 90% filtered reabsorption.11Alicic Neumiller J.J. Johnson E.J. al.Sodium-glucose cotransporter inhibition disease.Diabetes. 68: 248-257Crossref (55) Scholar,12Vallon Gerasimova M. Rose M.A. al.SGLT2 inhibitor empagliflozin reduces growth albuminuria proportion hyperglycemia prevents Akita mice.Am 306: F194-F204Crossref (318) hyperglycemic conditions, SGLT2 activity adaptation reclaim urine, but maladaptive consequence worsening hyperglycemia.11Alicic Scholar,13Heerspink H.J. 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Perco Mulder S. al.Canagliflozin inflammation fibrosis biomarkers: mechanism action beneficial effects disease.Diabetologia. 62: 1154-1166Crossref (145) 17Vallon Thomson S.C. tubular hypothesis nephron disease.Nat Rev 16: 317-336Crossref (102) relative balance between constriction may vary age. physiological studies humans normal GFR, younger T1D demonstrated constriction, whereas older T2D had dilation.18van Bommel E.J.M. Lytvyn Y. al.Renal hyperfiltering function.Kidney 97: 631-635Abstract (17) Irrespective precise vasoregulatory whole, restoration hypertension and, hyperfiltration.14Kidokoro Scholar,18van prompts series intracellular promote (Figure 1).3Alicic Scholar,19Zhao L. Zou Liu F. Transforming factor-beta1 disease.Front Cell Dev Biol. 8: 187Crossref (34) Scholar,20Reidy Kang H.M. Hostetter T. Susztak Molecular disease.J Clin Invest. 124: 2333-2340Crossref (448) Altered metabolism advanced glycation end products (AGEs), reactive oxygen species, kinase C Janus (JAK)-signal transducer activator transcription (STAT) pathways.20Reidy Podocytes exposed AGE nuclear factor κB–associated upregulation messenger RNA variety much 25-fold.21Pichler Afkarian Dieter B.P. Immunity translating biomarkers targets.Am 312: F716-F731Crossref (108) Scholar,22Anderberg R.J. Meek R.L. Hudkins K.L. al.Serum amyloid A podocytes.Lab 2015; 95: 250-262Crossref podocytes endothelial AGEs bind receptor (RAGE), produce nucleotide-binding oligomerization domain–like pyrin domain containing 3 inflammasome.21Pichler Scholar,23Shahzad Bock Dong W. al.Nlrp3-inflammasome non-myeloid-derived aggravates nephropathy.Kidney 87: 74-84Abstract (234) Scholar,24Sakai N. Wada Revisiting nephropathy: Nlrp3 inflammasome resident cells.Kidney 12-14Abstract Together, κB induce interleukins (IL), IL-1β IL-18, respectively.24Sakai Moreover, serum A, RAGE activator, perpetuates feed-forward cycle gene 1).21Pichler signals lead ongoing mediators, factors, immune cell recruitment.19Zhao Scholar,21Pichler Notably, newer glucose-lowering agents, glucagon-like peptide-1 agonists (GLP-1 RAs), prevent CKD T2D, independent their effects.25Neuen B.L. Young Heerspink prevention patients diabetes: meta-analysis.Lancet Endocrinol. 7: 845-854Abstract (339) 26Cannon C.P. Perkovic Agarwal al.Evaluating canagliflozin events mellitus according baseline HbA1c, HbA1c <7%: CREDENCE trial.Circulation. 141: 407-410Crossref (65) 27Mann J.F.E. Buse J.B. Idorn al.Potential protection liraglutide semaglutide: Exploratory mediation analysis.Diabetes Obes Metab. 2021; 23: 2058-2066Crossref (3) 28Tuttle Lakshmanan Rayner B. al.Dulaglutide versus glargine moderate-to-severe (AWARD-7): multicentre, open-label, randomised trial.Lancet 2018; 6: 605-617Abstract (233) 29Kang Jardine M.J. offer benefit beyond diabetes.Nat 17: 83-84Crossref (12) By ameliorating glucotoxicity influx into potent anti-inflammatory effects. preclinical models suppresses hyperglycemia-induced species generation formation attenuates surrounding tubulointerstitial fibrosis.11Alicic Scholar,30Ojima Matsui Nishino al.Empagliflozin, exerts antifibrotic experimental nephropathy partly suppressing AGEs-receptor axis.Horm Metab Res. 47: 686-692Crossref Scholar,31Eleftheriadis Pissas G. Tsogka unifying model human effect dapagliflozin.Int Urol 52: 1179-1189Crossref GLP-1 RAs downregulate pathways nonpancreatic organs.32Alicic Cox Incretin drugs biological evidence.Nat 227-244Crossref (27) rodent RA decreased oxidative stress, transforming factor-beta (TGF-β1), intercellular adhesion molecule-1, tumor necrosis factor-α, IL-1β, macrophages kidney.32Alicic stress nicotinamide adenine dinucleotide phosphatase oxidase cyclic monophosphate–dependent heme oxygenase-1.33Kawanami D. Takashi outcomes mechanisms.Front Pharmacol. 11: 967Crossref (22) Scholar,34Yang H. Li Wang Z. al.Exendin-4 ameliorates ischemia-reperfusion injury rat.J Surg 182: 825-832Abstract (25) Inhibition signaling proposed suppression cytokine chemokine expression.32Alicic exposure occur diet hyperglycemia.20Reidy Scholar,35Uribarri J. Woodruff Goodman al.Advanced foods practical guide reduction diet.J Diet Assoc. 2010; 110: 911-916.e912Abstract (746) Dietary escape gastrointestinal absorption interact colonic microbiota,36Yacoub Nugent Cai restriction bacterial gut microbiota peritoneal dialysis patients; randomized open label controlled trial.PLoS One. 12e0184789Crossref (63) Scholar,37Snelson Coughlan products: digestion, modulation microbial ecology.Nutrients. 22: 215Crossref (82) triggering mediators.38Garay-Sevilla Beeri M.S. la Maza M.P. al.The endproducts development non-infectious diseases: narrative review.Nutr Res Rev. 33: 298-311Crossref (6) Activation RAGE-dependent causes mucosal barrier dysfunction translocation systemic circulation.39Raman K.G. Sappington P.L. Yang intestinal hemorrhagic shock.Am Gastrointest Liver 2006; 291: G556-G565Crossref Scholar,40Snelson Tan S.M. Clarke al.Processed permeability microvascular diseases.Sci Adv. 7eabe4841Crossref As progresses, greater amounts ammonia urea shift toward Gram-negative bacteria gut. Lipopolysaccharides walls toll-like receptor-4 production, recruitment lipopolysaccharides.41Zhang Meng microbiome mellitus.Diabetes Pract. 172: 108645Abstract Scholar,42Ramezani Raj D.S. microbiome, targeted interventions.J 25: 657-670Crossref (397) Exposure podocytes, these lipopolysaccharides injury, inflammation, fibrosis.43Ma Chadban S.J. Zhao C.Y. al.TLR4 promotes podocyte interstitial nephropathy.PLoS 9: e97985Crossref Diabetes-associated protective short-chain fatty disruption.41Zhang Scholar,44Mosterd Kanbay van den Born al.Intestinal derived metabolites inmodulation progression.Best Pract Endocrinol 35: 101484Crossref 45Reichardt Duncan S.H. al.Phylogenetic distribution three propionate microbiota.ISME 1323-1335Crossref (530) 46Diener Reyes-Escogido M.L. Jimenez-Ceja L.M. al.Progressive shifts reflect prediabetes treatment-naive Mexican cohort.Front (Lausanne). 602326Crossref (2) Complex especially essentially "diseases diseases," such present major challenges deciphering reproducible genetic contributions susceptibility severity.47Cole Florez J.C. Genetics complications.Nat 377-390Crossref (163) Advances acquiring large datasets genome-wide association yielded insights shed light predisposition DKD. Missense mutations COL4A3 gene, encodes structural component basement membrane (GBM), known Alport syndrome.48Salem R.M. Todd J.N. Sandholm al.Genome-wide study highlights biology involved collagen.J 30: 2000-2016Crossref Recently, variant (rs55703767) linked "diabetic nephropathy" T1D, suggesting disordered collagen expression.48Salem was most evident glycated hemoglobin. less GBM thickening glomerulosclerosis among either who biopsy data. Thus, "second-hit" phenomenon operative consequences hyperglycemia, damage. Variants genes (DDR1, COLEC11, BMP7) various phenotypes.48Salem contrast variants, APOL-l G1/G2 alleles observed African ancestry nondiabetic often when accompanied "second hit," viral illness interferon state.49Friedman D.J. Pollak M.R. APOL1 genetics applications.Clin 294-303Crossref (11) Another APOL-1 (rs9622363) recently reported meta-analysis American it progression.50Guan Keaton Dimitrov identifies novel loci diabetes-attributed end-stage Americans.Hum Genomics. 13: 21Crossref Among European cohort GABRR1 (rs9942471) highly microalbuminuria.51van Zuydam N.R. Ahlqvist E. subjects diab

Language: Английский

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Global Impacts of Western Diet and Its Effects on Metabolism and Health: A Narrative Review

Nutrients, Journal Year: 2023, Volume and Issue: 15(12), P. 2749 - 2749

Published: June 14, 2023

The Western diet is a modern dietary pattern characterized by high intakes of pre-packaged foods, refined grains, red meat, processed high-sugar drinks, candy, sweets, fried conventionally raised animal products, high-fat dairy and high-fructose products. present review aims to describe the effect on metabolism, inflammation, antioxidant status; impact gut microbiota mitochondrial fitness; cardiovascular health, mental cancer; sanitary cost diet. To achieve this goal, consensus critical was conducted using primary sources, such as scientific articles, secondary including bibliographic indexes, databases, web pages. Scopus, Embase, Science Direct, Sports Discuss, ResearchGate, Web were used complete assignment. MeSH-compliant keywords “Western diet”, “inflammation”, “metabolic health”, fitness”, “heart disease”, “cancer”, “oxidative stress”, “mental “metabolism” used. following exclusion criteria applied: (i) studies with inappropriate or irrelevant topics, not germane review’s focus; (ii) Ph.D. dissertations, proceedings conferences, unpublished studies. This information will allow for better comprehension nutritional behavior its an individual’s metabolism well national systems. Finally, practical applications derived from are made.

Language: Английский

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Mediterranean Diet as an Antioxidant: The Impact on Metabolic Health and Overall Wellbeing

Nutrients, Journal Year: 2021, Volume and Issue: 13(6), P. 1951 - 1951

Published: June 6, 2021

It has been established, worldwide, that non-communicable diseases such as obesity, diabetes, metabolic syndrome, and cardiovascular events account for a high percentage of morbidity mortality in contemporary societies. Several modifiable risk factors, sedentary activities, sleep deprivation, smoking, unhealthy dietary habits have contributed to this increase. Healthy nutrition terms adherence the Mediterranean diet (MD), rich fruits, legumes, vegetables, olive oil, herbs, spices, fiber intake may contribute decrease pandemic. The beneficial effects MD can be mainly attributed its numerous components anti-inflammatory antioxidant properties. Moreover, further improvement reproductive health, modify neurodegenerative diseases, protect against depression psychosocial maladjustment. There is also evidence highlighting impact healthy female people on composition gut microbiota future overall health their offspring. therefore important highlight metabolic, reproductive, mental while shaping generations. enhanced by increased physical activity context well-balanced lifestyle.

Language: Английский

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Cross-sectional and longitudinal associations between adherence to Mediterranean diet with physical performance and cognitive function in older adults: A systematic review and meta-analysis

Ageing Research Reviews, Journal Year: 2021, Volume and Issue: 70, P. 101395 - 101395

Published: June 19, 2021

Language: Английский

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Nutrition as a Key Modifiable Factor for Periodontitis and Main Chronic Diseases

Journal of Clinical Medicine, Journal Year: 2021, Volume and Issue: 10(2), P. 197 - 197

Published: Jan. 7, 2021

Nutrition is recognized as an essential component in the prevention of a number chronic diseases, including periodontal disease. Based on these considerations, better understanding required regarding how diet, and more particularly intake macronutrients micronutrients, could impact potential relationship between nutrition diseases diseases. To overcome this complexity, up-to-date literature review nutriments related to was performed. High-sugar, high-saturated fat, low-polyols, low-fiber low-polyunsaturated-fat causes increased risk This pattern nutrients classically found Western which considered ‘unhealthy’ diet that cardiovascular diabetes cancers. Conversely, low-sugar, high-fiber high-omega-6-to-omega-3 fatty acid ratio reduces The Mediterranean, DASH, vegetarian Okinawa diets correspond nutritional intakes are ‘healthy’ diets, reducing role such vitamin D, E, K magnesium, remains unclear, while others, A, B, C, calcium, zinc polyphenols have been shown prevent PDs. Some evidence suggests probiotics prebiotics promote health. Periodontal share, with time delay, factor. Thus, any change health should be warning signal control dietary quality patients thus reduce developing later on.

Language: Английский

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Mediterranean Diet and Obesity-related Disorders: What is the Evidence?

Current Obesity Reports, Journal Year: 2022, Volume and Issue: 11(4), P. 287 - 304

Published: Sept. 30, 2022

Abstract Purpose of Review Obesity is a chronic disease, major public health problem due to its association with non-communicable diseases and all-cause mortality. Indeed, people obesity are at increased risk for variety obesity-related disorders including hypertension, dyslipidemia, type 2 diabetes mellitus, cardiovascular several cancers. Many popular diets very different macronutrient composition, the Mediterranean diet (MD), have been used, proposed, studied prevention management obesity. In particular, MD has subject countless studies over years now boasts large body scientific literature. this review, we aimed update current knowledge by summarizing most recent evidence on effect disorders. Recent Findings The negative effects partly reversed substantial weight loss that can be achieved MD, especially when low-calorie in combination adequate physical activity. addition, composition correlated an excellent reducing dyslipidemia. It also positively modulates gut microbiota immune system, significantly decreasing inflammatory mediators, common ground many Summary People medical disease. Therefore, there inevitable need measures manage related At point, proposed as valuable nutritional intervention. characterized high consumption vegetables, fruit, nuts, cereals, whole grains, extra virgin olive oil, well moderate fish poultry, limited intake sweets, red meat, dairy products. proves healthiest dietary pattern available tackle prevent diseases, disease diabetes.

Language: Английский

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The Burden of Carbohydrates in Health and Disease

Nutrients, Journal Year: 2022, Volume and Issue: 14(18), P. 3809 - 3809

Published: Sept. 15, 2022

Foods high in carbohydrates are an important part of a healthy diet, since they provide the body with glucose to support bodily functions and physical activity. However, abusive consumption refined, simple, low-quality has direct implication on mental pathophysiology. Then, carbohydrate is postulated as crucial factor development main Western diseases 21st century. We conducted this narrative critical review using MedLine (Pubmed), Cochrane (Wiley), Embase, CinAhl databases MeSH-compliant keywords: evolution, development, phylogenetic, GUT, microbiota, stress, metabolic health, behaviors, disease, cardiovascular anxiety, depression, cancer, chronic kidney failure, allergies, asthma order analyze impact health. Evidence suggests that carbohydrates, especially fiber, beneficial for well-being growth gut microorganisms consequently host symbiotic relationship, producing microbial alterations negative effect health different organic systems. In addition, evidence simple refined mood categories, including alertness tiredness, reinforcing vicious circle. Regarding sugar intake can affect prognosis uncontrolled puts individuals at risk developing syndrome subsequently disease.

Language: Английский

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Mediterranean Diet and Sarcopenia Features in Apparently Healthy Adults over 65 Years: A Systematic Review

Nutrients, Journal Year: 2023, Volume and Issue: 15(5), P. 1104 - 1104

Published: Feb. 22, 2023

Low muscle mass combined with changes in physical function and quality is defined as sarcopenia. In people > 60 years, sarcopenia reaches 10% tends to increase age. Individual nutrients, such protein, may have a protective role against sarcopenia, but recent evidence suggests that protein alone has been ineffective increasing strength. Dietary patterns, instead, high "anti-inflammatory" potential, the Mediterranean dietary pattern, considered an emerging remedy The aim of this systematic review was summarize diet prevention and/or improvement, including data, healthy elders. We searched published studies about until December 2022 Pubmed, Cochrane, Scopus search engine grey literature. total, ten articles were identified relevant: four cross-sectional six prospective. No clinical trial identified. Only three assessed presence measured mass, which essential criterion diagnosis. adherence had, general, positive function, while results less clear regard Additionally, there no effect on There need for conduction trials order reach cause-effects conclusions regarding importance management non-Mediterranean populations.

Language: Английский

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Phytate Intake, Health and Disease: “Let Thy Food Be Thy Medicine and Medicine Be Thy Food”

Antioxidants, Journal Year: 2023, Volume and Issue: 12(1), P. 146 - 146

Published: Jan. 7, 2023

Phytate (myo-inositol hexakisphosphate or InsP6) is the main phosphorus reservoir that present in almost all wholegrains, legumes, and oilseeds. It a major component of Mediterranean Dietary Approaches to Stop Hypertension (DASH) diets. recognized as nutraceutical classified by Food Drug Administration (FDA) Generally Recognized As Safe (GRAS). has been shown be effective treating preventing certain diseases. inhibit calcium salt crystallization and, therefore, reduce vascular calcifications, renal calculi soft tissue calcifications. Moreover, adsorption phytate crystal faces can hydroxyapatite dissolution bone resorption, thereby playing role treatment/prevention mass loss. potent antioxidation anti-inflammatory action. capable inhibiting lipid peroxidation through iron chelation, reducing iron-related free radical generation. this effect mitigating neuronal damage loss, shows promise neurodegenerative disease. reported improves carbohydrate metabolism, increases adiponectin, decreases leptin reduces protein glycation, which linked with macrovascular microvascular diabetes complications. In review, we summarize benefits intake seen vitro, animal model, epidemiological clinical trials, also identify questions answer future.

Language: Английский

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Energy metabolism in health and diseases

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 18, 2025

Language: Английский

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