Cell Metabolism, Journal Year: 2023, Volume and Issue: 35(12), P. 2165 - 2182.e7
Published: Dec. 1, 2023
Language: Английский
Clinical Journal of the American Society of Nephrology, Journal Year: 2022, Volume and Issue: 18(2), P. 279 - 289
Published: Oct. 11, 2022
The sodium-glucose cotransporter 2 (SGLT2) inhibitors have become an integral part of clinical practice guidelines to slow the progression CKD in patients with and without diabetes mellitus. Although initially developed as antihyperglycemic drugs, their effect on kidney is multifactorial resulting from profuse glycosuria natriuresis consequent primary site action. Hemodynamic metabolic changes ensue that mediate kidney-protective effects, including ( 1 ) decreased workload proximal tubular cells prevention aberrant increases glycolysis, contributing a risk AKI; lowering intraglomerular pressure by activating glomerular feedback reductions BP tissue sodium content; 3 initiation nutrient-sensing pathways reminiscent starvation ketogenesis, increased autophagy, restoration carbon flow through mitochondria production reactive oxygen species; 4 body weight loss reduction basal rate due nonshivering thermogenesis; 5 favorable quantity characteristics perirenal fat leading release adipokines, which adversely affect capillary signal sympathetic outflow. Additionally, these drugs stimulate phosphate magnesium reabsorption increase uric acid excretion. Familiarity kidney-specific mechanisms action, potential function, and/or alterations electrolytes volume status, are induced widely prescribed will facilitate usage for whom they indicated.
Language: Английский
Citations
58
Frontiers in Nutrition, Journal Year: 2022, Volume and Issue: 9
Published: June 24, 2022
Obesity is the epidemic of our era and its incidence supposed to increase by more than 30% 2030. It commonly defined as a chronic metabolic disease with an excessive accumulation body fat in relation fat-free mass, both terms quantity distribution at specific points on body. The effects obesity have important impact different clinical areas, particularly endocrinology, cardiology, nephrology. Indeed, increased rates been associated risk cardiovascular (CVD), cancer, type 2 diabetes (T2D), dyslipidemia, hypertension, renal diseases, neurocognitive impairment. Obesity-related kidney (CKD) has ascribed intrarenal along proximal tubule, glomeruli, sinus, around capsule, hemodynamic changes hyperfiltration, albuminuria, impaired glomerular filtration rate. In addition, diabetes, which arise consequence overweight, contribute amplifying dysfunction native transplanted kidney. Overall, several mechanisms are closely related onset progression CKD general population, including hemodynamics, neurohumoral pathways, adiposity, local systemic inflammation, dysbiosis microbiota, insulin resistance, fibrotic process. Unfortunately, there no practice guidelines for management patients obesity-related CKD. Therefore, dietary based nutritional care adults CKD, developed published National Kidney Foundation, Disease Outcome Quality Initiative common recommendations healthy population. Optimal these should follow Mediterranean diet, known be lower CVD beneficial diseases such obesity, cognitive health. Mediterranean-style diets often unsuccessful promoting efficient weight loss, especially altered glucose metabolism. For this purpose, review also discusses use non-classical loss approaches intermittent fasting ketogenic diet contrast
Language: Английский
Citations
56
Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13
Published: Sept. 12, 2022
Histone post-translational modifications (HPTMs) are essential epigenetic mechanisms that affect chromatin-associated nuclear processes without altering the DNA sequence. With application of mass spectrometry-based proteomics, novel histone lysine acylation, such as propionylation, butyrylation, crotonylation, malonylation, succinylation, glutarylation, and lactoylation have been successively discovered. The emerging diversity acylation landscape prompted us to investigate function mechanism these HPTMs in health disease. Recently, it has reported β-hydroxybutyrate (BHB), main component ketone body, various protective roles beyond alternative fuel provision during starvation. β-hydroxybutyrylation (Kbhb) is a identified by spectrometry, which regulates gene transcription response carbohydrate restriction or elevated BHB levels vivo vitro . Recent studies shown Kbhb strongly associated with pathogenesis metabolic cardiovascular diseases, kidney tumors, neuropsychiatric disorders, diseases suggesting different functions from acetylation methylation. This review focuses on writers, erasers, sites, underlying Kbhb, providing glimpse into their complex regulation mechanism.
Language: Английский
Citations
42
Nature Metabolism, Journal Year: 2023, Volume and Issue: 5(12), P. 2062 - 2074
Published: Dec. 13, 2023
Language: Английский
Citations
40
Cell Reports Medicine, Journal Year: 2023, Volume and Issue: 4(11), P. 101283 - 101283
Published: Nov. 1, 2023
Ketogenic dietary interventions (KDIs) are beneficial in animal models of autosomal-dominant polycystic kidney disease (ADPKD). KETO-ADPKD, an exploratory, randomized, controlled trial, is intended to provide clinical translation these findings (NCT04680780). Sixty-six patients were randomized a KDI arm (ketogenic diet [KD] or water fasting [WF]) the control group. Both induce significant ketogenesis on basis blood and breath acetone measurements. Ninety-five percent (KD) 85% (WF) report as feasible. KD leads reductions body fat liver volume. Additionally, associated with reduced volume (not reaching statistical significance). Interestingly, group exhibits improved function at end treatment, while WF groups show progressive decline, typical ADPKD. Safety-relevant events largely mild, expected (initial flu-like symptoms KD), transient. Safety assessment complemented by nuclear magnetic resonance (NMR) lipid profile analyses.
Language: Английский
Citations
37
American Journal of Kidney Diseases, Journal Year: 2023, Volume and Issue: 81(3), P. 352 - 360
Published: Jan. 20, 2023
Language: Английский
Citations
33
Aging Cell, Journal Year: 2023, Volume and Issue: 22(6)
Published: April 14, 2023
Accumulating evidence suggests health benefits of ketone bodies, and especially for longevity. However, the precise role endogenous ketogenesis in mammalian life span, safety efficacy long-term exogenous supplementation bodies remain unclear. In present study, we show that a deficiency ketogenesis, induced by whole-body Hmgcs2 deletion, shortens span mice, this is prevented daily body using diet containing 1,3-butanediol, precursor β-hydroxybutyrate. Furthermore, feeding 1,3-butanediol-containing from early increases midlife mortality normal but aged mice it extends prevents high associated with atherosclerosis ApoE-deficient mice. By contrast, an ad libitum low-carbohydrate ketogenic markedly mortality. conclusion, affects survival, may represent double-edged sword respect to depending on method administration status.
Language: Английский
Citations
26
BMJ Open Diabetes Research & Care, Journal Year: 2024, Volume and Issue: 12(2), P. e004101 - e004101
Published: April 1, 2024
Ketogenic diets have been widely used for weight loss and are increasingly in the management of type 2 diabetes. Despite evidence that ketones multiple positive effects on kidney function, common misconceptions about ketogenic diets, such as high protein content acid load, prevented their widespread use individuals with impaired function. Clinical trial focusing major adverse events is sparse. The aim this review to explore a diet, an emphasis pleiotropic actions ketones, health. Given minimal concerns relation potential renoprotective future studies should evaluate safety efficacy interventions disease.
Language: Английский
Citations
15
JAMA, Journal Year: 2025, Volume and Issue: unknown
Published: March 24, 2025
Importance Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive development of cysts and the most common inherited disorder worldwide. ADPKD accounts for 5% to 10% failure in US Europe, its prevalence 9.3 per 10 000 individuals. Observations typically diagnosed individuals aged 27 42 years primarily caused pathogenic variants PKD1 (78%) or PKD2 (15%) genes. Most persons with have an affected parent, but de novo suggested 25% families. More than 90% patients older 35 hepatic cysts, which may cause abdominal discomfort occasionally require medical surgical intervention. Hypertension affects 70% 80% ADPKD, approximately 9% 14% develop intracranial aneurysms, a rupture rate 0.57 1000 patient-years. Approximately 50% replacement therapy 62 age. The severity can be quantified using Mayo Imaging Classification (MIC), stratifies based on total volume adjusted height age ranges from 1A 1E. Patients MIC 1C 1E larger kidneys because more rapid growth (6%-10% year) compared those 1B (1%-5% earlier progression therapy, occurs at mean 58.4 1C, 52.5 1D, 43.4 Optimal management includes systolic blood pressure lower 120 mm Hg patients, 110/75 who estimated glomerular filtration (eGFR) greater 60 mL/min/1.73 m 2 are younger 50 years, dietary sodium restriction (<2000 mg/d), weight management, adequate hydration (>2.5 L daily). vasopressin type receptor antagonist tolvaptan reduces annual eGFR decline 0.98 1.27 indicated 3 year slow delay onset failure. Conclusion genetic worldwide cysts. hypertension liver aneurysms. First-line treatment control, hydration. Tolvaptan high risk
Language: Английский
Citations
1
AJP Renal Physiology, Journal Year: 2021, Volume and Issue: 322(1), P. F27 - F41
Published: Nov. 22, 2021
Metformin treatment improved ADPKD disease severity in a relevant, slowly progressive mouse model that recapitulates PKD-associated PKD1 mutation. Relative to controls, metformin reduced kidney weight/body weight, cystic index and BUN levels, while improving GFR, blood pressure anemia. also key inflammatory injury markers, along with cell proliferation markers. These findings suggest several beneficial effects of this model, which may help inform new therapies patients.
Language: Английский
Citations
53