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Nature Reviews. Disease Primers Feb 2016Kidney stones are mineral deposits in the renal calyces and pelvis that are found free or attached to the renal papillae. They contain crystalline and organic components... (Review)
Review
Kidney stones are mineral deposits in the renal calyces and pelvis that are found free or attached to the renal papillae. They contain crystalline and organic components and are formed when the urine becomes supersaturated with respect to a mineral. Calcium oxalate is the main constituent of most stones, many of which form on a foundation of calcium phosphate called Randall's plaques, which are present on the renal papillary surface. Stone formation is highly prevalent, with rates of up to 14.8% and increasing, and a recurrence rate of up to 50% within the first 5 years of the initial stone episode. Obesity, diabetes, hypertension and metabolic syndrome are considered risk factors for stone formation, which, in turn, can lead to hypertension, chronic kidney disease and end-stage renal disease. Management of symptomatic kidney stones has evolved from open surgical lithotomy to minimally invasive endourological treatments leading to a reduction in patient morbidity, improved stone-free rates and better quality of life. Prevention of recurrence requires behavioural and nutritional interventions, as well as pharmacological treatments that are specific for the type of stone. There is a great need for recurrence prevention that requires a better understanding of the mechanisms involved in stone formation to facilitate the development of more-effective drugs.
Topics: Calcium Oxalate; Humans; Kidney Calculi; Kidney Calices; Minerals; Prevalence; Uric Acid
PubMed: 27188687
DOI: 10.1038/nrdp.2016.8 -
International Journal of Molecular... Mar 2022The connection between uric acid (UA) and renal impairment is well known due to the urate capacity to precipitate within the tubules or extra-renal system. Emerging... (Review)
Review
BACKGROUND
The connection between uric acid (UA) and renal impairment is well known due to the urate capacity to precipitate within the tubules or extra-renal system. Emerging studies allege a new hypothesis concerning UA and renal impairment involving a pro-inflammatory status, endothelial dysfunction, and excessive activation of renin-angiotensin-aldosterone system (RAAS). Additionally, hyperuricemia associated with oxidative stress is incriminated in DNA damage, oxidations, inflammatory cytokine production, and even cell apoptosis. There is also increasing evidence regarding the association of hyperuricemia with chronic kidney disease (CKD), cardiovascular disease, and metabolic syndrome or diabetes mellitus.
CONCLUSIONS
Important aspects need to be clarified regarding hyperuricemia predisposition to oxidative stress and its effects in order to initiate the proper treatment to determine the optimal maintenance of UA level, improving patients' long-term prognosis and their quality of life.
Topics: Humans; Hyperuricemia; Oxidative Stress; Quality of Life; Renal Insufficiency, Chronic; Uric Acid
PubMed: 35328614
DOI: 10.3390/ijms23063188 -
American Family Physician Nov 2020Gout is caused by monosodium urate crystal deposition in joints and tissues. Risk factors include male sex; obesity; hypertension; alcohol intake; diuretic use; a diet... (Review)
Review
Gout is caused by monosodium urate crystal deposition in joints and tissues. Risk factors include male sex; obesity; hypertension; alcohol intake; diuretic use; a diet rich in meat and seafood; chronic kidney disease; a diet heavy in fructose-rich food and beverages; being a member of certain ethnic groups, including Taiwanese, Pacific Islander, and New Zealand Maori; and living in high-income countries. Gout is characterized by swelling, pain, or tenderness in a peripheral joint or bursa, including the development of a tophus. Diagnosis of gout can be made using several validated clinical prediction rules. Arthrocentesis should be performed when suspicion for an underlying septic joint is present; synovial fluid or tophus analysis should be performed if the diagnosis is uncertain. Colchicine, nonsteroidal anti-inflammatory drugs, and corticosteroids relieve pain in adults with acute gout episodes. Indications for long-term urate-lowering therapy include chronic kidney disease, two or more flare-ups per year, urolithiasis, the presence of tophus, chronic gouty arthritis, and joint damage. Allopurinol and febuxostat are used to prevent flare-ups, although febuxostat is associated with an increase in all-cause and cardiovascular mortality and is therefore not routinely recommended.
Topics: Adrenal Cortex Hormones; Allopurinol; Colchicine; Febuxostat; Gout; Gout Suppressants; Humans; Obesity; Risk Factors; Sex Factors; Uric Acid
PubMed: 33118789
DOI: No ID Found -
International Journal of Molecular... Jun 2021Chronic diseases represent a major challenge in world health. Metabolic syndrome is a constellation of disturbances affecting several organs, and it has been proposed to... (Review)
Review
Chronic diseases represent a major challenge in world health. Metabolic syndrome is a constellation of disturbances affecting several organs, and it has been proposed to be a liver-centered condition. Fructose overconsumption may result in insulin resistance, oxidative stress, inflammation, elevated uric acid levels, increased blood pressure, and increased triglyceride concentrations in both the blood and liver. Non-alcoholic fatty liver disease (NAFLD) is a term widely used to describe excessive fatty infiltration in the liver in the absence of alcohol, autoimmune disorders, or viral hepatitis; it is attributed to obesity, high sugar and fat consumption, and sedentarism. If untreated, NAFLD can progress to nonalcoholic steatohepatitis (NASH), characterized by inflammation and mild fibrosis in addition to fat infiltration and, eventually, advanced scar tissue deposition, cirrhosis, and finally liver cancer, which constitutes the culmination of the disease. Notably, fructose is recognized as a major mediator of NAFLD, as a significant correlation between fructose intake and the degree of inflammation and fibrosis has been found in preclinical and clinical studies. Moreover, fructose is a risk factor for liver cancer development. Interestingly, fructose induces a number of proinflammatory, fibrogenic, and oncogenic signaling pathways that explain its deleterious effects in the body, especially in the liver.
Topics: Animals; Fructose; Humans; Inflammation; Liver; NLR Family, Pyrin Domain-Containing 3 Protein; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Uric Acid
PubMed: 34203484
DOI: 10.3390/ijms22136969 -
American Journal of Hypertension Jul 2020The association between increased serum urate and hypertension has been a subject of intense controversy. Extracellular uric acid drives uric acid deposition in gout,... (Review)
Review
The association between increased serum urate and hypertension has been a subject of intense controversy. Extracellular uric acid drives uric acid deposition in gout, kidney stones, and possibly vascular calcification. Mendelian randomization studies, however, indicate that serum urate is likely not the causal factor in hypertension although it does increase the risk for sudden cardiac death and diabetic vascular disease. Nevertheless, experimental evidence strongly suggests that an increase in intracellular urate is a key factor in the pathogenesis of primary hypertension. Pilot clinical trials show beneficial effect of lowering serum urate in hyperuricemic individuals who are young, hypertensive, and have preserved kidney function. Some evidence suggest that activation of the renin-angiotensin system (RAS) occurs in hyperuricemia and blocking the RAS may mimic the effects of xanthine oxidase inhibitors. A reduction in intracellular urate may be achieved by lowering serum urate concentration or by suppressing intracellular urate production with dietary measures that include reducing sugar, fructose, and salt intake. We suggest that these elements in the western diet may play a major role in the pathogenesis of primary hypertension. Studies are necessary to better define the interrelation between uric acid concentrations inside and outside the cell. In addition, large-scale clinical trials are needed to determine if extracellular and intracellular urate reduction can provide benefit hypertension and cardiometabolic disease.
Topics: Animals; Clinical Trials as Topic; Humans; Hypertension; Mendelian Randomization Analysis; Uric Acid; Uricosuric Agents
PubMed: 32179896
DOI: 10.1093/ajh/hpaa044 -
The Korean Journal of Internal Medicine Nov 2020The prevalence of chronic kidney disease (CKD) is increasing worldwide. Although hyperuricemia has been associated with CKD in many studies, it remains controversial... (Review)
Review
The prevalence of chronic kidney disease (CKD) is increasing worldwide. Although hyperuricemia has been associated with CKD in many studies, it remains controversial whether this is the cause or the result of decreased renal function. Recent observational studies of healthy populations and patients with CKD have reported that uric acid (UA) has an independent role in the development or progression of CKD. Experimental studies have shown several potential mechanisms by which hyperuricemia may cause or promote CKD. However, other reports have indicated an association between hypouricemia and CKD. This opposing effect is hypothesized to occur because UA is a major antioxidant in human plasma and is associated with oxidative stress. In this article, we discuss the potential association between UA imbalance and CKD and how they can be treated.
Topics: Adolescent; Adult; Biomarkers; Child; Disease Progression; Female; Humans; Hyperuricemia; Kidney; Renal Insufficiency, Chronic; Renal Tubular Transport, Inborn Errors; Uric Acid; Urinary Calculi
PubMed: 32872730
DOI: 10.3904/kjim.2020.410 -
Cell Host & Microbe Jun 2023The microbes and microbial pathways that influence host inflammatory disease progression remain largely undefined. Here, we show that variation in atherosclerosis burden...
The microbes and microbial pathways that influence host inflammatory disease progression remain largely undefined. Here, we show that variation in atherosclerosis burden is partially driven by gut microbiota and is associated with circulating levels of uric acid (UA) in mice and humans. We identify gut bacterial taxa spanning multiple phyla, including Bacillota, Fusobacteriota, and Pseudomonadota, that use multiple purines, including UA as carbon and energy sources anaerobically. We identify a gene cluster that encodes key steps of anaerobic purine degradation and that is widely distributed among gut-dwelling bacteria. Furthermore, we show that colonization of gnotobiotic mice with purine-degrading bacteria modulates levels of UA and other purines in the gut and systemically. Thus, gut microbes are important drivers of host global purine homeostasis and serum UA levels, and gut bacterial catabolism of purines may represent a mechanism by which gut bacteria influence health.
Topics: Humans; Animals; Mice; Gastrointestinal Microbiome; Homeostasis; Purines; Bacteria; Uric Acid
PubMed: 37279756
DOI: 10.1016/j.chom.2023.05.011 -
International Heart Journal 2022
Topics: Humans; Hydrogen-Ion Concentration; Uric Acid
PubMed: 35650143
DOI: 10.1536/ihj.22-127 -
Journal of the American Society of... Nov 2015Obesity and diets rich in uric acid-raising components appear to account for the increased prevalence of hyperuricemia in Westernized populations. Prevalence rates of...
Obesity and diets rich in uric acid-raising components appear to account for the increased prevalence of hyperuricemia in Westernized populations. Prevalence rates of hypertension, diabetes mellitus, CKD, and cardiovascular disease are also increasing. We used Mendelian randomization to examine whether uric acid is an independent and causal cardiovascular risk factor. Serum uric acid was measured in 3315 patients of the Ludwigshafen Risk and Cardiovascular Health Study. We calculated a weighted genetic risk score (GRS) for uric acid concentration based on eight uric acid-regulating single nucleotide polymorphisms. Causal odds ratios and causal hazard ratios (HRs) were calculated using a two-stage regression estimate with the GRS as the instrumental variable to examine associations with cardiometabolic phenotypes (cross-sectional) and mortality (prospectively) by logistic regression and Cox regression, respectively. Our GRS was not consistently associated with any biochemical marker except for uric acid, arguing against pleiotropy. Uric acid was associated with a range of prevalent diseases, including coronary artery disease. Uric acid and the GRS were both associated with cardiovascular death and sudden cardiac death. In a multivariate model adjusted for factors including medication, causal HRs corresponding to each 1-mg/dl increase in genetically predicted uric acid concentration were significant for cardiovascular death (HR, 1.77; 95% confidence interval, 1.12 to 2.81) and sudden cardiac death (HR, 2.41; 95% confidence interval, 1.16 to 5.00). These results suggest that high uric acid is causally related to adverse cardiovascular outcomes, especially sudden cardiac death.
Topics: Aged; Biomarkers; Cardiovascular Diseases; Coronary Disease; Cross-Sectional Studies; Female; Follow-Up Studies; Genotype; Humans; Hypertension; Hyperuricemia; Male; Mendelian Randomization Analysis; Middle Aged; Models, Genetic; Multivariate Analysis; Odds Ratio; Oligonucleotide Array Sequence Analysis; Phenotype; Polymorphism, Single Nucleotide; Proportional Hazards Models; Prospective Studies; Regression Analysis; Risk Factors; Uric Acid
PubMed: 25788527
DOI: 10.1681/ASN.2014070660 -
New insights into purine metabolism in metabolic diseases: role of xanthine oxidoreductase activity.American Journal of Physiology.... Nov 2020Xanthine oxidoreductase (XOR) consists of two different forms, xanthine dehydrogenase and xanthine oxidase (XO), and is a rate-limiting enzyme of uric acid production... (Review)
Review
Xanthine oxidoreductase (XOR) consists of two different forms, xanthine dehydrogenase and xanthine oxidase (XO), and is a rate-limiting enzyme of uric acid production from hypoxanthine and xanthine. Uric acid is the end product of purine metabolism in humans and has a powerful antioxidant effect. The lack of ascorbic acid, known as vitamin C, in hominoids has been thought to cause a compensatory increase in uric acid as an antioxidant by unfunctional gene mutation of uricase to a pseudogene. Because XO is involved in an increase in reactive oxygen species (ROS) by generating superoxide and hydrogen peroxide, inadequate activation of XOR promotes oxidative stress-related tissue injury. Plasma XOR activity is associated with obesity, smoking, liver dysfunction, hyperuricemia, dyslipidemia, insulin resistance, and adipokines, indicating a novel biomarker of metabolic disorders. However, XOR activity in adipose tissue is low in humans unlike in rodents, and hypoxanthine is secreted from human adipose tissue. The concentration of hypoxanthine, but not xanthine, is independently associated with obesity in a general population, indicating differential regulation of hypoxanthine and xanthine. Treatment with an XOR inhibitor can decrease uric acid for preventing gout, reduce production of XO-related ROS, and promote reutilization of hypoxanthine and ATP production through the salvage pathway. It has recently been suggested that discontinuation of an XOR inhibitor causes adverse cardiovascular outcomes as XOR inhibitor withdrawal syndrome, possibly due to cardiac disturbance of conduction and contraction by reduced ATP production. New insights into purine metabolism, including the role of XOR activity in the past 5 yr, are mainly discussed in this review.
Topics: Biomarkers; Humans; Metabolic Diseases; Purines; Reactive Oxygen Species; Uric Acid; Xanthine Dehydrogenase
PubMed: 32893671
DOI: 10.1152/ajpendo.00378.2020