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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 -
Nephrology, Dialysis, Transplantation :... Sep 2013Serum uric acid is commonly elevated in subjects with chronic kidney disease (CKD), but was historically viewed as an issue of limited interest. Recently, uric acid has... (Review)
Review
Serum uric acid is commonly elevated in subjects with chronic kidney disease (CKD), but was historically viewed as an issue of limited interest. Recently, uric acid has been resurrected as a potential contributory risk factor in the development and progression of CKD. Most studies documented that an elevated serum uric acid level independently predicts the development of CKD. Raising the uric acid level in rats can induce glomerular hypertension and renal disease as noted by the development of arteriolosclerosis, glomerular injury and tubulointerstitial fibrosis. Pilot studies suggest that lowering plasma uric acid concentrations may slow the progression of renal disease in subjects with CKD. While further clinical trials are necessary, uric acid is emerging as a potentially modifiable risk factor for CKD. Gout was considered a cause of CKD in the mid-nineteenth century, and, prior to the availability of therapies to lower the uric acid level, the development of end-stage renal disease was common in gouty patients. In their large series of gouty subjects Talbott and Terplan found that nearly 100% had variable degrees of CKD at autopsy (arteriolosclerosis, glomerulosclerosis and interstitial fibrosis). Additional studies showed that during life impaired renal function occurred in half of these subjects. As many of these subjects had urate crystals in their tubules and interstitium, especially in the outer renal medulla, the disease became known as gouty nephropathy. The identity of this condition fell in question as the presence of these crystals may occur in subjects without renal disease; furthermore, the focal location of the crystals could not explain the diffuse renal scarring present. In addition, many subjects with gout also had coexistent conditions such as hypertension and vascular disease, leading some experts to suggest that the renal injury in gout was secondary to these latter conditions rather than to uric acid per se. Indeed, gout was removed from the textbooks as a cause of CKD, and the common association of hyperuricemia with CKD was solely attributed to the retention of serum uric acid that is known to occur as the glomerular filtration rate falls. Renewed interest in uric acid as a cause of CKD occurred when it was realized that invalid assumptions had been made in the arguments to dismiss uric acid as a risk factor for CKD. The greatest assumption was that the mechanism by which uric acid would cause kidney disease would be via the precipitation as crystals in the kidney, similar to the way it causes gout. However, when laboratory animals with CKD were made hyperuricemic, the renal disease progressed rapidly despite an absence of crystals in the kidney. Since this seminal study, there has been a renewed interest in the potential role uric acid may have in both acute and CKD. We briefly review some of the major advances that have occurred in this field in the last 15 years.
Topics: Animals; Humans; Rats; Renal Insufficiency, Chronic; Risk Factors; Uric Acid
PubMed: 23543594
DOI: 10.1093/ndt/gft029 -
International Heart Journal 2022
Topics: Humans; Hydrogen-Ion Concentration; Uric Acid
PubMed: 35650143
DOI: 10.1536/ihj.22-127 -
American Journal of Physiology.... Jun 2021Uric acid is the end metabolite derived from the oxidation of purine compounds. Overwhelming evidence shows the vital interrelationship between hyperuricemia (HUA) and...
Uric acid is the end metabolite derived from the oxidation of purine compounds. Overwhelming evidence shows the vital interrelationship between hyperuricemia (HUA) and nonalcoholic fatty liver disease (NAFLD). However, the mechanisms for this association remain unclear. In this study, we established a urate oxidase-knockout (Uox-KO) mouse model by clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 technology. To study the correlation between HUA and NAFLD, human HepG2 hepatoma cells were treated in culture medium with high level of uric acid. In vivo, the Uox-KO mice spontaneously developed hyperuricemia and aberrant lipid-metabolism, concomitant with abnormal hepatic fat accumulation. HUA activated c-Jun N-terminal kinase (JNK) in vivo and in vitro. Furthermore, inhibiting JNK activation by a JNK-specific inhibitor, SP600125, decreased fat accumulation and lipogenic gene expression induced by HUA. Overexpression of the lipogenic enzymes fatty acid synthase and acetyl-CoA carboxylase 1 was via activation of JNK, which was blocked by the JNK inhibitor SP600125. HUA activated AP-1 to upregulate lipogenic gene expression via JNK activation. In addition, HUA caused mitochondrial dysfunction and reactive oxygen species production. Pretreatment with the antioxidant -acetyl-l-cysteine could ameliorate HUA-activated JNK and hepatic steatosis. These data suggest that ROS/JNK/AP-1 signaling plays an important role in HUA-mediated fat accumulation in liver. Hyperuricemia and nonalcoholic fatty liver disease are global public health problems, which are strongly associated with metabolic syndrome. In this study, we demonstrate that uric acid induces hepatic fat accumulation via the ROS/JNK/AP-1 pathway. This study identifies a new mechanism of NAFLD pathogenesis and new potential therapeutic strategies for HUA-induced NAFLD.
Topics: Animals; Hep G2 Cells; Humans; Hyperuricemia; Lipid Metabolism; Lipogenesis; Liver; MAP Kinase Signaling System; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Oxidative Stress; Reactive Oxygen Species; Transcription Factor AP-1; Uric Acid
PubMed: 33900847
DOI: 10.1152/ajpendo.00518.2020 -
Gut Microbes 2022Hyperuricemia is the second most prevalent metabolic disease to human health after diabetes. Only a few clinical drugs are available, and most of them have serious side...
Hyperuricemia is the second most prevalent metabolic disease to human health after diabetes. Only a few clinical drugs are available, and most of them have serious side effects. The human body does not have urate oxidase, and uric acid is secreted via the kidney or the intestine. Reduction through kidney secretion is often the cause of hyperuricemia. We hypothesized that the intestine secretion could be enhanced when a recombinant urate-degrading bacterium was introduced into the gut. We engineered an Nissle 1917 strain with a plasmid containing a gene cassette that encoded two proteins PucL and PucM for urate metabolism from , the urate importer YgfU and catalase KatG from , and the bacterial hemoglobin Vhb from sp. The recombinant strain effectively degraded uric acid under hypoxic conditions. A new method to induce hyperuricemia in mice was developed by intravenously injecting uric acid. The engineered strain significantly lowered the serum uric acid when introduced into the gut or directly injected into the blood vessel. The results support the use of urate-degrading bacteria in the gut to treat hyperuricemia. Direct injecting bacteria into blood vessels to treat metabolic diseases is proof of concept, and it has been tried to treat solid tumors.
Topics: Animals; Escherichia coli; Escherichia coli Infections; Gastrointestinal Microbiome; Hyperuricemia; Mice; Oxygen; Urate Oxidase; Uric Acid
PubMed: 35491895
DOI: 10.1080/19490976.2022.2070391 -
Biomolecules Jul 2018Since 1963, various research studies and reports have demonstrated the role of uric acid (2,6,8-trihydroxypurine), an end product of adenosine and guanosine catabolism,... (Review)
Review
Since 1963, various research studies and reports have demonstrated the role of uric acid (2,6,8-trihydroxypurine), an end product of adenosine and guanosine catabolism, on semen quality and sperm function. However, this effect has not yet been collectively discussed, even though uric acid has been a well-recognized constituent in semen. Here, we systematically and comprehensively discuss and summarize the role/effect of uric acid in semen quality by searching the main databases for English language articles considering this topic. Additionally, certain significant and relevant papers were considered to support discussions and perceptions. In conclusion, uric acid contributes to maintaining and enhancing sperm motility, viability, and morphology; therefore, protecting sperm function and fertilizing ability. This contribution is performed mainly by neutralizing the damaging effect of oxidizing (e.g., endogenous free radicals and exogenous toxins) and nitrating agents and enhancing certain bioactive enzymes in spermatozoa. In contrast, high levels of uric acid may induce adverse effects to sperm function, at least in part, by reducing the activity of vital enzymes in spermatozoa. However, further research, mainly clinical, is still required to fully explore the role/effect of uric acid in semen.
Topics: Animals; Antioxidants; Humans; Male; Semen; Spermatozoa; Uric Acid
PubMed: 30065172
DOI: 10.3390/biom8030065 -
Nutrients Jun 2022Hyperuricemia (HUA) is a metabolic disease that threatens human health. Tea is a healthy beverage with an abundance of benefits. This study revealed the uric...
Hyperuricemia (HUA) is a metabolic disease that threatens human health. Tea is a healthy beverage with an abundance of benefits. This study revealed the uric acid-lowering efficacy of six types of tea water extracts (TWEs) on HUA in mice. The results revealed that under the intervention of TWEs, the expression of XDH, a key enzyme that produces uric acid, was significantly downregulated in the liver. TWE treatment significantly upregulated the expression of uric acid secretion transporters ABCG2, OAT1, and OAT3, and downregulated the expression of uric acid reabsorption transporter URAT1 in the kidney. Furthermore, HUA-induced oxidative stress could be alleviated by upregulating the Nrf2/HO-1 pathway. The intervention of TWEs also significantly upregulated the expression of the intestinal ABCG2 protein. On the other hand, TWE intervention could significantly upregulate the expression of intestinal ABCG2 and alleviate HUA by modulating the gut microbiota. Taken together, tea can comprehensively regulate uric acid metabolism in HUA mice. Interestingly, we found that the degree of fermentation of tea was negatively correlated with the uric acid-lowering effect. The current study indicated that tea consumption may have a mitigating effect on the HUA population and provided a basis for further research on the efficacy of tea on the dosage and mechanism of uric acid-lowering effects in humans.
Topics: Animals; Camellia sinensis; Gastrointestinal Microbiome; Hyperuricemia; Metabolic Networks and Pathways; Mice; Tea; Uric Acid
PubMed: 35807846
DOI: 10.3390/nu14132666 -
Acta Medica Indonesiana Apr 2017non-alcoholic fatty liver disease (NAFLD) is known to be associated with some metabolic disorders. Recent studies suggested the role of uric acid in NAFLD through... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
non-alcoholic fatty liver disease (NAFLD) is known to be associated with some metabolic disorders. Recent studies suggested the role of uric acid in NAFLD through oxidative stress and inflammatory process. This study is aimed to evaluate the association between serum uric acid and NAFLD.
METHODS
a systematic literature review was conducted using Pubmed and Cochrane library. The quality of all studies was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). All data were analyzed using REVIEW MANAGER 5.3.
RESULTS
eleven studies from America and Asia involving 100,275 subjects were included. The pooled adjusted OR for NAFLD was 1.92 (95% CI: 1.66-2.23; p<0.00001). Subgroup analyses were done based on study design, gender, non-diabetic subjects, non-obese subjects. All subgroup analyses showed statistically significant adjusted OR and most of which having low to moderate heterogeneity. Two studies revealed relationship between increased serum uric acid levels and severity of NAFLD. No publication bias was observed.
CONCLUSION
our study demonstrated association between serum uric acid level and NAFLD. This finding brings a new insight of uric acid in clinical practice. Increased in serum uric acid levels might serve as a trigger for physician to screen for NAFLD.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Severity of Illness Index; Uric Acid
PubMed: 28790228
DOI: No ID Found -
Blood Jun 2022Neutrophils are key players during host defense and sterile inflammation. Neutrophil dysfunction is a characteristic feature of the acquired immunodeficiency during...
Neutrophils are key players during host defense and sterile inflammation. Neutrophil dysfunction is a characteristic feature of the acquired immunodeficiency during kidney disease. We speculated that the impaired renal clearance of the intrinsic purine metabolite soluble uric acid (sUA) may account for neutrophil dysfunction. Indeed, hyperuricemia (HU, serum UA of 9-12 mg/dL) related or unrelated to kidney dysfunction significantly diminished neutrophil adhesion and extravasation in mice with crystal- and coronavirus-related sterile inflammation using intravital microscopy and an air pouch model. This impaired neutrophil recruitment was partially reversible by depleting UA with rasburicase. We validated these findings in vitro using either neutrophils or serum from patients with kidney dysfunction-related HU with or without UA depletion, which partially normalized the defective migration of neutrophils. Mechanistically, sUA impaired β2 integrin activity and internalization/recycling by regulating intracellular pH and cytoskeletal dynamics, physiological processes that are known to alter the migratory and phagocytic capability of neutrophils. This effect was fully reversible by blocking intracellular uptake of sUA via urate transporters. In contrast, sUA had no effect on neutrophil extracellular trap formation in neutrophils from healthy subjects or patients with kidney dysfunction. Our results identify an unexpected immunoregulatory role of the intrinsic purine metabolite sUA, which contrasts the well-known immunostimulatory effects of crystalline UA. Specifically targeting UA may help to overcome certain forms of immunodeficiency, for example in kidney dysfunction, but may enhance sterile forms of inflammation.
Topics: Animals; CD18 Antigens; Humans; Immunity, Innate; Inflammation; Mice; Neutrophil Infiltration; Neutrophils; Uric Acid
PubMed: 35303071
DOI: 10.1182/blood.2021011234 -
Circulation Journal : Official Journal... 2011
Topics: Blood Pressure; Humans; Hypertension; Male; Uric Acid
PubMed: 22056493
DOI: 10.1253/circj.cj-11-1222