Plasma Urate and Risk of a Hospital Stay with AKI
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Background and objectives Higher urate levels are associated with higher risk of CKD, but the association between urate and AKI is less established. This study evaluated the risk of hospitalized AKI associated with urate concentrations in a large population-based cohort. To explore whether urate itself causes kidney injury, the study also evaluated the relationship between a genetic urate score and AKI. Design, setting, participants, & measurements A total of 11,011 participants from the Atherosclerosis Risk in Communities study were followed from 1996–1998 (baseline) to 2010. The association between baseline plasma urate and risk of hospitalized AKI, adjusted for known AKI risk factors, was determined using Cox regression. Interactions of urate with gout and CKD were tested. Mendelian randomization was performed using a published genetic urate score among the participants with genetic data (n=7553). Results During 12 years of follow-up, 823 participants were hospitalized with AKI. Overall, mean participant age was 63.3 years, mean eGFR was 86.3 ml/min per 1.73 m2, and mean plasma urate was 5.6 mg/dl. In patients with plasma urate >5.0 mg/dl, there was a 16% higher risk of hospitalized AKI for each 1-mg/dl higher urate (adjusted hazard ratio, 1.16; 95% confidence interval, 1.10 to 1.23; P<0.001). When stratified by history of gout, the association between higher urate and AKI was significant only in participants without a history of gout (P for interaction=0.02). There was no interaction of CKD and urate with AKI, nor was there an association between genetic urate score and AKI. Conclusions Plasma urate >5.0 mg/dl was independently associated with risk of hospitalized AKI; however, Mendelian randomization did not provide evidence for a causal role of urate in AKI. Further research is needed to determine whether lowering plasma urate might reduce AKI risk.Idiopathic hyperuricemia is generally defined as hyperuricemia caused by unknown origin. Idiopathic hyperuricemia is categorized as overproducing or underexcretion of uric acid. Overproduced uric acid is caused by increased biosynthesis of purine bodies, hypermetabolization of purine bodies, or increased intake of dietary purine bodies. Idiopathic hyperuricemia with overproducing uric acid can be diagnosed by amount of excreted uric acid in the urine. Recently it has been identified that hypertension are frequently associated with myogenic hyperuricemia converted from overproduced hypoxanthine in the skeletal muscles. Some anti-hypertensive drugs including alpha1 blocker, ACE inhibitor, alphabeta blocker, or long-acting Ca blocker attenuated the myogenic hyperuricemia. Thus, these drugs may be helpful in the management of hypertension with hyperuricemia.
Hypoxanthine
Purine metabolism
Allopurinol
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There are two reasons for the high level of serum uric acid,which induces hyperuricemia.Excessive uricogenesis is considered to be one of the risk factors.Xanthine oxidase is the main drug therapy target in hyperuricemia,which is one of the key enzymes conducting the metabolism of uric acid.The lack of excretion is another reason for the excessive level of uric acid.Uric acid transport is achieved by various kinds of transporters expressed in the membranes of the renal tubular epithelial cells.Gene mutations or deletions of the transporters are the main reasons for abnormal serum uric acid level.Gene expression regulations of these transporters by relevant drugs are the main method to conduct the excretion of uric acid.In this paper,recent advances in the study of the drug therapy targets have been reviewed in those two aspects.
Xanthine
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In humans, the end product of purine metabolism is uric acid. Over 70% of uric acid is excreted through the kidneys. When renal function is impaired, uric acid secretion is also impaired. This directly correlates the prevalence of hyperuricemia with the severity of chronic kidney disease (CKD). It has been reported that the prevalence of hyperuricemia in patients with Stage I-III CKD is 40–60% and up to 70% in patients with Stage IV-V CKD. Some studies found a link between serum uric acid levels and decreased glomerular filtration rate (GFR), an independent risk factor for CKD development. Because CKD and serum uric acid levels are related, the relationship between the two frequently generates controversy. As such, this review of the literature discusses the role of uric acid in the pathogenesis and progression of CKD.
Pathogenesis
Purine metabolism
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Objective To evaluate a possible relationship between hyperuricemia (HUA) and meta -bolic syndrome (MS).Methods The prevalence rates of UA and MS were calculated and analyzed in 1278 persons who underwent health check up.Analysis was carried out on the blood uric acid and parameters of MS, and a multiple regression analysis was performed on blood uric acid and HOMA-IR. Results (1) The prevalences of obesity,high WHR, high IFG, HBP,HTG,HTC were significantly higher in high uric acid group that in normal uric acid group.(2)The blood uric acid was positively correlated with HOMA-IR. (3) The prevalence of high uric acid in MS group was significantmy higher than that in the group without MS. Conclusion High uric acid level may be an important factor for development and progress of MS.
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AIM To establish hyperuricemia animal model. METHODS The mice were given uric acid by ip and then the level of uric acid in serum was detected. RESULTS Uric acid 125,250,500, 1 000 mg·kg -1 ip significantly increased the level of uric acid in mouse serum. The level of uric acid in mouse serum was attained peak at 10 min and the hyperuricemia could lasted over 4 hours after uric acid 250 mg·kg -1 given. CONCLUSION Uric acid given by ip can form mouse hyperuricemia model, the dosage of 250 mg·kg -1 is better.
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Uric acid as the end-product of purine metabolism in human body is excreted through kidney. If the production of uric acid surpasses the level that excreted by kidney, the serum level of uric acid will increase and hyperuricemia will occur. Hyperuricemia is associated with the development and progression of gout, cardiovascular diseases, tumor lysis syndrome and renal disease. Therefore, clinical significance of serum uric acid was summarized in this article.
Purine metabolism
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Uric acid is an antioxidant in the extracellular environment, while it has prooxidative effects inside the cell. It is thought that antioxidative effects of uric acid may be protective, particularly in neurological diseases. While prooxidative effects of uric acid has a leading role in the development and progress of chronic kidney disease, metabolic syndrome and cardiovascular diseases. Uric acid is more than a product of purine metabolism. The uric acid paradox indicates that uric acid may play a central role in many diseases. This article was tried to review the researches and clinic studies of hyperuricemia from the viewpoint of the inflammation in recent years.
Key words:
Uric acid; Inflammatory; Oxidation; Antioxidant
Purine metabolism
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Hyperuricemia is a common metabolic syndrome. Elevated uric acid levels are risk factors for gout, hypertension, and chronic kidney diseases. Furthermore, various epidemiological studies have also demonstrated an association between cardiovascular risks and hyperuricemia. In hyperuricemia, reactive oxygen species (ROS) are produced simultaneously with the formation of uric acid by xanthine oxidases. Intracellular uric acid has also been reported to promote the production of ROS. The ROS and the intracellular uric acid itself regulate several intracellular signaling pathways, and alterations in these pathways may result in the development of atherosclerotic lesions. In this review, we describe the effect of uric acid on various molecular signals and the potential mechanisms of atherosclerosis development in hyperuricemia. Furthermore, we discuss the efficacy of treatments for hyperuricemia to protect against the development of atherosclerosis.
Pathogenesis
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Urea is the main product secreted in normal human urine, which will contain a small amount of uric acid.Uric acid is the end product of purines known as trioxypurines, which have a weakly acidic alcoholic form, and if purines are metabolized, the risk of hyperuricemia will be increased. It has been shown that the risk of developing CKD in patients with increased serum uric acid levels is 2.21 times that of normal patients. There are experimental data to divide patients into two groups, one is patients with hyperuricemia and the other is patients with normal serum uric acid, the results of the study show that patients with hyperuricemia have a significantly greater probability of developing acute kidney injury than patients with normal serum uric acid, and most of them need kidney replacement therapy. This review focuses on the development of kidney damage in hyperuricemia.
Purine metabolism
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