Explore the vast range of titles available.

The benefits of xanthine oxidase inhibitors to chronic heart failure (CHF) patients is controversial. We investigated the beneficial effects of a novel xanthine oxidoreductase inhibitor, topiroxostat, in patients with CHF and hyperuricemia (HU), in comparison to allopurinol. The prospective, randomized open-label, blinded-end-point study was performed in 141 patients with CHF and HU at 4 centers. Patients were randomly assigned to either topiroxostat or allopurinol group to achieve target uric acid level ≤6.0 mg/dL. According to the protocol, 140 patients were followed up for 24 weeks. Percent change in ln (N-terminal-proB-type natriuretic peptide) at week 24 (primary endpoint) was comparable between topiroxostat and allopurinol groups (1.6±8.2 versus -0.4±8.0%; P = 0.17). In the limited number of patients with heart failure with reduced ejection fraction (HFrEF) (left ventricle ejection fraction <45%), ratio of peak early diastolic flow velocity at mitral valve leaflet to early diastolic mitral annular motion velocity (E/e') decreased in topiroxostat group, but not in allopurinol group. Urinary 8-hydroxy-2'-deoxyguanosine and L-type fatty acid-binding protein levels increased and osmolality decreased significantly in allopurinol group, while these changes were less or absent in topiroxostat group. In allopurinol group HFrEF patients, additional to the increases in these urinary marker levels, urinary creatinine levels decreased, with no change in clearance, but not in topiroxostat group. Compared with allopurinol, topiroxostat did not show great benefits in patients with CHF and HU. However, topiroxostat might have potential advantages of reducing left ventricular end-diastolic pressure, not worsening oxidative stress in proximal renal tubule, and renoprotection over allopurinol in HFrEF patients.

Background: Hyperuricemia is an independent risk factor for renal progression in IgA nephropathy (IgAN). However, no study has evaluated the effect of allopurinol on the clinical outcome in hyperuricemic IgAN. Methods: First,a retrospective cohort study of 353 IgAN patients was conducted to explore the relationship between uric acid (UA) and the progression of renal disease over a mean period of 5 years. Then, 40 hyperuricemic IgAN patients were randomized to receive allopurinol (100–300 mg/day) or usual therapy for 6 months. The study outcomes were renal disease progression and/or blood pressure. Results: Hyperuricemia independently predicted renal survival at 1, 3, and 5 years after adjustment for different baseline estimated glomerular filtration rates. In the randomized controlled trial, allopurinol did not significantly alter renal progression or proteinuria. The antihypertensive drug dosage was reduced in 7 of 9 cases with hypertension in the allopurinol group compared to 0 of 9 cases in the control group (p < 0.01). UA levels correlated with mean arterial pressure in normotensive patients (r = 0.388, p < 0.001). Conclusion: Hyperuricemia predicts the progression of IgAN independently of baseline estimated glomerular filtration rate. Allopurinol may improve the control of blood pressure. Further studies are required to explore the effects of lowering UA on renal protection in IgAN.

Background and aim IgA nephropathy (IgAN) is one of the world’s most common glomerular diseases. Hyperuricemia was recently defined as risk factor for chronic kidney disease. We aimed to investigate the impact of baseline serum uric acid levels on progression of IgAN. Materials and methods A total of 93 patients with IgAN were screened. Demographic information and biochemical data were recorded. eGFR (using the CKD-EPI = Chronic Kidney Disease Epidemiology Collaboration formula) was used as renal function marker. Baseline and sixth month eGFR values were calculated. Progression of renal disease was defined as the difference between baseline eGFR and sixth month eGFR (delta eGFR). Results Mean age of the patients was 40 ± 11 years (60 % were males). Baseline mean eGFR was 77.9 ± 30.2 mL/min, and baseline mean serum uric acid was 5.65 ± 1.68 mg/dL. Importantly, baseline serum uric acid levels were found to be associated with the change in eGFR ( r  = 0.252, p  = 0.01). In multivariate analysis (adjusted R 2  = 0.171, p  = 0.031), adjusting for age, gender, baseline eGFR, blood pressure, baseline albumin concentration and ACEI and/or ARB use revealed that the baseline serum uric acid levels significantly predicted the change in eGFR. Conclusion Baseline serum uric acid concentration is directly proportional to the rate of decline in renal functions in patients with IgAN. Uric acid-lowering treatments may be beneficial for the prevention of progression of IgAN. However, randomized controlled studies are needed for this purpose.

Redox balance and methylation are crucial to homeostasis and are linked by the methionine-homocysteine cycle. We examined whether differences in methylation potential, measured as plasma levels of S-adenosyl methionine (SAM) and S-adenosyl homocysteine (SAH), occur at baseline and during anti-oxidant therapy with the xanthine oxidase inhibitor allopurinol in patients with heart failure with reduced ejection fraction. We analyzed plasma samples collected at baseline and 24 weeks in the Xanthine Oxidase Inhibition for Hyperuricemic Heart Failure Patients (EXACT-HF) study, which randomized patients with heart failure with reduced ejection fraction to allopurinol or placebo. Associations between plasma levels of SAM, SAH, SAM/SAH ratio, and outcomes, including laboratory markers and clinical events, were assessed. Despite randomization, median SAM levels were significantly lower at baseline in the allopurinol group. SAH levels at 24 weeks, and change in SAM from baseline to week 24, were significantly higher in the group of patients randomized to allopurinol compared to the placebo group. A significant correlation was observed between change in SAH levels and change in plasma uric acid (baseline to 24-week changes) in the allopurinol group. There were no significant associations between levels of SAM, SAH, and SAM/SAH ratio and clinical outcomes. Our results demonstrate significant biological variability in SAM and SAH levels at baseline and during treatment with an anti-oxidant and suggest a potential mechanism for the lack of efficacy observed in trials of anti-oxidant therapy. These data also highlight the need to explore personalized therapy for heart failure.

PURPOSE: Hyperuricemia is a recognized risk factor for cardiovascular diseases. Soy foods contain a moderate amount of purine and may predispose to raised serum uric acid (UA). However, no study has examined the long-term effect of soy intake on UA levels. We examined whether consumption of soy foods and isoflavone extracts for 6 months altered serum UA. METHODS: The analysis included two randomized controlled trials (soy protein trial and whole soy trial) among total 450 postmenopausal women with either prehypertension or prediabetes. We conducted a pooled analysis by combining participants from both the soy flour and soy protein groups (combined soy foods group), participants from both the isoflavone and daidzein groups (combined isoflavone group) and participants from both milk placebo groups. Fasting venous samples were obtained at baseline and the end of the trial for serum UA analysis. RESULTS: In the pooled data, 417 subjects completed the study according to protocol. The baseline serum UA levels were comparable among the three combined groups. There was a lower decrease in UA levels among women in the combined soy foods group compared with women in the other two groups (p = 0.028 and 0.026). The net decrease and % decrease in UA were 14.5 μmol/L (95 % CI 1.93–25.6, p = 0.023) or 4.9 % (95 % CI 1.3–8.5 %, p = 0.023) between the combined soy foods group and placebo group. CONCLUSIONS: Among Chinese postmenopausal women with either prehypertension or prediabetes, soy intake did not increase urate levels.

ObjectivesTo provide estimates of the cumulative incidence of gout according to baseline serum urate.MethodsUsing individual participant data from four publicly available cohorts (Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, and both the Original and Offspring cohorts of the Framingham Heart Study), the cumulative incidence of clinically evident gout was calculated according to baseline serum urate category. Cox proportional hazards modelling was used to evaluate the relation of baseline urate categories to risk of incident gout.ResultsThis analysis included 18 889 participants who were gout-free at baseline, with mean (SD) 11.2 (4.2) years and 212 363 total patient-years of follow-up. The cumulative incidence at each time point varied according to baseline serum urate concentrations, with 15-year cumulative incidence (95% CI) ranging from 1.1% (0.9 to 1.4) for <6 mg/dL to 49% (31 to 67) for ≥10 mg/dL. Compared with baseline serum urate <6 mg/dL, the adjusted HR for baseline serum urate 6.0–6.9 mg/dL was 2.7, for 7.0–7.9 mg/dL was 6.6, for 8.0–8.9 mg/dL was 15, for 9.0–9.9 mg/dL was 30, and for ≥10 mg/dL was 64.ConclusionsSerum urate level is a strong non-linear concentration-dependent predictor of incident gout. Nonetheless, only about half of those with serum urate concentrations ≥10mg/dL develop clinically evident gout over 15 years, implying a role for prolonged hyperuricaemia and additional factors in the pathogenesis of gout.

Increased serum levels of uric acid have been associated with the onset and development of chronic kidney disease (CKD), cardiovascular disease, and mortality, through several molecular pathogenetic mechanisms, such as inflammation and oxidative stress. Oxidative stress is present even in the early stages of CKD, progresses parallelly with the deterioration of kidney function, and is even more exacerbated in end-stage renal disease patients undergoing maintenance hemodialysis. Although acting in the plasma as an antioxidant, once uric acid enters the intracellular environment; it behaves as a powerful pro-oxidant. Exogenous intake of antioxidants has been repeatedly shown to prevent inflammation, atherosclerosis and oxidative stress in CKD patients. Moreover, certain antioxidants have been proposed to exert uric acid-lowering properties. This review aims to present the available data regarding the effects of antioxidant supplements on both oxidative stress and uric acid serum levels, in a population particularly susceptible to oxidative damage such as CKD patients.

ABCG2, also known as BCRP, is a high-capacity urate exporter, the dysfunction of which raises gout/hyperuricemia risk. Generally, hyperuricemia has been classified into urate 'overproduction type' and/or 'underexcretion type' based solely on renal urate excretion, without considering an extra-renal pathway. Here we show that decreased extra-renal urate excretion caused by ABCG2 dysfunction is a common mechanism of hyperuricemia. Clinical parameters, including urinary urate excretion, are examined in 644 male outpatients with hyperuricemia. Paradoxically, ABCG2 export dysfunction significantly increases urinary urate excretion and risk ratio of urate overproduction. Abcg2 -knockout mice show increased serum uric acid levels and renal urate excretion, and decreased intestinal urate excretion. Together with high ABCG2 expression in extra-renal tissues, our data suggest that the 'overproduction type' in the current concept of hyperuricemia be renamed 'renal overload type', which consists of two subtypes—'extra-renal urate underexcretion' and genuine 'urate overproduction'—providing a new concept valuable for the treatment of hyperuricemia and gout. Hyperuricemia, or gout, is thought to arise either from urate overproduction or from decreased renal excretion of urate. Ichida et al . show that the extra-renal excretion of urate also has a role in the pathogenesis of hyperuricemia, and propose a new classification for patients with this disease.

Purpose of the Review Our review explores the epidemiology, physiology, and clinical data surrounding the connection between hyperuricemia and metabolic syndrome, chronic kidney disease, and hypertension. Recent Findings Compelling physiologic mechanisms have been proposed to explain a causal relationship between hyperuricemia and metabolic syndrome, chronic kidney disease, and hypertension but clinical studies have given mixed results in terms of whether intervening with hyperuricemia using urate-lowering therapy has any beneficial effects for patients with these conditions. Summary Despite the large amount of research already put into this topic, more randomized placebo-controlled trials are needed to more firmly establish whether a cause-effect relationship exists and whether lowering uric acid levels in patients with these conditions is beneficial.

Because of its high prevalence worldwide, osteoporosis is considered a serious public health concern. Many known risk factors for developing osteoporosis have been identified and are crucial if planning health care needs. Recently, an association between uric acid (UA) and bone fractures had been explored. Extracellular UA exhibits antioxidant properties by effectively scavenging free radicals in human plasma, but this benefit might be disturbed by the hydrophobic lipid layer of the cell membrane. In contrast, intracellular free oxygen radicals are produced during UA degradation, and superoxide is further enhanced by interacting with NADPH oxidase. This intracellular oxidative stress, together with inflammatory cytokines induced by UA, stimulates osteoclast bone resorption and inhibits osteoblast bone formation. UA also inhibits vitamin D production and thereby results in hyper-parathyroidism, which causes less UA excretion in the intestines and renal proximal tubules by inhibiting the urate transporter ATP-binding cassette subfamily G member 2 (ABCG2). At normal or high levels, UA is associated with a reduction in bone mineral density and protects against bone fracture. However, in hyperuricemia or gout arthritis, UA increases bone fracture risk because oxidative stress and inflammatory cytokines can increase bone resorption and decrease bone formation. Vitamin D deficiency, and consequent secondary hyperparathyroidism, can further increase bone resorption and aggravated bone loss in UA-induced osteoporosis.