Asymptomatic Hyperuricemia Patients Research Articles

Musculoskeletal ultrasound abnormalities in asymptomatic hyperuricemic patients: Association with cardiovascular risk factors

To assess the relation between musculoskeletal ultrasound (MSUS) abnormalities and cardiovascular risk factors in asymptomatic and symptomatic hyperuricemic patients. The study included 66 hyperuricemic patients. 33 were asymptomatic and 33 were symptomatic. The socio-demographic features, body mass index (BMI), blood pressure measurement and musculoskeletal examination were recorded. Serum uric acid (SUA), serum creatinine (s.Cr.), total cholesterol, high density lipoprotein (HDL) and triglycerides (TG) were measured and estimated glomerular filtration rate (e GFR) was calculated using chronic kidney disease-epidemiology collaboration (CKD-EPI). Cardiovascular risk was calculated using Systematic Coronary Risk Evaluation of the European Society of Cardiology (SCORE/ESC) and Atherosclerotic Cardiovascular Disease of American College of Cardiology (ASCVD/ACC). MSUS of the knees, ankles and 1st metatarsophalangeal joints (MTPs) was performed and specific gout signs (aggregates, double contour and tophi) were assessed. There was no association between MSUS abnormalities and either individual or overall cardiovascular risk factors except the negative correlation between the age and the high density lipoprotein (HDL) level and the positivity of the patients (presence of at least one of the specific gout sign "aggregates, double contour or tophi" in at least one out of the six assessed joints "both knees, ankles and 1st MTPs" among the symptomatic group. The association between MSUS abnormalities and cardiovascular risk factors in the hyperuricemic patients is not yet clear and further studies are needed to introduce it as a screening modality for these patients.

Effect of the Xanthine Oxidase Inhibitor, Febuxostat, on WBC Count in Asymptomatic Hyperuricemia: Subanalysis of the Randomized PRIZE Study.

The anti-inflammatory effects of the xanthine oxidase inhibitor, febuxostat, a urate-lowering agent, have been reported in animal studies. However, the anti-inflammatory effects of urate-lowering therapy and its associated cardiovascular protective effects have not been fully determined in actual clinical practice. This study aimed to investigate the effect of febuxostat on white blood cell (WBC) count in patients with asymptomatic hyperuricemia and to assess for potential correlations between changes in WBC count and inflammatory biomarkers and atherosclerosis in this patient population. This was a post hoc subanalysis of the PRIZE study, a multicenter, prospective, randomized, open-label clinical trial. In the PRIZE study, asymptomatic hyperuricemia patients were randomized to febuxostat group or control group with non-pharmacological therapy and evaluated the effect on vascular. The primary endpoints of this study were the assessment of the time course of WBC count over 24 months and its changes from baseline. Correlations of WBC count with high-sensitivity C-reactive protein (hs-CRP) and mean common carotid artery (CCA)-IMT were also exploratorily examined in the febuxostat group. A total of 444 patients (febuxostat group, n=223; control group, n=221) with WBC measurements available at baseline and at least one of the follow-up time points of 12 or 24 months, were enrolled. Febuxostat modestly, but significantly, reduced WBC counts at 12 and 24 months compared with the baseline levels (P=0.002 and P=0.026, respectively). Notably, the WBC count in the febuxostat group at 12 and 24 months was significantly lower than that in the control group (P=0.007 and P=0.023, respectively). The changes in WBC count were associated with those of hs-CRP (P=0.038), but not with CCA-IMT (P=0.727). Febuxostat therapy for 24 months modestly, but significantly, decreased WBC count in patients with asymptomatic hyperuricemia. This might potentially reflect a modest anti-inflammatory action of febuxostat in clinical settings.

The impact of AIM2 inflammasome-induced pyroptosis on acute gouty arthritis and asymptomatic hyperuricemia patients.

This study aimed to evaluate the role of absent in melanoma 2 (AIM2) inflammasome-mediated pyroptosis in the pathogenesis of acute gouty arthritis (AGA) and asymptomatic hyperuricemia(AHU). A cohort of 30 AGA patients, 30 AHU individuals, and 30 healthy controls (HC) was assembled. Demographic and biochemical data, along with blood samples, were collected. Serum double-stranded DNA (dsDNA) levels were quantified using a fluorescent assay. Transcriptomic and proteomic analysis of AIM2, Caspase-1, GSDMD, IL-1β, and IL-18 in peripheral blood mononuclear cells was performed using qRT-PCR and Western blot. Enzyme-linked immunosorbent assay (ELISA) was employed to measure serum IL-1β and IL-18. Spearman correlation analysis was utilized to assess relationships between variables. Both AGA and AHU groups demonstrated elevated metabolic indicators and serum levels of dsDNA, IL-1β, and IL-18 compared to the HC group. AGA patients exhibited higher inflammatory markers than the AHU group. In the AGA group, there was a significant increase in the mRNA and protein levels of AIM2, Caspase-1, GSDMD, IL-1β, and IL-18 (P<0.05 to P<0.001). The AHU group showed higher AIM2, Caspase-1, GSDMD, and IL-18 mRNA levels than the HC group (P<0.001 to P<0.01), with a non-significant increase in AIM2, GSDMD, and IL-1β proteins (P>0.05). In contrast, Caspase-1 and IL-18 proteins were significantly higher in the AHU group (P<0.05). Notable correlations were observed between AIM2 protein expression and levels of Caspase-1 and GSDMD in both AGA and AHU groups. In the AGA group, AIM2 protein correlated with IL-1β, but not in the AHU group. The AIM2 protein in the AHU group was positively associated with IL-18, with no such correlation in the AGA group. AIM2 inflammasome may play a role in the inflammatory processes of AGA and AHU and that its activation may be related to the pyroptosis pathway.

To Assess the Association Between Decreased Uric Acid Level and Blood Pressure

Background: Asymptomatic hyperuricemia is commonly viewed as an entity that should not be treated. Treatment of asymptomatic hyperuricemia in patients with renal impairment is still in debate. There is no evidence to rationalize pharmacotherapy for patients with hyperuricemia with no complication and serum uric acid concentration is below 10 mg/dL. Objectives: To evaluate the association between decreased uric acid level and blood pressure. Methods: This was a single-center, single (patient blinded, placebo-controlled study conducted in chattogram medical college hospital over 1 year. Patients of both sexes aged above 18 years with eGFRs of 15 to 60 mL/ min/1.73 m2 (as calculated with the 4-variable MDRD) and serum uric acid levels ≥7 mg/dL were included. Patients were selected in purposive technique divided randomly by lottery into two groups. One group received febuxostat 40-mg tablet once daily and another group received placebo tablets at the same time. Both groups received antihypertensive and antidiabetic medication and diuretics as per needed. Drugs and placebo were continued throughout the study period. Patients were evaluated at baseline, 3rd and 6th months for history, physical examination, assessment of any adverse events or end points and relevant investigations. Results: 35 patients in each group were analyzed. Baseline characteristics were similar between the two groups. In febuxostat group the mean uric acid was decreased from 8.55 (±1.05) to 4.92 (±0.64) mg/dl, which was statistically significant (p &lt;0.001) and in placebo group increased from 8.10 (±0.6) to 8.99 (±0.27) mg/dl which was statistically significant (P=0.001) after 6 months follow up. In case of mean eGFR in the febuxostat showed a nonsignificant increased from 25.28 (± 7.59) to 27.01 (±8.29) ml/min/1.73 m2, but in placebo group there was decreased mean eGFR from 26.81 (± 7.31) to 23.32(±7.72) ml/min/1.73 m2 which was statistically significant (p &lt;0.001) and between group difference in eGFR was significant at 6 months (p = 0.048). Moreover after 6 months of treatment systolic and diastolic blood pressure were significantly lower in febuxostat group than placebo (p &lt;0.05). Conclusion: Compared to placebo, febuxostat slowed the decline in eGFR in CKD stage 3 and 4

Gegen Qinlian Decoction treatment of asymptomatic hyperuricemia by targeting circadian immune function

BackgroundThe Gegen Qinlian Decoction (GGQLD) is a renowned traditional Chinese medicinal formula that has been used for centuries to effectively treat asymptomatic Hyperuricemia (HUA). This study aims to investigate the underlying mechanism of GGQLD's therapeutic effects on HUA.MethodsThe study enrolled a total of 25 healthy participants and 32 middle-aged and elderly individuals with asymptomatic HUA. All asymptomatic HUA participants were treated with GGQLD. Venous blood samples were collected from all participants to isolate peripheral blood mononuclear cells (PBMCs), which were then analyzed for biological profiles using flow cytometry. Network pharmacology analysis was utilized to identify the potential pathways involved in the therapeutic effects of GGQLD. Transcriptomic patterns of cultured proximal tubule epithelial cells (PTECs) were evaluated via bulk RNA-seq, and critical differentially expressed genes (DEGs) were identified and verified through ELISA. Molecular docking and molecular dynamics (MD) simulation were employed to investigate the potential compounds in GGQLD that may be involved in treating HUA.ResultsNetwork pharmacology analysis revealed that immune-related pathways might be involved in the therapeutic mechanism of GGQLD. RNA-seq analysis confirmed the involvement of innate lymphoid cell (ILC) development-related genes and clock genes. Polychromatic flow cytometric analysis demonstrated that GGQLD treatment reduced the proportion of ILC3s in total ILCs in asymptomatic HUA patients. ELISA results showed that GGQLD treatment reduced the levels of activating factors, such as ILC3-IL-18 and IL-1β, in the plasma of HUA patients. GGQLD was also found to regulate circadian clock gene expression in PBMCs to treat asymptomatic HUA. Furthermore, the interaction between 40 compounds in GGQLD and HDAC3 (Histone Deacetylase 3), NLRP3 (NOD-like receptor protein 3), RORA (RAR-related orphan receptor A), and REV-ERBα (nuclear receptor subfamily 1) revealed that GGQLD may regulate ILCs and clock genes to treat asymptomatic HUA.ConclusionsThe regulation of circadian clock gene expression and the proportion of ILC cells may be involved in the therapeutic effects of GGQLD on asymptomatic HUA patients.

La gota preclínica es frecuente en el paciente con enfermedad renal crónica estadio 3-5. Relevancia de la ecografía articular

BackgroundOne in 10 patients with hyperuricemia may develop gout over time, with urate deposition sometimes asymptomatic. Recent reviews and guidelines support ultrasound (US) to assess asymptomatic hyperuricemic (AH) patients to detect gout lesions, showing double contour (DC) and tophus the highest specificities and positive predictive values. Hyperuricemia and gout are common in chronic kidney disease (CKD), especially with glomerular filtration rate (GFR) <60, and both are associated with worse prognosis, although treatment of AH in CKD is not yet recommended in all guidelines. US gout lesions have been found more frequently in AH (up to 35%) than in normouricemic (NU) patients, but evidence is scarce in CKD. ObjectivesTo assess the prevalence of urate deposit in stages 3–5 CKD detected by US, and to investigate if there are differences between AH and NU patients. MethodsMulticenter cross-sectional study, recruiting patients aged ≥18 years with AH and stages 3–5 CKD in four hospitals. A comparator group of NU patients with stages 3–5 CKD was included. Exclusion criteria: previous diagnosis of gout, tophi. Hyperuricemia was defined as serum uric acid (sUA) >7 mg/dl, documented at least twice during the last 12 months. A standardized US exam of the knees and bilateral first metatarsophalangeal joints was performed to assess patients for DC/tophus as defined by OMERACT. Demographic, clinical and laboratory data were recorded. A descriptive analysis was performed using SPSS. Pre-clinical gout (PCG: DC and/or tophus) was considered as outcome variable. Chi-square and Fisher's exact test were used for qualitative variables, and Mann–Whitney U test for quantitative variables; significant threshold p<0.05. ResultsFifty-three patients with stages 3–5 CKD (59.6% stage 3, 19.1% stage 4, 21.3% stage 5) were recruited, 38 AH (71.7%) and 15 NU. A higher prevalence of US findings was observed in HU patients compared to NU patients (DC 23.7% vs. 13.3%, tophus 31.6% vs. 26.7%, PCG 39.5% vs. 33.3%), although the differences were not statistically significant. NU patients had CKD of longer duration than HU patients [11 (7.2–13.5) vs. 6 (2–9.2) years; p = 0.02], with no differences in sex, age, comorbidities, or urate-lowering therapy (ULT) (66.7% vs. 44.7%; p = 0.05) and other treatments. Seventy percent of NU patients with TRU had AH before starting treatment. In patients with tophi, we observed a trend towards shorter duration of CKD and shorter duration of treatment with ULT compared to those without tophi [3.5 (2–6.7) vs. 7 (3–12) years; p = 0.05] and [22 (12–44) vs. 39 (29–73) months; p = 0.08], respectively. This trend was also observed in PCG, but not in DC, first US sign to disappear after initiation of ULT. Ninety percent of patients (100% in non-dialyzed patients) with PCG had a median uricemia ≥5 mg/dl in the past 12 months. ConclusionWe found a significant prevalence of asymptomatic urate deposition in patients with stages 3–5 CKD, mostly in subjects with median uricemia ≥5 mg/dl in the last 12 months. Early diagnosis of PCG by musculoskeletal US in CKD may allow earlier introduction and optimization of ULT. This will probably contribute to slowing down the progression of this pathology, which makes it essential to promote collaboration between Nephrology and Rheumatology.

Effect of febuxostat on the level of malondialdehyde-modified low-density lipoprotein, an oxidative stress marker: A subanalysis of the PRIZE study.

Febuxostat is a selective xanthine oxidase inhibitor that reportedly exhibits antioxidant properties. We previously performed a multicentre, randomized controlled (PRIZE) study for vascular evaluation under uric acid (UA) control by febuxostat to investigate the progression of carotid lesions in asymptomatic hyperuricemic patients with carotid atherosclerosis for 2 years. The current subanalysis of the PRIZE study aimed to assess the effect of febuxostat on the level of malondialdehyde-modified low-density lipoprotein (MDA-LDL), an oxidative stress marker. We recruited 383 patients (febuxostat group, n = 200; control group, n = 183) from the PRIZE trial for whom MDA-LDL measurements were available. The UA, MDA-LDL, low-density lipoprotein cholesterol (LDL-C) levels, and MDA-LDL/LDL-C ratio were identified, represented as the estimated difference from baseline to 24months. We also evaluated the relationship between febuxostat dose (10, ≤20 to <40, and ≤40 to ≤60 mg) and changes in the MDA-LDL level, LDL-C level, or MDA-LDL/LDL-C ratios. The estimated change in MDA-LDL/LDL-C ratio from baseline to 24monthswas significantly lower in the febuxostat group than in the control group (p = .025), whereas the estimated changes in MDA-LDL (p = .235) and LDL-C (p = .323) levels did not differ between the two groups. No significant correlation existed between the febuxostat doses and the estimated change in the MDA-LDL level (p = .626), LDL-C level (p = .896), or MDA-LDL/LDL-C ratio (p = .747). Our findings may indicate a possibility that febuxostat can lower the MDA-LDL/LDL-C ratio, a potential marker of atherosclerosis and oxidative stress, in asymptomatic hyperuricemic patients with carotid atherosclerosis. Further studies are required to validate our findings and elucidate the clinical antioxidant effect of febuxostat.

Rapid identification of early renal damage in asymptomatic hyperuricemia patients based on urine Raman spectroscopy and bioinformatics analysis.

Objective: The issue of when to start treatment in patients with hyperuricemia (HUA) without gout and chronic kidney disease (CKD) is both important and controversial. In this study, Raman spectroscopy (RS) was used to analyze urine samples, and key genes expressed differentially CKD were identified using bioinformatics. The biological functions and regulatory pathways of these key genes were preliminarily analyzed, and the relationship between them as well as the heterogeneity of the urine components of HUA was evaluated. This study provides new ideas for the rapid evaluation of renal function in patients with HUA and CKD, while providing an important reference for the new treatment strategy of HUA disease. Methods: A physically examined population in 2021 was recruited as the research subjects. There were 10 cases with normal blood uric acid level and 31 cases with asymptomatic HUA diagnosis. The general clinical data were collected and the urine samples were analyzed by Raman spectroscopy. An identification model was also established by using the multidimensional multivariate method of orthogonal partial least squares discriminant analysis (OPLS-DA) model for statistical analysis of the data, key genes associated with CKD were identified using the Gene Expression Omnibus (GEO) database, and key biological pathways associated with renal function damage in CKD patients with HUA were analyzed. Results: The Raman spectra showed significant differences in the levels of uric acid (640cm-1), urea, creatinine (1,608, 1,706cm-1), proteins/amino acids (642, 828, 1,556, 1,585, 1,587, 1,596, 1,603, 1,615cm-1), and ketone body (1,643cm-1) (p < 0.05). The top 10 differentially expressed genes (DEGs) associated with CKD (ALB, MYC, IL10, FOS, TOP2A, PLG, REN, FGA, CCNA2, and BUB1) were identified. Compared with the differential peak positions analyzed by the OPLS-DA model, it was found that the peak positions of glutathione, tryptophan and tyrosine may be important markers for the diagnosis and progression of CKD. Conclusion: The progression of CKD was related to the expression of the ALB, MYC, IL10, PLG, REN, and FGA genes. Patients with HUA may have abnormalities in glutathione, tryptophan, tyrosine, and energy metabolism. The application of Raman spectroscopy to analyze urine samples and interpret the heterogeneity of the internal environment of asymptomatic HUA patients can be combined with the OPLS-DA model to mine the massive clinical and biochemical examination information on HUA patients. The results can also provide a reference for identifying the right time for intervention for uric acid as well as assist the early detection of changes in the internal environment of the body. Finally, this approach provides a useful technical supplement for exploring a low-cost, rapid evaluation and improving the timeliness of screening. Precise intervention of abnormal signal levels of internal environment and energy metabolism may be a potential way to delay renal injury in patients with HUA.

PS-C34-7: EFFECT OF FEBUXOSTAT ON THE LEVEL OF MALONDIALDEHYDE-MODIFIED LOW-DENSITY LIPOPROTEIN, AS AN OXIDANT MARKER, FROM THE SUB-ANALYSES OF PRIZE STUDY

Background: Febuxostat is a selective xanthine oxidase inhibitor that has been reported to possess antioxidant properties in experimental and animal studies. We previously conducted the program of vascular evaluation under uric acid control by xanthine oxidase inhibitor, febuxostat: multicenter, randomized controlled (PRIZE) study to evaluate the progression of carotid lesions in asymptomatic hyperuricemic patients with carotid atherosclerosis treated with febuxostat for 2 years compared with a control group. In the present sub-analysis study of the PRIZE study, the effect of febuxostat on the level of malondialdehyde modified low density lipoprotein (MDA-LDL), one of the oxidative stress markers, was examined. Methods: The subjects were 381 patients enrolled in the PRIZE trial for whom MDA-LDL measurements were available at baseline and at 24 months (182 in the febuxostat group and 199 in the control group). Uric acid (UA) levels, MDA-LDL levels, and MDA-LDL/LDL-C were determined, expressed as the estimated difference from baseline to 24 months, and compared between the two groups. We also examined the relationship between febuxostat dose (10 mg, 20–40 mg, 40–60 mg) and changes in MDA-LDL or MDA-LDL/LDL-C. Results: Febuxostat significantly reduced the level of UA, compared with that in the control group, in a dose-dependent manner (p &lt; 0.001). The estimated difference in MDA-LDL/LDL-C from baseline to 24 months was significantly lower in the Febuxostat group than that in the control group (p = 0.025), while the estimated difference in MDA-LDL from baseline to 24 months was not different in the two groups (p = 0.235). There was no significant correlation between the dose of febuxostat and the estimated difference in MDA-L/LDL-C (p = 0.626). Conclusions: In asymptomatic hypereuricemia patients with carotid atherosclerosis, febuxostat may have some antioxidant effect, but the effect may not be dose-dependent.

Report from the European Society of Cardiology Congress 2022 in Barcelona: new discoveries in cardiovascular pharmacotherapy

The following paper presents an overview of the key studies presented at the European Society of Cardiology Congress 2022. The DELIVER study provided information on the efficacy of dapagliflozin independent of left ventricular ejection fraction. The ADVOR trial confirmed the beneficial effect of the inclusion of acetazolamide as a diuretic in the initial phase of acute decompensated heart failure. The REVIVED study showed no advantage of percutaneous revascularisation over optimal pharmacotherapy in stable coronary artery disease. The SECURE study demonstrated the benefit of the so-called polypill over taking each drug separately. The PANTHER meta-analysis indicated a better effect of using P2Y12 inhibitors over aspirin in chronic therapy. The ALL-HEART study revealed no benefit in treating asymptomatic hyperuricemia in patients with coronary artery disease with allopurinol. The INVICTUS trial demonstrated the superiority of vitamin K antagonists over non-vitamin K antagonist oral anticoagulants in preventing embolic complications in cases where valvular defects of rheumatic origin co-occur with atrial fibrillation.

Double Contour Sign In Early Detection Of Gout Among Asymptomatic Hyperuricemic Filipino Patients: A Single Center Tertiary Hospital Observational Study

Objective. Double contour sign (DCS) is considered part of the new gout classification. This study aims to determine the agreement of blinded musculoskeletal sonologists in identifying the double contour sign among asymptomatic hyperuricemic patients. Methods. Participants with asymptomatic hyperuricemia (n=65) underwent a gray-scale ultrasound assessment of both of their 1st metatarsophalangeal joints (MTPJs) done on 3 positions (dorsal, medial, plantar) in longitudinal view. The static images were read by 2 independent blinded sonologists for presence of double contour sign. Results. Among the 130 1st MTPJs, the sonologists were able to positively identify DCS on 48R and 52L, negative in 10R and 10L, with discordant readings in 7R, 3L. The overall kappa agreement was statistically significant at 0.674 (substantial agreement) and 0.842 (almost perfect agreement) on the right and left respectively, (both p&lt;0.001). Conclusion and Recommendation. There is a high proportion of positive double contour sign seen among persistently asymptomatic hyperuricemic patients. It might be prudent to perform musculoskeletal ultrasound early on to detect monosodium urate crystal deposits in similar patients. A close follow up to monitor clinical gouty arthritis may be necessary or consider utility of urate lowering drugs in crystal dissolution in prospective studies.

The impact of short-chain fatty acid-producing bacteria of the gut microbiota in hyperuricemia and gout diagnosis.

Persistent hyperuricemia is a key factor in gout; however, only 13.5% of hyperuricemic individuals manifest the disease. The gut microbiota could be one of the many factors underlying this phenomenon. We aimed to assess the difference in taxonomic and predicted functional profiles of the gut microbiota between asymptomatic hyperuricemia (AH) individuals and gout patients. The V3-V4 region of the 16S rRNA gene of the gut microbiota of AH individuals, gout patients, and controls was sequenced. Bioinformatic analyses were carried out with QIIME2 and phyloseq to determine the difference in the relative abundance of bacterial genera among the study groups. Tax4fun2 was used to predict the functional profile of the gut microbiota. AH individuals presented a higher abundance of butyrate- and propionate-producing bacteria than gout patients; however, the latter had more bacteria capable of producing acetate. The abundance of Prevotella genus bacteria was not significantly different between the patients but was higher than that in controls. This result was corroborated by the functional profile, in which AH individuals had less pyruvate oxidase abundance than gout patients and less abundance of an enzyme that regulates glutamate synthetase activation than controls. We observed a distinctive taxonomic profile in AH individuals characterized by a higher abundance of short-chain fatty acid-producing bacteria in comparison to those observed in gout patients. Furthermore, we provide scientific evidence that indicates that the gut microbiota of AH individuals could provide anti-inflammatory mediators, which prevent the appearance of gout flares. Key Points • AH and gout patients both have a higher abundance of Prevotella genus bacteria than controls. • AH individuals' gut microbiota had more butyrate- and propionate-producing bacteria than gout patients. • The gut microbiome of AH individuals provides anti-inflammatory mediators that could prevent gout flares.

The Prevalence of Asymptomatic Hyperuricemia in Patients with or Without Psoriatic Arthritis is Associated with a Similar Cardiovascular Risk

Abstract Aim: To investigate the association between cardiovascular burden and monosodium urate (MSU) deposits in the joints of patients with asymptomatic hyperuricemia and no evidence of arthritis and subjects with psoriatic arthritis and hyperuricemia. Patients and methods: A single-center, cross-sectional study including 52 individuals: 39 with asymptomatic hyperuricemia and 13 with psoriatic arthritis and hyperuricemia. All patients underwent ultrasound of the joints by which the presence or absence of MSU crystal deposits was assessed. Subjects underwent transthoracic echocardiography by which left ventricular mass index (LVMI) was estimated. Intima-media thickness (IMT) of the common carotid arteries was measured and the presence of atherosclerotic plaques was registered. Results: We found no difference in the distribution of cardiovascular risk factors between the two groups. Further, no difference in their distribution was found between those who were not treated and those who were treated with urate-lowering medications. The frequency of articular MSU deposits was similar between non-allopurinol-treated and allopurinol-treated individuals (p = 0.554). There was no difference in the frequency of articular deposits between benzbromarone recipients and non-recipients (p = 0.396). We observed no connection between articular MSU deposits and LVMI (p = 0.625), IMT (p = 0.117) and atherosclerotic plaques (p = 0.102). Among untreated and treated with urate-lowering drugs there was no difference in LVMI (p = 0.063), IMT (p = 0.975) and plaque distribution (p = 1.000). Conclusion: We can assume that in patients with asymptomatic hyperuricemia and no evidence of arthritis and in subjects with psoriatic arthritis and asymptomatic hyperuricemia, only the prescription of urate-lowering medications for reduction of urate load and cardiovascular risk is not sufficient.

Cardiological and rheumatological expert statement on the management of asymptomatic hyperuricemia in patients at high cardiovascular risk

Cardiological and rheumatological expert statement on the management of asymptomatic hyperuricemia in patients at high cardiovascular risk

The prevalence of asymptomatic hyperuricemia in patients with chronic kidney disease and its effect on the course and prognosis (experience of one center)

Objective: to analyze the prevalence of asymptomatic hyperuricemia (HU), as well as to assess its relationship with metabolic disorders, pathological conditions and complications in chronic kidney disease (CKD), we conducted a retrospective cohort study in the form of a total cross-section of patients hospitalized in a round-the-clock bed of the nephrology department. Material and methods: 261 patients were included in the study, the average age was 50.9±17.2 (M±SD), there were 261 males and 99 females. The structure of CKD in hospitalized patients was as follows: CKD C1 — 53 patients, C2 — 70 patients, C3A — 46, C3B — 46, C4 — 36, C5 — 7 patients. The study did not include patients diagnosed with gout. Results: the uric acid level in the examined cohort was 369.8±109.7 mmol/L, ranging from 157 to 768 mmol/l. As the glomerular filtration rate (GFR) decreased, the probability of HU increased. With the development and progression of dyslipidemia, there was an increase in the probability of detecting HU. In patients with CKD, an increase in the level of daily proteinuria was also accompanied by an increase in the probability of detecting HU. The risk of progression of CKD to the terminal stages, as well as LVH, arrhythmias, hypertension is associated with high values of uric acid in the blood. Conclusions: the high prevalence of HU in patients with CKD, along with data on its negative impact on the course of CKD, is an important argument in favor of its detection and control. The association of HU with metabolic disorders against the background of high proteinuria explains one of the mechanisms of its detrimental effect on the course of CKD. The influence of HU on the probability of detection of hypertension, LVH, arrhythmias and terminal stages of CKD is shown, which determines the importance of the modifiability of this risk factor in the prognosis of the course of CKD

POS-192 EFFICACY OF FEBUXOSTAT IN RETARDING PROGRESSION OF CHRONIC KIDNEY DISEASE WITH ASSYMPTOMATIC HYPERURICAEMIA

Asymptomatic hyperuricemia is commonly viewed as an entity that should not be treated. Treatment of asymptomatic hyperuricemia in patients with renal impairment is still in debate.There is no evidence to rationalize pharmacotherapy for patients with hyperuricemia with no complication and serum uric acid (SUA) concentration is below 10 mg/dL. Our objective isto evaluate the efficacy of febuxostat in retarding the progression of chronic kidney disease (stages 3 and 4) with asymptomatic hyperuricemia.

To Treat or Not to Treat? Effect of Urate-Lowering Therapy on Renal Function, Blood Pressure and Safety in Patients with Asymptomatic Hyperuricemia: A Systematic Review and Network Meta-Analysis.

Hyperuricemia is associated with increased cardiovascular risk. Because patients with asymptomatic hyperuricemia (AH) experience no immediate discomfort and there are possible side effects of urate-lowering drugs, treatment for AH is controversial. We aimed to perform a network meta-analysis (NMA) to investigate the effects of different urate-lowering therapies (ULTs) on serum uric acid level, renal function, blood pressure (BP), and safety in AH patients. This NMA focused on AH patients. The intervention group (patients receiving urate-lowering drugs) was compared with others using other types of drugs, placebo, or usual care. We undertook a NMA under the frequentist framework by R. Thirteen eligible trials were identified. The interventions included allopurinol, febuxostat, and benzbromarone, which are not approved in the United States. Benzbromarone and allopurinol had the best efficacy on lowering serum uric acid level in short-term and long-term follow-up (mean difference [MD] = -3.05; 95% CI, -5.19 to -0.91 vs MD = -3.17; 95% CI, -5.19 to -1.15). Patients using allopurinol had significantly higher eGFR than using placebo in both short-term and long-term follow-up (MD = 3.07; 95% CI, 0.18 to 5.95 vs MD = 4.10; 95% CI, 2.66 to 5.54). No difference in BP was found between groups, except for febuxostat to diastolic BP after long-term treatment (MD = -1.47; 95% CI, -2.91 to -0.04). No statistically increased odds of safety events were found with the use of ULT. Our result showed that in AH patients, allopurinol has a renoprotective effect. Febuxostat has a significant impact in lowering diastolic BP. ULT does not result in a higher risk of safety events.

Quantitative proteomics by iTRAQ-PRM based reveals the new characterization for gout

BackgroundGout is a common and complex form of immunoreactive arthritis based on hyperuricemia, while the symptoms would turn to remission or even got worse. So, it is hard to early identify whether an asymptomatic hyperuricemia (AHU) patient will be susceptible to get acute gout attack and it is also hard to predict the process of gout remission to flare. Here, we report that the plasma proteins profile can distinguish among acute gout (AG), remission of gout (RG), AHU patients, and healthy controls.MethodsWe established an isobaric tags for relative and absolute quantification (iTRAQ) and parallel reaction monitoring (PRM) based method to measure the plasma proteins for AG group (n = 8), RG group (n = 7), AHU group (n = 7) and healthy controls (n = 8).ResultsEleven differentially expressed proteins such as Histone H2A, Histone H2B, Thrombospondin-1 (THBS1), Myeloperoxidase (MPO), Complement C2, Complement component C8 beta chain (C8B), Alpha-1-acid glycoprotein 1 (ORM1), Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4), Carbonic anhydrase 1 (CA1), Serum albumin (ALB) and Multimerin-1 (MMRN1) were identified. Histone H2A, Histone H2B and THBS1 might be the strongest influential regulator to maintain the balance and stability of the gout process. The complement and coagulation cascades is one of the main functional pathways in the mechanism of gout process.ConclusionsHistone H2A, Histone H2B and THBS1 are potential candidate genes for novel biomarkers in discriminating gout attack from AHU or RG, providing new theoretical insights for the prognosis, treatment, and management of gout process.Trial registrationThis study is not a clinical trial.

Serum lipidomics reveals distinct metabolic profiles for asymptomatic hyperuricemic and gout patients.

This study aimed to characterize the systemic lipid profile of patients with asymptomatic hyperuricemia (HUA) and gout using lipidomics, and to find potential underlying pathological mechanisms therefrom. Sera were collected from Affiliated Hospital of Nanjing University of Chinese Medicine as centre 1 (discovery and internal validation sets) and Suzhou Hospital of Traditional Chinese Medicine as centre 2 (external validation set), including 88 normal subjects, 157 HUA and 183 gout patients. Lipidomics was performed byultra high performance liquid chromatography plus Q-Exactive mass spectrometry (UHPLC-Q Exactive MS). Differential metabolites were identifed by both variable importance in the projection ≥1 in orthogonal partial least-squares discriminant analysis mode and false discovery rate adjusted P ≤ 0.05. Biomarkers were found by logistic regression and receiver operating characteristic (ROC) analysis. In the discovery set, a total of 245 and 150 metabolites, respectively, were found for normal subjects vs HUA and normal subjects vs gout. The disturbed metabolites included diacylglycerol, triacylglycerol (TAG), phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, etc. We also found 116 differential metabolites for HUA vs gout. Among them, the biomarker panel of TAG 18:1-20:0-22:1 and TAG 14:0-16:0-16:1 could differentiate well between HUA and gout. The area under the receiver operating characteristic ROC curve was 0.8288, the sensitivity was 82% and the specificity was 78%, at a 95% CI 0.747, 0.9106. In the internal validation set, the predictive accuracy of TAG 18:1-20:0-22:1 and TAG 14:0-16:0-16:1 panel for differentiation of HUA and gout reached 74.38%, while it was 84.03% in external validation set. We identified serum biomarkers panel that have the potential to predict and diagnose HUA and gout patients.

Asymptomatic Hyperuricemia and Functional State of the Kidneys in Patients with Essential Arterial Hypertension and Concomitant Diabetes Mellitus Type 2

Introduction: The manuscript analyzes the frequency of asymptomatic hyperuricemia in association with disturbance of glucose and lipid metabolism, inflammatory process, and kidney changes in patients with essential arterial hypertension (EAH) and concomitant diabetes mellitus type 2 (DM2).&#x0D; Aim: To determine the frequency of asymptomatic hyperuricemia in patients with EAH and concomitant DM2 and their effects on the main indicators of comorbid pathology.&#x0D; Materials and methods: 120 patients (51 males and 69 females), aged 45-69 years with average age being (58.2±5.7) years, were studied: 25 patients with treatment-compensated EAH, 1-2 degree, II stage (Group I); 25 patients with subcompensated DM2 (Group II) and 70 patients with treatment-compensated EAH, 1-2 degree, II stage and concomitant subcompensated DM2 (Group III). Control group consisted of 20 practically healthy volunteers - 8 (40.0%) males and 12 (60.0%) females, aged (54.7±4.9) years. Groups were randomized according to age, sex, BMI, duration of EAH and DM2.&#x0D; Results and discussion: Asymptomatic hyperuricemia were observed in 36.0% of group І patients, in 24.0% of group II patients and in 46.7% of group ІІІ patients. Relevant correlations were found between uric acid level in the blood and such indicators as/for systolic blood pressure (SBP), glycated hemoglobin (HbA1C), dyslipidemia, inflammatory process, and kidney damage.&#x0D; Conclusion: Asymptomatic hyperuricemia has a negative effect on the main indicators of comorbid pathology - in this case, EAH and concomitant DM2.