Renal interstitial fibrotic assessment using non-Gaussian diffusion kurtosis imaging in a rat model of hyperuricemia.

BACKGROUND: To investigate the feasibility of Diffusion Kurtosis Imaging (DKI) in assessing renal interstitial fibrosis induced by hyperuricemia. METHODS: A hyperuricemia rat model was established, and the rats were randomly split into the hyperuricemia (HUA), allopurinol (AP), and AP + empagliflozin (AP + EM) groups (n = 19 per group). Also, the normal rats were selected as controls (CON, n = 19). DKI was performed before treatment (baseline) and on days 1, 3, 5, 7, and 9 days after treatment. The DKI indicators, including mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) of the cortex (CO), outer stripe of the outer medulla (OS), and inner stripe of the outer medulla (IS) were acquired. Additionally, hematoxylin and eosin (H&E) staining, Masson trichrome staining, and nuclear factor kappa B (NF-κB) immunostaining were used to reveal renal histopathological changes at baseline, 1, 5, and 9 days after treatment. RESULTS: The HUA, AP, and AP + EM group MKOS and MKIS values gradually increased during this study. The HUA group exhibited the highest MK value in outer medulla. Except for the CON group, all the groups showed a decreasing trend in the FA and MD values of outer medulla. The HUA group exhibited the lowest FA and MD values. The MKOS and MKIS values were positively correlated with Masson's trichrome staining results (r = 0.687, P < 0.001 and r = 0.604, P = 0.001, respectively). The MDOS and FAIS were negatively correlated with Masson's trichrome staining (r = -626, P < 0.0014 and r = -0.468, P = 0.01, respectively). CONCLUSION: DKI may be a non-invasive method for monitoring renal interstitial fibrosis induced by hyperuricemia.

Associations between hyperuricemia and ultrasound-detected knee synovial abnormalities in middle-aged and older population: a cross-sectional study.

OBJECTIVES: Knee synovial abnormalities, potentially treatment targets for knee pain and osteoarthritis, are common in middle-aged and older population, but its etiology remains unclear. We examined the associations between hyperuricemia and knee synovial abnormalities detected by ultrasound in a general population sample. METHODS: Participants aged ≥ 50 years were from a community-based observational study. Hyperuricemia was defined as serum urate (SU) level > 416 µmol/L in men and > 357 µmol/L in women. Ultrasound of both knees was performed to determine the presence of synovial abnormalities, i.e., synovial hypertrophy, effusion, or Power Doppler signal (PDS). We examined the relation of hyperuricemia to prevalence of knee synovial abnormalities and its laterality, and the dose-response relationships between SU levels and the prevalence of knee synovial abnormalities. RESULTS: In total, 3,405 participants were included in the analysis. Hyperuricemia was associated with higher prevalence of knee synovial abnormality (adjusted odds ratio [aOR] = 1.21, 95% confidence interval [CI]: 1.02 to 1.43), synovial hypertrophy (aOR = 1.33, 95% CI: 1.05 to 1.68), and effusion (aOR = 1.21, 95% CI: 1.02 to 1.44), respectively. There were dose-response relationships between SU levels and synovial abnormalities. Additionally, the hyperuricemia was more associated with prevalence of bilateral than with that of unilateral knee synovial abnormality, synovial hypertrophy, or effusion; however, no significant association was observed between hyperuricemia and PDS. CONCLUSION: In this population-based study we found that hyperuricemia was associated with higher prevalence of knee synovial abnormality, synovial hypertrophy and effusion, suggesting that hyperuricemia may play a role in pathogenesis of knee synovial abnormalities.

The Role of Ultrasound Semi-Quantitative Scoring in the Diagnosis and Assessment of Gout and Hyperuricemia.

OBJECTIVES: To develop an ultrasound semi-quantitative scoring system for the diagnosis and evaluation of gout and hyperuricemia. METHODS: This study included 348 male patients: 81 patients with asymptomatic hyperuricemia, 182 patients with gout, and 85 patients with other arthritis. Clinical data were collected, ultrasound was detected, gout activity score was calculated to assess disease activity, and statistical analysis was performed. RESULTS: Monosodium urate crystal deposition and subclinical arthritis were detected in 17 patients with asymptomatic hyperuricemia, with lesions concentrated in the metatarsophalangeal joint, ankle and peroneus-longus and brevis at rate of 91.8%. Gout was significantly higher than non-gouty arthritis in crystal scores (sum scores of double contour, aggregates, and tophi), but not in inflammation scores (sum scores of synovial hypertrophy, power Doppler [PD] activity, and tenosynovitis) and bone erosion. The optimal cut-off score for the diagnosis of gout by the crystal score was 2. The sensitivity, specificity, and AUC were 95.4%, 97.1%, and .965, respectively. Gout flare had higher inflammation scores than intercritical gout, while bone erosion scores were lower than intercritical gout. The active gout patients had higher ultrasound scores of tophi, bone erosion, and PD activity than the remission group (P < .001). The sensitivity, specificity and area under the receiver operating characteristic curve (AUC) for the identification with high disease activity gout by ultrasound semi-quantitative composite score were 76.2%, 84.2%, and .812, respectively. CONCLUSION: Ultrasound helps early identification of patients at risk in asymptomatic hyperuricemia. Ultrasound semi-quantitative scoring allows for more objective and accurate assessment of gout lesions, correlates with disease activity, and helps in the diagnosis and assessment of gout.

Uric acid and left ventricular hypertrophy: a gender-based meta-analysis of echocardiographic studies.

AIM: Gender-based evidence on the association between serum uric acid (SUA) and left ventricular hypertrophy (LVH), as assessed by echocardiography, is still based on single studies. Thus, we performed a systematic meta-analysis of echocardiographic studies in order to provide an updated and comprehensive information on this issue. METHODS: The PubMed, OVID-MEDLINE, and Cochrane library databases were analyzed to search English-language articles published from the inception up to March 31, 2023. Studies were identified by using MeSH terms and crossing the following search items: 'uric acid', 'hyperuricemia', 'left ventricular mass', 'left ventricular hypertrophy', 'echocardiography', 'female', 'male'. RESULTS: Six studies including 2791 normotensive and hypertensive individuals were considered for the analysis. In women, increasing values of SUA were associated with progressively higher values of age, body mass index (BMI) and systolic blood pressure (SBP). This was not the case for men. In women, the meta-analysis comparing LV mass index (LVMI) in low versus high SUA group showed a greater pooled LVMI in the high SUA group [standard means difference (SMD): 0.81 ±â€Š0. 24, confidence interval (CI) 0.34-1.27, P  < 0.0001]. On the contrary, in men no statistical difference was found between the low group and high SUA group (SMD: 0.27 ±â€Š0.27, CI: -0.27/0.81, P  = 0.32). CONCLUSIONS: Our meta-analysis suggests that hyperuricemia portends the likely presence of increased LVMI in women but not in men. However, as hyperuricemia in the female pooled population, different from men, was associated with older age, higher BMI and SBP, the present findings do not support an independent role of the SUA in LV remodelling process in women.

Prevalence and clinical association of hyperechoic crystal deposits on ultrasonography in patients with chronic kidney disease: a cross-sectional study from a single center.

BACKGROUND: Hyperechoic crystal deposits can be detected in the kidney medulla of patients with gout by ultrasonography examination. Chronic kidney disease (CKD) is usually accompanied with hyperuricemia. Whether hyperechoic crystal deposition could be detected by ultrasonography in CKD patients, and its clinical association are unknown. METHODS: Five hundred and fifteen consecutive CKD patients were included in this observational study. Clinical, biochemical and pathological data were collected and analyzed. RESULTS: Altogether, 234 (45.4%) patients were found to have hyperuricemia and 25 patients (4.9%) had gout history. Hyperechoic crystal deposits in kidney medulla were found in forty-four (8.5%) patients, on ultrasonography. Compared with patients without hyperechoic crystal deposits, patients with deposits were more likely to be male, younger, with gout history and presenting with higher serum uric acid level, lower estimated glomerular filtration rate, lower urine pH, lower 24 h-urinary citrate and uric acid excretion, and with a higher percentage of ischemic nephropathy (all p < 0.05). On multivariable logistic analysis, the hyperechoic depositions were associated with age [0.969 (0.944, 0.994), p = 0.016], serum uric acid level [1.246 (1.027, 1.511), p = 0.026], Sqrt-transformed 24 h-urine uric acid excretion [0.923 (0.856, 0.996), p = 0.039], and ischemic nephropathy [4.524 (1.437, 14.239), p = 0.01], respectively. CONCLUSIONS: Hyperechoic crystal deposition can be detected in kidney medulla by ultrasonography; in CKD patients their presence was associated with hyperuricemia as well as with ischemic nephropathy.

ULTRASONOGRAPHIC EVALUATION OF FEMORAL CARTILAGE THICKNESS IN PARTICIPANTS WITH ASYMPTOMATIC HYPERURICEMIA: A CASE-CONTROL STUDY.

The aim was to evaluate the effect, if any, of asymptomatic hyperuricemia on distal femoral cartilage thickness through musculoskeletal ultrasonography. A total of 66 participants were evaluated in this prospective, controlled study, including 33 asymptomatic hyperuricemic patients who presented at our outpatient clinic between January and April 2020, and 33 normouricemic subjects matched for age, gender and body mass index. Participants with systemic diseases affecting uric acid level such as chronic renal failure, psoriasis, gout, etc., participants using drugs that can affect uric acid level, and those with knee complaints were excluded from the study. Cartilage thickness measurements were taken using musculoskeletal ultrasonography from the right medial condyle, right lateral condyle, right intercondylar area, left medial condyle, left lateral condyle and left intercondylar area. Distal femoral cartilage thickness was lower in all measurement areas in the asymptomatic hyperuricemia group than in the normouricemic group (p<0.05 all). No correlation was noted between uric acid levels and cartilage thickness in all measurement areas in either the asymptomatic hyperuricemic or normouricemic group (p>0.05 all). We think that distal femoral cartilages seem to be thinner in participants with asymptomatic hyperuricemia. Longitudinal studies are needed to determine whether asymptomatic hyperuricemia will lead to knee osteoarthritis in individuals, although we believe that people with asymptomatic hyperuricemia should be informed accordingly in order to prevent development of potential knee osteoarthritis.

Evaluation of renal microperfusion in hyperuricemic nephropathy by contrast-enhanced ultrasound imaging.

Diagnostic tools for the early detection of renal injury caused by hyperuricemia are still lacking. Here, we investigated whether contrast-enhanced ultrasound (CEUS) could be used as a diagnostic tool for hyperuricemic nephropathy (HN). In the HN rat model, CEUS detected a significant decline in renal cortical perfusion compared with that in control rats. Peak intensity (PI) values correlated significantly with serum KIM-1 levels and fibrosis scores in HN rats. An early decline in PI values was also observed in chronic kidney disease (CKD) stage 1 patients with HN compared with the controls (61.1±4.52 dB versus 65.80±7.10 dB) and correlated with renal function in the patients with HN. In contrast, an increase in time to reach PI values was detected in HN patients with stage 1 CKD (15.14±1.75 s versus 14.52±4.75 s) and was more pronounced in CKD stage 4 patients (67.32±3.29 s). CEUS was able to detect abnormal renal perfusion in early CKD with HN, which correlated with renal function decline, suggesting that CEUS could be used as a noninvasive tool for assessing renal function in patients with HN.

T2 MRI at 3T of cartilage and menisci in patients with hyperuricemia: initial findings.

OBJECTIVE: To compare and evaluate T2 values of compartmental femorotibial cartilage and subregional menisci in patients with hyperuricemia at 3T. MATERIALS AND METHODS: Thirty-two subjects were included in this study and subdivided into two subgroups: 15 healthy controls (3 females, 12 males; mean age = 45.3 ± 10.9 years), 17 patients with hyperuricemia (2 females, 15 males; mean age = 44.4 ± 12.7 years). All subjects were assessed on a 3T MR scanner using an 8-channel phased-array knee coil (transmit-receive). Wilcoxon rank sum test and analysis of covariance (ANCOVA) were performed to determine whether there were any statistically significant differences in T2 values of compartmental femorotibial cartilage and subregional menisci between the two subgroups. RESULTS: Lateral tibial cartilage (48.6 ± 3.5 ms) in healthy subgroup had significantly lower (p < 0.05) T2 values than all subcompartments of femorotibial cartilage in hyperuricemia subgroup. Medial tibial cartilage (56.5 ± 4.3 ms) in hyperuricemia subgroup had significantly higher (p < 0.05) T2 values than all subcompartments of femorotibial cartilage except medial tibial cartilage in healthy subgroup. Medial anterior horn of meniscus (39.4 ± 2.9 ms) in healthy subgroup had significantly lower (p < 0.05) T2 values than all subregional menisci except both medial anterior horn and medial body segment of meniscus in hyperuricemia subgroup. CONCLUSION: T2 values in certain compartmental femorotibial cartilage and subregional menisci in patients with hyperuricemia are evidently and abnormally heightened compared with those in healthy subjects, to which special attention should be paid when diagnosing and treating the patients with hyperuricemia in the clinical setting. The LT cartilage had significantly lower T2 values (48.6 ± 3.5 ms) in healthy subgroup compared to all compartmental femorotibial cartilage in cohort with HU. MF cartilage had significantly lower T2 values (51.6 ± 2.9 ms) in healthy subgroup compared to both LF (54.4 ± 4.1 ms) and MT (56.5 ± 4.3 ms) in cohort with HU. MT cartilage had significantly higher T2 values (56.5 ± 4.3 ms) in cohort with HU subgroup compared to LF (52.5 ± 3.0 ms) in healthy subgroup. T2 mapping may be promising and potential sensitive discriminator of understanding and examining the early compositional and structural change in proteoglycan-collagen matrix of human femorotibial cartilage in patients with hyperuricemia.

Update of the current role of ultrasound in asymptomatic hyperuricemia. A systematic literature review.

Ultrasound (US) is a recognized imaging modality for the assessment of gout. Recently it is being explored for its potential role in the evaluation of subjects with asymptomatic hyperuricemia (AH). Preliminary reports demonstrated the presence of monosodium urate (MSU)-crystal deposits including aggregates, double contour sign and/or tophi in both intra-articular and periarticular tissues of AH individuals. Although these results are exciting, the value and potential application of US in AH remain to be clearly delineated. In this systematic literature review, we aim to summarise the recent publications regarding the role of US in the assessment of AH. We analyzed possible application of US in the daily clinical practice and its future clinical and research potential in the evaluation of AH individuals.

Multiparametric MRI analysis for the evaluation of renal function in patients with hyperuricemia: a preliminary study.

BACKGROUND: To investigate the renal dysfunction in patients with hyperuricemia by employing a multiparametric MRI protocol, consisting of quantitative water molecule diffusion, microstructure, microscopic perfusion, and oxygenation measurements in kidneys. MATERIALS AND METHODS: A total of 48 patients with hyperuricemia (HU) and 22 age-matched healthy control subjects (HC) were enrolled in the study. For each participant, three different functional magnetic resonance imaging (fMRI) sequences were acquired and analyzed, including intravoxel incoherent motion imaging (IVIM), diffusion tensor imaging (DTI), and blood-oxygen-level-dependent MRI (BOLD). Thereafter, an independent two-sample t-test was applied to discover the significant differences of MRI indices between the hyperuricemia (HU) and HC groups, and the specific potential biomarkers between two subgroups of HU group (asymptomatic hyperuricemia group (AH) and gouty arthritis group (GA)). Further, multivariate logistic regression analyses were performed to classify the AH from the GA group using the MRI indices with significant between-group differences. The receiver operating characteristic (ROC) curve was plotted, and the area under the ROC curve (AUC) was calculated to assess the performance of each MR index for differentiation between the AH and GA groups. RESULTS: Ten parametric values of the HU group were significantly lower than those of the HC group among the 14 fMRI parameters (P < 0.05). The cortical D, D*, and f values and medullary D and R2*values had significant differences between the AH and GA groups (P < 0.05). Combining the cortical D and f values and medullary R2* value gave the best diagnostic efficacy, yielding an AUC, sensitivity, and specificity of 0.967 ± 0.022, 91.67%, and 95.83%, respectively. CONCLUSIONS: A multiparametric MR analysis plays an important role in the evaluation of renal dysfunction in hyperuricemia from multiple perspectives. It could be a promising method for noninvasive detection and identification of the early-stage renal damage induced by hyperuricemia.

Combined application of DTI and BOLD-MRI in the assessment of renal injury with hyperuricemia.

OBJECTIVE: To explore the value of combined diffusion tensor imaging (DTI) and blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) in detecting early renal alterations in patients with hyperuricemia. MATERIALS AND METHODS: Seventy-one individuals were enrolled in this study and divided into three groups according to their serum uric acid (SUA) level and clinical symptoms: healthy controls (HC, n = 23), asymptomatic hyperuricemia (AH, n = 22) and gouty arthritis (GA, n = 26). All patients underwent both DTI and BOLD-MRI examination. Renal cortical and medullary ADC, FA and R2* values were calculated, respectively, and compared among the three groups. Correlations between ADC, FA and R2* with estimated glomerular filtration rate (eGFR) and SUA in hyperuricemia were evaluated, respectively. RESULT: In the renal cortex, the ADC, FA and R2* values of the AH and GA groups were significantly lower than those of the HC groups (p < 0.05). In the renal medulla, the ADC and FA values in AH and GA patients were significantly lower than those in healthy controls (p < 0.05). The R2* value of the GA group significantly decreased, compared to that of the AH and HC groups (p < 0.05). SUA was negatively correlated with cortical ADC, FA and R2* values (p < 0.05) as well as with medullary ADC and FA values. No significant correlation was discovered between the eGFR and ADC, FA and R2* values. CONCLUSION: The combined evaluation of DTI and BOLD might provide a sensitive and non-invasive approach for detection of renal microstructural alterations and oxygen metabolism abnormality in hyperuricemia.

High-Protein Diet Induces Hyperuricemia in a New Animal Model for Studying Human Gout.

Hyperuricemia is a central risk factor for gout and increases the risk for other chronic diseases, including cardiometabolic disease, kidney disease, and hypertension. Overproduction of urate is one of the main reasons for hyperuricemia, and dietary factors including seafoods, meats, and drinking are contributed to the development of it. However, the lack of a suitable animal model for urate metabolism is one of the main reasons for the delay and limitations of hyperuricemia research. Combining evolutionary biological studies and clinical studies, we conclude that chicken is a preferred animal model for hyperuricemia. Thus, we provided chickens a high-protein diet (HPD) to evaluate the changes in the serum urate levels in chickens. In our study, the HPD increased the serum urate level and maintained it at a long-term high level in chickens. Long-term high serum urate levels induced an abnormal chicken claw morphology and the precipitation of monosodium urate (MSU) in joint synovial fluid. In addition, a long-term HPD also decreased the glomerular filtration rate and induced mild renal injury. Most importantly, allopurinol and probenecid displayed the positive effects in decreasing serum urate and then attenuated hyperuricemia in chicken model. These findings provide a novel model for hyperuricemia and a new opportunity to further investigate the effects of long-term hyperuricemia on other metabolic diseases.

Diffusional kurtosis imaging of kidneys in patients with hyperuricemia: initial study.

BACKGROUND: At present, there remains a lack of a reliable indicator for monitoring renal function in patients with hyperuricemia. PURPOSE: This study aimed to evaluate the feasibility of diffusion kurtosis imaging in the assessment of renal function in patients with hyperuricemia. MATERIAL AND METHODS: A total of 75 male participants, including 25 with asymptomatic hyperuricemia, 25 with gouty arthritis, and 25 age-matched male healthy controls, were enrolled in this study. Diffusion kurtosis imaging data were acquired to derive axial (Ka), radial (Kr), and mean kurtosis (MK), fractional anisotropy, axial (Da), radial (Dr), and mean diffusivity (MD) for comparisons among the three groups. They were also correlated with estimated glomerular filtration rate (eGFR). RESULTS: The MK values of the renal cortex and medulla and Kr value of the renal medulla in patients with asymptomatic hyperuricemia and gouty arthritis significantly increased compared with those in the controls (P < 0.05). Patients with gouty arthritis showed significant higher cortical and medullary Ka values compared with the other two groups (P < 0.05). The cortical Kr values of the asymptomatic hyperuricemia and gouty arthritis patients were significantly higher than that of the controls (P < 0.05). The medullary fractional anisotropy value showed a significant difference between the control and gouty arthritis groups (P < 0.05). No correlation was found between any diffusion kurtosis imaging parameters and eGFR value. CONCLUSION: Diffusion kurtosis imaging is feasible in the assessment of the early changes of renal cortex and medulla in patients with hyperuricemia.

Intravoxel incoherent motion imaging of the kidney: The application in patients with hyperuricemia.

BACKGROUND: Hyperuricemia is an independent risk factor for onset and progression of kidney disease. However, there remains a lack of a reliable and noninvasive biomarker to identify and monitor the changes of renal function in patients with hyperuricemia. PURPOSE: To assess the utility of intravoxel incoherent motion (IVIM) parameters in identifying the early changes of renal function in patients with hyperuricemia. STUDY TYPE: Retrospective case-control study. POPULATION: Eighty-four male participants, including asymptomatic hyperuricemia (AH, 27 cases), gouty arthritis (GA, 31 cases), and 26 age-matched healthy controls. FIELD STRENGTH/SEQUENCE: 3.0T; intravoxel incoherent motion (IVIM). ASSESSMENT: Differences in the IVIM parameters among the three groups were assessed. Pure molecular diffusion (D value); perfusion-related diffusion (D* value); pseudodiffusion fraction (f value); apparent diffusion coefficient (ADC value); estimated glomerular filtration rate (eGFR). Also, they were correlated with eGFR. STATISTICAL TESTS: Bonferroni test, Tamhane's T2 method, and Pearson correlation analysis. RESULTS: The D values in renal cortex and medulla significantly decreased from the control, AH to GA groups (P < 0.05). The GA patients had a significantly lower cortical f value than the controls and AH patients (P < 0.05). The medullary f values in the AH and GA patients were significantly lower than that in the controls (P < 0.05). Also, the cortical and medullary ADC values had similar results across the three groups (P < 0.05), except for the comparison between the AH and GA groups (P = 0.668, P = 0.111, respectively). No significant correlation was found between any IVIM parameters with eGFR. DATA CONCLUSION: IVIM imaging may be helpful for detecting the early changes of renal function induced by hyperuricemia. The D value could be the most sensitive IVIM-derived parameter in the assessment of renal function in patients with hyperuricemia in this study. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020;51:833-840.

Association between musculoskeletal ultrasonography and bone remodelling markers and its role in disease monitoring of gout and hyperuricaemia.

OBJECTIVES: To evaluate associations between bone destruction markers and musculoskeletal ultrasonography (MU) findings in patients with gout and hyperuricaemia and clarify the role of MU in treatment responsiveness. METHODS: One-hundred and fifty patients with gout and 100 patients with hyperuricaemia were divided into five groups according to MU manifestations. Circulating Dickkopf-1 (DKK-1) and receptor activator of nuclear factor-κB ligand (RANKL) levels were measured. Thirty patients from the gout group and 10 from the hyperuricaemia group, were treated for 1 year with urate-lowering therapy (ULT). RESULTS: Patients with gout and tophus and/or bone erosion had the highest DKK-1 and RANKL levels. Patients with gout and MU-evidenced aggregates and/or double-contour signs had higher DKK-1 and RANKL levels than the normal MU group (p<0.001). Patients with hyperuricaemia and abnormal MU findings had significantly higher DKK-1 and RANKL levels than those with normal MU findings. DKK-1 and RANKL levels positively correlated with disease duration in patients with gout (r=0.430, p<0.001; r=0.359, p<0.001, respectively) and hyperuricaemia (r=0.446, p<0.001; r=0.379, p<0.001, respectively). After ULT, MU abnormalities disappeared in 12 and 8 patients with gout and hyperuricaemia, respectively. The largest tophus diameter decreased in patients with gout (t=6.092, p<0.001). DKK-1 and RANKL concentrations significantly decreased in all patients. Lower serum urate levels corresponded with higher ratios of normal MU features in all patients. CONCLUSIONS: In patients with gout and hyperuricaemia, MU manifestations were associated with DKK-1 and RANKL levels and were ameliorated after ULT. Thus, MU could be a useful tool in assessing bone remodelling and monitoring disease responsiveness.

Prevalence and discrimination of OMERACT-defined elementary ultrasound lesions of gout in people with asymptomatic hyperuricaemia: A systematic review and meta-analysis.

OBJECTIVES: Ultrasound lesions of gout have been described in people with asymptomatic hyperuricemia. However, the anatomical sites and ultrasound lesions most frequently involved in asymptomatic hyperuricemia have not yet been established. This systematic review and meta-analysis aimed to determine the prevalence of the Outcome Measures in Rheumatology (OMERACT) elementary ultrasound lesions of gout (double contour, aggregates, tophus, erosion) at various sites in people with asymptomatic hyperuricemia and to determine which sites and lesions discriminate from people with normouricemia. METHODS: A systematic search of electronic databases, conference abstracts and reference lists was undertaken. Studies were included if they used ultrasound to image people with asymptomatic hyperuricemia and reported ≥1 OMERACT-defined lesion of gout. Meta-analyses were undertaken for the pooled prevalence of site-specific lesions in people with asymptomatic hyperuricemia, and the pooled odds ratios of these lesions compared to people with normouricemia. RESULTS: Twenty studies were included. The most common site scanned was the first metatarsophalangeal joint (1MTP) (n = 17 studies) and the most common lesion reported, the double contour (n = 18). Meta-analyses of pooled prevalence showed 1MTP double contour was the most frequent finding in people with asymptomatic hyperuricemia (0.31, 95% confidence interval (CI) 0.20-0.42), followed by femoral condyle double contour (0.16, 95%CI 0.08-0.24) and 1MTP tophus (0.16, 95%CI 0.03-0.29). The highest pooled odds ratios for asymptomatic hyperuricemia vs. normouricemia were 6.98 (95%CI 3.14-15.57) for 1MTP double contour, 13.67 (95%CI 5.42-34.49) for femoral condyle double contour and 6.10 (95%CI 1.55-24.04) for 1MTP tophus. CONCLUSION: In people with asymptomatic hyperuricemia, scanning of the 1MTP and femoral condyle for double contour, plus the 1MTP for tophus, has the highest prevalence and discrimination compared to those with normouricemia.

Juvenile-onset gout and adipsic diabetes insipidus: A case report and literature review.

The prevalence of juvenile-onset gout has been increasing. Hereditary factors and secondary diseases should be considered in these patients. Adipsic diabetes insipidus (ADI) is characterized by arginine vasopressin (AVP) deficiency, which results in hypotonic polyuria, and dysfunction of thirst osmoreceptors, which results in failure to generate a thirst sensation in response to hypernatremia. We herein report a case of a boy with gouty arthritis, refractory hyperuricemia, prominent hypernatremia, a high creatinine concentration, and a history of surgery for a hypothalamic hamartoma. The patient was diagnosed with central diabetes insipidus after endocrine evaluation. Because he never had symptoms of thirst, the final diagnosis was corrected to ADI. This is the first report of gout due to chronic ADI in an adolescent. Volume contraction due to ADI might be one cause of hyperuricemia and renal impairment in such patients. Moreover, AVP deficiency might directly lead to low urate clearance due to the lack of vasopressin receptor 1 stimulation. Lack of polydipsia and polyuria may delay the diagnosis of ADI and lead to severe complications of a chronic hyperosmolar status. Sufficient and effective establishment of normovolemia is critical for these patients.

Levels of Cytokines and MicroRNAs in Individuals With Asymptomatic Hyperuricemia and Ultrasonographic Findings of Gout: A Bench-to-Bedside Approach.

OBJECTIVE: To assess potential associations among serum cytokines and microRNA (miR) levels with ultrasound (US) findings suggestive of urate deposits in chronic asymptomatic hyperuricemia and gout. METHODS: All participants underwent musculoskeletal US and measurements of serum interleukin-1ß (IL-1ß), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, interferon-γ, tumor necrosis factor, monocyte chemoattractant protein 1, and epithelial neutrophil-activating peptide 78, as well as miR-146a, miR-155, and miR-223 levels. RESULTS: Thirty individuals with asymptomatic hyperuricemia, 31 normouricemic controls, and 30 patients with gout were included. The frequency of synovitis and double contour sign using US was similar between asymptomatic hyperuricemia (67% and 27%, respectively) and patients with gout (77% and 27%, respectively), and each had a higher frequency than controls (45% and 0%, respectively). Serum IL-6 and IL-8 levels were similar between patients with asymptomatic hyperuricemia (mean ± SD 69.7 ± 73.4 and 18.5 ± 25.6 pg/ml, respectively) and gout (mean ± SD 75.8 ± 47.6 and 24.4 ± 31.7 pg/ml, respectively), and higher than controls (mean ± SD 28.2 ± 17.6 and 7.4 ± 6.0 pg/ml, respectively). A similar distribution was observed for miR-155 levels in asymptomatic hyperuricemia, patients with gout, and controls (mean ± SD 0.22 ± 0.18, 0.20 ± 0.14, and 0.08 ± 0.04, respectively). Associations between morphostructural abnormalities suggestive of urate deposits (regardless of clinical diagnosis) and serum markers were assessed. Subjects with urate deposits had higher IL-6 (257.2 versus 47.0 pg/ml; P = 0.005), IL-8 (73.2 versus 12.0 pg/ml; P = 0.026), and miR-155 (0.21 versus 0.16; P = 0.015) levels than those without deposition findings. CONCLUSION: In individuals with chronic asymptomatic hyperuricemia, the presence of synovitis and double contour sign by US may represent a subclinical manifestation of monosodium urate crystal nucleation, capable of triggering inflammatory pathways (IL-6 and IL-8) and mechanisms of intercellular communication (miR-155), similar to what is observed in patients with gout.

Predictive effect of hyperuricemia on left atrial stasis in non-valvular atrial fibrillation patients.

OBJECTIVES: To investigate the relationship between hyperuricemia and left atrial thrombus (LAT)/spontaneous echo contrast (SEC) and to determine the predictive value of hyperuricemia in non-valvular (NV) atrial fibrillation (AF) patients. METHODS: The study retrospectively reviewed 1198 consecutive patients (male 801, female 397, and mean age of 56.84 ±â€¯12.22) who were diagnosed with AF and accepted transesophageal echocardiography (TEE) prior to catheter ablation, appendage occlusion and electrical cardioversion using a single-center database. The clinical baseline characteristics were collected from medical record review and analyzed. Patients were categorized into an LAT/SEC group and a normal group. RESULTS: According to the TEE examination, there were 97 (8.1%) patients with abnormality; of these, 49 were with LAT and 48 with SEC. The mean serum uric acid (SUA) level and hyperuricemia proportion were markedly higher in patients with LAT/SEC. The significant predictive effect was observed in the SUA level (OR = 1.006) and hyperuricemia (OR = 2.04). After adjustment for persistent/permanent-AF, age, gender, LA dimension > 40 mm, previous stroke, hypertension and diabetes, the SUA level (OR = 1.004) and hyperuricemia (OR = 1.69) were independent predictors for LAT/SEC. The SUA level (OR = 1.004) and hyperuricemia (OR = 1.69) were independent predictors for LAT/SEC, Further subgroup analysis in different CHA2DS2-VASc categories, it might be helpful to refine the LAT/SEC risk via combination area CHA2DS2-VASc score and hyperuricemia, especially in those with CHA2DS2-VASc score < 2. CONCLUSIONS: The SUA level and hyperuricemia proportion are closely associated with LA stasis. Hyperuricemia might independently predict and refine LA stasis risk among NVAF patients, especially in those with CHA2DS2-VASc score < 2.

Serum uric acid and non-alcoholic fatty liver disease in non-obesity Chinese adults.

BACKGROUND: Previous studies found elevated serum uric acid (SUA) was associated with the development or progression of non-alcoholic fatty liver disease (NAFLD) in general population; in this study we aim to investigate the association of SUA and the severity of NAFLD based on grade of fatty liver on ultrasonography in non-obese subjects. METHODS: Data were obtained from subjects via routine physical examinations in the Public Health Center of our hospital between 2011 and 2014. The data included completed anthropometry and blood biochemical indicators and the results of abdominal ultrasound. The diagnosis of NAFLD was according to the clinical diagnosis of the Guidelines for the diagnosis and treatment of nonalcoholic fatty liver disease in 2008. RESULTS: In total, 95,924 subjects were analyzed in this study. The prevalence rate of lean-NAFLD was 8.16%, among which 7.58% had mild steatosis, and 0.58% had moderate and severe steatosis. The prevalence of fatty liver was increased progressively with SUA. Among which the prevalence of mild fatty liver from Q1 to Q4 were 10.33%, 18.39%, 23.11% and 25.93%; the prevalence of moderate and severe fatty liver from Q1 to Q4 were 1.06%, 2.82%, 5.05% and 7.27%. Lean-subjects with hyperuricemia had an OR of 1.718 (95% CI 1.622-1.820) to have NAFLD, after adjusted for other metabolic disorders. The area under curve (AUC) for detecting mild fatty liver based on SUA was 0.70; and the AUC for detecting moderate and severe fatty liver based on SUA was 0.78. CONCLUSIONS: Our data showed positive associations between elevated SUA levels and lean-NAFLD risk in the inland Chinese adults, independent of other metabolic factors. Our study also suggests that SUA could be considered as a simple and non-invasive method to follow up patients with lean-NAFLD.