Baseline Uric Acid Research Articles

PS-BPP06-2: ASSOCIATIONS BETWEEN URIC ACID LEVELS AND HYPERTENSION INCIDENCE IN AN APPARENTLY HEALTHY JAPANESE POPULATION

Objective: Uric acid (UA) has been linked to the development of hypertension. However, it is not known if this association is significant in men and women who are apparently healthy at baseline. Design and Methods: This retrospective cohort study included individuals who participated in a health checkup at the Kagoshima Kouseirin Hospital from October 2008 to April 2019. We excluded participants with hypertension, diabetes, dyslipidemia, obesity, estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2, history of gout, hyperuricemia medication, and missing data at baseline. To assess the association between baseline UA levels and 5 year hypertension incidence, we performed univariable and multivariable logistic regression analysis by sex according to their UA quartiles as follows: In men: 1st quartile ≧ 4.8 mg/dL, 2nd quartile 4.9 to 5.6 mg/dL, 3rd quartile 5.7 to 6.4 mg/dL, and 4th quartile ≧ 6.5 mg/dL; In women: 1st quartile ≧ 3.4 mg/dL, 2nd quartile 3.5 to 4.0 mg/dL, 3rd quartile 4.1 to 4.7 mg/dL, and 4th quartile ≧ 4.8 mg/dL. The ORs were adjusted for age, body mass index, systolic blood pressure (SBP), diastolic blood pressure (DBP), current smoking, alcohol consumption, exercise habit, serum triglyceride, low density lipoprotein cholesterol, high density lipoprotein cholesterol, fasting plasma glucose and eGFR. Hypertension incidence was defined as SBP ≧ 140 mmHg and/or DBP ≧ 90 mmHg at follow up, or newly prescribed antihypertensive medication during 5 years of follow up. Results: In total, 21,514 participants (age, 52.9 ± 10.9 years; men, 39.8%), were enrolled. During the 5 year of follow-up, 1415 (16.5%) men and 1408 (10.9%) women developed hypertension. In univariable analysis, the UA levels were significantly associated with hypertension in both men (OR for fourth to first quartile, 1.45; 95% confidence interval [CI], 1.24 to 1.70, P < 0.0001) and women (OR for fourth to first quartile, 1.62; 95%CI, 1.38 to 1.90, P < 0.0001). After adjusting for covariates, the UA levels were significantly associated with hypertension in men (OR for fourth to first quartile, 1.35; 95%CI, 1.13 to 1.62, P = 0.0011), but was not in women (OR for fourth to first quartile, 1.14; 95%CI, 0.95 to 1.36, P = 0.1541) Conclusion: Elevated UA levels are associated with hypertension incidence in Japanese men without hypertension, diabetes, dyslipidemia, obesity, and decreased kidney function.

The glucocerebrosidase mutations and uric acid levels in Parkinson’s disease: A 3-years investigation of a potential biomarker”

BackgroundBlood uric acid level indicates an emerging biomarker in Parkinson's disease (PD). This study aimed to evaluate longitudinal uric acid levels among different kinds of glucocerebrosidase (GBA) mutations and to compare it among sporadic PD, genetic cohort Parkinson's disease (GENPD), genetic cohort unaffected (GENUN), and healthy control (HC) patients. MethodsWe conducted a study on 654 individuals from the Parkinson's progression markers initiative (PPMI) database. Baseline characteristics, uric acid levels, movement disorder society unified Parkinson's disease rating scale III (MDS-UPDRS III), Hoehn and Yahr Parkinson stage (H&Y stage), and DaT scan specific binding ratio (SBR) data were obtained. Different GBA mutations were collected and categorized into three groups. Longitudinal measurements of uric acid and MDS-UPDRS III score were evaluated during 3-years of follow-up. ResultGENPD cohort exhibited a greater MDS-UPDRS III score, H&Y stage, and lower SBR in the right caudate, left caudate, and right putamen compared to sporadic PD. Baseline uric acid level was similar among all groups and different GBA variants. After adjustment for age, sex, and body mass index, the uric acid level was significantly lower in the GENPD group than in HC during year 2 (P-value: 0.009). No significant longitudinal differences were detected for the MDS-UPDRS III score and three groups of GBA mutations. ConclusionThis is the first study to assess uric acid levels and MDS-UPDRS III scores among different GBA mutation variants within 3 years of follow-up. We found similar clinical characteristics among different subtypes of GBA mutations.

Bidirectional temporal relationships between uric acid and insulin and their joint impact on incident diabetes

Background and aimsThis study aims to examine the temporal relationship between uric acid (UA) and insulin and their joint impact on T2DM in middle-aged adults. Methods and resultsThe cohort consisted of 1351 non-diabetic adults who had serum UA and insulin measured twice at baseline and follow-up over 7.7 years on average, and incidence of T2DM in the outcome survey12.2 years later.After adjusting for covariates, the path coefficient from baseline UA to follow-up insulin was 0.082 (p < 0.001); the path from baseline insulin to follow-up UA was 0.060 (p = 0.030). In the mediation model with baseline UA as the predictor, total effect of baseline UA on incident T2DM was 0.089 (p = 0.016). The mediation effect through follow-up insulin on the UA-T2DM association was 28.1%. The direct effect of baseline UA on T2DM (0.064) became nonsignificant (p = 0.078). In the mediation model with baseline insulin as the predictor, total effect of baseline insulin on T2DM was 0.218 (p < 0.001). The mediation effect through follow-up UA on the insulin-T2DM association was 5.5%. The direct effect of baseline insulin on T2DM (0.206) remained significant (p < 0.001). The baseline hyperinsulinemia-follow-up hyperuricemia group showed the highest incidence rate of T2DM (27.9%). ConclusionsThe bidirectional temporal relationship suggests that UA and insulin influence each other in non-diabetic individuals, and the directionality plays pathogenic roles in the development of T2DM.

Age patterns of nonalcoholic fatty liver disease incidence: heterogeneous associations with metabolic changes

BackgroundAs the nonalcoholic fatty liver disease (NAFLD) epidemic matures, understanding how metabolic changes in NAFLD development vary over the age distribution is important to guide precise prevention. We aimed to clarify metabolic trends in age-specific NAFLD incidence.MethodsWe conducted a 4-year longitudinal retrospective cohort study enrolling 10,240 consecutive healthy individuals who received annual physical examination during 2012–2019. Baseline and dynamic changes in metabolism and hepatic steatosis determined with ultrasound were collected and analyzed stratified by age into the following groups: 20–34, 35–49, 50–64, and over 65 years.ResultsOverall, 1701 incident NAFLD participants (16.6%) were identified. Adjusted Cox regression analysis showed that the baseline and increased body mass index were the main risk factors for NAFLD in people ≤ 65 years old. Baseline high-density lipoprotein (HR = 0.56; 95% CI 0.39–0.78) was a protective factor for newly onset NAFLD in the 50-to-64-year-old group, while baseline SBP (HR = 1.03; 95% CI 1.01–1.05), baseline uric acid (HR = 1.04; 95% CI 1.01–1.07), triglyceride increase (HR = 4.76; 95% CI 3.69–6.14), fasting blood glucose increase (HR = 1.32; 95% CI 1.06–1.65) were independently associated with incident NAFLD in over-65-year-old group.ConclusionsNAFLD incidence attributable to potentially metabolic risk factors varied substantially across age groups in a cohort of Chinese people. The adoption of age targeted metabolic prevention strategies might reduce the burden of NAFLD.

Abstract 11758: Sex Differences in the Associations Between Uric Acid and Incidence of Hypertension, Diabetes, and Chronic Kidney Disease in a Healthy Japanese Population

Introduction: Uric acid (UA) has been linked to the development of cardiometabolic diseases. However, the effects of UA levels by sex have not been reported. Hypothesis: We hypothesized that UA plays a critical role in the development of hypertension, diabetes, and chronic kidney disease (CKD) in Japanese men and women who are apparently healthy at baseline. Methods: This retrospective cohort study included individuals who participated in a health checkup at the Kagoshima Kouseiren Hospital from October 2008 to April 2019 who had a 5-year follow-up. We excluded participants with hypertension, diabetes, dyslipidemia, obesity, estimated glomerular filtration rate (eGFR) &lt;60 ml/min/1.73m2, history of gout, hyperuricemia medication, and missing data at baseline. Uric acid levels were divided into quartiles as follows: men: 1st quartile UA &lt; 4.8 mg/dL, 2nd quartile 4.9-5.6 mg/dL, 3rd quartile 5.7-6.4 mg/dL, and 4th quartile UA &gt; 6.5 mg/dL; women: 1st quartile UA &lt; 3.4 mg/dL, 2nd quartile 3.5-4.0 mg/dL, 3rd quartile 4.1-4.7 mg/dL, and 4th quartile UA &gt; 4.8 mg/dL. To assess the association between baseline UA levels and the development of hypertension, diabetes, and CKD, we performed a multivariable logistic regression analysis adjusted for age, body mass index, systolic blood pressure, diastolic blood pressure, current smoking, alcohol consumption, exercise habit, serum triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting plasma glucose, and eGFR by sex. Results: In total, 21,514 participants (age, 52.9±10.9 years; men, 39.8%), were enrolled. In men, the OR and 95% CI for the fourth to first quartile was associated with increased risk for hypertension (OR, 1.35; 95% CI, 1.13-1.62, P=0.0011), and CKD (OR, 1.42; 95% CI, 1.04-1.95, P=0.0287), and inversely related with diabetes (OR, 0.60; 95% CI, 0.39-0.93, P=0.0221). In women, the OR and 95% CI for the fourth to first quartile showed no association with neither hypertension (OR, 1.14; 95% CI, 0.95-1.36, P=0.1541), diabetes (OR, 0.97; 95% CI, 0.53-1.77, P=0.9271), nor CKD (OR, 1.26; 95% CI, 0.97-1.65, P=0.0828). Conclusion: Elevated serum UA indicates the risk of future hypertension and CKD, and an inverse relation with diabetes in apparently healthy Japanese men.

Bempedoic Acid's Use as an Adjunct in Lowering Low-Density Lipoprotein Cholesterol in Patients With Coronary Artery Disease: A Systematic Review.

Coronary artery disease (CAD) is one of the leading causes of death worldwide. Atherosclerosis begins in childhood as fatty streaks, progresses with age, and lifestyle influences the progression of atherosclerotic plaque. Over time, with significant narrowing of the blood vessels, blood flow into the coronary arteries is compromised, resulting in various symptoms of coronary heart disease. Many drugs are used in clinical practice to prevent atherosclerotic cardiovascular events in patients with CAD. This review aims to investigate the efficacy and safety of a non-statin novel lipid-lowering drug, bempedoic acid (BDA), an adenosine triphosphate (ATP) citrate lyase inhibitor, in lowering serum low-density lipoprotein cholesterol (LDL-C) levels among patients with CAD. BDA is a new drug that recently got approval for clinical use. Following its discovery, BDA has been researched in order to investigate its role in the treatment of hypercholesterolemia. A search for studies was conducted using databases such as PubMed, PMC, ScienceDirect, and Google Scholar up untilApril 30, 2022. This systematic review has followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 11 studies were finalized to explore the role of BDA alone or as an adjunct in lowering serum LDL-C levels in high-risk patients under maximally tolerated statins, statin-intolerant groups, or treatment with other lipid-lowering drugs. These studies are three randomized controlled trials (RCTs), one pre-proof RCT, two systematic reviews and meta-analyses, and five narrative review articles. This review included 8465 participants from recently conducted RCTs and systematic reviews. Another 14014 participants, enrolled for the Cholesterol Lowering via Bempedoic Acid, an Adenosine Triphosphate-Citrate Lyase-Inhibiting Regimen (CLEAR) Outcomes clinical trial, were also included. BDA in combination with ezetimibe showed good evidence of LDL-C lowering effect. Patients on maximally tolerated statin failing to achieve desired LDL-C when treated in combination with BDA showed a significant decrement in serum LDL-C levels, high sensitivity C-reactive protein (HsCRP), and triglyceride. BDA use showed no adverse side effects. The most common side effect seen in several trials was the rise in serum uric acid level. When treating patients with BDA, baseline uricacid levels should be obtained and regular monitoring of uricacid should be done. The CLEAR Outcomes trial, scheduled to be completed by December 2022, will provide further information on BDA. BDA appears to be a promising alternative to currently available secondary lipid-lowering agents.

The Impact of Radiographic, Metabolic and Demographic Characteristics on Kidney Stone Recurrence.

Urolithiasis is a frequent disease with cited rates of recurrence after initial diagnosis that vary widely and range between 35% and 50%. We assessed the radiographic recurrence rate in patients with urinary stones and its risk factors. We retrospectively identified patients who were diagnosed with urinary stones on non-contrast computed tomography from 2010 to 2011, and underwent another imaging examination at least six months afterwards. We collected patient demographic, clinical, laboratory and radiologic data and compared patients with and without urinary stone recurrence. Ultimately, 237 patients were included in the study; the mean follow-up was 6.7 years; 88 patients (37.1%) had recurrence based on our recurrence criteria. On univariate analysis, the significant parameters for recurrence were baseline serum calcium and uric acid, stone location in the kidney, surgical intervention and stone burden volume. On multivariate analysis, surgical intervention (OR 3.07, p = 0.001), baseline calcium (OR 2.56, p = 0.011), baseline uric acid (OR 1.30, p = 0.021) and stone location in the kidney (OR 2.16, p = 0.012) were associated with higher risk of recurrence. These findings may guide personalized follow-up protocols for patients with urolithiasis based on their risk factors.

Uric acid as a prognostic predictor in COVID-19.

The purpose of our study was to investigate the incidence and prognostic significance of baseline and control uric acid values in COVID-19. The study population included patients admitted with the diagnosis of SARS-CoV-2 between March 2020 and March 2021. The demographic data, clinical, laboratory, and radiological findings were recorded. Uric acid levels were measured at the time of admission for 498 patients and at the most severe period of the disease in 143 patients. Length of hospital stay, need for admission to intensive care unit, the course, and outcomes during hospitalization were recorded. The mean age of 261 male and 207 female patients was 62.7(21-95) years. At the time of admission, 21 patients had hypouricemia and 170 had hyperuricemia. The need for ICU was 47.6% in the hypouricemic, 19.2% in the normouricemic, and 21.2% in the hyperuricemic groups. The mean uric acid level was 5.24±2.54 mg/dl in patients who required ICU admission and 5.18±1.98 mg/dl in patients who were discharged from the ward. The difference was not statistically significant. The mean uric acid level was not significantly different in the deceased and survivors. In 143 subjects, uric acid levels were measured after the progression of COVID-19; 73 of them were admitted to the ICU. The mean uric acid levels were found to be significantly decreased in patients with a negative prognosis. In our study, hypouricemia was not found to be a major feature of SARS-CoV-2 infection. Low baseline uric acid levels were associated with increased ICU admission. The decline in uric acid levels during hospital stay predicted poor prognosis, as well.

SARS-CoV-2 omicron variant clearance delayed in breakthrough cases with elevated fasting blood glucose

BackgroundOmicron variant (B.1.1.529) is a dominant variant worldwide. However, the risk factors for Omicron variant clearance are yet unknown. The present study aimed to investigate the risk factors for early viral clearance of Omicron variant in patients with a history of inactivated vaccine injection.MethodsDemographic, clinical, and epidemiological data from 187 patients were collected retrospectively during the Omicron variant wave.Results73/187 and 114/187 patients were administered two and three doses of vaccine, respectively. The median duration of SARS-CoV-2 RNA positivity was 9 days, and the difference between patients with two and three vaccine injections was insignificant (P = 0.722). Fever was the most common symptom (125/187), and most patients (98.4%) had a fever for < 7 days. The RNA was undetectable in 65/187 patients on day 7. Univariable logistic analysis showed that baseline glucose, uric acid, lymphocytes count, platelet count, and CD4+ T lymphocyte count were associated with SARS-CoV-2 RNA-positivity on day 7. Multivariable analysis showed that glucose ≥ 6.1 mmol/L and CD4+T lymphocytes count were independent risk factors for RNA positivity on day 7. 163/187 patients had an undetectable RNA test on day 14, and uric acid was the only independent risk factor for RNA positivity. Moreover, baseline glucose was negatively correlated with uric acid and CD4+ and CD8+ T cell count, while uric acid was positively correlated with CD4+ and CD8+ T cell count.ConclusionsOmicron variant clearance was delayed in breakthrough cases with elevated fasting blood glucose, irrespective of the doses of inactivated vaccine.

Association Between Baseline Uric Acid and the Risk of Acute Pancreatitis

The aim of the study is explore the association between serum uric acid (UA) and acute pancreatitis (AP) risk in a Chinese population. We included 124,316 participants who enrolled in the Kailuan cohort from 2006 to 2009. We fitted Cox models to estimate the correlation between UA and AP. During an average follow-up of 11.97 years (standard deviation, 2.16 years), 396 AP developed. The incidence rates from quartile 1 to quartile 4 of AP were 20.76, 18.78, 30.58, and 36.79 per 100,000 person-years, respectively. Multivariate analysis showed a significantly increased risk in quartile 3 (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.05-1.91) and quartile 4 (HR, 1.61; 95% CI, 1.19-2.17) compared with quartile 1. The association may be modified by alcohol use (P for interaction = 0.017). The quartile 4 group with excessive alcohol consumption showed an enormously increased risk of AP (HR, 9.09; 95% CI, 1.18-70.21) than those without (HR, 1.46; 95% CI, 1.07-2.00). Elevated serum UA is an independent risk factor for AP. Surveillance of serum UA, especially among heavy drinkers, may be helpful for AP prevention.

The potential role of insulin resistance in predicting outcome from intravenous thrombolytic therapy

BackgroundThe potential impact of insulin resistance on stroke prognosis after IV thrombolysis is poorly understood. This study aimed to assess the effect of insulin resistance and metabolic syndrome on the outcome of IV thrombolysis in non-diabetic patients with acute ischaemic stroke.MethodsThis prospective observational study was conducted on 70 non-diabetic acute ischaemic stroke patients who received rt-PA within 3 h of stroke onset. Patients were subjected to baseline and follow-up NIHSS measurements at 24 h and 3 months post-treatment. Stroke outcome was assessed after 3 months using the Modified Rankin Scale (mRS). The homeostasis model assessment–insulin resistance (HOMA-IR) was calculated for the included patients at stroke onset.ResultsThe mean age of included patients was 57.04 ± 14.39 years. Patients with unfavourable outcome had a significantly higher frequency of insulin resistance and metabolic syndrome, higher values of baseline NIHSS, insulin, HOMA-IR, uric acid and lower levels of HDL than those with favourable outcome (P value = 0.035, 0.007, ≤ 0.001, 0.001, ≤ 0.001, 0.002, 0.033, respectively). Each point increase in NIHSS before rt-PA increased the odds of an unfavourable outcome by 2.06 times (95% CI 1.22 − 3.478). Also, insulin resistance increased the odds of the unfavourable outcome by 11.046 times (95% CI 1.394–87.518). There was a statistically significant improvement in NIHSS 3 months after receiving rt-PA in all patients, significantly higher in patients who did not have insulin resistance or metabolic syndrome.ConclusionInsulin resistance and metabolic syndrome were associated with worse functional outcomes in non-diabetic stroke patients after receiving rt-PA.

The serum uric acid is longitudinally related to patients global assessment of disease activity in male patients with axial spondyloarthritis

ObjectivesTo investigate longitudinal relationship between serum uric acid (SUA) and disease activity among Chinese males with axial spondyloarthritis (axSpA).MethodsTwo-year data from the NASA study cohort of male patients with axial spondyloarthritis were analyzed. Patients global assessment of disease activity (PtGA), BASDAI, ASDAS-CRP, BASFI, and SF-36 were used as the outcomes. The autoregressive Generalized Estimation Equation (GEE) model was used to investigate the longitudinal relationship between SUA and the above outcomes. Age and gender and symptom duration were tested as effect modifiers or confounders.ResultsIn total, 102 male axSpA patients were included, 33.3% of who were hyperuricemia at baseline. Over time,serum uric acid levels associated with the global assessment of patient global assessment of disease activity (PtGA)[P=0.041, β=-2.059,95%CI(-4.032, -0.086)], SF-36: Vitality (VT) [P=0.01, β=1.751, 95%CI (0.415,3.087)], SF-36: Social Functioning (SF)[P=0.002, β= 2.968,95%CI (1.067,4.869)]). And these relationgships were independent of age, symptom duration, baseline uric acid levels, and medication use.ConclusionsIn summary, SUA levels is longitudinally related to PtGA and mental health assessment. Age, gender and symptom duration do not have an impact on the relationships.

Uric Acid Predicts Recovery of Left Ventricular Function and Adverse Events in Heart Failure With Reduced Ejection Fraction: Potential Mechanistic Insight From Network Analyses.

Background and AimsHeart failure with reduced ejection fraction (HFrEF) still carries a high risk for a sustained decrease in left ventricular ejection fraction (LVEF) even with the optimal medical therapy. Currently, there is no effective tool to stratify these patients according to their recovery potential. We tested the hypothesis that uric acid (UA) could predict recovery of LVEF and prognosis of HFrEF patients and attempted to explore mechanistic relationship between hyperuricemia and HFrEF.MethodsHFrEF patients with hyperuricemia were selected from the National Inpatient Sample (NIS) 2016–2018 database and our Xianyang prospective cohort study. Demographics, cardiac risk factors, and cardiovascular events were identified. Network-based analysis was utilized to examine the relationship between recovery of LVEF and hyperuricemia, and we further elucidated the underlying mechanisms for the impact of hyperuricemia on HFrEF.ResultsAfter adjusting confounding factors by propensity score matching, hyperuricemia was a determinant of HFrEF [OR 1.247 (1.172–1.328); P < 0.001] of NIS dataset. In Xianyang prospective cohort study, hyperuricemia is a significant and independent risk factor for all-cause death (adjusted HR 2.387, 95% CI 1.141–4.993; P = 0.021), heart failure readmission (adjusted HR 1.848, 95% CI 1.048–3.259; P = 0.034), and composite events (adjusted HR 1.706, 95% CI 1.001–2.906; P = 0.049) in HFrEF patients. UA value at baseline was negatively correlated to LVEF of follow-ups (r = −0.19; P = 0.046). Cutoff UA value of 312.5 μmmol/L at baseline can work as a predictor of LVEF recovery during follow-up, with the sensitivity of 66.7%, the specificity of 35.1%, and the accuracy of 0.668 (95% CI, 0.561–0.775; P = 0.006). Moreover, gene overlap analysis and network proximity analysis demonstrated a strong correlation between HFrEF and Hyperuricemia.ConclusionLower baseline UA value predicted the LVEF recovery and less long-term adverse events in HFrEF patients. Our results provide new insights into underlying mechanistic relationship between hyperuricemia and HFrEF.

Phase II Trial of Sipuleucel-T and Stereotactic Ablative Body Radiation for Patients with Metastatic Castrate-Resistant Prostate Cancer.

(1) We hypothesized that adding concurrent stereotactic ablative radiotherapy (SAbR) would increase the time to progression in patients with metastatic castrate-resistant prostate cancer (mCRPCA) treated with sipuleucel-T. (2) Patients with a history of prostate cancer (PC), radiographic evidence of metastatic disease, and rising prostate-specific antigen (PSA) > 0.2 ng/dL on castrate testosterone levels were enrolled in this single-arm phase II clinical trial and treated with sipuleucel-T and SAbR. The primary endpoint was time to progression (TTP). Cellular and humoral responses were measured using ELISpot and Luminex multiplex assays, respectively. (3) Twenty patients with mCRPC were enrolled and treated with SAbR to 1–3 sites. Treatment was well tolerated with 51, 8, and 4 treatment-related grade 1, 2, and 3 toxicities, respectively, and no grade 4 or 5 adverse events. At a median follow-up of 15.5 months, the median TTP was 11.2 weeks (95% CI; 6.8–14.0 weeks). Median OS was 76.8 weeks (95% CI; 41.6–130.8 weeks). This regimen induced both humoral and cellular immune responses. Baseline M-MDSC levels were elevated in mCRPC patients compared to healthy donors (p = 0.004) and a decline in M-MDSC was associated with biochemical response (p = 0.044). Responders had lower baseline uric acid levels (p = 0.05). No clear correlation with radiographic response was observed. (4) While the regimen was safe, the PC-antigen-specific immune response induced by SAbR did not yield a synergistic clinical benefit for patients treated with sipuleucel-T compared to the historically reported outcomes.

Longitudinal changes in uric acid concentration and their relationship with chronic kidney disease progression in children and adolescents.

Elevated serum uric acid concentration is a risk factor for CKD progression. Its change over time and association with CKD etiology and concomitant changes in estimated glomerular filtration rate (eGFR) in children and adolescents are unknown. Longitudinal study of 153 children/adolescents with glomerular (G) and 540 with non-glomerular (NG) etiology from the CKD in Children (CKiD)study. Baseline serum uric acid, change in uric acid and eGFR over time, CKD etiology, and comorbidities were monitored. Adjusted linear mixed-effects regression models quantified the relationship between within-person changes in uric acid and concurrent within-person changes in eGFR. Participants with stable uric acid over follow-up had CKD progression which became worse for increased baseline uric acid (average annual percentage changes in eGFR were - 1.4%, - 7.7%, and - 14.7% in those with G CKD with baseline uric acid < 5.5mg/dL, 5.5 - 7.5mg/dL, and > 7.5mg/dL, respectively; these changes were - 1.4%, - 4.1%, and - 8.6% in NG CKD). Each 1mg/dL increase in uric acid over follow-up was independently associated with significant concomitant eGFR decreases of - 5.7% (95%CI - 8.4 to - 3.0%) (G) and - 5.1% (95%CI - 6.3 to - 4.0%) (NG) for those with baseline uric acid < 5.5mg/dL and - 4.3% (95%CI - 6.8 to - 1.6%) (G) and - 3.3% (95%CI - 4.1 to - 2.6%) (NG) with baseline uric acid between 5.5 and 7.5mg/dL. Higher uric acid levels and increases in uric acid over time are risk factors for more severe progression of CKD in children and adolescents. A higher resolution version of the Graphical abstract is available as Supplementary information.

MO351: Effect of Allopurinol Versus Saline Hydration in Preventing Contrast-Induced Nephropathy

Abstract BACKGROUND AND AIMS Contrast-induced nephropathy (CIN) is a generally reversible form of acute kidney injury that occurs soon after the .administration of radiocontrast media. Several therapies are being used for the prevention of CIN. We aimed to gather the data about protective role of a single oral dose of Allupurinol along with hydration with normal saline as compared with normal saline only in our settings. METHOD Duration of study was 6 months. It was done at Department of Nephrology/Cardiology, Pakistan Institute of Medical Sciences (PIMS), SZABMU, Islamabad. In this randomized controlled trial, a total of 76 (n = 76) adult (age 18–75 years) patients of either gender who were planned to undergo coronary intervention were selected for this study. All the enrolled patients had an eGFR &amp;lt;60 mL/min. Participants were divided into two groups randomly by using random number tables. Patients in group A received a single dose of 300 mg Allopurinol orally 12 h before contrast-based procedure and intravenous normal saline hydration at the rate of 0.5 mL/kg/h in continuous infusion 12 h before and 12 h after contrast-based procedure. Group B received normal saline hydration alone in dose equal to group A. Blood samples were drawn 12 h before procedure. Samples were analyzed for serum creatinine levels. Blood samples were drawn after 48 h and 5 days of procedure for serum creatinine analysis. CIN was assessed in all patients, which was defined as an absolute .increase in .serum creatinine level of &amp;gt; 0.05 mg/dL or a relative increase of &amp;gt; 25% from baseline at 48 h after contrast exposure and compared in both treatment groups. RESULTS Gender distribution was similar in both groups with M:F of 1.71 in group A and 1.53 in group B (P = 0.813). Mean age was 57.6 years ± 7.4 SD in group A, while it was 58.4 years ± 6.5 SD in group B (P = 0.612). There were 63.2% (n = 24/38) patients in group A who were between ≤60 years of age and 36.8% (n = 14/38) had an age &amp;gt;60 years. Mean eGFR at baseline in group A was 53.7 mL/min ± 4.7 SD, and it was 54.8 mL/min/1.73 m2 ± 3.8 SD in group B (P = 0.277). Mean maximal allowable contrast dose (MACD) in group A was 323.3 mL ± 51.7 SD, and it was 313.4 mL ± 0.09 SD in group B (P = 0.445). Mean contrast volume was 55.1 mL ± 5.9 SD in group A, and it was 56.9 mL ± 5.6 SD in group B (P = 0.171). The mean CV/MACD ratio was similar in both groups (0.17 versus 0.19, P = 0.160, Table 7). Contrast-induced nephropathy (CIN) was observed in 5.3% (n = 2/38) patients in group A, while it was observed in 21.1% (n = 8/38) patients in group B as per pour operational definitions (P = 0.042). CIN in both the groups were stratified with respect to age, gender, BMI and baseline comorbids. In patients with baseline uric acid within normal limits, CIN was observed in 3.4% (n = 1/29) patients in group A, while it was observed in 9.7% (n = 3/31) patients in group B (P = 0.334, Table 10). In patients with raised uric acid levels at baseline, CIN was observed in 11.1% (n = 1/9) patients in group A, while it was observed in 71.4% (n = 5/7) patients in group B (P = 0.013). Efficacy of a single dose of Allopurinol dose along with hydration with normal saline was significantly better in patients with raised serum uric acid levels at baseline when compared with normal saline only (P = 0.013). No other significant difference noted across all groups (P&amp;gt;0.05 in all cases). CONCLUSION CIN developed in a significantly lesser number of patients who received a single dose of 30 mg of Allopurinol 12 h before administration of contrast along with saline hydration as compared with patients receiving hydration alone.

Uric acid as a predictor of weight gain and cardiometabolic health in the Study of Novel Approaches to Weight Gain Prevention (SNAP) study

Young adulthood is often a period of substantial weight gain increasing risk for obesity and cardiometabolic disease. Uric acid (UA), a clinical marker of oxidative stress, is associated with cardiometabolic dysfunction in established CVD, type 2 diabetes, and CKD. Yet, few trials have examined UA as a predictor of cardiometabolic risk in young, healthy populations, particularly in the context of weight gain prevention intervention. The purpose of this ancillary study was to examine UA in the Study of Novel Approaches to Weight Gain Prevention (SNAP), a randomized, controlled trial of weight gain prevention strategies in young healthy adults. UA was examined as a predictor of weight and cardiometabolic outcomes over 6 years; the impact of weight gain prevention interventions on UA was also examined. We found that higher baseline UA was a significant predictor of less favorable BMI, triglycerides, HDL, glucose, insulin, and HOMA, independent of age, sex, baseline weight, baseline level of the outcome variable, and weight gain prevention intervention. Additionally, ≥1% weight loss was associated with lower UA. UA is a promising biomarker for future weight gain and cardiometabolic risk in young adults that may respond to weight gain prevention.Clinical trial registration: clinicaltrials.gov identifier NCT01183689.

The efficacy and cost-impact of rasburicase 3 mg versus 6 mg for the management of tumor lysis syndrome: A multicenter analysis.

Purpose: Hyperuricemia is a complication arising from tumor lysis syndrome (TLS). Literature has shown that a single 3 mg dose was just as efficacious as a single 6 mg dose when the uric acid (UA) levels were ≤12 mg/dL. Here, we present a multi-center analysis rasburicase utilization and its effect on healthcare costs. Methods: This is a multi-center, retrospective analysis of adult cancer patients who were admitted to Methodist Le Bonheur Healthcare hospitals and received rasburicase from February 2020 to February 2021. The primary endpoint was to test whether rasburicase 3 mg had similar rates of uric acid normalization (defined as uric acid ≤7.5 mg/dL) within 24 h as a dose of 6 mg. Results: Seventy-nine patients were included in the study. While the baseline uric acid was lower in the 3 mg arm compared to the 6 mg arms, there was no difference in the uric acid normalization at 24 h between the 3 mg arm (95%) and 6 mg arm (82%) (p = 0.134). A cost-savings of over $300,000 annually can be achieved with the proposed protocol. Conclusion: A single, fixed rasburicase dose of 3 mg was effective in normalizing uric acid levels within 24 h, and is associated with significant cost-savings.

Serum uric acid level predicts the progression of amyotrophic lateral sclerosis following treatment with edaravone

ABSTRACT Introduction Uric acid and edaravone might exert a neuroprotective effect in amyotrophic lateral sclerosis (ALS) by reducing oxidative stress. We analyzed whether the treatment effect of edaravone is pronounced in patients whose uric acid level increased after the treatment with edaravone. Materials and methods Forty patients with ALS who underwent treatment with edaravone were included. Baseline uric acid level and the rate of decline in uric acid after edaravone treatment were recorded. The rate of change of ALS functional rating scale-revised (ΔALSFRS-R/month) was calculated based on baseline ALSFRS-R score and ALSFRS-R score 6–24 weeks after the treatment. Results The serum uric acid levels decreased after treatment in 26 (65%) patients and increased in 12 (30%) patients. The ΔALSFRS-R/month was significantly faster in patients whose uric acid decreased (median 1.5 [Q1–Q3, 0.7–3.1]) than in patients whose uric acid increased (0.2 [0–1.0], p = 0.021). A high baseline uric acid level and low rate of decline in uric acid was associated with slower disease progression after adjusting for age, initial symptoms, and riluzole administration (p = 0.030 and p = 0.041, respectively). Discussion High baseline values and low rate of decline in uric acid may predict slow disease progression in ALS patients treated with edaravone.

Abstract EP12: Uric Acid Predicts Recovery Of Left Ventricular Function And Adverse Events In Heart Failure With Reduced Ejection Fraction: Potential Mechanistic Insight From Network Analyses

Background and Aims: Heart failure with reduced ejection fraction (HFrEF) still carries a high risk for a sustained decrease in left ventricular ejection fraction (LVEF) even with the optimal medical therapy. Currently, there is no effective tool to stratify these patients according to their recovery potential. We tested the hypothesis that uric acid (UA) could predict recovery of LVEF and prognosis of HFrEF patients and attempted to explore mechanistic relationship between hyperuricemia and HFrEF. Methods: HFrEF patients with hyperuricemia were selected from the National Inpatient Sample (NIS) 2016-2018 database and our Xianyang prospective cohort study. Demographics, cardiac risk factors, and cardiovascular events were identified. Network-based analysis was utilized to examine the relationship between recovery of LVEF and hyperuricemia, and we further elucidated the underlying mechanisms for the impact of hyperuricemia on HFrEF. Results: After adjusting confounding factors by propensity score matching, hyperuricemia was a determinant of HFrEF [OR 1.247 (1.172-1.328); P &lt;0.001] of NIS dataset. In Xianyang prospective cohort study, hyperuricemia is a significant and independent risk factor for all-cause death (adjusted HR 2.387, 95% CI 1.141-4.993; P =0.021), heart failure readmission (adjusted HR 1.848, 95% CI 1.048-3.259; P =0.034), and composite events (adjusted HR 1.706, 95% CI 1.001-2.906; P =0.049) in HFrEF patients. UA value at baseline was negatively correlated to LVEF of follow-ups (r=-0.19; P =0.046). Cutoff UA value of 312.5 μmmol/L at baseline can work as a predictor of LVEF recovery during follow-up, with the sensitivity of 66.7%, the specificity of 35.1%, and the accuracy of 0.668 (95% CI, 0.561-0.775; P =0.006). Moreover, gene overlap analysis and network proximity analysis demonstrated a strong correlation between HFrEF and Hyperuricemia. Conclusion: Lower baseline UA value predicted the LVEF recovery and less long-term adverse events in HFrEF patients. Our results provide new insights into underlying mechanistic relationship between hyperuricemia and HFrEF.