Baseline Levels Of Uric Acid Research Articles

Malondialdehyde and Uric Acid as Predictors of Adverse Outcome in Patients with Chronic Heart Failure.

In chronic heart failure (HF), some parameters of oxidative stress are correlated with disease severity. The aim of this study was to evaluate the importance of oxidative stress biomarkers in prognostic risk stratification (death and combined endpoint: heart transplantation or death). In 774 patients, aged 48-59 years, with chronic HF with reduced ejection fraction (median: 24.0 (20-29)%), parameters such as total antioxidant capacity, total oxidant status, oxidative stress index, and concentration of uric acid (UA), bilirubin, protein sulfhydryl groups (PSH), and malondialdehyde (MDA) were measured. The parameters were assessed as predictive biomarkers of mortality and combined endpoint in a 1-year follow-up. The multivariate Cox regression analysis was adjusted for other important clinical and laboratory prognostic markers. Among all the oxidative stress markers examined in multivariate analysis, only MDA and UA were found to be independent predictors of death and combined endpoint. Higher serum MDA concentration increased the risk of death by 103.0% (HR = 2.103; 95% CI (1.330-3.325)) and of combined endpoint occurrence by 100% (HR = 2.000; 95% CI (1.366-2.928)) per μmol/L. Baseline levels of MDA in the 4th quartile were associated with an increased risk of death with a relative risk (RR) of 3.64 (95% CI (1.917 to 6.926), p < 0.001) and RR of 2.71 (95% CI (1.551 to 4.739), p < 0.001) for the occurrence of combined endpoint as compared to levels of MDA in the 1st quartile. Higher serum UA concentration increased the risk of death by 2.1% (HR = 1.021; 95% CI (1.005-1.038), p < 0.001) and increased combined endpoint occurrence by 1.4% (HR = 1.014; 95% CI (1.005-1.028), p < 0.001), for every 10 μmol/L. Baseline levels of UA in the 4th quartile were associated with an increased risk for death with a RR of 3.21 (95% CI (1.734 to 5.931)) and RR of 2.73 (95% CI (1.560 to 4.766)) for the occurrence of combined endpoint as compared to the levels of UA in the 1st quartile. In patients with chronic HF, increased MDA and UA concentrations were independently related to poor prognosis in a 1-year follow-up.

PB2282 REASSESSING THE EFFICACY OF LOW DOSE RASBURICASE FOR MANAGEMENT OF TUMOR LYSIS SYNDROME IN HIGH RISK HEMATOLOGIC MALIGNANCIES

Background:Tumor lysis syndrome (TLS) is a potentially life‐threatening metabolic derangement seen in aggressive hematologic malignancies which is characterized by the massive release of toxic metabolic byproducts and consequent kidney damage. Whereas rasburicase is an established standard of care for management of TLS, the high cost of administering standard dosing of rasburicase has led to exploring lower doses of rasburicase.Aims:Assess our center's experience with lower dosing of rasburicase for management of TLS in aggressive hematologic malignancies.Methods:We studied all adult patients with hematologic malignancies who were treated with rasburicase in our institution between the years 2011‐2018. Charts were reviewed and demographic, clinical, and laboratory data were collected. Subjects were defined to be at high risk for TLS if they had any of the following features: acute leukemia, elevated uric acid levels at baseline (&gt;7.5 mg/dL) or aggressive lymphoma.Results:Fifty‐five patients were evaluated. The median age of patients was 67 years (range 22‐92) consisting of 20 patients with acute leukemia, 21 with aggressive lymphoma, 11 with multiple myeloma, and 3 with other hematologic cancers. Nearly all analyzed patients (98%) were considered to be at high risk for TLS and 44 patients did meet criteria for clinical TLS. Twenty‐six patients (47%) received allopurinol prophylaxis. The median dose of rasburicase administered was 3 mg (range 1.5‐9) with 10 patients being given a second dose of rasburicase. The median baseline levels of uric acid and creatinine were 13.9 mg/dL (range 6.5‐42.8) and 2.18 mg/dL (range 0.63‐8.15), respectively. At 24 hours post administration of rasburicase the median uric acid levels were 7.9 mg/dL (range 0.8‐17.5) while at 48 hours they were 4.9 mg/dL (range 0.8‐13.5). Notably, 54 patients (98%) experienced a decrease in uric acid levels of at least 10% within the first 24 hours following rasburicase administration and 40% of patients had normal uric levels by that time. Within the initial 24 hours, creatinine levels were significantly improved in only a minority of patients with only 10 patients (18%) experiencing a decrease of more than 10% compared to baseline levels. Of note, 15 patients required dialysis during their admission and 26 patients died during the index hospitalization.Summary/Conclusion:The majority of subjects in our analysis of a high‐risk patient population responded favorably to low dose rasburicase in terms of rapid uric acid reduction although rates of dialysis and early mortality were substantial. Our data illustrate and confirm the feasibility of lower dosing of rasburicase to patients with aggressive hematologic malignancies.

Abstract P414: The Interrelations Between Serum Uric Acid, Silent Myocardial Infarction and Mortality in the General Population

Background: Whether elevated uric acid (UA) is associated with silent myocardial infarction (SMI) or whether their joint association predicts an increased risk of mortality has not been explored. Methods: This analysis included 6,323 participants (58.4±13.1 years, 53.9% women, and 49.7% Non-Hispanic whites) without clinical cardiovascular disease (CVD) from the Third National Health and Nutrition Examination Survey (NHANES-III). SMI was defined as electrocardiographic evidence of myocardial infarction (MI) without a history of MI. Multivariable logistic regression model was used to examine the cross-sectional association between baseline UA and SMI. Cox-proportional hazard analysis was used to calculate hazard ratio (HR) with 95% confidence interval (CI) for the risk of all-cause and CVD mortality with UA in the absence and presence of SMI. Results: Higher baseline level of UA was associated with higher odds of baseline SMI. The prevalence of SMI was 0.79%, 1.18%, 1.59% and 2.27% across the UA quartiles respectively; multivariable-adjusted OR (95% CI): 2.53 (1.19-5.37) comparing the upper with lower quartile. During a median follow up of 14 years, there were 1916 all-cause death of whom 774 were CVD deaths. Compared to participants with the lowest UA quartile values and without SMI, those with highest UA had a 34% increased the risk of all-cause mortality (multivariable-adjusted HR: (95%CI): 1.34 (1.15-1.56)). This risk increased by 112% in the presence of SMI (multivariable-adjusted HR (95%CI): 2.12(1.41-3.70)). Similar results were observed for CVD mortality. SMI carried an increased risk of all-cause and CVD mortality only in higher quartiles of UA. Conclusion: The strong association of UA with SMI and the additive effect of UA and SMI on mortality further support the potential role of UA as a marker of poor outcomes. Both UA and electrocardiogram are simple, inexpensive markers which can potentially be used in risk stratification and identification of high-risk individuals.

Baseline predictors for progression 4 years after Parkinson's disease diagnosis in the De Novo Parkinson Cohort (DeNoPa).

The objectives of this study were to investigate (1) the annual rate of progression of motor and cognitive symptoms and (2) baseline predictors of different modalities for this progression in early Parkinson's disease (PD) when compared with healthy controls. A total of 135 de novo PD and 109 healthy controls (of the De Novo Parkinson cohort) were investigated at baseline and after 24 and 48 months. To delineate motor progression and cognitive decline, the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) and the Mini-Mental Status Examination (MMSE) were selected. Baseline variables used to predict progression included sociodemographic factors, comorbidities, motor/nonmotor symptoms, polysomnography, MRI, and laboratory biomarkers in serum and CSF. Symptoms worsened over 4 years in PD with an annual change of 1.8 points on the MDS-UPDRS III and 0.2 points on the MMSE. Baseline predictors of worse progression of motor symptoms in PD included male sex, orthostatic blood pressure drop, diagnosis of coronary artery disease, arterial hypertension, elevated serum uric acid, and CSF neurofilament light chain. Predictors of cognitive decline in PD included previous heavy alcohol abuse, current diagnoses of diabetes mellitus, arterial hypertension, elevated periodic limb movement index during sleep, decreased hippocampal volume by MRI, higher baseline levels of uric acid, C-reactive protein, high density lipoprotein (HDL) cholesterol, and glucose levels. Cardiovascular risk factors, deregulated blood glucose, uric acid metabolism, and inflammation were identified as risk markers for faster disease progression. Our panel of risk parameters needs validation during our continuing follow-up and also in independent patient cohorts. © 2018 International Parkinson and Movement Disorder Society.

USE OF HERBAL REMEDY URISAN AS BASIC THERAPY FOR GOUT

Objective: to evaluate the efficacy, safety, and tolerance of the herbal complex Urisan used in patients with gout. Subjects and methods. Thirty allopurinol-untreated patients with a verified diagnosis of gout (by the ACR criteria) were followed up during a relapse-free interval. Subjective appraisals of the tolerance of Urisan were provided by a physician and a patient. General clinical examination, anthropometry, monitoring blood pressure and uric acid (UA) in blood and urine, and lipid metabolism were made to define the efficiency of therapy before and after it. Results. Urisan exhibited a positive effect in reducing the blood levels of UA (p< 0,003). For more detailed evaluation of the effect of Urisan on hyperuricemia, the patients were divided into 3 groups in accordance with the baseline level of UA; positive changes were observed in all the groups. Significantly lower UA levels were seen in Groups 1 and 2 (p< 0,007 and p< 0,04, respectively). The remedy was found to have no effect on UA excretion. Its tolerance was good. Conclusion. Urisan has a positive effect, by lowering hyperuricemia despite the latter's baseline values

Effect of Long-Term Administration of Cross-Sex Hormone Therapy on Serum and Urinary Uric Acid in Transsexual Persons

Transsexual persons afford a very suitable model to study the effect of sex steroids on uric acid metabolism. This was a prospective study to evaluate the uric acid levels and fractional excretion of uric acid (FEUA) in a cohort of 69 healthy transsexual persons, 22 male-to-female transsexuals (MFTs) and 47 female-to-male transsexuals (FMTs). The subjects were studied at baseline and 1 and 2 yr after starting cross-sex hormone treatment. The baseline levels of uric acid were higher in the MFT group. Compared with baseline, uric acid levels had fallen significantly after 1 yr of hormone therapy in the MFT group and had risen significantly in the FMT group. The baseline FEUA was greater in the FMT group. After 2 yr of cross-sex hormone therapy, the FEUA had increased in MFTs (P = 0.001) and fallen in FMTs (P = 0.004). In MFTs, the levels of uric acid at 2 yr were lower in those who had received higher doses of estrogens (P = 0.03), and the FEUA was higher (P = 0.04). The FEUA at 2 yr was associated with both the estrogen dose (P = 0.02) and the serum levels of estradiol-17beta (P =0.03). In MFTs, a correlation was found after 2 yr of therapy between the homeostasis model assessment of insulin resistance and the serum uric acid (r = 0.59; P = 0.01). Serum levels of uric acid and the FEUA are altered in transsexuals as a result of cross-sex hormone therapy. The results concerning the MFT group support the hypothesis that the lower levels of uric acid in women are due to estrogen-induced increases in FEUA.