Median Uric Acid Levels Research Articles

Pyrazinamide-induced Hyperuricemia in Pulmonary Tuberculosis Patients.

Pyrazinamide is one of the antitubercular drugs used for 2 months in the intensive phase. One of the adverse effects of pyrazinamide is hyperuricemia, with a symptom of arthralgia. This study aims to analyze the incidence of hyperuricemia and arthralgia and their causality in pulmonary tuberculosis (TB) patients undergoing treatment in the intensive phase. It was an analytic observational study with a prospective cohort design. Three ml of blood from each pulmonary TB patient was withdrawn to examine uric acid levels before and after 2 months of treatment with pyrazinamide. The Wilcoxon test was used to analyze changes in uric acid levels and the Chi-square test to analyze the association between uric acid levels and arthralgia. Naranjo algorithm is used to analyze the causality of hyperuricemia. Twenty pulmonary TB patients met the inclusion criteria in this study. Eight out of 12 (60%) TB patients showed uric acid levels ≥7 mg/dl and 8 of them (66.6%) showed symptoms of arthralgia. The median uric acid level increased significantly before (5.14 mg/dl) and after 2 months of treatment (7.74 mg/dl), P-value = 0.001. Uric acid levels ≥7 mg/dl were significantly associated with arthralgia (P-value = 0.017; odds ratio 14.00; 95% confidence interval 1.25-156.61). Based on the Naranjo algorithm, those with hyperuricemia, eight and four patients had a total score of 7 and 8, respectively, which are classified as probable. Uric acid levels significantly increased during the intensive phase. Pulmonary TB patients with hyperuricemia are a risk factor for arthralgia.

Hip circumference has independent association with the risk of hyperuricemia in middle-aged but not in older male patients with type 2 diabetes mellitus

BackgroundObesity and type 2 diabetes mellitus (T2DM) are risk factors for hyperuricemia. However, which anthropometric indices can better predict incident hyperuricemia in patients with T2DM remains inconsistent. This study aimed to examine the associations between hyperuricemia and different anthropometric indices in middle-aged and older male patients with T2DM.MethodsIn this retrospective study, a total of 1447 middle-aged (45—65 years, n = 791) and older (≥ 65 years, n = 656) male patients with T2DM were collected from December 2015 to January 2020 at Shanghai Xinhua Hospital. Hyperuricemia was defined as a serum uric acid level above 7.0 mg/dL. Weight, height, waist circumference (WC) and hip circumference (HC) were measured by trained nurses at visit.ResultsThe median uric acid level of subjects was 5.6 (interquartile ranges: 4.7—6.7) mg/dl, and 279 (19.3%) were hyperuricemia, with 146 (18.5%) in the middle-aged group, and 133 (20.3%) in the older group. After adjusting for age, duration of T2DM, fasting plasma glucose and insulin, homeostasis model assessment-β, aspartate aminotransferase, triglycerides, high-density lipoprotein cholesterol and estimated glomerular filtration rate, body mass index (BMI), WC, HC, and waist-to-height ratio (WHtR) were associated with a higher risk of hyperuricemia in both middle-aged and older group (P < 0.05). After further adjusting for BMI and WC, HC still showed a positive relationship with the risk of hyperuricemia (Odds Ratio = 1.51, 95% confidence intervals: 1.06—2.14) in the middle-aged group, but such relationship was not found in the older group. Moreover, according to receiver operating characteristic analysis, the optimal cutoff value was 101.3 cm of HC for hyperuricemia screening in the middle-aged male patients with T2DM.ConclusionIn middle-aged male patients with T2DM, more attention should be paid to HC with the cutoff value of 101.3 cm in clinical practice for early recognition of individuals with a high risk of hyperuricemia for targeted guidance on disease prevention, such as community screening.

RELATION OF METABOLIC PROFILE WITH DIFFERENT TYPES OF CAROTID LESIONS IN HYPERTENSIVE PATIENTS

Objective: The aim of our study was to identify the relations of lipid profile and uric acid (UA) with the types of carotid artery lesions (CL) in hypertensive patients. Design and method: 67 hypertensive patients (35 men and 32 women) were examined (median age 51[45;55], hypertension duration was 3[2;5]). The subjects underwent duplex scanning of the carotid arteries (Samsung HS50, 2021). Metabolic profile included total cholesterol(TC), low density lipoproteins(LDL), high density lipoproteins(HDL), triglycerides(TG), and uric acid(UA). The results of the study were processed by the program Statistica 10.0. Results: All patients were divided into 4 groups according to on the type of CL: group 1 (n = 39) without pathological carotid tortuosity(PCAT) and atherosclerotic plaques(AP); group 2 (n = 11) with PCAT, but without AP; group 3 (n = 11) with AP&lt;70% stenosis and without PCAT, and group 4 (n = 6), with both PCAT and AP&lt;70% stenosis. The groups did not differ significantly in gender and age (p&gt;0.05). Group 1 had TC level of 5.1[4.5;6.4]mmol/L, LDL of 2.3[2.05;2.8]mmol/L, HDL of 1.3[1.06;1.57]mmol/L, TG 1.2[0.7;1.6]mmol/L. The medians of the lipid profile in group 1 were not statistically different from those in group 2: TC - 4.85[4.5;7.69]mmol/l, LDL- 2.34[2.03;5.05]mmol/L, HDL- 1.38[1.3;1.6]mmol/L, TG- 1.1[0.9;1.23], p&gt;0.05. Group 3, when compared with groups 1 and 2, had the highest levels of TC - 6.7[5.87;6.8]mmol/L (p = 0.001), LDL - 2.97[2.9;3.8]mmol/L (p = 0.0005), HDL - 1.5[0.6;1.64]mmol/L (p&gt;0.05), and TG 1.9[1.8;2.35]mmol/L (p = 0.002), but did not significantly differed from those in group 4 (p&gt;0.05), where median of TC was 6.32[6.02;6.7]mmol/L, LDL 3.5[2.89;3.28]mmol/L, HDL 0.69[0.6;1.64]mmol/L, and TG 2.1[2.01;2.85]mmol/L, p&lt;0.05 when compared with groups 1 and 2. Median UA levels in group 1 (254 [212;310]mmol/L) was significantly lower (p = 0.011), when compared with patients in groups 2, 3, and 4 (311[301;395], 302[286;407], and 325[305;346], mmol/L, accordingly). There were correlations between the presence of PCAT+AP and levels of TC (r = 0.37; p&lt;0.05), LDL (r = 0.53; p&lt;0.05), TG (r = 0.47; p&lt;0.05), presence of dyslipidemia (r = 0.44; p&lt;0.05), and UA level (r = 0.4; p&lt;0.05). Conclusions: We have demonstrated a relation of metabolic markers (TC, LDL, and UA) not only with atherosclerotic carotid lesion, but also with pathological carotid tortuosity in hypertensive patients.

Elevated serum uric acid is associated with infertility in women living in America

Excessive uric acid levels may affect several organs and systems in the body. There is limited evidence of the effects of high serum uric acid levels on the female reproductive system. This study used the National Health and Nutrition Examination Survey (NHANES) database to explore the relationship between serum uric acid and female infertility. This cross-sectional study included a total of 2197 eligible subjects using data from NHANES 2013-March 2020 pre-pandemic data. Self-reported infertility (ever experiencing an inability to conceive after 12 months of trying to become pregnant) was the main outcome. Logistic regression models and restricted cubic spline were used to analyze the relationship between serum uric acid and female infertility, and stratified analysis was carried out. A total of 295 women self-reported infertility (13.43%). The median uric acid level for all study subjects was 4.4 mg/dL (interquartile range [IQR]: 3.7, 5.1). Serum uric acid levels were higher in the infertility group than in the control group (4.7 mg/dL [IQR: 4.0, 5.3] vs. 4.4 mg/dL [IQR: 3.7, 5.1], P < 0.001). After adjusting for age, race, marital status, smoking, alcohol, history of pregnancy, history of diabetes, history of hypertension, fasting glucose, total cholesterol, creatinine in refrigerated serum, low-density lipoprotein cholesterol, direct high-density lipoprotein cholesterol, glycohemoglobin, and body mass index confounders, women with serum uric acid levels at Q3 (4.4–5.1 mg/dL) had a 73% (odds ratio [OR] = 1.73, 95% confidence interval [CI] 1.18, 2.54, P = 0.005) higher risk of infertility, and women with uric acid levels at Q4 (5.1–18.0 mg/dL) had an 83% (OR = 1.83, 95% CI 1.22, 2.75, P = 0.003) increased risk of infertility compared to women at Q1 (1.6–3.7 mg/dL). The restricted cubic spline also showed that when serum uric acid levels exceeded the reference value, the risk of infertility gradually increased. We also performed a sensitivity analysis based on the complete dataset and found that the results were robust. Higher serum uric acid levels were significantly associated with an increased risk of female infertility. Women planning a pregnancy should have increased serum uric acid monitoring.

Correlation of Uric Acid with Disease Severity, Prognosis, and Complications in Patients with Severe Acute Pancreatitis

This study aimed to investigate the role of serum uric acid (UA) in early identification of the severity, prognosis and complications in patients with severe acute pancreatitis (SAP). The clinical data of SAP patients were collected retrospectively (n=268), and patients were divided into high UA group and low UA group based on the median UA level. Propensity score matching was used to make the baseline data comparable, and 85 patients were selected in each group. Spearman correlation analysis was performed to assess the relationship between UA level and severity and prognosis. The ROC curve was designed to evaluate the ability of UA to predict complications. In the high UA group, disease severity scores were higher, ICU stay and total hospital days were longer. UA levels were found to be positively associated to disease severity scores, ICU stay and total hospital days. The ROC curve revealed that the UA level had an useful predictive value for infectious pancreatic necrosis (IFN). UA level can be used as a convenient indicator of disease severity and IFN risk in SAP patients.

Uric acid shown to contribute to increased oxidative stress level independent of xanthine oxidoreductase activity in MedCity21 health examination registry

Uric acid has both antioxidant and pro-oxidant properties in vitro by scavenging and production of reactive oxygen species (ROS). This cross-sectional study examined whether uric acid possesses effects on oxidative stress under physiological conditions independent of xanthine oxidoreductase (XOR), which is involved in uric acid and ROS production. Serum uric acid level was measured, while plasma XOR activity was determined using our high-sensitive assay in 192 participants (91 males, 101 females) who underwent health examinations and were not taking an antihyperuricemic agent. For antioxidant potential and oxidative stress level, biological antioxidant potential (BAP) and derivative of reactive oxygen metabolites (d-ROMs) in serum, respectively, were measured. Median uric acid level and plasma XOR activity were 5.6 mg/dL and 26.1 pmol/h/mL, respectively, and BAP and d-ROMs levels were 2112.8 μmol/L and 305.5 Carr U, respectively. Multivariable regression analyses revealed no significant association of serum uric acid level with BAP level, whereas serum uric acid level showed a significant association with d-ROMs level independent of plasma XOR activity (p = 0.045), which was prominent in females (p = 0.036; p for interaction = 0.148). Uric acid might contribute to increased oxidative stress independent of XOR activity by increasing ROS production, without affecting ROS scavenging, especially in females.

Can uric acid blood levels in renal transplant recipients predict allograft outcome?

Background Hyperuricemia is common after renal transplantation, especially in those receiving calcineurin inhibitors. Little, however, is known about the relationship between uric acid (UA) levels and allograft outcome. Methods We conducted a retrospective single-center analysis (N = 368) in order to assess UA blood levels post-transplant association with allograft outcome. For this study, a median serum UA level of all measured UA levels from 1 month to 1 year post renal transplantation was calculated. Results Patients were divided into 2 groups based on the median UA level measured between 1 and 12 months post-transplant. Those with median UA level ≥ 7 and ≥ 6 mg/dL (N = 164) versus median UA level < 7 and < 6 mg/dL for men and women respectively (N = 204) had lower GFR values at 1, 3 and 5 years posttransplant (mean GFR ± SD of 43.4 ± 20.6 and 58 ± 19.9 at 3 years post-transplant, p < 0.001). In multivariate models, UA levels were no longer significantly associated with renal allograft function. In a multivariate cox proportional hazard model, UA level was found to be independently associated with increased risk for death-censored graft loss (HR of 1.3, 95% CI 1.0–1.7, p < 0.05 for every increase of 1 mg/dL in UA level). Conclusion Hyperuricemia was found to be associated with increased death- censored graft loss but not with allograft function. Increased UA levels were not found to be an independent predictor of long-term allograft function despite the known association of hyperuricemia with the progression of cardiovascular and renal disease.

Higher serum uric acid levels are associated with reduced risk of hip osteoporosis in postmenopausal women with rheumatoid arthritis.

Although the positive correlation between serum uric acid (UA) levels and bone mineral density (BMD) has been reported in the general population, there are little data regarding the effect of serum UA levels on bone loss in patients with rheumatoid arthritis (RA).We investigated whether increased serum UA levels were associated with a reduced risk of osteoporosis in postmenopausal women with RA.In this retrospective cross-sectional study, 447 postmenopausal female patients with RA and 200 age-matched, postmenopausal healthy controls underwent BMD examination by dual energy x-ray absorptiometry and serum UA levels measurement. Osteoporosis was diagnosed when the T-score was <−2.5.The median UA level in postmenopausal RA patients was found to be significantly lower than that in the healthy women (4 vs 4.1 mg/dL, P = .012) and the frequency of osteoporosis incidence in the lumbar spine, hip, and either site in RA patients was 25.5%, 15.9%, and 32.5%, respectively; the values were significantly higher than those of the controls. After adjusting for confounding factors, a significantly lower risk for osteoporosis of the hip in RA patients was observed within the highest quartile (odds ratio [OR] = 0.37, 95% confidence interval [CI] = 0.16–0.72, P = .021) and the second highest quartile (OR = 0.44, 95% CI = 0.2–0.95, P = .038) of serum UA levels as compared with the lowest quartile, but this association was not found to be consistent with respect to the lumbar spine. Serum UA levels also showed an independently positive correlation with femoral neck BMD (β = 0.0104, P = .01) and total hip BMD (β = 0.0102, P = .017), but not with lumbar BMD.Our data suggest that UA may exert a protective effect on bone loss in RA, especially in the hip.

Is There Any Impact of Uric Acid Levels during the Peri-Transplant Period on Acute Graft Vs. Host Disease Incidence and Allotransplant Outcome?

Background: Damage associated molecular patterns (DAMPs) are considered important contributors to acute Graft vs Host Disease (aGvHD) pathogenesis. Uric acid (UA), a DAMPs family molecule, upon its release from damaged tissues post high dose chemo/radio therapy, triggers activation of donor derived T-cells. Currently, only two published studies evaluated the association between UA levels at day 0 and aGvHD occurrence, with totally conflicting results. Given that aGvHD is a dynamic process which takes place during the whole early post-transplant period, contrasting to previous studies, we evaluated serum UA levels not only once but in 4 different time points during the early transplant period, at days -7, 0, +7, +14, and investigated its correlation to aGvHD incidence, non-relapse mortality (NRM) and survival rates. Methods: We retrospectively evaluated 57 patients (pts), with a median age of 36.8 years (range, 17-62), who underwent allogeneic stem cell transplantation (alloSCT) from full matched sibling donors for malignant (n=48) or non-malignant (very severe aplastic anemia =9) hematological diseases. A median of 5.6 x106/kg CD34+ cells were infused after a myeloablative (n=34) or reduced intensity (n=23) regimen. At the time of alloSCT, 42 pts were in remission (CR1: 30, CR2: 10, &gt;CR2: 2). All pts received either allopurinol or rasburicase from the day of conditioning initiation till day -1. The ROC-curve method, t-test, Kaplan-Meir method, and log-rank test were used for the univariate while the binary logistic regression method for the multivariate statistical analysis. Disease phase [early (CR1) vs. intermediate (CR2) and advanced (&gt;CR2 or presence of residual disease)], donor gender, patient and donor age, UA levels at day -7, 0, +7, +14, type of conditioning regimens and number of infused CD34+ cells were tested as possible factors that can affect aGvHD incidence. Results: Median UA levels were 3.2, 2.4, 2.2 and 2.9 mg/dl at days -7, 0, +7 and +14 respectively; using the ROC curve method the cutoff point was determined at 4.4 mg/dl for day -7 and 2.2 mg/dl for days 0, +7 and +14. Overall, 20/57 (35%) pts developed aGvHD; 18 (31%) were assessed as gr ≥II, while 10 (17%) as gr III-IV. The incidence of the aGvHD gr ≥II was higher for pts with UA levels ≤ 4.4 mg/dl at day -7 (14 vs 4) and for pts with UA levels ≥2.2 mg/dl at days 0 (12 vs. 6 pts) and +14 (13 vs. 5 pts) however these differences did not reach statistical significance. UA levels at +7 day had no impact on aGvHD incidence. In multivariate analysis, only the number of CD34+ &gt;6x106/kg was an adverse factor for aGVHD gr≥II (p=0.04) while intermediate &amp; advanced disease phase along with a number of CD34+ cells &gt;6x106/kg, proved to be significant contributors for severe aGvHD (gr III-IV) occurrence (p&lt;0.03). We observed a better 4 years overall survival for patients with UA levels &lt; 2.2 mg/dl at day +14 (85% vs. 55%, p=0.06). Fifteen pts succumbed to NRM causes; 8/15 deaths were attributed to aGvHD complications. The NRM was higher in patients who had UA levels ≥2.2 mg/dl at day +14 (32% vs. 15%) though this difference was not significant (p=0.2). Conclusions: The present study bears the limitations of a small series of pts and it's retrospective nature. However, it has the advantage of evaluation of UA levels, as an aGvHD mediator, at multiple time points during the peri-transplant period. Our results, though not of strong statistical significance, demonstrated that UA levels might affect aGvHD incidence as well as survival and the NRM rates post alloSCT. Definitely, well designed prospective clinical trials are warranted to clarify the role of UA on alloSCT outcome. Disclosures No relevant conflicts of interest to declare.

Gender difference in the effect of uric acid on striatal dopamine in early Parkinson's disease.

High uric acid (UA) levels have been shown to exert a neuroprotective effect in Parkinson's disease (PD) by inhibiting oxidative stress in the nigrostriatal pathway. However, the association between striatal dopamine activity and UA level has not been clarified. A total of 213 patients with early PD were enrolled. All patients underwent positron emission tomography using 18 F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane and a venous blood test for quantification of serum UA. All patients were stratified into either the lower UA group or the higher UA group using the median UA level. After normalizing the positron emission tomography images, differences in the regional standardized uptake value ratios (SUVRs) were analyzed with a volume-of-interest template. All tested SUVRs were also compared after categorizing patients by gender. The UA affected dopamine transporter SUVRs in different ways by gender. In female patients, the higher UA level group showed a smaller reduction in dopamine transporter uptake in the posterior putamen, whereas there was no such association observed in male patients. Higher UA levels were correlated with higher dopamine transporter uptake in the putamen in female patients with early PD. This finding suggests that UA has a neuroprotective effect, as demonstrated by the relatively preserved striatal dopamine activity in women.

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.

Associations between Uric Acid Level and 3-Month Functional Outcome in Acute Ischemic Stroke Patients Treated with/without Edaravone

Background: Uric acid (UA), an antioxidant with neuroprotective effects, favorably affects stroke outcome. However, the effect has not been examined in patients treated with edaravone, a frequently used free radical scavenger. We investigated whether the use of edaravone affected the relationship between UA levels and outcome in acute ischemic stroke. Methods: We retrospectively evaluated 1,114 consecutive ischemic stroke patients with premorbid modified Rankin Scale (mRS) scores <2 admitted within 24 h of onset (mean, 74 years; median UA levels, 333 μmol/L). We divided the patients into 2 groups using the median UA value as a cutoff, a low UA group (≤333 μmol/L; n = 566) and a high UA group (>333 μmol/L; n = 548), and compared their clinical characteristics and favorable outcomes (mRS <2) at 90 days. We investigated the associations between UA levels and 90-day stroke outcome in patients with and without edaravone treatment. Results: The high UA group had a higher proportion of men, hypertension, atrial fibrillation, and cardioembolic stroke than the low UA group. The high UA group also had a higher proportion of patients with mRS <2 at 90 days (61.5 vs. 54.1%, p = 0.013), but the significance was diminished in multivariate analysis (OR 1.30, 95% CI 0.94–1.71). In subgroup analysis, the high UA group without edaravone exhibited a higher proportion of patients with mRS <2 at 90 days than the low UA group (OR 2.87, 95% CI 1.20–7.16). The high UA group with edaravone did not exhibit this difference. Conclusions: In acute ischemic stroke, the favorable association between high UA levels and outcome at 90 days was not evident in patients treated with edaravone.

Thalassemia Major and Intermedia in Older Patients – a Single Center Experience

Introduction Survival of beta thalassemia major (TM) and intermedia (TI) patients have improved significantly over the past few decades as better treatment and follow up became available. However, complications are still common and affect patients’ quality of life, and systemic iron overload, particularly in the heart, liver, and endocrine organs, continues to be the main contributor to severe morbidity and early mortality in these patients. Traditionally, most thalassemia patients worldwide are treated in pediatric clinics by pediatricians. Consequently, in contrast to young patients, less data is available for complications and morbidity among adult TM & TI patients. We aimed to characterize disease and patients’ characteristics in patients >35 years of age.Methods We retrospectively reviewed medical charts of all consecutive patients above the age of 35 years with TI/TM who were treated in a tertiary thalassemia center. Liver iron load was defined as at least one of the following: elevation of liver enzymes, signs of steatosis by sonography, and evidence of iron accumulation by T2* MRI. We used descriptive statistics to describe characteristics of disease and patients and the Mann-Whiteny test to compare between patients with TI and patients with TM.Results Between the years 2006 and 2013, 62 adult patients with TM & TI >18 years old were followed and treated in our center. Of the 62 patients, 14 (TM, n=10 and TI, n=4) were above the age 35 years and were included in the study. The median age was 37 years (range, 35-50), 66% were male, 50% were of Arab ethnicity, 93% had at least high school education and 78% were employed, 93% were splenectomized. Twelve patients (85%) were regularly transfused every 3-4 weeks. The median pre-transfusion hemoglobin and mean corpuscular volume levels were lower in patients with TI compared to TM (8.1 vs. 10 g/dl, p=.002 and 72 vs. 84, p=.004, respectively). Median erythropoietin level in the transfused patients was 43.3 mlU/ml, indicating reduced RBC production. Median LDH and indirect bilirubin levels were higher in patients with TI compared to TM (603 vs. 330 u/L, p=.004 and 2.02 vs. 1.1 mg/dl, p=.06, respectively) indicating increased hemolysis. Median uric acid level was higher in patients with TI compared to TM (7.7 vs. 4.2 mg/dl, p=.0004), resulting in symptomatic gout in one TI patient. At the time of data collection, all TM and half of TI patients were treated with iron chelation therapy (ICT), deferasirox (n=6, 50%), deferiprone (n=2, 16%) and combination of deferioxamine (IV or SC) and deferiprone (n=4, 33%). Good compliance and adherence to ICT were reported in 75% of the patients.Complications associated with thalassemia are shown in the table. No statistically significant difference was observed in any complication, probably due to relatively small size of study cohort.Four TM patients (40%) had a history of heart failure. Nevertheless, with intensified ICT heart function was normalized in all cases, followed by normalization of T2* cardiac MRI. Four TM patients (40%) had hypothyroidism, two of them were treated with thyroid hormone. None of the patients had diabetes requiring hypoglycemic agents. All TM patients had hypogonadism. All females had amenorrhea and were treated with hormone replacement therapy, and none of them tried to conceive. All males, but one, were treated with monthly testosterone injections, 3 patients fathered children. All TM patients had osteoporosis, all treated with hormonal therapy (testosterone or hormone replacement therapy), in addition to calcium and vitamin D supplements. Three TI patients (75%) had metabolic bone disease; two had osteoporosis and one had osteopenia. All TI patients were treated with calcium and vitamin D supplements. None of the patients underwent allogeneic hematopoietic stem cell transplantation and none developed secondary malignancy.Conclusion we show a data set of adult thalassemia patients with prolonged survival, highlighting the long term co-morbidities of this unique population. Our data emphasizes the unmet needs for long term surveillance for identification of organ specific risk factors and early disease manifestations as well as the needs for global transition from pediatric to adult medicine, and from pediatric clinics to dedicated comprehensive adult thalassemia clinics. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Fixed, low-dose rasburicase for the treatment or prevention of hyperuricemia in adult oncology patients

Rasburicase is a recombinant urate oxidase enzyme administered to high risk patients or to those with preexisting hyperuricemia from tumor lysis syndrome (TLS). The objective of this retrospective review is to evaluate and characterize the use of fixed, low-dose rasburicase for the treatment of hyperuricemia in adult patients. A retrospective chart review from 1 October 2005 to 31 December 2011 was conducted in adult oncology patients who received fixed, low-dose rasburicase. Patients who met the inclusion criteria were evaluated for the uric acid level change from baseline and the achievement of uric acid level less than 8 mg/dL. Forty-five patients were included in the analysis in which 26 (58%) patients received 3 mg rasburicase. For the 39 patients with baseline uric acid levels 8 mg/dL or higher, 80% achieved a uric acid level lower than 8 mg/dL with a single rasburicase dose. Six patients (13%) required renal replacement therapy despite rasburicase. The median uric acid level reduction 24 h post rasburicase dose 1.5 mg, 3 mg, 4.5 mg, and 6 mg were 5.5, 5.8, 3.8, and 10.05 mg/dL, respectively. There was no clinical difference between obese and non-obese patients in terms of their median uric acid reduction, 5.5 vs. 7 mg/dL, respectively. Fixed, low dose rasburicase produced a consistent lowering of uric acid levels and may be utilized in the management of hyperuricemia in TLS. Further study is necessary to determine if a larger fixed dose would be required in those patients with a higher baseline uric acid level.

Outcomes Of Repeated Administration Of Rasburicase In Recurrent Cycles For Patients With Leukemia

IntroductionRasburicase, a recombinant urate oxidase, is effective at reducing plasma uric acid levels in patients who are at risk for tumor lysis syndrome. Since rasburicase is produced by a genetically modified Saccharomyces cerevisiae strain using the cDNA from an Aspergillus flavus strain, it may cause anti-rasburicase antibodies to develop. Anti-rasburicase antibodies pose a major safety and efficacy concern in that they can contribute to hypersensitivity reaction and/or the loss of uricolytic activity in patients who receive more than one cycle of rasburicase. We sought to evaluate the efficacy and rate of adverse reactions in those patients who received more than one cycle of rasburicase. MethodsPharmacy records were used to identify patients treated on the adult leukemia service who received more than one cycle of rasburicase therapy during the time period of January 2003 to May 2013. To be classified as a new cycle, a break in rasburicase therapy of at least 21 days needed to occur. Electronic medical records were used to document demographic, laboratory and clinical course information for the first 3 cycles of rasburicase administered. Uric acid levels as well as adverse events possibly attributable to rasburicase were collected for up to 3 days following the first dose of a cycle. Tumor lysis risk was determined using the method described by Cairo, et al (Cairo MS, et al on behalf of the TLS expert panel. Br J Haematol 2010; 149: 578-586.). ResultsTwo hundred and forty-two patients were identified that received at least 2 cycles of rasburicase therapy. Fifty-two of the patients received a third cycle of rasburicase therapy. Median patient age was 61 years for those patients receiving a second cycle and 56 years for those receiving a third cycle. The majority of the patients had AML (45%), ALL (20%) or CLL (16%). The second and third cycles of rasburicase were administered a median of 86.5 (range: 22-3736) and 52.5 (range: 21-690) days, respectively, from the previous cycle. The median uric acid level measured the day following the first dose of rasburicase therapy was below the laboratory normal range (2.6 – 7.1 mg/dL) on all cycles: 1.5 mg/dL on Cycle 1, 2.4 mg/dL on Cycle 2 and 2.15 mg/dL on Cycle 3. Seventeen patients (7%) experienced adverse events that could possibly be attributed to rasburicase therapy, including shortness of breath, chills, nausea, itching and rash. In 11 of the 17 patients, concomitantly administered agents, such as monoclonal antibodies, were more likely to be causative of the adverse events based on temporal or clinical findings. Only 1 patient (0.4%), who experienced shortness of breath and rash approximately 30 minutes following the rasburicase dose, had symptoms that would be consistent with a hypersensitivity reaction due to rasburicase. Despite the reaction, the patient's uric acid level following rasburicase decreased into the normal range. ConclusionsThis study indicates that, in our population of adult patients with leukemia, subsequent cycles of rasburicase therapy remain safe and effective. Rasburicase was able to lower baseline uric acid levels to below the normal range following the first dose. Additionally, only 1 patient experienced a hypersensitivity reaction that was clearly attributable to rasburicase administration. Prospective studies evaluating antibody production in those patients who develop hypersensitivity reactions, or fail to have a clinical response, to rasburicase therapy would help validate our observations. Disclosures:Off Label Use: Rasburicase is not approved for the administration of repeated courses of therapy. Ravandi:Sanofi: Research Funding. Cortes:Sanofi: Research Funding.

Oncology: Fixed-Dose Rasburicase 6 mg for Hyperuricemia and Tumor Lysis Syndrome in High-Risk Cancer Patients

Rasburicase is indicated for the initial management of plasma uric acid levels in adults receiving anticancer therapy who are at risk for acute tumor lysis syndrome (TLS) and subsequent hyperuricemia. The labeled dose is 0.2 mg/kg/day administered intravenously over 30 minutes for up to 5 days. Our institutional adult guidelines recommend rasburicase 6 mg for uric acid levels >8 mg/dL in most adults with TLS, or 4-8 mg/dL in high-risk patients. Repeat dosing is indicated for uric acid levels >4 mg/dL determined ≥12 hours following the initial dose. To determine the efficacy of a single dose of rasburicase 6 mg per institutional adult TLS guidelines to decrease uric acid levels to <4 mg/dL by day 3, as well as to determine the effect on serum creatinine and phosphorus concentrations. The secondary objectives were to evaluate the appropriateness of our institutional guidelines and identify TLS risk factors. The study was approved by the University of Maryland Medical Center Institutional Review Board. A retrospective review of all adults between July 2008 and February 2009 who received at least one 6-mg dose of rasburicase, with redosing, if indicated, before day 3, was conducted. Subsequent TLS monitoring over 7 days after initial dosing was recorded. Patients were excluded if dosing did not adhere to institutional guidelines. We observed a decline in median uric acid levels from 9.2 mg/dL (interquartile range 8.1-10.4) on day 1 to between 1.8 (1.0-3.8) on day 3 and 3.8 mg/dL (2.1-4.4) on day 7 (p < 0.0001) with 2 patients requiring repeat dosing before day 3 (n = 34). The majority of the population was hyperuricemic (>8 mg/dL; 76%) or at high risk for TLS (85%). A 6-mg dose of rasburicase effectively decreased uric acid to <4 mg/dL by day 3, rarely requiring repeat dosing, in a high-risk population.

Rasburicase Effectively Lowers Serum Uric Acid Levels in High Risk, Poor Performance Status Patients with Hematologic Malignancies

Tumor lysis remains a significant cause of morbidity and mortality in patients with highly proliferative hematologic malignancies. Traditionally, intravenous hydration and oral allopurinol have been the mainstays of therapy. However in some patients, hyperuricemia and renal failure still occur. The resultant renal failure precludes the administration of full doses of chemotherapy and results in a poor treatment outcome. Recently we participated in a large phase III randomized trial comparing rasburicase with standard allopurinol therapy. Rasburicase is a recombinant urate oxidase that effectively reduces serum uric acid due to conversion of uric acid into allantoin, a readily excretable and soluble substance. The results of that study are reported in a separate abstract. However while the study was open, we treated 12 extremely high risk, newly diagnosed hematologic malignancy patients who were ineligible for the study with commercially available rasburicase off study. The reasons for study ineligibility were ECOG Performance Status 4 and/or expected survival of less than one month. Other baseline characteristics: Diagnosis: Burkitts ALL: 3, AML: 7, CML-BP: 1, T-ALL: 1; Age: 64 (27–85), Sex: 6M/6F; WBC: 58,000/mm3 (1.6- 245,000); LDH: 2201 U/l (1068- >2500); # of preexisting comorbid medical conditions: 4 (0–7); chemotherapy: hyper-CVAD: 4, standard ara-c based rx: 5, high dose ara-C based rx: 3. Nine patients received one dose of rasburicase (0.2 mg/kg IV), 3 patients required a second dose. The median uric acid levels were: pretreatment : 9.2 mg/dl (2.8–28.6), at 24 hours: <0.2 (0.2–7.5) and at 48 hours: <0.2 (<0.2–4.9). All patients achieved normal serum uric acid level by day 2. The median baseline creatinine was 2.6 mg/dl (0.7 – 5.6); by day seven 10 patients had a serum creatinine less than 2 mg/dl (day 7 median creatinine 0.9, range 0.4–5.5). Four patients achieved CR to chemotherapy, 5 had refractory disease and 3 had induction death. Administration of rasburicase in this extremely high risk group of patients resulted in a rapid decrease in serum uric acid levels. In many patients this allowed for preservation of or improvement in renal function and administration of chemotherapy. Although some patients had a poor outcome due to the aggressive nature of their underlying disease, 4 of 12 patients (33%) attained CR and were able to receive subsequent cycles of intensive chemotherapy without incident.

Serum urate is associated with baseline renal dysfunction but not survival or deterioration in renal function in malignant phase hypertension.

There has been speculation whether serum uric acid levels are an independent prognostic factor in patients with hypertension. To investigate the clinical associations and prognostic value of serum urate in patients with malignant phase hypertension (MHT), by comparing clinical features in patients with serum urate levels above and below the median levels for this population, and secondly, by performing a survival analysis in these patients. Review of the data on 153 patients (98 males; mean age 50.3 years, SD 13.5) with MHT on the west Birmingham MHT register. Median uric acid levels in this population was 0.41 mmol/l (6.9 mg/dl), with an interquartile range of 0.34-0.50 mmol/l (5.7-8.4 mg/dl). Clinical characteristics of patients with a serum urate <0.41mmol/1 (group 1) were compared to those with levels above the median (0.41 mmol/l, group 2). Mean duration of follow-up was similar in both groups. The mean diastolic blood pressure at presentation and both mean systolic and diastolic blood pressures at follow-up were significantly higher in group 2 (that is, those with high serum urate levels) (unpaired t test, P= 0.039). There was also more renal dysfunction in group 2 patients with MHT, with higher mean serum urea and creatinine levels, both at presentation and at follow-up (unpaired t test, P< 0.01). The commonest causes of death were myocardial infarction (n = 7), heart failure (n = 4), stroke (n = 10) and renal failure (n = 5). There was no difference in mean survival duration between groups 1 and 2 (Kaplan-Meier, 64.6 versus 66.8 months; log-rank test, P= 0.519). Serum urate levels also did not predict the rise in serum creatinine levels (log-rank test, P= 0.84) or urea (P= 0.4033) amongst these patients. Using a multivariate Cox proportional hazards analysis, the only independent predictors of outcomes (death or the need for dialysis) were age (P = 0.007) and serum creatinine levels at presentation (P = 0.0046). Our analysis of a large series of patients with MHT shows that those with high urate levels had higher diastolic blood pressures and greater renal impairment at baseline. At follow-up, patients with median serum urate >0.41 mmol/l showed a greater deterioration in renal function and higher blood pressures, but no significant difference in survival. Serum urate levels also do not appear to be predictive of the deterioration in renal function or overall survival in patients with MHT.