Mean Serum Uric Acid Concentration Research Articles

Serum uric acid levels and their correlation with clinical and cerebrospinal fluid parameters in patients with neuromyelitis optica

Although uric acid (UA) concentration has been considered a surrogate marker for monitoring the progression of multiple sclerosis (MS), less is known about the relationship between UA and the progression of neuromyelitis optica (NMO). We therefore investigated the correlations between serum UA concentrations and the clinical and cerebrospinal fluid (CSF) parameters in patients with NMO. Factors assessed in patients with NMO included gender, disease duration, disease disability, CSF white blood cell (WBC) counts, oligoclonal bands (OB), 24hour immunoglobulin (Ig)G index, and myelin basic protein (MBP) concentration. Mean serum UA concentrations were compared in patients with NMO and in a control group of patients with cerebral infarction (CI). We found that mean serum UA concentrations were significantly lower in patients with NMO compared to those with CI (206.81 compared to 274.00μmol/L, p=0.00). Serum UA concentration was correlated directly with NMO duration (p=0.013) and was inversely correlated with the Expanded Disability Status Scale score (p=0.021). Patients with NMO with lower serum UA concentrations tended to be positive for OB, to have higher CSF protein and MBP concentrations, and to have higher WBC counts and 24hour IgG index, but no correlation was statistically significant. UA may be a useful surrogate marker for monitoring NMO activity.

Urate Oxidase (Rasburicase) to Inhibit Graft Versus Host Disease (GVHD) After Myeloablative HLA-Matched Allogeneic Hematopoietic Cell Transplantation (HCT).

Abstract 3063 Background:Dying mammalian cells release danger signals that stimulate antigen presenting cells (APCs) to promote an immune response. It has been demonstrated that uric acid released from injured cells alerts the immune system to cell death, acts as a danger signal to stimulate cytotoxic T cell responses and that elimination of uric acid in mouse models reduces this immune response (Ref: Nature 2003; 425:516–521). Rasburicase is a recombinant urate-oxidase enzyme that catalyzes oxidation of uric acid into an inactive soluble metabolite and is currently used to prevent tumor lysis syndrome. We hypothesized that rasburicase administered during myeloablative conditioning prior to allogeneic HCT will reduce the serum levels of uric acid and thereby may decrease the incidence of acute GVHD via inhibition of danger signal-mediated activation of host APCs. Methods:In this pilot trial at the Massachusetts General Hospital, between 2007 and 2010, 23 patients (median age: 41 years, range: 19–59) with hematologic malignancies in complete remission (AML, n=13; ALL, n=8; MDS, n=1; MPD, n=1;) received myeloablative preparative regimens (Bu/Cy, n=14; Cy/TBI, n=7; Bu/Flu, n=2) followed by GCSF-mobilized HLA-matched (MRD, n=18; MUD, n=5) peripheral blood HCT. GVHD prophylaxis consisted of cyclosporine or tacrolimus and methotrexate for MRD transplants and tacrolimus/MTX and anti-thymocyte globulin (Thymoglobulin) for MUD transplants. Rasburicase was administered beginning on the first day of conditioning therapy, at a dose of 0.20 mg/kg intravenously daily for 5 consecutive days. Outcomes were compared to 44 controls at this institution from the same time period identified using retrospective chart review. Patients in the control group received allopurinol during the conditioning as a part of the institutional guidelines. Associations between categorical variables were evaluated using Fisher’s exact test. Overall and disease-free survival (OS and DFS) were estimated using the method of Kaplan and Meier. Results:The mean serum uric acid concentration was 0.2 mg/dl (range, 0–1.7) on 6 consecutive days, beginning the day after the first dose of rasburicase. Engraftment was achieved in all patients, and the median times to neutrophil (at least 0.5 × 109/ul) and platelet engraftment (at least 20 × 109/ul) were 18 days (range, 7–26 × 109/ul) and 16 days (range, 8–57 × 109/ul), respectively. The only serious toxicity caused by rasburicase was intravascular hemolysis in one patient who was found to have G6PD deficiency; this patient received only 2 doses of rasburicase. Greater than or equal to grade II-IV acute GVHD occurred in 5 out of 23 patients (22%), 4/18 in MRD and 1/5 in MUD recipients: grade II, n=1; grade III, n=2; and grade IV, n=2. When compared with 44 patients (AML 28, ALL 5, MDS 4, NHL 5, MPD 1, CML 1), comparable to rasburicase-treated patients with respect to age, gender, disease status, donor sources, conditioning and GVHD prophylaxis, who received myeloablative HCT (MRD, n=32; MUD, n=12) at the MGH during the same time period as the patients in the rasburicase-treated group, there was significantly less grade II or higher aGVHD in the rasburicase group (rasburicase: 22% vs. institutional control: 48% [total 21/44, 13/32 in MRD and 8/12 MUD recipients], Fisher’s exact test, p=0.033). There was no significant difference in the incidence and severity of chronic GVHD between the two groups (rasburicase, 61%, control 48%; Fisher’s exact test, p=0.721). At 3 years, there was no significant difference in disease-free survival (DFS) or overall survival (OS) between the rasburicase-treated and control groups (DFS: rasburicase vs. control 51.2% vs. 40.4%, p=0.97; OS: rasburicase vs. control 55.3% vs. 44.9%, p=0.88). Conclusion:Rasburicase can be safely administered during myeloablative conditioning, results in a profound lowering of serum uric acid levels and has the potential to reduce the incidence of acute GVHD. Based on these data a prospective randomized phase II trial is planned in order to verify whether rasburicase inhibits acute GVHD after myeloablative HCT and to study the possible mechanisms of protection from GVHD. Disclosures:Off Label Use: Rasburicase for GVHD prevention in allo-HSCT.

Hyperuricemia beyond 1 year after kidney transplantation in pediatric patients: Prevalence and risk factors

Hyperuricemia is frequent among adult renal transplant recipients; however, data among pediatric kidney recipients are scarce. This study is designed to estimate the prevalence and risk factors of late post-transplant hyperuricemia in pediatric recipients. A retrospective observational multicenter study on 179 pediatric renal recipients (5–18 years) was conducted between April 2008 and January 2011 from five kidney transplant centers of Tehran, Iran. All recipients were followed up for more than 1 year (5.9 ±3.3 years) after transplantation. A total of 17686 blood samples were obtained for serum uric acid (SUA). The normal range of SUA was defined as SUA 1.86–5.93 mg/dl for children between 2 and 15 years in both genders; 2.40–5.70 mg/dl for girls aged >15 years; 3.40–7.0 mg/dl for boys aged >15 and more than 6 and 7 mg/dl in boys and girls older than 15 years old. The median age of the children was 13 years. Male recipients were more popular than female (male/female 59/41%). Hyperuricemia was detected in 50.2% of patients. Mean SUA concentration was 5.9±1.7 mg/dl and mean SUA concentration in hyperuricemic patients was 7.7±1.2 mg/dl. While at multivariate logistic regression elevated serum creatinine concentration (P<0.001) and the time span after renal transplantation (P=0.02) had impact on late post-transplant hyperuricemia. High cyclosporine level (C0 and C2) was not risk factor for huperuricemia. Late post-transplant hyperuricemia was found in about half of pediatric renal recipients, and was associated with impaired renal allograft function.

Lack of association between dietary fructose and hyperuricemia risk in adults

BackgroundHigh serum uric acid concentration (hyperuricemia) has been studied for its relationship with multiple adverse health outcomes, such as metabolic syndrome. Intervention studies have produced inconsistent outcomes for the relationship between fructose intake and serum uric acid concentration.MethodsThe association of dietary fructose intake with hyperuricemia risk in adults was examined using logistic regression and U.S. NHANES 1999-2004 databases. A total of 9,384 subjects, between the ages 20 and 80 years, without diabetes, cancer, or heart disease, were included.ResultsThe highest added or total fructose intake (quartiles by grams or % energy) was not associated with an increase of hyperuricemia risk compared to the lowest intake with or without adjustment (odds ratios = 0.515-0.992). The associations of alcohol and fiber intakes with the risk were also determined. Compared to the lowest intake, the highest alcohol intake was associated with increased mean serum uric acid concentration (up to 16%, P < 0.001) and hyperuricemia risk (odds ratios = 1.658-1.829, P = 0.057- < 0.001); the highest fiber intake was correlated with decreases of uric acid concentration (up to 7.5%, P < 0.002) and lower risk (odds ratios = 0.448-0.478, P = 0.001- < 0.001). Adults who were over 50 y old, male, or obese had significantly greater risk.ConclusionsThe data show that increased dietary fructose intake was not associated with increased hyperuricemia risk; while increased dietary alcohol intake was significantly associated with increased hyperuricemia risk; and increased fiber intake was significantly associated with decreased hyperuricemia risk. These data further suggest a potential effect of fructose consumption in an ordinary diet on serum uric acid differs from results found in some short-term studies using atypical exposure and/or levels of fructose administration.

Changes and Implications of Serum Uric Acid Levels After Living-Donor Nephrectomy

Purpose: The aim of this study was to investigate the changes in and implications of preoperative and postoperative serum uric acid levels in patients with living donor nephrectomy. Materials and Methods: We studied 207 patients between 1998 and 2007 at our hospital undergoing living-donor nephrectomy for kidney transplantation. The serum uric acid level and estimated glomerular filtration rate (eGFR) were measured preoperatively and at 1 year postoperatively. We also analyzed multiple independent variables such as age, sex, blood pressure, body mass index (BMI), serum total cholesterol, hemoglobin, hematocrit, total protein, albumin, calcium, and phosphorus. Results: The mean age of the study patients was 38.3±10.8 years. The mean serum uric acid concentration at 1 year after kidney donation was higher than preoperatively (5.05±1.39 mg/dl preoperatively vs. 5.85±1.14 mg/dl postoperatively) and was significantly greater in patients with hyperuricemia (uric acid≥6.8 mg/dl) than in patients without hyperuricemia (uric acid<6.8 mg/dl): 1.63±0.75 mg/dl vs. 0.69±0.66 mg/dl, respectively. The multivariate analysis showed that preoperative serum uric acid was the primary predictive factor of postoperative serum uric acid (r=1.136, p=0.001), and preoperative GFR was an independent secondary predictive factor (r=−0.004, p=0.047). The receiver operator characteristics (ROC) curves for the preoperative serum uric acid cutoff of 5.7 mg/dl showed the highest sensitivity and specificity of 96% and 86%, respectively. Conclusions: These results suggest that preoperative serum uric acid and GFR were important predictive factors of postoperative serum uric acid after living-donor nephrectomy. Therefore, in the selection and management of kidney donors, not only patients with a low GFR but also those with high uric acid (serum uric acid≥5.7 mg/dl) require careful observation before and after living-donor nephrectomy. (Korean J Urol 2009; 50:1144-1150) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

Formation of 8-nitroguanine in blood of patients with inflammatory gouty arthritis

Background NOx causes DNA damage due to an inflammatory effect of gouty arthritis. We investigated the concentration of 8-nitroguanine (8-NO 2-G) in the blood of patients with arthritis. Methods Subjects were divided into 3 groups: (1) high inflammatory (HI) group ( n = 21) with hyperuricemia (mean, 8.9 mg/dl) and leukocytosis, (2) low inflammatory (LI) group ( n = 14) with mild hyperuricemia (mean, 7.6 mg/dl) but normal leukocyte count, (3) non-inflammatory (NI) healthy control ( n = 19) with mean serum uric acid concentration 5.3 mg/dl and normal leukocyte count. Serum C-reactive protein (CRP) concentrations were measured by a visual agglutination method. The blood concentrations of 8-NO 2-G were determined by high performance liquid chromatography-electrochemical detection and were compared between groups. Results There was significant difference in percentage of positive CRP (NI: 55.6%, LI: 64.3%, HI: 100%, p = 0.003) between the 3 groups. The leukocyte count (mean ± S.E., NI: 7400 ± 528, LI: 7686 ± 433, HI: 10952 ± 691/mm 3, p < 0.001), uric acid (NI: 5.3 ± 0.24, LI: 7.6 ± 0.4, HI: 8.9 ± 0.36 mg/dl, p < 0.001), NO 2 (NI: 6.5 ± 1.2, LI: 11.1 ± 2.9, HI: 35.6 ± 5.1 μg/ml, p < 0.001) and the 8-NO 2-G (NI: 0.08 ± 0.03; LI: 0.34 ± 0.13; HI: 0.59 ± 0.09 ng/μg DNA, p = 0.002) were significantly increased by inflammation. Conclusion Gouty inflammation induces DNA damage by increasing 8-NO 2-G through endogenous NO and ROS formation.

Pharmacokinetics and Pharmacodynamics of Febuxostat, a New Non-purine Selective Inhibitor of Xanthine Oxidase in Subjects with Renal Impairment

To assess the safety, pharmacokinetics, and pharmacodynamics of febuxostat in subjects with normal renal function or renal impairment, febuxostat (80 mg/d) was orally administered for 7 days to subjects with normal renal function (n = 11, CLcr >80 mL/min/1.73 m) or to subjects with mild (n = 6, CLcr 50-80 mL/min/1.73 m), moderate (n = 7, CLcr 30-49 mL/min/1.73 m), or severe renal impairment (n = 7, CLcr 10-29 mL/min/1.73 m). The pharmacokinetics of febuxostat and its active quantifiable metabolites 67M-1, 67M-2, and 67M-4 as well as the pharmacodynamics of uric acid, xanthine, and hypoxanthine were determined in plasma (or serum) and urine. Febuxostat was safe and well tolerated. Regression analyses indicated that febuxostat tmax and Cmax,u values were not affected by CLcr. However, for AUC24,u, CLu/F, and t1/2z, regression analyses indicated a statistically significant relationship with CLcr. With the exception of 67M-1 Cmax, regression analyses for 67M-2 and 67M-4 Cmax, and for AUC24 for all 3 metabolites indicated a statistically significant linear relationship with CLcr. Irrespective of renal function group, the mean serum uric acid concentrations decreased by 55% to 64% by day 7. Although plasma exposure to febuxostat and its metabolites was generally higher in subjects with increasing degrees of renal impairment, the percentages of decrease in serum uric acid were comparable regardless of the renal function group. A once-daily 80-mg dose of febuxostat appears to be safe and well tolerated in different renal function groups and does not appear to require any dose adjustment based on differences in renal function.

Diastolic dysfunction and increased serum homocysteine concentrations may contribute to increased cardiovascular risk in patients with polycystic ovary syndrome

Objective: To assess cardiac flow parameters in patients with polycystic ovary syndrome (PCOS). Design: A prospective case-control study. Setting: University-based hospital. Patient(s): Thirty consecutive patients with PCOS were enrolled. Thirty women with regular menstrual cycles served as the controls. Intervention(s): Systolic and diastolic function parameters were assessed by standard two-dimensional and M-mode echocardiography. Insulin sensitivity was evaluated by a standard 75-g oral glucose tolerance test and area-under-curve insulin analysis. Serum hormones, lipid profile, homocysteine, vitamin B 12, folate, fibrinogen, uric acid, and plasminogen activator inhibitor-I concentrations were measured. Main Outcome Measure(s): Systolic and diastolic function parameters, insulin sensitivity and serum homocysteine levels. Result(s): The mean serum homocysteine and uric acid concentrations were significantly higher in the PCOS group. Patients with PCOS had significant hyperinsulinemia. All systolic function parameters were comparable between the two groups. However, patients with PCOS had significantly lower peak mitral flow velocity in early diastole and significantly lower ratio between the early and late peak mitral flow velocities and also had significantly longer isovolumic relaxation time, reflecting a trend for nonrestrictive-type diastolic dysfunction. The area-under-curve insulin correlated positively with peak mitral flow velocity in late diastole ( r = 0.375). The mean cholesterol/high-density lipoprotein ratio correlated negatively with mean mitral flow velocity in early diastole (E) peak ( r = −0.474). The mean fasting insulin level correlated negatively with mean E/A ratio ( r = −0.387). Conclusion(s): Diastolic dysfunction and increased serum homocysteine concentrations may contribute to increased cardiovascular disease risk in patients with PCOS.

Uric acid levels in sera from patients with multiple sclerosis

The levels of uric acid (UA), a natural peroxynitrite scavenger, were measured in sera from 240 patients with multiple sclerosis (MS) and 104 sex- and age-matched control patients with other neurological diseases (OND). The mean serum UA concentration was lower in the MS than in the OND group, but the difference did not reach the level of statistical significance (P = 0.068). However, the mean serum UA level from patients with active MS (202.6 + 67.1 mumol/l) was significantly lower than that in inactive MS patients (226.5 + 78.6 mumol/l; P = 0.046) and OND controls (P = 0.007). We found a significant inverse correlation of serum UA concentration with female gender (P = 0.0001), disease activity (P = 0.012) and duration (P = 0.017), and a trend towards an inverse correlation with disability as assessed by EDSS score, which did not reach statistical significance (P = 0.067). Finally, multivariate linear regression analyses showed that UA concentration was independently correlated with gender (P = 0.0001), disease activity (P = 0.014) and duration of the disease (P = 0.043) in MS patients. These findings suggest that serum UA might serve as a possible marker of disease activity in MS. They also provide support to the potential beneficial therapeutic effect of radical-scavenging substances in MS.

Clinical manifestations of Korean female gouty patients.

In an endeavor to analyse the clinical characteristics of female gout, we reviewed 36 women with gout. Twenty-seven (75%) developed the first symptomatic episode of gout after the onset of the menopause. The mean age at onset of gout was 54.3 years (range 15-87 years). Twenty-two patients (61%) had hypertension, 17 (47%) had renal insufficiency, 13 (36%) used diuretics and 10 (28%) were taking cyclosporine for a renal allograft. Tophaceous gout occurred in 10 patients (27%) and polyarticular involvement was seen in 16 (44%) at initial presentation. Five of nine premenopausal patients were taking cyclosporine and four had renal insufficiency. A comparison with a control group of 72 randomly selected male patients with gout showed that the female patients were frequently receiving diuretics at the time of the attack and had significantly lower mean uric acid excretion, whereas significantly more male patients showed heavy alcohol consumption and precipitating events for an acute attack compared with the female patients. There were no significant differences between the sexes for onset age, hypertension, renal insufficiency, distribution of joint involvement, tophi and mean serum uric acid concentration. The female patients in this study had a lower mean age at onset of gout than in previous studies, which was attributed to the inclusion of renal transplantation patients. Transplantation gout patients receiving cyclosporine lower the mean age at onset of female gout and this is an emerging problem in female gout.

Relationship between hyperuricemia and other cardiovascular disease risk factors among adult males in Taiwan.

Hyperuricemia is associated with cardiovascular disease risk factors such as obesity, impaired glucose tolerance, hypertension, and hyperlipidemia. However, this relationship between serum uric acid (SUA) concentrations and cardiovascular disease (CVD) is a controversial one, especially among males. The purpose of this study is to evaluate the association between SUA concentrations and other CVD risk factors among adult males in Taiwan. After multi-stage sampling procedures, we randomly selected 1743 Taiwanese males with a mean age of 35 years (from 22 to 54) in this study. Anthropometric, blood pressure and biochemical variables, including serum uric acid, glucose, total cholesterol and triglyceride concentrations, were measured. Among the study population, the mean SUA concentration was 6.5 +/-1.5 mg/dl. There were 290 (16.6%) subjects with SUA concentrations > or = 8.0 mg/dl (defined as hyperuricemia). Compared to normouricemic subjects, hyperuricemic subjects had significantly greater age-adjusted body weight (75.3 vs. 69.2 kg, p < 0.001), body mass index (BMI, 25.5 vs. 23.6 kg/m2, p < 0.001), higher blood pressure (BP, 120.2 vs. 115.2 mmHg for systolic BP and 78.5 vs. 75.3 mmHg for diastolic BP, both p < 0.001) and blood lipid concentrations (193.8 vs. 182.1 mg/dl for total cholesterol and 123.7 vs. 94.4 mg/dl for triglycerides, both p < 0.001). SUA concentration was positively correlated with body weight, BMI, BP and serum lipid concentrations (all p < 0.001). In multivariate regression analyses, after adjusting for potential confounders, SUA concentration was significantly positively associated with diastolic BP, serum total cholesterol and triglyceride concentrations. An increase of 1 mg/dl of SUA was associated with a 2.1 mg/dl elevation in serum total cholesterol (p < 0.001) and a 5.4 mg/dl increase in triglyceride (p < 0.001). From this study, we found that hyperuricemia in subjects is associated with being overweight, and having high blood pressure and hyperlipidemia. There is a significantly positive association between SUA concentration and other CVD risk factors among adult males in Taiwan.

Inverse association between coffee drinking and serum uric acid concentrations in middle-aged Japanese males

Consumption of caffeine-rich beverages, which have diuretic properties, may decrease serum uric acid concentrations. We examined cross-sectionally the relationship of coffee and green tea consumption to serum uric acid concentrations in 2240 male self-defence officials who received a pre-retirement health examination at four hospitals of the Self-Defence Forces between 1993 and 1994. The mean levels of coffee and green tea consumption were 2.3 and 3.1 cups/d respectively. There was a clear inverse relationship between coffee consumption and serum uric acid concentration. When adjusted for hospital only, those consuming less than one cup of coffee daily had a mean serum uric acid concentration of 60 mg/l, while that of those drinking five or more cups of coffee daily was 56 mg/l (P < 0.0001). No such relationship was observed for green tea, another major dietary source of caffeine in Japan. The relationship between coffee consumption and serum uric acid concentration was independent of age, rank in the Self-Defence Forces, BMI, systolic blood pressure, serum creatinine, serum total cholesterol and serum HDL-cholesterol concentrations, smoking status, alcohol use, beer consumption and intake of dairy products. These findings suggest that coffee drinking may be associated with lower concentrations of serum uric acid, and further studies are needed to confirm the association.

Maternal serum uric acid levels in twin gestations

To establish normative values of serum uric acid levels in women with twin gestations and to compare maternal serum uric acid levels of twins and singletons, stratified by the presence or absence of preeclampsia. Sixty-seven normotensive and 16 preeclamptic women with twin gestations, who had no underlying chronic hypertension or renal insufficiency, had serum uric acid levels measured on admission to the labor and delivery unit. These levels were compared with those of 83 normotensive and 10 preeclamptic singleton gravidas admitted to the same unit. A receiver operating characteristic (ROC) curve was used to determine the optimal maternal serum uric acid cutoff value for twin gestations and to compare this value with that of singleton gestations. Women with non-preeclamptic twin pregnancies had significantly higher mean (+/- standard deviation) serum uric acid concentration than women with non-preeclamptic singleton pregnancies (5.4 +/- 1.6 versus 4.7 +/- 1.2 mg/dL, respectively, P = .001). Gravidas with twin gestations complicated by preeclampsia had significantly higher serum uric acid levels than their preeclamptic singleton counterparts (7.7 +/- 1.3 versus 5.9 +/- 1.1 mg/dL, respectively, P = .001). Using a ROC curve, we determined that a maternal serum uric acid level of 6.5 mg/dL appeared to be the optimal cutoff for identifying preeclampsia in twin gestations, with a sensitivity of 94% and specificity of 78%. With or without preeclampsia, women carrying twins have significantly higher serum uric acid levels than their singleton counterparts, which suggests a need for separate normative values for twin gestations. We propose that a serum uric acid level of 6.5 mg/dL or greater be used to identify those women with twin gestations who are at higher risk for preeclampsia.

Changes in insulin and lipid metabolism in males with asymptomatic hyperuricaemia.

To define the effect of asymptomatic hyperuricaemia on various facets of glucose, insulin, and lipoprotein metabolism. Case control study in health volunteers. The volunteers for this study were selected on the basis of their laboratory results from a larger population participating in a general survey in one large factory. The study population consisted of 40 healthy males: 20 with asymptomatic hyperuricaemia (serum uric acid concentration equal to or greater than 420 mmol l-1) and 20 with normal serum uric acid concentrations (180-320 mmol l-1). The two groups were similar in terms of age, general obesity (estimated by body mass index), smoking and alcohol intake, and estimate of work and leisure time activity. All subjects received a 75 g oral glucose challenge, with blood taken before and at frequent intervals thereafter. Fasting plasma glucose, insulin, and lipid concentrations and plasma glucose and insulin responses to the oral glucose challenge. By selection, mean (+/- SEM) serum uric acid concentration was higher in the hyperuricaemic individuals (454 +/- 7 vs. 274 +/- 12 mmol l-1). In addition, the plasma insulin response to oral glucose was increased in individuals with asymptomatic hyperuricaemia (P < 0.005) as were both systolic (136 +/- 3 vs. 126 +/- 3 mmHg, P < 0.05) and diastolic (91 +/- 1 vs. 82 +/- 1, P < 0.01) blood pressure. Furthermore, subjects with asymptomatic hyperuricaemia were dyslipidaemic (higher plasma TG and cholesterol and lower HDL-cholesterol concentrations) as compared to the normouricaemic control group (P < 0.07-0.005). These results provide a possible explanation for the well-known association of hyperuricaemia with coronary heart disease, as well as suggesting that hyperuricaemia be added to the cluster of metabolic and haemodynamic abnormalities associated with insulin resistance and/or hyperinsulinaemia and designated as Syndrome X.

Hyperuricemia, Gout, and Autosomal Dominant Polycystic Kidney Disease

The relationship between hyperuricemia, gout, and autosomal dominant polycystic kidney disease (ADPKD) is not widely recognized. In an attempt to further clarify this relationship, the authors have studied 17 patients with ADPKD, 9 controls, 9 patients with proven gout and chronic renal failure, 11 patients with gout and normal renal function, and 11 patients with chronic renal failure. The mean serum uric acid concentration was higher in patients with ADPKD as a group than in controls (8.0 +/- 1.7 mg/dl vs. 6.4 +/- 1.6 mg/dl, p less than .02). Clinical gout was identified in 24% of patients with ADPKD; none of the patients with chronic renal failure of other etiologies had gout. Fractional excretion of uric acid and the activity of the enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT) were not different among the groups studied. From this study the authors conclude that ADPKD should be included among those diseases associated with hyperuricemia and gout. A partial deficiency in HGPRT or abnormal renal handling of uric acid do not appear to be responsible for the increased incidence of gout in patients with ADPKD.

Diuretics and hyperuricemia in the elderly.

Serum uric acid (SUA) was studied in a rural population of 420 males and 592 females aged 65 years or more. The mean SUA concentration was 0.313 mmol/l in males and 0.316 mmol/l in females. In males, 47 (11.2%) and in females 60 (10.1%) had a SUA level of 0.42 mmol/l or more. Both the mean serum values and the frequency of hyperuricemia were higher than 11 years earlier in another, similar study. The SUA concentration was 0.361 mmol/l in the 435 individuals using diuretics and 0.281 mmol/l in the remaining 578. Of the 107 hyperuricemic individuals, 82% used diuretics, and only 2 out of those 20 where the SUA level was 0.50 mmol/l or more did not use diuretics. Apart from diuretics, only the serum creatinine concentration, the Body Mass Index, body weight and the hematocrit level were significantly associated with hyperuricemia in both sexes.

Migration and gout: the Tokelau Island migrant study.

The prevalence and 14 year incidence of clinical gout and its precursors were investigated in the Polynesian population of Tokelauans living in the Pacific basin, non-migrant Tokelauans living in their isolated atoll homeland being compared with migrant Tokelauans living in urban New Zealand. The age standardised prevalence of gout in Tokelauan men in New Zealand was higher than that in non-migrant Tokelauan men, being 21.0 and 19.5/1000 subjects at the beginning of the study and 51.0 and 14.6/1000 at the end of study, respectively. Migrant men in New Zealand aged under 55 had higher mean serum uric acid concentrations than non-migrant men of the same age. The prevalence of gout was low in women in both environments. The age standardised relative risk of developing gout between 1968 and 1982 was 9.0 times higher in the migrant men than in the non-migrant men. Age, serum uric acid concentration, serum cholesterol concentration, and self reported alcohol consumption at entry to the study were the best set of predictors of gout in men. Preventive strategies to change body mass, diet, and patterns of alcohol use need to be developed in this population.

Hypouricemia in cirrhosis reflects hemodynamic alterations

In a population of 27 consecutive patients with liver cirrhosis, systemic hemodynamics were investigated and correlated to uric acid concentrations, fractional uric acid excretion, and creatinine clearances. Mean serum uric acid concentration was lower than in normal controls, and this was related to abnormally high uric acid clearances. Uric acid concentrations correlated positively to total peripheral resistances and negatively to cardiac output. Fractional uric acid excretions correlated negatively to total peripheral resistances and positively to cardiac output. There was no correlation between creatinine clearances and any variable of systemic hemodynamics. Serum uric acid concentration and fractional uric acid excretion are dependent of the hemodynamic state in cirrhosis.

Die Aussagekraft einer einmaligen Bestimmung der Harnsäurekonzentration im Serum zur Früherfassung der hypertensiven Schwangerschaftskomplikationen* **

In 200 healthy, normotensive nulliparous women, a single determination of serum uric acid concentration was done between weeks 28-32 of gestation in order to identify a possible increased risk of developing hypertensive complications. If serum concentrations higher than 3.6 mg/dl were considered as increased ("positive test"), women who developed toxaemia of late pregnancy (proteinuric hypertension), had a significantly elevated mean serum uric acid concentration already at the beginning of the third trimester (p less than 0.01). The incidence of toxaemia and hypertensive disease without proteinuria was significantly higher in the group of women with an elevated uric acid value (p less than 0.001). Only 9% of pregnant women with a "negative test" ultimately developed a mild form of a hypertensive complication. Conversely, 74% of the patients with a "positive test" remained normotensive. Thus, the predictive value of a "positive test" is low (26%) and that of a "negative test" relatively high (91%).

Renal hypouricaemia in insulin treated diabetes mellitus

Uric acid metabolism was investigated in 69 insulin-treated male diabetic outpatients and in 23 healthy male subjects, because of a reported coincidence between diabetes and gout. All subjects had normal serum creatinine concentrations and none received diuretic treatments. Compared with normal, the diabetics had significantly lower mean serum uric acid concentrations (0.34 ± 0.08 (SD) mmol/l versus 0.23 ± 0.06 mmol/1, p < 0.001). 17% of the diabetic patients had serum concentrations below the normal mean—2 SD. In contrast, the diabetic patients had a 42% increase in renal uric acid excretion rate ( p <0.01), and an 83% increase in the ratio of uric acid clearance/creatinine clearance ( p < 0.001). These indices of renal uric acid excretion were both positively correlated to fasting blood glucose levels ( r = 0.57, p < 0.001, and r = 0.50, p < 0.001, respectively), to the degree of glycosuria ( r = 0.73, p < 0.001, and r = 0.63, p < 0.001, respectively), and to the magnitude of water diuresis ( r = 0.60, p < 0.001, and r = 0.39, p < 0.01, respectively). The hypouricaemia observed in these insulin-dependent diabetic male subjects may probably be caused by the increased renal excretion of uric acid in the presence of hyperglycaemia. The study gave no evidence of increased serum uric acid concentrations in insulin-dependent diabetics. It is therefore likely that any coincidence between gout and diabetes derives from other coexisting serum uric acid raising factors.