Urine multi-index intelligent detection based on polymer/paper hybrid microfluidic biochip for hyperuricemia monitoring.

Hyperuricemia (HUA) has gradually become a public health burden as an independent risk factor for a variety of chronic diseases. Herein, a user-friendly point-of-care (POC) detection system (namely "Smart-HUA-Monitor") based on smartphone-assisted paper-based microfluidic is proposed for colorimetric quantification of HUA urinary markers, including uric acid (UA), creatinine (CR) and pH. The detection limits of UA and CR were 0.0178 and 0.5983 mM, respectively, and the sensitivity of pH were 0.1. The method was successfully validated in artificial urine samples and 100 clinical samples. Bland-Altman plots showed a high consistency between µPAD and the testing instruments (HITACHI 7600 Automatic Analyzer, URIT-500B Urine Analyzer and AU5800B automatic biochemical analyzer) in hospital. Smart-HUA-Monitor provides an accurate quantitative, rapid, low-cost and reliable tool for the monitoring and early diagnosis of HUA urine indicators.

Genetic Determinants of Thiazide-Induced Hyperuricemia, Hyperglycemia, and Urinary Electrolyte Disturbances - A Genome-Wide Evaluation of the UK Biobank.

Thiazide diuretics, widely used in hypertension, cause a variety of adverse reactions, including hyperglycemia, hyperuricemia, and electrolyte abnormalities. In this study, we aimed to identify genetic variants that interact with thiazide-use to increase the risk of these adverse reactions. Using UK Biobank data, we first performed genomewide variance quantitative trait locus (vQTL) analysis of ~ 6.2 million SNPs on 95,493 unrelated hypertensive White British participants (24,313 on self-reported bendroflumethiazide treatment at recruitment) for 2 blood (glucose and urate) and 2 urine (potassium and sodium) biomarkers. Second, we conducted direct gene-environment interaction (GEI) tests on the significant (P < 2.5 × 10-9) vQTLs, included a second UK Biobank cohort comprising 13,647 unrelated hypertensive White British participants (3,478 on thiazides other than bendroflumethiazide) and set significance at P = 0.05 divided by the number of vQTL SNPs tested for GEIs. The vQTL analysis identified eight statistically significant SNPs for blood glucose (5 SNPs) and serum urate (3 SNPs), with none being identified for the urinary biomarkers. Two of the SNPs (1 glucose SNP: CDKAL1 intron rs35612982, GEI P = 6.24 × 10-3; and 1 serum urate SNP: SLC2A9 intron rs938564, GEI P = 4.51 × 10-4) demonstrated significant GEI effects in the first, but not the second, cohort. Both genes are biologically plausible candidates, with the SLC2A9-mediated interaction having been previously reported. In conclusion, we used a two-stage approach to detect two biologically plausible genetic loci that can interact with thiazides to increase the risk of thiazide-associated biochemical abnormalities. Understanding how environmental exposures (including medications such as thiazides) and genetics interact, is an important step toward precision medicine and improved patient outcomes.

Study of purine derivatives and their relation to renal disorders in patients with psoriasis.

BACKGROUND: Psoriasis (Pso) is a chronic proliferative skin condition associated with hyperuricemia that may impair renal function. OBJECTIVES: The current study investigates the correlation between purine derivatives (PDs) and renal function in patients with Pso. PATIENTS/METHODS: This case-control study comprises 30 psoriatic patients and 30 age- and sex-matched healthy controls. The enzyme-linked immunosorbent assay (ELISA) was used to assess serum xanthine oxidase (XO) and urine albumin levels. Serum uric acid (SUA) and urinary creatinine were measured using the colorimetric method. RESULTS: There was a rise in the related PDs levels in patients with Pso compared to controls, as evidenced by the enhanced SUA levels (p < 0.001) and XO levels (p < 0.001). The presence of the related PDs in the serum was linked to the severity of Pso, and there was also a connection between the related PDs levels in the blood and indicators of renal dysfunction. Moreover, SUA and urinary albumin creatinine ratio (UACR) were found to be significantly correlated (r = 0.371 and p = 0.044), as were XO and UACR (r = 0.422 and p = 0.020). In psoriatic patients with itching and palmoplantar affection, mean SUA levels were considerably more significant than those in other instances (p = 0.005 and p = 0.018, respectively). CONCLUSION: Pso, being a hyperproliferative disease, is associated with hyperuricemia, which has a harmful effect on kidney function. The related PDs may be unique serological biomarkers for patients with Pso who are at high risk of developing renal abnormalities, especially with higher severity scores.

Eggshell Membrane Ameliorates Hyperuricemia by Increasing Urate Excretion in Potassium Oxonate-Injected Rats.

Hyperuricemia is the primary cause of gouty arthritis and other metabolic disorders. Eggshell membrane (EM) is an effective and safe supplement for curing pain and stiffness connected with osteoarthritis. However, the effect of EM on hyperuricemia is unclear. This study determines the effects of EM on potassium oxonate-injected hyperuricemia. Uric acid, creatinine, blood urea nitrogen concentrations in the serum, and xanthine oxidase activity in the liver are measured. Protein levels of renal urate transporter 1 (URAT1), organic anion transporters 1 (OAT1), glucose transporter 9 (GLUT9), and ATP-binding cassette transporter G2 (ABCG2) in the kidney are determined with renal histopathology. The results demonstrate that EM reduces serum uric acid levels and increases urine uric acid levels in hyperuricemic rats. Moreover, EM downregulates renal URAT1 protein expression, upregulates OAT1 and ABCG2, but does not change GLUT9 expression. Additionally, EM does not change xanthine oxidase activity in the liver or the serum. EM also decreases uric acid uptake into oocytes expressing hURAT1. Finally, EM markedly reduces renal inflammation and serum interleukin-1ß levels. These findings suggest that EM exhibits antihyperuricemic effects by promoting renal urate excretion and regulating renal urate transporters. Therefore, EM may be useful in the prevention and treatment of gout and hyperuricemia.

Predialysis predictors for identifying patients requiring dialysis at a higher glomerular filtration rate.

BACKGROUND: Current evidence suggests that the initiation of maintenance hemodialysis should not be based on a specific glomerular filtration rate (GFR) but on symptoms or signs attributable to kidney disease. However, it is difficult to predict the time point at which overt uremic syndrome develops in individuals. The estimated GFR is poorly correlated with occurrence of uremic symptoms, and some patients require dialysis at a higher eGFR than others. In this case, patients are more likely to be improperly prepared for dialysis. We investigated the predialysis characteristics of patients who require dialysis at a higher eGFR. METHODS: A total of 453 incident dialysis patients being monitored by a nephrologist from January 2013 to December 2018 were included. The predialysis characteristics when eGFR decreased to 20 mL/min/1.73 m2 were obtained. RESULTS: The mean age was 61 years, and 65.7% were men. Overall, the median eGFR at the first dialysis was 5.8 (interquartile range 4.6-7.3) mL/min/1.73 m2 and initiation of dialysis at the first quintile (≥7.8 mL/min/1.73 m2) was defined as 'early initiation of dialysis' Among the predialysis characteristics, heart failure (adjusted odds ratio 3.68; 95% confidence interval, 1.59-8.03), serum albumin <4.0 mg/dL (2.22; 1.30-3.77), blood urea nitrogen (BUN)/creatinine (Cr) ratio >15 mg/mg (1.92, 1.16-3.18), and hyperuricemia (1.84; 1.05-3.23) were independent predictors of early initiation. Diabetes mellitus and the causes of kidney disease were not independent predictors of early initiation. The early initiation group was less likely to initiate dialysis with a permanent vascular access than the late initiation group. CONCLUSIONS: For patients with heart failure, low serum albumin level, high BUN/Cr ratio, or hyperuricemia, clinicians can provide predialysis counseling in advance and consider early creation of vascular access.

A phase 2 trial of single low doses of rasburicase for treatment of hyperuricemia in adult patients with acute leukemia.

BACKGROUND: Rasburicase can markedly and rapidly decrease uric acid (UA) levels, thereby preventing and treating tumor lysis syndrome. However, rasburicase is expensive, especially when used as per the manufacturer's recommended dosage of 0.2 mg/kg/day for up to 5 days. Numerous reports have shown that lower, and even single doses are effective in lowering UA levels but prospective randomized studies comparing low doses have not been performed. OBJECTIVES: To prospectively determine the efficacy and safety of two single low doses of rasburicase in adult patients (pts) with acute leukemia and elevated plasma UA. METHODS: Eligible pts aged ≥ 18 years old with acute leukemia and UA ≥ 7.5 mg/dL were randomized to receive an initial single dose of rasburicase 1.5 mg (Arm A) or 3 mg (Arm B) on day 1 in an unblinded fashion. All pts received allopurinol 300 mg daily on days 1-6. RESULTS: Twenty-four pts (median age 69 years; 14 males and 10 females) were enrolled in this phase 2 study (12 on each arm). Twenty pts had acute myeloid leukemia while 3 had acute lymphoblastic leukemia, and 1 had acute promyelocytic leukemia. Median initial UA level was 9.8 mg/dL. Eighty-three percent of pts in both arms achieved UA < 7.5 mg/dL by 24 h after therapy. Five pts (21 %; 2 from Arm A and 3 from Arm B) required additional doses of rasburicase. The majority (23/24) of pts achieved UA goals after 1-2 doses of rasburicase. None had worsening renal function. Both doses were well tolerated, and no treatment related adverse events were reported. CONCLUSIONS: Single doses of rasburicase (as low as 1.5-3 mg) used in addition to allopurinol were well tolerated and highly efficacious (83 % response rate) in decreasing UA levels within 24 h of administration in adult acute leukemia pts with hyperuricemia.

A semi-mechanistic exposure-response model to assess the effects of verinurad, a potent URAT1 inhibitor, on serum and urine uric acid in patients with hyperuricemia-associated diseases.

Verinurad, a uric acid transporter 1 (URAT1) inhibitor, lowers serum uric acid by promoting its urinary excretion. Co-administration with a xanthine oxidase inhibitor (XOI) to simultaneously reduce uric acid production rate reduces the potential for renal tubular precipitation of uric acid, which can lead to acute kidney injury. The combination is currently in development for chronic kidney disease and heart failure. The aim of this work was to apply and extend a previously developed semi-mechanistic exposure-response model for uric acid kinetics to include between-subject variability to verinurad and its combinations with XOIs, and to provide predictions to support future treatment strategies. The model was developed using data from 12 clinical studies from a total of 434 individuals, including healthy volunteers, patients with hyperuricemia, and renally impaired subjects. The model described the data well, taking into account the impact of various patient characteristics such as renal function, baseline fractional excretion of uric acid, and race. The potencies (EC50s) of verinurad (reducing uric acid reuptake), febuxostat (reducing uric acid production), and oxypurinol (reducing uric acid production) were: 29, 128, and 13,030 ng/mL, respectively. For verinurad, symptomatic hyperuricemic (gout) subjects showed a higher EC50 compared with healthy volunteers (37 ng/mL versus 29 ng/mL); while no significant difference was found for asymptomatic hyperuricemic patients. Simulations based on the uric acid model were performed to assess dose-response of verinurad in combination with XOI, and to investigate the impact of covariates. The simulations demonstrated application of the model to support dose selection for verinurad.

Olsalazine Sodium Increases Renal Urate Excretion by Modulating Urate Transporters in Hyperuricemic Animals.

Hyperuricemia is mainly the result of relative underexcretion of urate. Urate is mainly eliminated by kidney and several important transporters expressed on the membrane of renal tubular cells involved in urate excretion. Olsalazine sodium was screened from 3167 authorized small compounds/drugs, targeting xanthine oxidoreductase. In previous study, we reported that olsalazine sodium significantly reduced the serum urate levels, and the anti-hyperuricemic activity linked with inhibiting urate formation by reducing the activity of xanthine oxidoreductase. The current research aimed to assess olsalazine sodium renal urate excretion and likely molecular mechanism. The results showed that administration of olsalazine sodium 5.0 mg/kg decreased the levels of serum urate in hyperuricemic rats, and noticeably improved the fractional excretion of urate and urate clearance, exhibiting an uricosuric action. Moreover, olsalazine sodium (2.5, 5.0, 10.0 mg/kg) reduced the level of blood urea nitrogen in rats. Further study showed that olsalazine sodium reduced the mRNA expression of urate reabsorptive transporter glucose transporter 9 (GLUT9), increased the mRNA expression of urate secretory transporters, organic anion transporter 1 (OAT1), OAT3 and type 1 sodium-dependent phosphate transporter (NPT1) as well as the protein expression of OAT3 in the kidney in hyperuricemic mice. In conclusion, olsalazine sodium exhibited a promotion of urate excretion in kidney by increasing the expression of OAT3.

Efficacy of different urinary uric acid indicators in patients with chronic kidney disease.

BACKGROUND: Mounting studies have shown that hyperuricemia is related to kidney diseases through multiple ways. However, the application of urinary uric acid indicators in patients with reduced renal function is not clear. In this study, we aim to determine the effects of renal function on various indicators reflecting uric acid levels in patients with chronic kidney disease (CKD). METHODS: Anthropometric and biochemical examinations were performed in 625 patients with CKD recruited from Dept of Nephrology of Huadong hospital affiliated to Fudan University. Multiple regression analyses were used to study correlations of the estimated glomerular filtration rate (eGFR) with serum uric acid (SUA) and renal handling of uric acid. For further study, smooth curve plots and threshold effect analyses were applied to clarify associations between renal function and uric acid levels. RESULTS: The nonlinear relationships were observed between eGFR and urinary uric acid indicators. The obvious inflection points were observed in smooth curve fitting of eGFR and fractional excretion of uric acid (FEur), excretion of uric acid per volume of glomerular filtration (EurGF). In subsequent analyses where levels of eGFR< 15 mL/min/1.73m2 were dichotomized (CKD5a/CKD5b), patients in the CKD5a showed higher levels of FEur and EurGF while lower levels of urinary uric acid excretion (UUA), clearance of uric acid (Cur) and glomerular filtration load of uric acid (FLur) compared with CKD5b group (all P < 0.05). And there was no significant difference of SUA levels between two groups. On the other hand, when eGFR< 109.9 ml/min/1.73 m2 and 89.1 ml/min/1.73 m2, the resultant curves exhibited approximately linear associations of eGFR with Cur and FLur respectively. CONCLUSION: FEur and EurGF showed significantly compensatory increases with decreased renal function. And extra-renal uric acid excretion may play a compensatory role in patients with severe renal impairment to maintain SUA levels. Moreover, Cur and FLur may be more reliable indicators of classification for hyperuricemia in CKD patients.

Roles of peritoneal clearance and residual kidney removal in control of uric acid in patients on peritoneal dialysis.

BACKGROUND: There have been few systematic studies regarding clearance of uric acid (UA) in patients undergoing peritoneal dialysis (PD). This study investigated peritoneal UA removal and its influencing factors in patients undergoing PD. METHODS: This cross-sectional study enrolled patients who underwent peritoneal equilibration test and assessment of Kt/V from April 1, 2018 to August 31, 2019. Demographic data and clinical and laboratory parameters were collected, including UA levels in dialysate, blood, and urine. RESULTS: In total, 180 prevalent patients undergoing PD (52.8% men) were included. Compared with the normal serum UA (SUA) group, the hyperuricemia group showed significantly lower peritoneal UA clearance (39.1 ± 6.2 vs. 42.0 ± 8.0 L/week/1.73m2; P = 0.008). Furthermore, higher transporters (high or high-average) exhibited greater peritoneal UA clearance, compared with lower transporters (low or low-average) (42.0 ± 7.0 vs. 36.4 ± 5.6 L/week/1.73 m2; P < 0.001). Among widely used solute removal indicators, peritoneal creatinine clearance showed the best performance for prediction of higher peritoneal UA clearance in receiver operating characteristic curve analysis [area under curve (AUC) 0.96; 95% confidence interval [CI], 0.93-0.99]. Peritoneal UA clearance was independently associated with continuous SUA [standardized coefficient (ß), - 0.32; 95% CI, - 6.42 to - 0.75] and hyperuricemia [odds ratio (OR), 0.86; 95% CI, 0.76-0.98] status, only in patients with lower (≤2.74 mL/min/1.73 m2) measured glomerular filtration rate (mGFR). In those patients with lower mGFR, lower albumin level (ß - 0.24; 95%CI - 7.26 to - 0.99), lower body mass index (ß - 0.29; 95%CI - 0.98 to - 0.24), higher transporter status (ß 0.24; 95%CI 0.72-5.88) and greater dialysis dose (ß 0.24; 95%CI 0.26-3.12) were independently associated with continuous peritoneal UA clearance. Furthermore, each 1 kg/m2 decrease in body mass index (OR 0.79; 95% CI 0.63-0.99), each 1 g/dL decrease in albumin level (OR 0.08; 95%CI 0.01-0.47), and each 0.1% increase in average glucose concentration in dialysate (OR 1.56; 95%CI 1.11-2.19) were associated with greater peritoneal UA clearance (> 39.8 L/week/1.73m2). CONCLUSIONS: For patients undergoing PD who exhibited worse residual kidney function, peritoneal clearance dominated in SUA balance. Increasing dialysis dose or average glucose concentration may aid in controlling hyperuricemia in lower transporters.

Population-specific factors associated with fractional excretion of uric acid.

BACKGROUND: Reduced renal clearance of uric acid is a major contributor to hyperuricemia. The aim of this study was to examine clinical and genetic variables associated with fractional excretion of uric acid (FEUA). METHODS: Participants (with and without gout) in the Genetics of Gout in Aotearoa study with available genotyping and FEUA data were included (n = 1713). Ten FEUA-associated loci detected within a genome-wide association study for serum urate in a European population were analysed. A polygenic score for FEUA was calculated in each ancestry group to model the cumulative effects of the genetic variants on FEUA. Associations between FEUA and both clinical variables and polygenic score were tested using linear regression models. RESULTS: The mean (SD) FEUA was 5.13 (2.70) % in Eastern Polynesian participants, 4.70 (5.89) % in Western Polynesian participants, and 5.89 (2.73) % in New Zealand European participants. Although association with FEUA was observed for SLC2A9 rs11942223 in New Zealand European participants (P = 2.39 × 10- 8), this association was not observed in Eastern or Western Polynesian participants. The polygenic score was positively associated with FEUA in all ancestry groups. In New Zealand European participants, body mass index, diuretic use, polygenic score, and male sex were associated with FEUA and explained 22% of FEUA variance in the regression model. In Eastern and Western Polynesian participants, the tested variables explained 10% and 4% of FEUA variance respectively. CONCLUSIONS: Both clinical and genetic variables contribute to renal clearance of uric acid. SLC2A9 exerts effects on FEUA variance in people of European ancestry, but not in those of Polynesian ancestry. There is a large unexplained variance in FEUA, particularly in people of Polynesian ancestry.

Coexistence of hyper-uricaemia and low urinary uric acid excretion further increases risk of chronic kidney disease in type 2 diabetes.

AIM: To investigate whether hyper-uricaemia and decreased urinary uric acid excretion (UUAE) are associated with increased risk of chronic kidney disease (CKD), and whether the coexistence of hyper-uricaemia and low UUAE further increases CKD risk in type 2 diabetes mellitus (T2DM). METHODS: In this cross-sectional study based on serum uric acid (SUA) and UUAE levels, 2846 T2DM inpatients were divided into those with normal SUA and UUAE (group 1), normal SUA and low UUAE (group 2), hyper-uricaemia and normal UUAE (group 3), and hyper-uricaemia and low UUAE (group 4). Hyper-uricaemia was defined as SUA levels ≥ 420 µmol/L in men and ≥ 360 µmol/L in women. Low UUAE was defined as levels below the first UUAE quintiles (< 2161 µmol/24 h in men, 1977 µmol/24 h in women). RESULTS: There were trends for significantly increased prevalences of CKD (4.3%, 12.6%, 18.3%, 47.8%; P < 0.001), albuminuria (20.2%, 26.4%, 36.9%, 54.9%; P < 0.001) and macroalbuminuria (3.3%, 10.1%, 10.7%, 31.9%; P < 0.001) from groups 1 to 4, respectively. After controlling for multiple confounding factors, prevalences of CKD (P < 0.001) and urinary albumin levels (P = 0.013) showed significantly increasing trends, whereas eGFR levels were markedly decreased from groups 1 to 4 (P < 0.001). CONCLUSION: Hyper-uricaemia and low UUAE levels are closely associated with presence of CKD, and the concomitant presence of hyper-uricaemia and decreased UUAE levels further increased CKD risk in T2DM. Thus, the combined consideration of SUA and UUAE levels may help to identify those T2DM patients at higher CKD risk.

Lactobacillus brevis DM9218 ameliorates fructose-induced hyperuricemia through inosine degradation and manipulation of intestinal dysbiosis.

OBJECTIVE: High fructose consumption exacerbates purine degradation and intestinal dysbiosis, which are closely related to the development of hyperuricemia. Probiotics are powerful weapons to combat metabolic disturbance and intestinal dysbiosis. Previously we isolated a Lactobacillus strain named DM9218 that could reduce the serum uric acid (UA) level by assimilating purine nucleosides. The present study aimed to evaluate the effects of DM9218 on high-fructose-induced hyperuricemia and to elucidate the underlying mechanisms. METHODS: Mice were fed a normal diet, a high-fructose diet, or high-fructose diet with DM9218. Metabolic parameters, fructose- and UA-related metabolites, and fecal microbiota were investigated. Whole-genome sequencing of strain DM9218 was also conducted. In addition, an inosine hydrolase from DM9218 was heterologously expressed in Escherichia coli, and its inosine-degrading activity was detected. RESULTS: Our results indicated that DM9218 could decrease serum UA level and hepatic xanthine oxidase activity in fructose-fed mice. It could protect against high-fructose-induced liver damage and retard UA accumulation by degrading inosine. The modulation effect of DM9218 on high-fructose-induced intestinal dysbiosis resulted in enhancement of intestinal barrier function and reduction of liver lipopolysaccharide, which was closely correlated with the down-regulation of inflammatory cytokine-stimulated xanthine oxidase expression and activity. CONCLUSIONS: Lactobacillus brevis DM9218 is a probiotic strain with the potential to ameliorate fructose-induced hyperuricemia.

Increased urinary glucose excretion is associated with a reduced risk of hyperuricaemia.

AIM: To investigate the association of urinary glucose excretion with levels of serum uric acid in adults with newly diagnosed diabetes. METHODS: A total of 597 people with newly diagnosed diabetes, confirmed in an oral glucose tolerance test, were included in the present study. The participants were divided into two groups: 142 participants with low urinary glucose excretion and 455 with high urinary glucose excretion. Demographic characteristics and clinical variables were evaluated. The association of urinary glucose excretion with uric acid was analysed using multivariable regression analysis. RESULTS: The low urinary glucose excretion group had a significantly higher prevalence of hyperuricaemia than the high urinary glucose excretion group. Moreover, urinary glucose excretion was negatively associated with uric acid level. The correlation remained significant after adjusting for potential confounders, including gender, age, fasting plasma glucose, 2-h plasma glucose and BMI. The results also showed that participants with high urinary glucose excretion were at decreased risk of hyperuricaemia (odds ratio 0.47, 95% CI 0.27-0.80; P = 0.006). CONCLUSION: Urinary glucose excretion was independently associated with uric acid level in participants with newly diagnosed diabetes. In addition to lowering blood glucose, promoting urinary glucose excretion may also be an effective approach to reducing serum uric acid levels, especially for people with diabetes complicated with hyperuricaemia.

Hyperuricemia, urine uric excretion, and associated complications in thalassemia patients.

Thalassemia patients have a high cell turnover rate due to chronic hemolysis and ineffective erythropoiesis; therefore, hyperuricemia is anticipated. This study aimed to identify the prevalence of hyperuricemia, gout and nephrolithiasis, conditions associated with serum uric acid (SUA), and urine uric acid excretion (UUA) in thalassemia patients. This was a cross-sectional study in patients aged 15 years or older at Chiang Mai University Hospital. All patients had blood and 24-h urine collection test. We enrolled 112 thalassemia patients in which 67.0% were female, 64.3% had beta thalassemia/Hb E, 76.8% were transfusion dependent, and 59.8% were post splenectomy. The median age was 29 (16-58) years. Mean SUA was 6.7 ± 2.0 mg/dl and hyperuricemia (SUA > 6.8 mg/dl) was found in 47 cases (45.2%). Intact spleen (ORs 4.3, 95%CI 1.55-12.50, p = 0.01) and lower FEuric (ORs 2.08, 95%CI 1.35-3.33, p < 0.01) were associated with hyperuricemia significantly. Seven (6.3%) had gouty arthritis and nine (8%) had microscopic hematuria, one case being confirmed nephrolithiasis. The mean UUA excretion was 981.3 ± 335.0 mg/day and UUA hyperexcretion (> 700 mg/24 h) was found in 83.3%. UUA hyperexcretion patients had renal hyperfiltration 46%, glomerular dysfunction 84%, and tubular dysfunction 7.7%. From our study, hyperuricemia was found in approximately 40% of thalassemia patients but gouty arthritis occurred only in few patients (6%). This may be explained by urinary uric hyperexcretion which is found in over 80%. The significant risk factors for hyperuricemia were intact spleen and lower fraction excretion of uric acid.

Production Inhibition and Excretion Promotion of Urate by Fucoidan from Laminaria japonica in Adenine-Induced Hyperuricemic Mice.

This work aims to explore the amelioration of fucoidan on adenine-induced hyperuricemia and hepatorental damage. Adenine-induced hyperuricemic mice were administered with fucoidan, allopurinol and vehicle control respectively to compare the effects of the drugs. Serum uric acid, urea nitrogen, hepatorenal functions, activities of hepatic adenosine deaminase (ADA), xanthine oxidase (XOD), renal urate transporter 1 (URAT1) and NF-κB p65 were assessed. As the serum uric acid, urea nitrogen, creatinine, glutamic oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) data demonstrated, the adenine not only mediated hepatorenal function disorders, but also induced hyperuricemia in mice. Meanwhile, activities of hepatic ADA and XOD were markedly augmented by adenine, and the expression of URAT1 was promoted, which was conducive to the reabsorption of urate. However, exposure to fucoidan completely reversed those adenine-induced negative alternations in mice, and the activities of hepatic ADA and XOD were recovered to the normal level. It was obvious that hepatic and renal functions were protected by fucoidan treatment. The expression of URAT1 was returned to normal, resulting in an increase of renal urate excretion and consequent healing of adenine-induced hyperuricemia in mice. Expression and activation of NF-κB p65 was promoted in kidneys of adenine treated mice, but suppressed in kidneys of mice exposed to fucoidan from Laminaria japonica or allopurinol. In conclusion, the fucoidan is a potential therapeutic agent for the treatment of hyperuricemia through dual regulatory roles on inhibition of hepatic metabolism and promotion of renal excretion of urate.

Renal excretion is a cause of decreased serum uric acid during acute gout.

AIMS: To evaluate the fluctuation of serum uric acid (SUA) during acute gout (AG) and explore its potential mechanisms. METHODS: Data such as SUA, urinary uric acid and 24-hour uric acid urinary excretion were collected from 126 patients diagnosed with gout and were analyzed. RESULTS: Serum uric acid was negatively correlated with age in gout patients, and significantly elevated in patients aged ≤50 years. Twenty-four-hour uric acid urinary excretion was affected by SUA, creatinine clearance, age, body mass index and urine volume. In contrast, clearance of uric acid and fractional excretion of uric acid (FEur) were more stable. SUA was significantly downregulated during acute attacks. Of the AG patients, 34.92% had detected SUA <420 µmol/L. Clearance of uric acid and FEur were notably increased in patients during acute attacks, especially in patients with SUA <420 µmol/L. CONCLUSION: This study demonstrated that the level of SUA was remarkably upregulated in young gout patients. Therefore, early onset of gout should be considered of great importance. SUA was downregulated during acute gouty arthritis, which might be associated with increased urinary excretion of uric acid.

The association of hyperuricemia and immediate postpartum hypertension in women without a diagnosis of chronic hypertension.

Our objective was to determine if elevated uric acid (UA) is associated with postpartum hypertension (PP HTN) in women without chronic hypertension. This is a secondary analysis of a randomized trial. We compared those with elevated UA to those with normal UA. Logistic regression was conducted to determine the association of elevated UA with PP HTN. Five hundred and fifty-six women met criteria. An UA level ≥ 5.2 mg/dL was associated with immediate PP HTN (adjusted odds ratio 2.44, 95% CI 1.63-3.64). The association was stronger among overweight and obese women. We conclude that hyperuricemia is associated with PP HTN, especially among obese women.

Renal Handling of Uric Acid.

Hyperuricemia occurs in 21.4% of the adult population and is associated with several conditions that increase oxidative stress and contributes to the pathogenesis of inflammatory mechanisms for the development and progression of diseases. Serum blood or urine samples of uric acid levels were used to mainly identify clinical problems, depending on the uric acid pathway alterations, which include synthesis, reabsorption or its excretion. Several proteins that act particularly as transporters (URAT1, GLUT9, 1-NPT1, 1-NPT4, OAT4, 9-MCT9, hUAT1, etc.) have been identified in the recent past involving tubular transport and clearance leading to clinical benefits. Until now, the knowledge of uric acid homeostasis centers its primary investigation on understanding molecular and genetic mechanisms, including the genetic polymorphisms that induce genetic and acquire renal tubular disorder, which increases or diminishes urate excretion.