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.

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.

Effect of acupuncture on rats with acute gouty arthritis inflammation: a metabonomic method for profiling of both urine and plasma metabolic perturbation.

Acute gouty arthritis is a common inflammation model with multiple pathogenic mechanisms seen in clinical practice, for which acupuncture may potentially be an alternative therapy. To investigate the effect of acupuncture on acute gouty arthritis and search for its mechanism, a metabonomic method was developed in this investigation. Acute gouty arthritis model rats were induced by monosodium urate (MSU) crystals. The urine and plasma samples were collected at several time points and the endogenous metabolites were analyzed by an ultra-performance liquid chromatography coupled with a mass spectrometry (UPLC-MS). Data were analyzed using principal components analysis (PCA) and partial least squares (PLS) analysis to compare metabolic profiles of MSU crystal-induced acute gouty arthritis rats with MSU crystal-induced acute gouty arthritis, treated with acupuncture rats. The results showed that acupuncture could restore the metabolite network that disturbed by MSU administration. Our study indicates that UPLC-MS-based metabonomics can be used as a potential tool for the investigation of biological effect of acupuncture on acute gouty arthritis.

[Metabonomic study of the urine of rat acute gouty arthritis model].

UNLABELLED: [ OBJECTIVE: To analysis the metabonome characteristics of the urine of MSU crystal-induced acute gouty arthritis rats by the method of metabolomics. METHODS: Based on the method of metabolomics, which applies LC/MS as data acquisition platform, incorporating with the means of stoechiometry such as principal component analysis, we analyzed the metabonome difference between the urine of acute gouty arthritis rats and that of normal rats. RESULTS: Compare with control group, the metabolism status of acute gouty arthritis model group deviated. After that, with the time lapsed, it retrieved gradually to the incipient metabolism status. The variation of metabolism locus of rats measured by the methods of metabolomics properly reflects the genesis, development, and recuperation course of acute gouty arthritis. CONCLUSION: The whole metabolism status of rat model is able to be presented finely with the method of metabolomics. The metabolomics study could offer a satisfactory research approach to acute gouty arthritis.

[Molecular basis of primary renal hyperuricemia : role of the human urate transporter hURAT1]. / Molekulare Grundlagen der primär-renalen Hyperurikämie : Zur Rolle des humanen Urattransporters hURAT1.

In highly industrialized countries hyperuricemia is one of the most common metabolic disorders. High uric acid blood levels may lead to the manifestation of gout owing to the precipitation of urate crystals in connective tissue, the skeletal system and kidneys. A primary reduction of renal uric acid excretion can be detected in more than 90% of all cases of hyperuricemia. Despite the identification of several uric acid transporting proteins their pathogenetic role for the induction of primary reduced renal uric acid excretion has not yet been verified. As a result of a case-control study on individuals with normal and reduced renal uric acid excretion, an association of polymorphisms in the human urate transporter 1 gene (hURAT1) with primary reduced urate excretion has been demonstrated for the first time. The hURAT1 gene is an organic anion transporter (SLC22A12), which is preferentially expressed in the apical membrane of proximal renal tubule cells. Functioning as an antiporter, hURAT1 mediates the uptake of urate from the lumen into proximal tubule cells in exchange for organic and inorganic anions. Loss-of-function mutations in the hURAT1 gene are a cause of hereditary renal hypouricemia. The precisely regulated hURAT1 is a candidate gene for hyperuricemia and an important target for the development and optimization of new diagnostic approaches and pharmacological interventions of primary reduced renal uric acid excretion.

McArdle's disease and gout.

We report the first case of McArdle's disease (muscle phosphorylase deficiency) and tophaceous gout. To examine the contribution of adenine nucleotide degradation to the disturbance of uric acid metabolism, we labeled the adenine nucleotide pool with [8-14C]adenine, and measured plasma and urine purines following vigorous exercise tests. Plasma and urinary hypoxanthine and xanthine concentrations and the specific radioactivity of urinary purines increased markedly, but plasma urate levels and uric acid excretion were not substantially modified. We suggest that, in this patient, the association of McArcle's disease with gout is coincidental.

[Treatment of arthritis urica and hyperuricemia]. / Behandling av arthritis urica og hyperurikemi.

The diagnosis of gout is confirmed by detection of monosodium urate crystals in the fluid of the joint or from tophi. This article discusses treatment of acute gout, prevention of acute attacks and treatment of hyperuricemia. Non-steroidal anti-inflammatory drugs are recommended as drugs of choice in treatment of acute gout. Self-administration of non-steroidal anti-inflammatory drugs is recommended for prevention of gout. Drugs to counteract hyperuricemia should be used only on specific indications. Measurement of the "24-hour" urinary uric acid content is important when deciding treatment.

Clinical profile, therapeutic approach and outcome of gouty arthritis in northern India.

Thirty patients with gouty arthritis were studied over 3 years. The diagnosis was established with the help of polarised light microscopy. All the patients were males, with a median age of 45 years. They belonged to the middle or upper socio-economic class and were obese (mean body mass index 29.7). Chronic alcoholism, diabetes mellitus and hypertension were present in one patient each. No patient had symptomatic coronary artery disease. Although 6 patients had a history of renal colic, only one had gouty nephropathy with chronic renal failure. Six patients had a positive family history of gout. The disease involved mostly the joints of the lower extremity and podagra was observed in 70% of patients. Eight patients had tophi at various sites. There were 17 'over producers' and 13 'under excretors' of uric acid. The treatment consisted of patient education, symptomatic control with non steroidal anti-inflammatory drugs and/or colchicine and antihyperuricaemic therapy. The overproducers were treated with allopurinol while the under excretors were treated with [corrected] sulfinpyrazone. In general, there was a good response to therapy as indicated by lowering of serum uric acid and the number of painful episodes per year. The overall profile of the disease appears similar to that seen in the West.