Gout Group Research Articles

Ozonated autohemotherapy modulates the serum levels of inflammatory cytokines in gouty patients.

ObjectivesOzonated autohemotherapy (O3-AHT) has been used to effectively treat gout, but the underlying therapeutic mechanisms remain unknown. In this study, as an initial effort to understand the therapeutic mechanisms of O3-AHT, we aim to examine the effect of O3-AHT on serum inflammatory cytokine levels in gouty patients.Patients and methodsThree groups of patients and healthy subjects were recruited, including the gouty (n=10), hyperuricemia (n=10), and healthy control (n=11) groups. Cytometric bead array was applied to examine 12 cytokines before (T0), during (T1), and after (T2) therapies.ResultsThree cytokines, IL-8, IL-12, and MCP-1, were detectable in all participants. Before O3-AHT, the average serum levels of IL-8 and MCP-1 were higher in the gout group than in the hyperuricemia and healthy control groups, confirming the inflammation status in gouty patients. After the 5th course of O3-AHT (T1), IL-8 level was significantly increased compared to that at T0. IL-12 level was also raised at T1, although the difference did not reach statistical significance. After completing the therapy, both IL-8 and IL-12 levels decreased to levels lower than those at T0. MCP-1 level remained essentially unchanged during and after treatment.ConclusionOur results indicate that O3-AHT induces a significant change in serum cytokine levels, suggesting that modulating the inflammatory process is one of the therapeutic mechanisms underlying O3-AHT. In addition, the sensitive response of serum IL-8 and IL-12 levels to O3-AHT suggests that these cytokines may be developed as biomarkers to evaluate the therapeutic effect of O3-AHT in gouty patients.

124. PLANTAR PRESSURE PATTERNS IN PEOPLE WITH GOUT AND DIABETES

Background: Gout and hyperuricaemia have been associated with an increased risk of diabetes and cardiovascular disease. Gout commonly affects the foot with a predilection for the first metarsophalangeal joint and diabetes is frequently associated with foot ulceration. However there are limited studies that explore associations between altered mechanics in those with gout/diabetes. We aimed to determine whether plantar pressure significantly differed between patients with diabetes, gout and age-matched controls. Methods: Using a TekscanTM pressure mat, peak plantar pressures and pressure time integrals were calculated for seven predetermined regions of the foot. Participants comprised: gout n = 25, diabetes n=21, concomitant gout & diabetes n= 17 and n=33 healthy age/sex matched control subjects Results: Compared to controls, all patient groups demonstrated reduced heel, increased midfoot and reduced second metatarsal peak pressure. The diabetes and diabetes plus gout groups demonstrated increased first metatarsal peak pressures. Whereas the diabetes and gout group demonstrated increased hallux peak pressures and increased third to fifth metatarsal peak pressures compared to the gout group (all p<0.05) (Table 1). Compared to controls, participants with gout demonstrated increased midfoot pressure time integrals. Whereas those with diabetes demonstrated increased hallux pressure time integrals. Patients with diabetes plus gout demonstrated increased hallux and toe pressure time integrals. Finally, Participants with gout also demonstrated increased midfoot and reduced hallux pressure time integrals compared to diabetes and diabetes plus gout groups (all p<0.05). Conclusion: The current study provides insights into the dynamic function of the foot in gout and diabetes as well as how plantar pressures can vary between pathologies Table 1: Mean, adjusted (SE) peak pressure (normalised to BMI) (kPa) Control Diabetes Gout Diabetes & Gout Heel 282 (11) 243 (13) a 234 (12) a 233 (16) a Midfoot 75 (12) 228 (14) a 183 (13) a, b 239 (17) a, c First metatarsal 206 (12) 269 (13) a 236 (13) 260 (17) a Second metatarsal 310 (10) 136 (12) a 134 (11) a 131 (14) a Third to fifth metatarsals 246 (13) 245 (14) 209 (14) 272 (18) c Hallux 232 (16) 293 (18) a 293 (17) a 275 (23) Toes 103 (8) 118 (9) 109 (9) 120 (11) a Significant difference compared to control group, p < 0.05; b Significant difference compared to diabetes group, p < 0.05; c Significant difference compared to gout group, p < 0.05.

Comparative analysis of different factors associated with hypertension between subjects with and without gout

Objective To compare and analyze different factors that influence hypertension between subjects with and without gout, and to recognize and understand them further. Methods A total of 7 395 patients(6 935 males and 460 females)from the gout clinic of Affiliated Hospital of Qingdao University between May 2009 and January 2016 were chosen as gout group, while 8 379 people without gout(7 858 males and 521 females)were served as control group. The height, weight, waist circumference, hip circumference, blood pressure, fasting plasma glucose(FPG), triglyceride(TG), cholesterol(TC), blood urea nitrogen(BUN), creatinine(Cr), and uric acid(UA)of both groups were monitored. Clinical and biochemical differences of the two groups were analyzed. The morbidity rate of hypertension in the two groups was also compared. According to different criteria, the subjects were divided into several subgroups. The data were analyzed mainly by Empower statistical software. Results The risk ratio of hypertension in gout group was 63.25%, and it was higher than that in control group(49.19%, χ2=316.25, P<0.01). The risk ratio of hypertension in gout group was 1.173 times higher than that in control group. After adjusting UA, it would drop to 1.065 times, but the difference still remained significant. In groups with diabetes, hyperlipidemia, hypercholesterolemia, obesity, the risk ratio of hypertension increased by 13.7%, 15.3%, 21.8%, and 23.6% respectively, in gout group. FPG, TG, TC, BMI, and WHR were all associated with HP in both gout and normal groups, but Cr was associated with HP in gout group only(OR=1.396, 95%CI 1.197-1.629). Age had different saturation effects in two groups. Conclusion The factors influence hypertension differently in patients with and without gout, especially those of gout itself and creatinine. The precision medicine should be applied. (Chin J Endocrinol Metab, 2017, 33: 98-102) Key words: Hypertension; Gout; Related factors; Comparative analysis

Vitamin C supplementation and serum uric acid: A reaction to hyperuricemia and gout disease

Hyperuricemia and gout are commonly diagnosed in subjects with abnormal purine metabolism. Hyperuricemia is the earliest stage of the gout disease, which is the most common cause of inflammatory arthritis in males over 40 years and females over 60 years old. This work was design to investigate the effect of vitamin C supplements on the serum level of uric acid (UA) in patients suffering from either hyperuricemia or gout disease. The serum creatinine (Cr) level and glomerular filtration rate (GFR) were measured before and after the treatment with vitamin C to study if this treatment would improve the functionality of the renal system of such patients. Thirty males and females' patient were divided into two groups based on their disease condition; hyperuricemia group and gout group 15 patients each, and patients were given 500mg vitamin C chewable tablet daily for two consecutive months. By the end of the treatment period, the UA level decreased (P<0.05) in the blood of the hyperuricemic individuals, while no significant change was seen on the serum UA concentration in the gouty patients. Additionally, there was no significant effect on the serum creatinine level or on the GFR in both study groups. In conclusion, 500mg vitamin C oral daily dosing might be of the therapeutic value in lowering UA levels in hyperuricemic patients.

Single source dual-energy computed tomography in the diagnosis of gout: Diagnostic reliability in comparison to digital radiography and conventional computed tomography of the feet

ObjectivesTo investigate the diagnostic value of single-source dual-energy computed tomography (SDECT) in gouty arthritis and to compare its capability to detect urate depositions with digital radiography (DR) and conventional computed tomography (CT). MethodsForty-four patients who underwent SDECT volume scans of the feet for suspected gouty arthritis were retrospectively analyzed. SDECT, CT (both n=44) and DR (n=36) were scored by three blinded readers for presence of osteoarthritis, erosions, and tophi. A diagnosis was made for each imaging modality. Results were compared to the clinical diagnosis using the American College of Rheumatology (ACR) classification criteria. ResultsThe patient population was divided into a gout (n=21) and control (n=23) group based on final clinical diagnosis. Osteoarthritis was evident in 15 joints using CT and 30 joints using DR (p=0.165). There were 134 erosions detected by CT compared to 38 erosions detected by DR (p<0.001). In total 119 tophi were detected by SDECT, compared to 85 tophi by CT (p=0.182) and 25 tophi by DR (p<0.001). SDECT had best diagnostic value for diagnosis of gout compared to DR and conventional CT (sensitivity and specificity for SDECT: 71.4% and 95.7%, CT: 71.4% and 91.3% and DR: 44.4% and 83.3%, respectively). For all three readers, Cohen’s kappa for DR and conventional CT were substantial for all scoring items and ranged from 0.75 to 0.77 and 0.72–0.76, respectively. For SDECT Cohen’s kappa was good to almost perfect with 0.77–0.84. ConclusionsSDECT is capable to detect uric acid depositions with good sensitivity and high specificity in feet, therefore diagnostic confidence is improved. Using SDECT, inter-reader variance can be markedly reduced for the detection of gouty tophi.

Development of a Dual-Energy Computed Tomography Scoring System for Measurement of Urate Deposition in Gout.

To develop a semiquantitative dual-energy computed tomography (DECT) scoring system for measurement of urate deposition in gout. Following a structured review of images, a semiquantitative DECT urate scoring method for foot/ankle scans was developed for testing. This method included 4 regions, each scored 0-3, with a maximum total DECT urate score of 12. DECT scans from 224 patients (182 with gout, 42 without gout) were scored by 2 independent readers. Automated urate volumes were also measured. Paired scans from 8 patients receiving pegloticase were analyzed, and a timing exercise was undertaken. The properties of the DECT urate score were analyzed according to the Outcome Measures in Rheumatology (OMERACT) filter. The interreader intraclass correlation coefficient (95% confidence interval) for the DECT urate score was 0.98 (0.97-0.98). All scored regions contributed to the total DECT urate score. DECT urate scores and volumes were highly correlated (r = 0.91, P < 0.0001). Both DECT urate scores and volumes discriminated between gout and nongout control participants and between the tophaceous gout, nontophaceous gout, and control groups. Compared with urate volume, the DECT urate score had greater ability to discriminate between responders and nonresponders to pegloticase therapy (P < 0.001 for DECT urate score and P > 0.05 for volume). The mean ± SD time required for the DECT urate score was 121 ± 2 seconds and for urate volume was 240 ± 2 seconds (P = 2 × 10(-31) ). We have developed a novel semiquantitative DECT scoring method for measurement of urate deposition in the feet/ankles. This method fulfills many aspects of the OMERACT filter.

Clinical utility of dual-energy CT for gout diagnosis

ObjectiveThe present study was to evaluate the clinical value of dual-energy computed tomography (DECT) for detecting monosodium urate crystals in patients with gouty arthritis. MethodsTwo hundred and two patients, who experienced arthrocele and (or) joint pain, were enrolled into our study. DECT scans of upper or lower extremity were performed. One hundred and sixty one patients who conformed to the American College of Rheumatology classification standard were defined as the gout group. The rest (41) of the patients were regarded as the without-gout group. DE (80kV/140kV) datasets were reconstructed via DE gout software. Images were reviewed independently by two senior radiologists. ResultsIn the gout group, DECT scans revealed a total of 379 areas of urate deposition in 121 patients. In the without-gout group, 3 areas of green urate deposition were detected. The sensitivity and specificity were 75.2% and 92.7%, respectively; when we increased the ratio to 1.32 and decreased the range to 3, the number of patients with green urate deposition increased, and the areas of urate deposition were more extensive. The sensitivity and specificity were 91.9% and 85.4%. DECT images could illustrate the palpable reduction in the tissue urate deposits compared to baseline images before and after treatment. ConclusionsDECT has comparable sensitivity and specificity for the detection of gouty arthritis in a clinical setting, and DECT can monitor the clinical treatment. However, DECT results should be interpreted carefully because there could be some false-negative or false-positive findings.

Urate crystal deposition in asymptomatic hyperuricaemia and symptomatic gout: a dual energy CT study

BackgroundThe aim of this study was to compare the frequency and volume of dual energy CT (DECT) urate deposits in people with asymptomatic hyperuricaemia and symptomatic gout.MethodsWe analysed DECT scans...

The relationship of apolipoprotein B and very low density lipoprotein triglyceride with hyperuricemia and gout.

IntroductionGout results from an innate immune response to monosodium urate (MSU) crystals deposited in joints. Increased very low-density lipoprotein (VLDL) has been associated with gout. The apolipoprotein B (apo B), which is present on VLDL, regulates neutrophil response to MSU crystals and has been positively associated with gout. Furthermore, the gene (A1CF) encoding the complementation factor for the APOB mRNA-editing enzyme is associated with urate levels. However, the relationship of apo B and VLDL with gout and hyperuricaemia (HU) is still unclear. Therefore, we tested the association of VLDL and apo B with HU and with gout compared to HU.MethodsNew Zealand European (n = 90) and Māori and Pacific Island (Polynesian) (n = 90) male gout case and control sample sets were divided into normouricaemia (NU), asymptomatic HU and gout groups. Size exclusion chromatography and enzyme-linked immunosorbant assay was used to measure VLDL and apo B. Multivariate logistic regression was used to assess the risk of gout and HU per unit change in VLDL and apo B.ResultsIncreased levels of VLDL triglycerides (Tg) were observed in the gout sample set compared to NU and HU in Europeans (P = 1.8 × 10-6 and 1 × 10-3, respectively), but only compared to NU in Polynesians (P = 0.023). This increase was driven by increased number of VLDL particles in the European participants and by the Tg-enrichment of existing VLDL particles in the Polynesian participants. Each mmol/L increase in VLDL Tg was significantly associated with gout in the presence of HU in Europeans, with a similar trend in Polynesians (OR = 7.61, P = 0.011 and 2.84, P = 0.069, respectively). Each μmol/L increase in total apo B trended towards decreased risk of HU (OR = 0.47; P = 0.062) and, conversely, with increased risk of gout compared to HU (OR = 5.60; P = 0.004).ConclusionsIncreased VLDL Tg is associated with the risk of gout compared to HU. A genetic approach should be taken to investigate the possibility for causality of VLDL in gout. Apolipoprotein B may have pleiotropic effects in determining HU and gout.

Study on the diversity of Bacteroides and Clostridium in patients with primary gout.

To analyze the diversity of both Bacteroides and Clostridium in patients with primary gout and the difference from that of normal individuals. And to investigate the relationship between the primary gout and the intestinal flora. Fecal samples of 90 cases with the primary gout and 94 cases normal comparison group were selected, together with the cases that match the filter criteria. The DNA is extracted from the feces. 16S rRNA specific primers of both Bacteroides and Clostridium were adopted for the PCR amplification. The molecular fingerprints of Bacteroides and Clostridium in both the primary gout group and the normal control group were obtained through DGGE and subjected for further analysis on both the diversity and the similarity. Compared with normal individuals, the number of bands and Shannon-Weaver (H') of Bacteroides in patients with primary gout was not reduced, but significantly decreased in Clostridium. Furthermore, the intra-group and inter-group similarity of both Bacteroides and Clostridium were lower. The primary gout has caused the structural change of both Bacteroides and Clostridium, inducing the low similarity, especially for Clostridium. It has statistic significance. The gut predominant flora may play an important role in the development of primary gout.

SAT0092 A Risky “Metabolic Intersection”: the Risk of Incident Diabetes in Patients with Gout

BackgroundGrowing evidence supports that hyperuricemia is independently associated with a greater future risk of metabolic syndrome and diabetes mellitus (DM). A previous cohort study that included men with a high...

Elevated serum homocysteine levels were not correlated with serum uric acid levels, but with decreased renal function in gouty patients.

Hyperhomocysteinemia is one of the important factors of the cardiovascular disease, and gout is well known to be associated with cardiovascular disease. There are a few reports on the serum homocysteine (Hcy) levels in patients with gout, however, the results showed discrepancies. In this study, we measured Hcy levels in patients with gout and examined factors associated with the levels of serum Hcy. Ninety-one male patients with gout and 97 age-matched healthy male controls were enrolled in the study. Serum uric acid levels were not significantly different between gout and healthy control groups. However, serum Hcy levels were significantly higher in patients with gout compared to controls (13.96 ± 4.05 µM/L vs 12.67 ± 3.52 µM/L, P=0.035). In gout group, patients with 1-2 stages of chronic kidney disease (CKD) had significantly lower serum Hcy than those with 3-5 stages of CKD (13.15 ± 3.46 µM/L vs 17.45 ± 4.68 µM/L, P<0.001). Multivariate linear analysis revealed an inverse association between serum Hcy and estimated glomerular filtration rate (eGFR) (β=-0.107, P<0.001). In conclusion, serum Hcy was elevated in male patients with gout. Hyperhomocysteinemia was not correlated with serum uric acid, but it was inversely associated with impaired renal function.

OP0103 Risk of end-stage renal disease associated with gout: A nationwide population study

BackgroundTraditionally, diabetes mellitus (DM) and hypertension have been considered the most important risk factors for CKD. Since gout frequently coexists with diabetes mellitus (DM) and hypertension, it is often overlooked...

SAT0374 Elevated Serum Homocysteine Levels in Gouty Patients were Related Not with Serum Uric Acid Levels but with Decreased Renal Function

BackgroundHyperhomocysteinemia, which is related with cardiovascular diseases and metabolic syndrome, is regarded as one of the important factors in endothelial cell damage processes. It is well known that gout is...

Gout, hyperuricaemia, sleep apnoea-hypopnoea syndrome and vascular risk

This study aimed to evaluate cardiovascular (CV) and atherothrombosis risk factors in patients with gout and hyperuricaemia with suspected sleep apnoea-hypopnoea syndrome (SAHS) compared with a control group of subjects with knee OA and SAHS. Clinical information on CV risk factors and atherothrombosis was collected in a rheumatology department in patients with gout and hyperuricaemia and suspicion of SAHS. Confirmation polysomnography that registered apnoea-hypopnoea index (AHI) and oxygen saturation during sleep (SaO2) was performed. The control group consisted of patients with OA and polysomnographically confirmed SAHS. In the gout patient group (54 patients, 48 men), CV risk factors were found in 77.8% and evidence of atherothrombosis in 46.3%. In the OA group (36 patients, 27 men), CV risk factors were found in 66.7% and evidence of atherothrombosis in 0%. SAHS diagnosis was confirmed by polysomnography in 88.9% of patients. AHI showed mild, moderate and severe SAHS in 12%, 26% and 66% of the gout patients and 45%, 24% and 30% of the OA patients, respectively. SaO2 was 90.18% in the gout group and 91.26% in the OA group. Patients with gout and hyperuricaemia and suspicion of SAHS had polysomnographically confirmed SAHS in 88.9% of cases. These patients had more severe forms of SAHS and a greater prevalence of documented atherothrombotic disease compared with a control group with OA.

Arthropathy and Tendinopathy in Patients with Tophaceous and Non-tophaceous Gout: A Case-controlled Ultrasonographic Study

Objective: To determine the characteristics of tendon and joint involvement in patients with tophaceous and non-tophaceous gout on ultrasonography (US). Method: We performed a prospective, observational, case-controlled study using US to evaluate the knee, ankle, 1st and 2nd metatarsal-phalangeal (MTP) joints, and the tendons and entheses of the lower limbs. Differences were analyzed by Fisher’s exact or Mann-Whitney U-tests. Results: Twenty-four patients with tophaceous gout and 36 subjects with nontophaceous gout were recruited. Double contour signs (DCS) of the femoral condyles were significantly more prevalent in the tophaceous gout group compared to the non-tophaceous group (50% vs. 15.3%; p=0.001). The 1st and 2nd MTP joints of patients with tophaceous gout had significantly more DCS, periarticular tophi, and bone erosions than patients with non-tophaceous gout (p≤0.002). Intratendinous tophi in the Achilles tendons (43.8% vs. 6.9%), proximal/distal patella tendons (29.2%/41.7% vs. 1.4%/8.3%), tibialis anterior/posterior tendons (14.6%/39.6% vs. 0/1.4%), and peroneus longus and brevis tendons (29.2% vs. 0) were significantly more frequent in patients with tophaceous gout than patients with non-tophaceous gout (p≤0.002). Enthesopathies were commonly observed; specifically 7.5% of proximal patella tendons, 20% of distal patella tendons, and 13.3% of Achilles tendons presented with enthesopathies. No statistical differences existed between groups. Conclusion: Patients with tophaceous gout had significantly more prevalent intra- and extra-articular pathology on US, suggesting a larger quantity of monosodium urate depositions, than patients with non-tophaceous gout. We thus recommend a more aggressive and longer duration of urate-lowering therapy in patients with tophaceous gout.

Hospital admissions associated with gout and their comorbidities in New Zealand and England 1999-2009

To describe the national demographics, comorbidities and mortality of admissions associated with gout in New Zealand (NZ) from 1999 to 2009 and compare this with English gout admission data from the same period. The characteristics of all admissions due to or complicated by gout in NZ from 1999 to 2009 were analysed. These findings were then compared with the wider NZ population and the English National Health Service (NHS) gout admission rates from 1999 to 2009. There were 10 241 admissions due to gout (group A) and 34 318 admissions complicated by gout (group B) in NZ from 1999 to 2009. There were 32 741 admissions due to gout in England over the same period. Gout admissions rose at 5.5% per year in NZ and at 7.2% per year in England over the study period. NZ gout patients admitted to hospital were more likely to be Māori or a Pacific Islander and had 3-7 comorbidities. Multiple admissions were common with 1479 NZ gout patients admitted more than once. Comorbidities varied between the NZ groups A and B: hypertension (19-39%), renal disease (16-27%) and diabetes mellitus (20-27%) were common. Heart failure (27.6%) and cardiovascular disease (39.1%) were common in those who had gout complicating their hospital admission. This group also had poorer survival compared with those admitted primarily for gout. This is the first study to describe the epidemiology of admissions associated with gout across an entire country. Admissions are rising in both countries studied and those admitted in NZ have a high rate of comorbidity and re-admission.

Risk of end-stage renal disease associated with gout: a nationwide population study

IntroductionWe explored the risk of end-stage renal disease (ESRD) among gout patients in a representative cohort in Taiwan.MethodsThe primary database used was the Taiwan National Health Insurance Research Database. Subjects older than 20 years without ESRD, coronary heart disease, or stroke were included in the study. The case definition of gout in the present study was gout diagnosis and medical treatment for gout. An ESRD case was defined by the presence of chronic renal failure necessitating long-term renal replacement therapy. Multivariate Cox proportional hazards models were used to evaluate the risk of ESRD among gout patients.ResultsThe analysis included data of 656,108 patients who were followed up for a mean of 8.0 years. Among them, 19,963 (3.0%) patients had gout. At the end of 2008, 2,377 individuals (gout, n = 276; non-gout, n = 2,101) had ESRD, and 861 individuals (gout, n = 77, 27.9%; non-gout, n = 521, 24.8%) died due to ESRD. The rates of incidence of ESRD were 1.73 and 0.41 cases per 1,000 patient-years in the gout and non-gout groups. After adjustment for age, sex, and history of diabetes mellitus and/or hypertension, gout was associated with a hazard ratio (HR) of 1.57 for ESRD (95% confidence interval [CI], 1.38-1.79; P < 0.001). In patients with ESRD, the adjusted HR for death in patients with gout was 0.95 (0.74-1.23, P = 0.71), which was similar to the HR obtained in patients without gout.ConclusionsGout is associated with an increased hazard for development of ESRD.

Progress in Measurement Instruments for Acute and Chronic Gout Studies

Consensus exercises have identified and prioritized domains of measurement for studies in acute and chronic gout. In parallel, the technical properties of instruments for measurement in many of these domains have been assessed, with the main objective to consider the instruments in the context of the OMERACT filter of truth, discrimination, and feasibility. These data were presented and discussed at OMERACT 9 in the gout workshop, in breakout groups, and at informal meetings of the gout group. In acute gout, instruments for domains of pain, joint swelling, joint tenderness, and patient and physician global assessment have been assessed. In chronic gout, some validation exercises have been performed in instruments for domains serum urate, tophus measurement, health-related quality of life (HRQOL). In voting at OMERACT 9, the Medical Outcomes Study Short-Form 36 was endorsed as a valid instrument for measurement of HRQOL. Methods of tophus measurement were considered to have met some criteria of the OMERACT filter, but these require further work, particularly regarding sensitivity to change over shorter time periods. Priorities for future research include measurement of joint inflammation in acute gout and disability in acute and chronic gout.

Sodium-dependent phosphate cotransporter type 1 sequence polymorphisms in male patients with gout

ObjectivesMolecular biological approaches have recently identified urate transporters in renal proximal tubular cells. Human sodium-dependent phosphate cotransporter type 1 encoded by SLC17A1 is a urate transporter localised to the renal...