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A Randomized Pilot Study of DASH Patterned Groceries on Serum Urate in Individuals with Gout.
Juraschek, SP, Miller, ER, Wu, B, White, K, Charleston, J, Gelber, AC, Rai, SK, Carson, KA, Appel, LJ, Choi, HK
Nutrients. 2021;(2)
Abstract
The Dietary Approaches to Stop Hypertension (DASH) diet reduces serum urate (SU); however, the impact of the DASH diet has not been previously evaluated among patients with gout. We conducted a randomized, controlled, crossover pilot study to test the effects of ~$105/week ($15/day) of dietitian-directed groceries (DDG), patterned after the DASH diet, on SU, compared with self-directed grocery shopping (SDG). Participants had gout and were not taking urate lowering therapy. Each intervention period lasted 4 weeks; crossover occurred without a washout period. The primary endpoint was SU. Compliance was assessed by end-of-period fasting spot urine potassium and sodium measurements and self-reported consumption of daily servings of fruit and vegetables. We randomized 43 participants (19% women, 49% black, mean age 59 years) with 100% follow-up. Mean baseline SU was 8.1 mg/dL (SD, 0.8). During Period 1, DDG lowered SU by 0.55 mg/dL (95% CI: 0.07, 1.04) compared to SDG by 0.0 mg/dL (95% CI: -0.44, 0.44). However, after crossover (Period 2), the SU difference between groups was the opposite: SDG reduced SU by -0.48 mg/dL (95% CI: -0.98, 0.01) compared to DDG by -0.05 mg/dL (95% CI: -0.48, 0.38; P for interaction by period = 0.11). Nevertheless, DDG improved self-reported intake of fruit and vegetables (3.1 servings/day; 95% CI: 1.5, 4.8) and significantly reduced total spot urine sodium excretion by 22 percentage points (95% CI: -34.0, -8.6). Though relatively small in scale, this pilot study suggests that dietitian-directed, DASH-patterned groceries may lower SU among gout patients not on urate-lowering drugs. However, behavior intervention crossover trials without a washout period are likely vulnerable to strong carryover effects. Definitive evaluation of the DASH diet as a treatment for gout will require a controlled feeding trial, ideally with a parallel-design.
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Hypouricemia and Mortality Risk in the US General Population.
D'Silva, KM, Yokose, C, Lu, N, McCormick, N, Lee, H, Zhang, Y, Choi, HK
Arthritis care & research. 2021;(8):1171-1179
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Abstract
OBJECTIVE The most recent European Alliance of Associations for Rheumatology (EULAR) recommendations for gout advise against maintaining a serum urate (SU) level of <3 mg/dl for prolonged periods of time. While several Asian cohort studies have shown higher rates of mortality in individuals with extremely low SU levels, data from non-Asian cohort studies are scarce, and the relationship between hypouricemia, cardiovascular risk, and mortality remains unclear. METHODS Using data collected from the 1988-1994 and 1999-2008 National Health and Nutrition Examination Survey (NHANES), we examined the relationship between SU level and overall and cause-specific mortality in 41,807 adults in the US. We calculated multivariable hazard ratios (HRs) that were compared to a referent SU level of 5-6 mg/dl for SU categories <4, 4-5, 6-7, 7-8, and >8 mg/dl in men and SU categories <3, 3-4, 4-5, 6-7, and >7 mg/dl in women. RESULTS A higher mortality risk was not observed in women who had an SU level of <3 mg/dl (HR 1.09 [95% confidence interval (95% CI) 0.92-1.28]). A 28% higher mortality risk was observed in men who had an SU level of <4 mg/dl (HR 1.28 [95% CI 1.13-1.45]), with a nearly three-times higher mortality risk from diabetes mellitus also noted (HR 2.89 [95% CI 1.59-5.23]), but no increase in mortality from any other specific cause. CONCLUSION We found no long-term excess mortality risk among American women with SU levels as low as <3 mg/dl, a finding which is incompatible with the notion of a causal relationship between hypouricemia and premature mortality in women. We found excess all-cause mortality and diabetes mellitus-related mortality among hypouricemic American men, which may in part be attributable to the uricosuric effect of hyperglycemia in fatal uncontrolled diabetes mellitus (analogous to reverse causality).
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Metabolic diagnoses of recurrent stone formers: temporal, geographic and gender differences.
Huynh, LM, Dianatnejad, S, Tofani, S, Carrillo Ceja, R, Liang, K, Tapiero, S, Jiang, P, Youssef, RF
Scandinavian journal of urology. 2020;(6):456-462
Abstract
BACKGROUND Metabolic factors underlying the recent increase in stone prevalence over the past decades are not well understood. Herein, we evaluate temporal, geographic and gender-specific trends in metabolic risk factors in recurrent kidney stone formers. PATIENTS AND METHODS A systematic literature review of metabolic risk factors for stone formation was conducted, inclusive of the last four decades. Studies with inadequate 24 h urine metabolic data, pediatric or those with less than 50 patients were excluded. The primary outcome was prevalence of each metabolic risk factor, compared between studies published prior to the year 2000 vs those following. Geographic and gender differences were secondary outcomes. RESULTS Twenty-eight articles met inclusion criteria, of which 10 (n = 1578) were published prior to the year 2000 and 18 (n = 8747) were published thereafter. Comparing these groups, an increase in hyperoxaluria (29% vs 33%; p = 0.002), hypercalciuria (35 vs 36%; p = 0.446), hyperuricosuria (17% vs 22%; p < 0.0001), low urine volume (28 vs 38%; p < 0.0001) and hypocitraturia (23% vs 44%; p < 0.0001) was observed. The prevalence of hyperoxaluria, hypercalciuria, hyperuricosuria and hypocitraturia were significantly higher in males. There were also significant geographical differences, with higher prevalence of hyperoxaluria and hypocitraturia in non-Western countries and higher prevalence of hypercalciuria in Western countries. Prevalence of hyperoxaluria is increasing in the US. CONCLUSION Prevalence of metabolic risk factors for nephrolithiasis significantly increased in recent years. These findings are hypothesis-generating and may provide valuable insight into the epidemiology, prevention and management of recurrent stone disease. Dietary modifications and innovative medical therapies are needed to decrease metabolic risk factors underlying nephrolithiasis.
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The Association of Longitudinal Serum Uric Acid and All-Cause Mortality in Incident Peritoneal Dialysis Patients.
Chang, W, Zhang, W, Wang, X, Liu, Y, Han, Y, Tu, Y, Uchida, S
Blood purification. 2019;(1-3):185-192
Abstract
BACKGROUND Time-averaged uric acid (TA-UA) value was calculated to investigate the association of longitudinal UA and all-cause mortality in incident peritoneal dialysis (PD) patients. METHODS Three hundred PD patients were divided into 3 groups based on the serum TA-UA level (Group 1: < 6 mg/dL; Group 2: 6-8 mg/dL; Group 3: ≥8 mg/dL). Hazards ratio (HR) of all-cause mortality was calculated. Logistic regression was conducted to identify the associated clinical factors of lower and higher TA-UA level. RESULTS Increased HRs for death existed in Group 1 and Group 3 compared with Group 2 (HR 3.24, 95% CI 1.25-8.39, p = 0.016; HR 4.69, 95% CI 1.24-17.72, p = 0.023). Lower residual renal function, lower albumin, and higher high-density lipoprotein cholesterol were related to the lower serum TA-UA. Higher body mass index and higher C-reactive protein were associated with higher serum TA-UA in PD patients. CONCLUSION Both TA-UA < 6 and ≥8 mg/dL increased the all-cause mortality in incident PD patients.
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Long-term effects of L- and N-type calcium channel blocker on uric acid levels and left atrial volume in hypertensive patients.
Masaki, M, Mano, T, Eguchi, A, Fujiwara, S, Sugahara, M, Hirotani, S, Tsujino, T, Komamura, K, Koshiba, M, Masuyama, T
Heart and vessels. 2016;(11):1826-1833
Abstract
Left ventricular (LV) diastolic dysfunction is associated with hypertension and hyperuricemia. However, it is not clear whether the L- and N-type calcium channel blocker will improve LV diastolic dysfunction through the reduction of uric acid. The aim of this study was to investigate the effects of anti-hypertensive therapy, the L- and N-type calcium channel blocker, cilnidipine or the L-type calcium channel blocker, amlodipine, on left atrial reverse remodeling and uric acid in hypertensive patients. We studied 62 patients with untreated hypertension, randomly assigned to cilnidipine or amlodipine for 48 weeks. LV diastolic function was assessed with the left atrial volume index (LAVI), mitral early diastolic wave (E), tissue Doppler early diastolic velocity (E') and the ratio (E/E'). Serum uric acid levels were measured before and after treatment. After treatment, systolic and diastolic blood pressures equally dropped in both groups. LAVI, E/E', heart rate and uric acid levels decreased at 48 weeks in the cilnidipine group but not in the amlodipine group. The % change from baseline to 48 weeks in LAVI, E wave, E/E' and uric acid levels were significantly lower in the cilnidipine group than in the amlodipine group. Larger %-drop in uric acid levels were associated with larger %-reduction of LAVI (p < 0.01). L- and N-type calcium channel blocker but not L-type calcium channel blocker may improve LV diastolic function in hypertensive patients, at least partially through the decrease in uric acid levels.
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Comprehensive dietary education in treated gout patients does not further improve serum urate.
Holland, R, McGill, NW
Internal medicine journal. 2015;(2):189-94
Abstract
BACKGROUND/AIM: This study aims to investigate the influence of dietary education in patients with gout on a stable dose of urate-lowering therapy (ULT). METHODS Males and females aged >18 years with a history of gout, receiving an appropriate and stable dose of ULT, were recruited from two tertiary hospitals and randomised into two groups. The control group received basic advice regarding the importance of compliance with therapy and the benefit of weight loss. The intervention group received comprehensive dietary advice based on the British Society of Rheumatology Guidelines. Both groups received education at baseline and 3 months. Serum urate was measured at baseline, 3 months and 6 months, and a questionnaire was completed at baseline and at 6 months. The primary outcome of the study was to compare the change in serum urate between groups. RESULTS Thirty patients were recruited into the study. There was no difference in serum urate between the control and intervention group at 6 months (0.29 mmol/L vs 0.29 mmol/L at baseline and 0.27 mmol/L vs 0.30 mmol/L at 6 months). The intervention group showed a statistically significant improvement in knowledge (8/13 in control group at baseline to 9/13 at 6 months vs 8/13 in intervention group at baseline to 12/13 at 6 months, P < 0.05) and self-reported dietary modification (1 in control vs 7 in intervention P < 0.05) at 6 months. CONCLUSION This randomised controlled trial shows that in patients on ULT, providing education on diet does not lead to any clinically significant difference in serum urate at 6 months.
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Can soy intake affect serum uric acid level? Pooled analysis from two 6-month randomized controlled trials among Chinese postmenopausal women with prediabetes or prehypertension.
Liu, ZM, Ho, CS, Chen, YM, Woo, J
European journal of nutrition. 2015;(1):51-8
Abstract
PURPOSE Hyperuricemia is a recognized risk factor for cardiovascular diseases. Soy foods contain a moderate amount of purine and may predispose to raised serum uric acid (UA). However, no study has examined the long-term effect of soy intake on UA levels. We examined whether consumption of soy foods and isoflavone extracts for 6 months altered serum UA. METHODS The analysis included two randomized controlled trials (soy protein trial and whole soy trial) among total 450 postmenopausal women with either prehypertension or prediabetes. We conducted a pooled analysis by combining participants from both the soy flour and soy protein groups (combined soy foods group), participants from both the isoflavone and daidzein groups (combined isoflavone group) and participants from both milk placebo groups. Fasting venous samples were obtained at baseline and the end of the trial for serum UA analysis. RESULTS In the pooled data, 417 subjects completed the study according to protocol. The baseline serum UA levels were comparable among the three combined groups. There was a lower decrease in UA levels among women in the combined soy foods group compared with women in the other two groups (p = 0.028 and 0.026). The net decrease and % decrease in UA were 14.5 μmol/L (95 % CI 1.93-25.6, p = 0.023) or 4.9 % (95 % CI 1.3-8.5 %, p = 0.023) between the combined soy foods group and placebo group. CONCLUSIONS Among Chinese postmenopausal women with either prehypertension or prediabetes, soy intake did not increase urate levels.
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Effects of combined enalapril and folic acid therapy on the serum uric acid levels in hypertensive patients: a multicenter, randomized, double-blind, parallel-controlled clinical trial.
Li, H, Qin, X, Xie, D, Tang, G, Zhang, Y, Li, J, Hou, F, Wang, X, Huo, Y, Xu, X
Internal medicine (Tokyo, Japan). 2015;(1):17-24
Abstract
Objective The efficacy of combined treatment consisting of enalapril and folic acid (FA) was compared to that of enalapril alone in reducing the serum uric acid (UA) levels in adult hypertensive patients in China. Methods Patients with mild to moderate hypertension (n=480) were randomly assigned to one of three treatment groups: (1) 10 mg enalapril (control group), (2) 10 mg enalapril plus 0.4 mg FA (low-FA group) or (3) 10 mg enalapril plus 0.8 mg FA (high-FA group) daily for eight weeks. The primary outcome was the UA ratio (week 8 UA: baseline UA). Results The final analysis included 450 patients (43.1% men, 27-75 years of age). An adjusted multivariable regression analysis revealed no significant differences in the UA ratio between the three groups after eight weeks of treatment. In the subgroup analysis stratified according to the baseline UA level, the high-FA group demonstrated a significantly greater UA-lowering response among the patients with an elevated baseline UA concentration (UA ≥310 μmol/L) [median UA ratio (25th percentile, 75th percentile): 0.94 (0.83, 1.01)], compared with that observed in the control group [0.97 (0.90, 1.00), p=0.025]. Similar results were found in the participants with baseline hyperuricemia (HUA; UA: men >420 μmol/L, women >350 μmol/L). Conclusion In this sample of adult hypertensive patients, the administration of a daily dose of 10 mg of enalapril combined with 0.8 mg of FA had a greater beneficial effect on the serum UA levels than did that of 10 mg of enalapril alone in patients with either an elevated UA concentration or HUA.
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Improvement in Renal Function and Reduction in Serum Uric Acid with Intensive Statin Therapy in Older Patients: A Post Hoc Analysis of the SAGE Trial.
Deedwania, PC, Stone, PH, Fayyad, RS, Laskey, RE, Wilson, DJ
Drugs & aging. 2015;(12):1055-65
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BACKGROUND Improvement in renal function and decreases in serum uric acid (SUA) have been reported following prolonged high-intensity statin (HMG-CoA reductase inhibitor) therapy. This post hoc analysis of the SAGE trial examined the effect of intensive versus less intensive statin therapy on renal function, safety, and laboratory parameters, including SUA, in elderly coronary artery disease (CAD) patients (65-85 years) with or without chronic kidney disease (CKD). METHODS Patients were randomized to atorvastatin 80 mg/day or pravastatin 40 mg/day and treated for 12 months. Patients were stratified using Modification of Diet in Renal Disease (MDRD) estimated glomerular filtration rates (eGFRs) in CKD (eGFR <60 mL/min/1.73 m(2)) and non-CKD populations. RESULTS Of the 893 patients randomized, 858 had complete renal data and 418 of 858 (49%) had CKD (99% Stage 3). Over 12 months, eGFR increased with atorvastatin and remained stable with pravastatin (+2.38 vs. +0.18 mL/min/1.73 m(2), respectively; p < 0.0001). MDRD eGFR improved significantly in both CKD treatment arms; however, the increased eGFR in patients without CKD was significantly greater with atorvastatin (+2.08 mL/min/1.73 m(2)) than with pravastatin (-1.04 mL/min/1.73 m(2)). Modest reductions in SUA were observed in both treatment arms, but a greater fall occurred with atorvastatin than with pravastatin (-0.52 vs. -0.09 mg/dL, p < 0.0001). Change in SUA correlated negatively with changes in eGFR and positively with changes in low-density lipoprotein cholesterol. Reports of myalgia were rare (3.6% CKD; 5.7% non-CKD), and there were no episodes of rhabdomyolysis. Elevated serum alanine and aspartate transaminase to >3 times the upper limit of normal occurred in 4.4% of atorvastatin- and 0.2% of pravastatin-treated patients. CONCLUSION Intensive management of dyslipidemia in older patients with stable coronary heart disease may have beneficial effects on renal function and SUA.
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Comparison of two plasma urate assays in patients receiving vitamin C supplementation.
Sies, CW, Florkowski, CM, Frampton, CM, O'Donnell, JL, Chapman, PT, Stamp, LK
Pathology. 2014;(4):333-5
Abstract
The aim of this study was to compare plasma urate (PU) concentrations using two different assays in patients receiving vitamin C supplementation. PU was measured using two routinely available enzymatic uricase methods: (1) uric acid plus method (ascorbate oxidase assay), and (2) uric acid method (non-ascorbate oxidase assay). Twenty patients receiving allopurinol were randomised to an increase in allopurinol dose or commence vitamin C 500 mg/d on a 1:1 ratio. Twenty patients not receiving allopurinol were randomised to start allopurinol or vitamin C 500 mg/d on a 1:1 ratio. Trough fasting samples for plasma ascorbate and urate were measured weekly until week 8. There was no significant difference in the mean PU measured by the two assays. In patients not receiving supplemental vitamin C the mean PU concentrations were identical for both assays. For patients receiving supplemental vitamin C the mean PU concentrations for the ascorbate oxidase assay was 0.525 mmol/L (SE 0.034) and for the non-ascorbate oxidase assay 0.510 mmol/L (SE 0.033), p = 0.079.There is a small non-significant difference in measured PU in patients receiving supplemental vitamin C between the two assays. The assay which does not include ascorbate oxidase results in consistently lower PU concentrations compared to the assay which includes ascorbate oxidase.