-
1.
Serum uric acid level and all-cause and cardiovascular mortality in peritoneal dialysis patients: A systematic review and dose-response meta-analysis of cohort studies.
Kang, T, Hu, Y, Huang, X, Amoah, AN, Lyu, Q
PloS one. 2022;(2):e0264340
Abstract
BACKGROUND The association between serum uric acid (SUA) and all-cause and cardiovascular disease (CVD) mortality in peritoneal dialysis (PD) patients is controversial. Therefore, we aimed to determine the relationship between SUA and all-cause and CVD mortality in PD patients. METHOD Web of Science, EMBASE, PubMed and the Cochrane Library databases were searched from their inception to 7 April 2021. Effect estimates were presented as hazard ratios (HRs) with 95% confidence intervals (95% CIs) and pooled using random effects model. RESULT Thirteen cohort studies with 22418 patients were included in this systematic review, of which 9 were included in the meta-analysis. Before switching the reference group, pooled result for the highest SUA category was significantly greater than the median for all-cause mortality (HR = 2.41, 95% CI: 1.37-4.26). After switching the reference group, the highest SUA category did not demonstrate an increased all-cause (HR = 1.40, 95% CI: 0.95-2.05) or CVD (HR = 1.30, 95% CI: 0.72-2.34) mortality compared with the lowest SUA category. Dose-response analysis suggested a nonlinear association between SUA and all-cause mortality risk (Pnonlinearity = 0.002). CONCLUSION This meta-analysis didn't find the relationship between SUA levels and all-cause and CVD mortality risk in PD patients. More rigorously designed studies are warranted in the future.
-
2.
Impacts of Sodium/Glucose Cotransporter-2 Inhibitors on Circulating Uric Acid Concentrations: A Systematic Review and Meta-Analysis.
Akbari, A, Rafiee, M, Sathyapalan, T, Sahebkar, A
Journal of diabetes research. 2022;:7520632
Abstract
BACKGROUND Several trials have assessed the antihyperglycemic effects of sodium/glucose cotransporter-2 inhibitors (SGLT2i) in patients with type 2 diabetes mellitus (T2DM). We conducted a quantitative analysis to assess the impact of SGLT2is on serum uric acid (SUA) in patients with T2DM. METHODS Placebo-controlled trials published before 13 August 2021 were identified by searching PubMed, Embase, Web of Science, and Scopus. The intervention group received SGLT2i as monotherapy or add-on treatment, and the control group received a placebo that was replaced with SGLT2i. Clinical trials providing changes in SUA were included. The mean change of SUA, glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and body weight were calculated (PROSPERO CRD42021287019). RESULTS After screening of 1172 papers, 59 papers were included in the systematic review. A total of 55 trials (122 groups) of 7 types of SGLT2i on patients with T2DM were eligible for meta-analysis. All SGLT2is significantly decreased SUA levels compared with the placebo groups: empagliflozin mean difference (MD) = -40.98 μmol/L, 95% CI [-47.63, -34.32], dapagliflozin MD = -35.17 μmol/L, 95% CI [-39.68, -30.66], canagliflozin MD = -36.27 μmol/L, 95% CI [-41.62, -30.93], luseogliflozin MD = -24.269 μmol/L, 95% CI [-33.31, -15.22], tofogliflozin MD = -19.47 μmol/L, 95% CI [-27.40, -11.55], and ipragliflozin MD = -18.85 μmol/L, 95% CI [-27.20, -10.49]. SGLT2i also decreased FPG, body weight, and HbA1c levels. SUA reduction persisted during long-term treatment with SGLT2i (except for empagliflozin), while the SUA reduction was affected by the duration of diabetes. CONCLUSIONS SGLT2i can be a valid therapeutic strategy for patients with T2DM and comorbid hyperuricemia. Besides reducing FPG, body weight, and HbA1c, SGLT2i can significantly decrease SUA levels compared to placebo (Total MD = -34.07 μmol/L, 95% CI [-37.00, -31.14]).
-
3.
Uric acid extrarenal excretion: the gut microbiome as an evident yet understated factor in gout development.
Méndez-Salazar, EO, Martínez-Nava, GA
Rheumatology international. 2022;(3):403-412
Abstract
Humans do not produce uricase, an enzyme responsible for degrading uric acid. However, some bacteria residing in the gut can degrade one-third of the dietary and endogenous uric acid generated daily. New insights based on metagenomic and metabolomic approaches provide a new interest in exploring the involvement of gut microbiota in gout. Nevertheless, the exact mechanisms underlying this association are complex and have not been widely discussed. In this study, we aimed to review the evidence that suggests uric acid extrarenal excretion and gut microbiome are potential risk factors for developing gout. A literature search was performed in PubMed, Web of Science, and Google Scholar using several keywords, including "gut microbiome AND gout". A remarkable intestinal dysbiosis and shifts in abundance of certain bacterial taxa in gout patients have been consistently reported among different studies. Under this condition, bacteria might have developed adaptive mechanisms for de novo biosynthesis and salvage of purines, and thus, a concomitant alteration in uric acid metabolism. Moreover, gut microbiota can produce substrates that might cross the portal vein so the liver can generate de novo purinogenic amino acids, as well as uric acid. Therefore, the extrarenal excretion of uric acid needs to be considered as a factor in gout development. Nevertheless, further studies are needed to fully understand the role of gut microbiome in uric acid production and its extrarenal excretion, and to point out possible bacteria or bacterial enzymes that could be used as probiotic coadjutant treatment in gout patients.
-
4.
Factors Influencing Change in Serum Uric Acid After Administration of the Sodium-Glucose Cotransporter 2 Inhibitor Luseogliflozin in Patients With Type 2 Diabetes Mellitus.
Chino, Y, Kuwabara, M, Hisatome, I
Journal of clinical pharmacology. 2022;(3):366-375
-
-
Free full text
-
Abstract
Although sodium-glucose cotransporter 2 (SGLT2) inhibitors lower serum uric acid, their long-term effect on uric acid metabolism is not well understood. We analyzed pooled data from studies wherein patients with type 2 diabetes mellitus received luseogliflozin, an SGLT2 inhibitor. Upon stratifying patients by baseline glycated hemoglobin (HbA1c ) or serum uric acid, lower HbA1c or higher serum uric acid level was associated with a greater reduction in serum uric acid after treatment. At week 12 of treatment, significant increases in urinary glucose/creatinine (Cr) ratio and urinary uric acid clearance/Cr clearance ratio (CUA /CCr ratio) and a significant reduction in serum uric acid were observed. Comparison of the subgroups of patients with a reduction or an increase in serum uric acid showed that the increase subgroup had a higher estimated glomerular filtration rate (eGFR) at baseline, and the eGFR was significantly reduced, associated with a significant reduction in the CUA /CCr ratio. Multiple regression analysis showed that the reduction in serum uric acid in the luseogliflozin group was strongly associated with baseline high serum uric acid, low HbA1c levels, and an increase in eGFR. Luseogliflozin was shown to reduce serum uric acid by enhancing urinary uric acid excretion in association with increased urinary glucose. Treatment with luseogliflozin resulted in increased serum uric acid in some patients, which may be due to reduced glomerular filtration of uric acid via the tubuloglomerular feedback. SGLT2 inhibitors reduced serum uric acid desirably in patients with type 2 diabetes mellitus with low HbA1c and high serum uric acid.
-
5.
Effects of a Behavioral Weight Loss Intervention and Metformin Treatment on Serum Urate: Results from a Randomized Clinical Trial.
Hu, JR, Yeh, HC, Mueller, NT, Appel, LJ, Miller, ER, Maruthur, NM, Jerome, GJ, Chang, AR, Gelber, AC, Juraschek, SP
Nutrients. 2021;(8)
Abstract
Background: Lower body mass index (BMI) has been associated with lower serum urate (SU), but only in observational studies. We sought to determine the effects of behavioral weight loss and metformin treatment on SU in a randomized trial. Methods and Findings: The Survivorship Promotion In Reducing IGF-1 Trial (SPIRIT) was a parallel three-arm randomized controlled trial of overweight/obese adult cancer survivors without gout at a single center in Maryland, United States. Participants were randomized to: (1) coach-directed weight loss (behavioral telephonic coaching), (2) metformin (up to 2000 mg daily), or (3) self-directed weight loss (informational brochures; reference group). SU and BMI were assessed at baseline and at 3, 6, and 12 months post-randomization. The 121 participants had a mean ± standard deviation (SD) age of 60 ± 9 years, 79% were female, and 45% were Black. At baseline, BMI was 35 ± 5 kg/m2, and SU was 5.6 ± 1.3 mg/dL. Compared to the self-directed group, at 12 months, the coach-directed group reduced BMI by 0.9 kg/m2 (95% confidence interval (CI): -1.5, -0.4) and metformin reduced BMI by 0.6 kg/m2 (95% CI: -1.1, -0.1). However, compared to the self-directed group, the coach-directed group unexpectedly increased SU by 0.3 mg/dL (95% CI: 0.05, 0.6), and metformin non-significantly increased SU by 0.2 mg/dL (95% CI: -0.04, 0.5); these effects were attenuated when analyses included change in estimated glomerular filtration rate (eGFR). Conclusions: In this randomized trial of cancer survivors without gout, reductions in BMI either increased or did not change SU, potentially due to effects on eGFR. These results do not support a focus on BMI reduction for SU reduction; however, long-term studies are needed. ClinicalTrials.gov Registration: NCT02431676.
-
6.
Serum uric acid and blood pressure among adolescents: data from the Nutrition and Health Survey in Taiwan (NAHSIT) 2010-2011.
Lin, KH, Yen, FS, Chen, HS, Hwu, CM, Yang, CC
Blood pressure. 2021;(2):118-125
Abstract
PURPOSE Elevated serum uric acid (UA) is frequently observed in adults with high blood pressure (BP); however, data from adolescents are limited. We examined the association between serum UA and BP in a nationally representative sample of Taiwan adolescents. MATERIAL AND METHODS Some 1384 participants, aged 14-19 years, from the Nutrition and Health Survey in Taiwan 2010-2011 were included for the study. Elevated BP was defined as systolic or diastolic BP ≥120/80 mmHg. The analyses examined the relationship between serum UA and BP using linear regression and odds ratios of having an elevated BP using logistic regression. RESULTS In this study population, the mean age was 16.0 years, mean serum UA was 5.8 mg/dL, 22.5% were obese (body mass index ≥24 kg/m2) and 9.8% had an elevated BP. Compared to girls, boys are more likely to be obese and to have higher serum UA and BP. After full adjustments, systolic BP, diastolic BP and mean arterial pressure increased 0.45, 0.48 and 0.47 mmHg, respectively, for each 1-mg/dL increase in UA (p = 0.07, 0.03 and 0.02, respectively). The odds of having an elevated BP were 3.4 times higher in subjects of the upper tertile of serum UA than those of the lower tertile (p = 0.02). CONCLUSION Adolescents with factors as male, obesity, and UA ≥5.5 mg/dL were prone to have an elevated BP, regardless of age and family history of hypertension. The present study found that serum UA levels are significantly correlated to BP in Taiwanese adolescents.
-
7.
Clinical implications of synovial fluid specimen handling for crystal associated arthritides: A systematic review.
Meyer, MM, Marks, LA, Aslam, F
International journal of rheumatic diseases. 2021;(1):10-20
Abstract
AIM: To identify the appropriate methods of synovial fluid (SF) specimen storage, manipulation and handling for crystal associated arthritides (CAA) diagnosis. METHOD A systematic literature review was conducted using 5 medical databases to identify diagnostic studies assessing SF specimen handling for calcium pyrophosphate (CPP) and monosodium urate (MSU) crystals identification. All included studies were rated for quality using the Quality Assessment of Diagnostic Accuracy Studies 2. RESULTS Fifteen studies, including 2 non-English language manuscripts, were included. Eight studies examined both types of crystals, while 3 studies examined CPP and 4 studies examined MSU crystals only. Overall, MSU crystals were more stable over time compared to CPP crystals. MSU stability was generally independent of time, preservative and temperature. CPP crystals deteriorated with time and were more stable if refrigerated. Ethylenediaminetetraacetic acid (EDTA) was a suitable preservative. Re-examining an initially negative SF sample at 24 hours facilitated detection of additional cases. Very few studies had an overall low risk of bias and applicability. CONCLUSION Monosodium urate crystals remain stable over time independent of storage time, temperature and preservative. CPP crystals are mostly stable for 24-48 hours but can deteriorate with time. Overall, SF crystal examination should ideally be done within 24-48 hours. They may be stored at room temperature without any preservative. Otherwise, refrigeration (4°C/39°F) and EDTA preservation is reasonable. Stored SF re-examination, at 24 hours, helps identify a small number of additional MSU and CPP cases. Centrifugation techniques allow better and easier crystal identification, particularly CPP. Most studies were of unclear or low quality.
-
8.
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
-
-
Free full text
-
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).
-
9.
The miscibility and solubility of uric acid and vitamin C in the solution phase and their structural alignment in the solid-liquid interface.
Chattaraj, KG, Paul, S
Physical chemistry chemical physics : PCCP. 2021;(28):15169-15182
Abstract
The crystallization of uric acid (UA) in humans is correlated with unpropitious medical predicaments, including gout and kidney stone germination. Its comparatively low solubility in physiological solutions is a significant contributory factor to UA biomineralization. The inhibition of UA aggregation is investigated as a reasonable approach for reducing kidney and gout-related problems. Therefore, we examine the role of vitamin C (Vit-C), a water-soluble vitamin, in the aggregation of UA, and its potency in solubilizing UA has been confirmed experimentally. We notice that Vit-C encapsulates the aggregated UA. Moreover, it can dismantle the assemblies of UA. We have proffered comprehensive molecular mechanisms of the interplay between the aggregated UA and Vit-C. Vit-C molecules are interspersed in solution due to its non-aggregating nature. We perceive that, through hydrogen bonding and aromatic stacking interactions, Vit-C molecules interact with UA molecules. The determination of the Flory-Huggins interaction parameters suggests that the presence of Vit-C enhances the solubility of UA aggregates. In addition, UA molecules are conformed on a monolayer graphene sheet, where they are assembled to create a 2D self-assembly. Vit-C, however, encapsulates and disseminates itself within the aggregated UA molecules on the surface. Therefore, the molecular mechanisms of the impact of Vit-C on UA aggregation can provide relevant insights into drug design against chronic diseases.
-
10.
Sodium-Glucose Cotransporter-2 (SGLT-2) Attenuates Serum Uric Acid (SUA) Level in Patients with Type 2 Diabetes.
Hussain, M, Elahi, A, Hussain, A, Iqbal, J, Akhtar, L, Majid, A
Journal of diabetes research. 2021;:9973862
Abstract
BACKGROUND Hyperuricemia has a strong association with diabetes mellitus. Hyperuricemia can lead to cardiovascular and renal complications in patients with diabetes. The goal of this study was to compare the effect of sodium-glucose cotransporter-2 (SGLT-2) inhibitors dapagliflozin and empagliflozin on serum uric acid (SUA) levels in patients with type 2 diabetes against traditional oral antihyperglycemic drugs (OADs). METHODS In this double-blind randomized controlled trial, 70 patients with type 2 diabetes and elevated SUA levels were assigned to two treatment groups. Patients in group A received SGLT-2 inhibitors tablet dapagliflozin 5 mg to 10 mg and empagliflozin 10 mg to 25 mg. Group B patients received OADs such as glimepiride, metformin, sitagliptin, gliclazide, and glibenclamide as monotherapy or combination therapy. The changes in SUA level were primary end points while changes in body weight and body mass index (BMI) from baseline to end point were secondary end points. RESULTS After four weeks of treatment, we noted a significant reduction of mean SUA levels in the SGLT-2 inhibitor group from 7.5 ± 2.5 to 6.3 ± 0.8 mg/dl versus comparator group from 7.1 ± 1.8 to 6.8 ± 2.2 mg/dl (p = 0.001). Mean body weight was significantly reduced in the SGLT-2 group from 82 ± 10.4 to 78 ± 12.5 kg versus comparator group from 78 ± 13.2 to 79.2 ± 9.7 kg (p = 0.001). Similarly, the mean BMI of patients in the SGLT-2 group was significantly reduced from 25.7 ± 3.2 to 24.2 ± 3.2 kg/m2 versus comparator group from 27.5 ± 4.2 to 28 ± 3.6 kg/m2 (p = 0.002). CONCLUSION SGLT-2 inhibitors have a strong potential to decrease SUA levels in patients with type 2 diabetes.