Uric Acid Variability Research Articles

Association between annual changes and visit-to-visit variability of serum uric acid and the kidney outcome in a general population.

To determine whether variability of serum uric acid (UA) is associated with risk of chronic kidney disease (CKD) in a healthy population. Retrospective, longitudinal cohort study was conducted at a health examination center in China. The study enrolled subjects who had a minimum of three visits between 2011 and 2018. We assessed UA change and visit-to-visit UA variability including standard deviation (SD), coefficient of variation (CV), variability independent of the mean (VIM), and average real variability (ARV). Rapid estimated glomerular filtration rate (eGFR) decline was defined by annual eGFR change < -4 mL/min/1.73m2/year. We conducted a multivariable-adjusted logistic regression analysis. Ten thousand seven hundred and thirty-eight participants were included. During 4.43±1.31years follow-up, there were 535 cases with rapid eGFR decline and 240 cases developed CKD. Compared to the non-rapid eGFR decline group and non-CKD group, the UA annual changes and variability were higher in the rapid eGFR decline group and CKD group. The highest quartile of UA annual changes and variability showed a higher incident rate of rapid eGFR decline and that of CKD. After adjusting for covariates, OR for eGFR rapid decline in UA variability were 1.69 [1.53, 1.86] for annual changes of UA, 1.17 [1.08, 1.27] for SD of UA, 1.16 [1.06, 1.25] for CV of UA, 1.16 [1.07, 1.25] for VIM of UA, and 1.10 [1.02, 1.19] for ARV of UA. Consistent results were observed when CKD is used as the outcome. Higher variability of serum UA was independently associated with the risk of kidney impairment.

Uric Acid Variability and All-Cause Mortality: A Prospective Cohort Study in Northern China.

Uric acid(UA) is related with cardiovascular disease, but the association of UA variability with all-cause mortality is rarely known. This study aimed to investigate the relationship between UA variability and all-cause mortality in Kailuan cohort study in northern China. Cohort study. Kailuan community hospitals in Tangshan, Hebei province, Northern China. A total of 55717 participants from Kailuan Study were enrolled, and our study followed up biennially from 2006 to 2010. Clinical records of the participants enrolled were analyzed. UA variation independent of mean (UAVIM) values were calculated and all the participants were quartile grouped into four groups as: Q1(UAVIM<0.68), Q2(0.68≤UAVIM<1.10), Q3(1.10≤UAVIM<1.67) and Q4(UAVIM≥1.67). The endpoint event was all-cause death. Cox regression model was performed to evaluate the hazard ratios(HRs) of all-cause mortality based on UAVIM groups. During a median follow-up of 6.83 years, 2926 deaths occurred. The accumulated mortality rates were 4.6%, 4.8%, 5.4% and 6.1% in group Q1, Q2, Q3 and Q4 respectively. When adjusted potential confounders, the highest risk for all-cause mortality was in group Q4 and the adjusted HRs and 95% confidence intervals(CIs) of group Q2-Q4 for all-cause death were 1.044(0.937, 1.164), 1.182(1.064, 1.314) and 1.353(1.220, 1.501) compared with group Q1, respectively. Further analysis showed that the risk for all-cause death increased as UAVIM value increased. Sensitive analysis still showed the similar results when excluding participants with hyperuricemia or severe chronic kidney diseases. Sub-group analysis by age, gender, BMI or hypertension history also indicated analogous results. Elevated UAVIM was related with increased all-cause mortality and UAVIM was an independent risk factor for all-cause mortality in the community cohort study.

Prediction models and nomograms of 3-year risk of chronic kidney disease in China: a study from the Shanghai Suburban Adult Cohort and Biobank (2016-2020).

BackgroundChronic kidney disease (CKD) is a serious public health problem in China that requires the development and verification of sex-specific 3-year risk prediction models and nomograms of CKD to further guide personalized care.MethodsA 3-year community-based observational cohort study of 10,049 Chinese participants without CKD was begun in 2016 and participants were followed until August 2020. Stepwise multivariable-adjusted Cox regression analyses were conducted to select the candidate variables, including demographics and clinical parameters such as blood urea nitrogen (BUN) and estimated glomerular filtration rate (eGFR), into the prediction model. We used the C-statistic to evaluate discrimination, and the Brier score for calibration. A 10-fold cross-validation was conducted for internal validation to assess the model’s stability.ResultsThe cumulative incidence of CKD was 4.25% (male: 3.81%, female: 4.55%). The eGFR, HbA1c variability, uric acid (UA), UA variability, BUN, albumin, and Hb were significant predictors for both sexes. In the female model, age, triglycerides and age at menarche were additional predictors. The models showed C-statistics of 0.934/0.951 (male/female). The model calibrated well across the deciles of predicted risk, with a Brier score of 0.007/0.009 (male/female).ConclusionsIn this study, we fitted the CKD 3-year risk prediction models with an accuracy rate of >90%. At the same time, we developed two nomograms to facilitate routine CKD risk prediction to provide individualized care in preventing or delaying CKD.

Determinants of serum uric acid levels in an adult general population: results from the Moli-sani Study.

High levels of serum uric acid (UA) are associated with cerebro-cardiovascular disease risk factors. This study aimed at evaluating the main determinants of serum UA levels in relation to biochemical, lifestyle, and clinical variables. The study population included 15,594 participants (48% men, age ≥ 35years) to the Moli-sani Study, for whom data on serum UA levels were available. Association of UA with dependent variables was investigated by multivariable linear regression analysis separately for men and women. Average serum UA levels were higher in men than in women (6.1 ± 1.3 vs 4.6 ± 1.2mg/dL, respectively). Cystatin C, creatinine, albumin, triglycerides, body mass index (BMI), and diuretic therapy were the major determinants of the heterogeneity of UA levels. In women, the final model, resulting from the stepwise analysis, explained 41.6% of the UA variability. In particular, cystatin C explained 22.5% of UA variance, followed by BMI (7.2%), albumin (4.0%), and creatinine (1.9%). The final model in men fitted the data less than in women (total R2 = 29.1%), and creatinine was found to be the main determinant of UA levels (10.1%), followed by triglycerides (7.6%), BMI (3.7%), and albumin (2.0%). In a general adult population, the major determinants of serum UA levels are cystatin C, creatinine, BMI, triglycerides, albumin, and the use of diuretics. Knowledge of its main determinants will be useful to better evaluate the relationship between UA levels and detrimental health outcomes and to clarify if an increase in uricemia is a marker or an independent risk factor. Key Points • Increased serum uric acid (UA) levels are reportedly associated with cardiovascular disease risk factors. • The major determinants of heterogeneity of UA levels are cystatin C, creatinine, BMI, triglycerides, albumin, and the use of diuretics, in a general adult population. • Studying the main determinants associated with high levels of serum uric acid would help better understanding if uric acid is a marker or an independent cardiovascular risk factor.

Association of variability in uric acid and future clinical outcomes of patient with coronary artery disease undergoing percutaneous coronary intervention

Background and aimsHyperuricemia is independently associated with cardiovascular disease (CVD) and is considered to be one of the major risk factors for CVD. However, the impact of inter-visit uric acid (UA) variability on cardiovascular risk remains undetermined. MethodsWe enrolled 3202 patients with coronary artery disease (CAD), who received successful coronary intervention, in a cohort from Taipei Veterans General Hospital from 2006 to 2015. All post-baseline visits UA measurements using standard deviation (SD) were analyzed to correlate with long-term outcome. The primary outcome was the composite of cardiac death, nonfatal MI, nonfatal stroke (MACE). The secondary event was MACE and hospitalization for heart failure. ResultsDuring an average 65.06 ± 32.1-month follow-up, there were 66 cardiovascular deaths, 175 nonfatal myocardial infarctions, 64 nonfatal strokes, 287 hospitalizations for heart failure, and 683 revascularization procedures. There was a linear association between high UA SD and future adverse events. Compared to the lowest quartile SD, subjects in the highest quartile SD had a higher risk of MACE (HR: 2.53, 95% CI: 1.78–3.59), myocardial infarction (HR: 2.43, 95% CI: 1.53–3.86), cardiovascular death (HR: 6.45, 95% CI: 2.52–16.55), heart failure-related hospitalization (HR: 3.43, 95% CI: 2.32–5.05), and total major CV events (HR: 2.72, 95% CI: 2.09–3.56). Furthermore, compared to the average achieved on-treatment UA value, increasing UA SD had a stronger association of higher risk of developing MACE (HR: 1.51, 95% CI: 1.36–1.68), myocardial infarction (HR: 1.37, 95% CI: 1.38–1.68), ischemic stroke (HR: 1.43, 95% CI: 1.13–1.82), CV death (HR: 1.77, 95% CI: 1.50–2.11), HF (HR: 1.43, 95% CI: 1.29–1.58), and total major CV events (HR: 1.46, 95% CI: 1.34–1.58). ConclusionsHigh UA variability is associated with a higher risk of developing future cardiovascular events, suggesting the importance of maintaining stable serum UA levels and avoiding large fluctuations in CAD patients after percutaneous coronary intervention (PCI).

Association of Serum Uric Acid Concentration and Its Change with Cardiovascular Death and All-Cause Mortality.

Objective There is no consensus on the role of abnormal uric acid (UA) levels in the prognosis of patients undergoing hemodialysis. We therefore aimed to investigate the effects of changes in UA concentration on the risk of all-cause death and cardiac death in such patients. Method In this retrospective cohort study, patients admitted to two hemodialysis centers performing maintenance hemodialysis (MHD) in Wuhan First Hospital and Fourth Hospital Hemodialysis Center from January 1, 2007, to October 31, 2017, were included. Results In all, 325 patients undergoing MHD aged 59.7 ± 14.7 years, including 195 men (60%), were enrolled, with a median follow-up of 37 months. Serum UA (p < 0.001) was significantly higher in the surviving group than in the death group. No significant difference was found in UA variability (p < 0.001) was significantly higher in the surviving group than in the death group. No significant difference was found in UA variability (p < 0.001) was significantly higher in the surviving group than in the death group. No significant difference was found in UA variability (p < 0.001) was significantly higher in the surviving group than in the death group. No significant difference was found in UA variability (p < 0.001) was significantly higher in the surviving group than in the death group. No significant difference was found in UA variability (p < 0.001) was significantly higher in the surviving group than in the death group. No significant difference was found in UA variability (p < 0.001) was significantly higher in the surviving group than in the death group. No significant difference was found in UA variability (p < 0.001) was significantly higher in the surviving group than in the death group. No significant difference was found in UA variability (Conclusion Low UA levels were closely related to all-cause mortality in patients undergoing MHD. Although UA levels had no significant effect on cardiac death, they had a good predictive value for long-term prognosis in patients on MHD.

Donor-specific individuality of red blood cell performance during storage is partly a function of serum uric acid levels.

Previous investigations in leukoreduced units of red blood cells (RBCs) in mannitol additive solution revealed the close association of uric acid (UA) levels in vivo with the susceptibility of RBCs to storage lesion markers. In this study, we examined whether UA has a similar correlation with the capability of RBCs to cope with the oxidative provocations of storage under different conditions, namely, in CPDA-1 and in the absence of leukoreduction. The UA-dependent antioxidant capacity of the supernatant was measured in nonleukoreduced units of RBCs in CPDA (n=47). The possible effect of UA variability on the storage lesion profile was assessed by monitoring several physiologic properties of RBCs and supernatant, including cell shape, reactive oxygen species, and size distribution of extracellular vesicles, in units exhibiting the lowest or highest levels of UA activity (n=16) among donors, throughout the storage period. In stored RBC units, the UA-dependent antioxidant activity of the supernatant declined as a function of storage duration but always in strong relation to the UA levels in fresh blood. Contrary to units of poor-UA activity, RBCs with the highest levels of UA activity exhibited better profile of calcium- and oxidative stress-driven modifications, including a significant decrease in the percentages of spherocytes and of 100- to 300-nm-sized vesicles, typically associated with the exovesiculation of stored RBCs. The antioxidant activity of UA is associated with donor-specific differences in the performance of RBCs under storage in nonleukoreduced CPDA units.

Variability in HbA1c, blood pressure, lipid parameters and serum uric acid, and risk of development of chronic kidney disease in type 2 diabetes.

Variability in HbA1c and blood pressure is associated with the risk of diabetic kidney disease (DKD). No evidence exists on the role of variability in lipids or serum uric acid (UA), or the interplay between the variability of different parameters, in renal outcomes. Within the AMD Annals database, we identified patients with ≥5 measurements of HbA1c, systolic blood pressure (SBP) and diastolic blood pressure (DBP), total-, high-density lipoprotein (HDL)- and low-density lipoprotein (LDL)-cholesterol, triglycerides, and UA. Patients were followed-up for up to 5 years. The impact of measures of variability on the risk of DKD was investigated by Cox regression analysis and recursive partitioning techniques. Four-thousand, two-hundred and thirty-one patients were evaluated for development of albuminuria, and 7560 for decreased estimated glomerular filtration rate (eGFR; <60 mL/min/1.73 m2 ). A significantly higher risk of developing albuminuria was associated with variability in HbA1c [upper quartile hazard ratio (HR) = 1.3; 95% confidence interval (CI) 1.1-1.6]. Variability in SBP, DBP, HDL-C, LDL-C and UA predicted the decline in eGFR, the association with UA variability being particularly strong (upper quartile HR = 1.8; 95% CI 1.3-2.4). The concomitance of high variability in HbA1c and HDL-C conferred the highest risk of developing albuminuria (HR = 1.47; 95% CI 1.17-1.84), while a high variability in UA (HR = 1.54; 95% CI 1.19-1.99) or DBP (HR = 1.47; 95% CI 1.11-1.94) conferred the highest risk of decline in eGFR. The variability of several parameters influences the development of DKD, having a different impact on albuminuria development and on the decline in GFR.