Association of serum 25-hydroxyvitamin D concentrations with all-cause and cause-specific mortality among individuals with gout and hyperuricemia.

BACKGROUND: We aimed to probe the association of serum 25-hydroxyvitamin D [25(OH)D] concentrations with all-cause and cause-specific mortality among patients with gout and hyperuricemia (HUA). METHODS: The study included 1169 gout patients and 7029 HUA patients from the National Health and Nutrition Examination Survey (NHANES) 2007-2018 and 2001-2018, respectively. The association between serum 25(OH)D and mortality was evaluated by Cox proportional hazard and restricted cubic spline models. RESULTS: Among participants with gout and HUA, the weighted mean concentrations of serum 25(OH)D were 71.49 ± 30.09 nmol/L and 64.81 ± 26.92 nmol/L, respectively. Vitamin D deficiency occurred in 29.68% of gout patients and 37.83% of HUA patients. During 6783 person-years of follow-up among gout patients, 248 all-cause deaths occurred, among which 76 died from cardiovascular disease (CVD) and 49 died from cancer. 1375 HUA patients were recorded for all-cause mortality during 59,859 person-years of follow-up, including 427 CVD deaths and 232 cancer deaths. After multifactorial adjustment, per one-unit increment in natural log-transformed 25(OH)D was associated with lower risk of 55% all-cause mortality and 61% CVD mortality among gout patients, and a 45% reduced risk of cancer mortality among HUA patients. Restricted cubic splines showed a U-shaped relationship with all-cause and CVD mortality among HUA patients, with inflection points of 72.7 nmol/L and 38.0 nmol/L, respectively. The results were robust in subgroup and sensitivity analyses. CONCLUSIONS: Serum 25(OH)D was negatively linearly correlated with mortality among gout patients, whereas U-shaped correlated with mortality in HUA patients. These results indicate that adequate vitamin D status could prevent premature death.

Association between urate-lowering therapy initiation and all-cause mortality in patients with type 2 diabetes and asymptomatic hyperuricemia.

AIMS: To assess the relationships between urate-lowering therapy (ULT) initiation with all-cause mortality in patients with asymptomatic hyperuricemia and Type 2 Diabetes (T2D). METHODS: This nationwide retrospective cohort study involved patients with T2D and asymptomatic hyperuricemia from 19 academic hospitals across China between 2000 and 2021. The primary exposure was ULT initiation, including allopurinol, febuxostat, or benzbromarone. The primary outcome was all-cause mortality. The secondary outcomes were cardiovascular (CV) and non-CV mortality. Propensity score matching was employed to create a 1:2 matched cohort with balanced likelihood of ULT initiation. Associations between ULT initiation with all-cause and CV mortality were assessed in the matched cohort. RESULTS: Among 42 507 patients, 5028 initiated ULT and 37 479 did not. In the matched cohort, comprising 4871 ULT initiators and 9047 noninitiators, ULT initiation was significantly associated with reduced risk of all-cause mortality (hazard ratio [HR] 0.77; 95% confidence interval [CI], 0.71-0.84), CV mortality (HR 0.86; 95% CI, 0.76-0.97), and non-CV mortality (HR 0.72; 95% CI, 0.64-0.80) over an average 3.0 years of follow-up. Among the ULT initiators, post-treatment SUA levels of 360-420 µmol/L was related to a significantly lower risk for all-cause mortality compared to levels >420 µmol/L (HR 0.74; 95% CI, 0.59-0.94) while levels ≤360 µmol/L did not (HR, 0.96; 95% CI, 0.81-1.14), suggesting a U-shaped relationship. CONCLUSIONS: Initiating ULT was associated with a significant reduction in all-cause mortality in patients with T2D and asymptomatic hyperuricemia. Notably, maintaining post-treatment SUA concentrations within 360-420 µmol/L could potentially enhance this reduced mortality.

Hyperuricemia and gout enhanced the risk of long-term mortality in hypertension: insights from the National Health and Nutrition Examination Survey 2007-2018.

BACKGROUND: Asymptomatic hyperuricemia (HUA) and normouricemic gout are common in clinic but recommendations for them in hypertension management are absent. The present study aims to simultaneously evaluate the effect of HUA and gout on long-term mortality in hypertension. METHODS: Individuals from 2007-2018 National Health and Nutrition Examination Survey were enrolled. Hazard ratios and 95% confidence intervals (CIs) were calculated with the aid of the Cox proportional-hazards model. The restricted cubic spline (RCS) analysis was made to show the dose-response relationship between uric acid and mortality. All-cause mortality and cardiovascular mortality were compared using the Kaplan-Meier curve with a log-rank test. RESULTS: Thirty thousand eight hundred and nineteen eligible individuals were included, of which 5841 suffered from HUA and 1476 suffered from gout. During a median follow-up of 7.25 (95% CI 7.18-7.32) years, 2924 (6.8%) patients died, including 722 (1.6%) cases of cardiovascular death. Hypertensive patients with HUA and gout showed 1.34 and 1.29 times higher all-cause mortality compared with those without HUA or gout. For hypertensive patients without gout, HUA was significantly associated with higher risk of all-cause [1.27 (1.13, 1.43)] and cardiovascular [1.80 (1.44, 2.24)] mortality compared with normouricemia. However, for hypertensive patients without HUA, gout was associated with a higher mortality but not statistically significant. A J-shaped relationship was found between serum uric acid and mortality. CONCLUSION: HUA and gout are additive risk factors for all-cause and cardiovascular mortality in hypertension. Furthermore, asymptomatic HUA is significantly associated with poor long-term prognosis but normouricemic gout is not.

Influence of xanthine oxidase inhibitors on all-cause mortality in adults: a systematic review and meta-analysis.

Xanthine oxidase inhibitors, including allopurinol and febuxostat, are the first-line treatment of hyperuricemia. This meta-analysis investigated the association between urate-lowering therapy and all-cause mortality in different chronic diseases to match its users and non-users in a real-world setting. Overall, 11 studies were included, which reported adjusted hazard ratios for all-cause mortality over at least 12 months. Meta-analysis of all included studies showed no effect of the therapy on all-cause mortality. However, subgroup analyses showed its beneficial effect in patients with chronic kidney disease (14% risk reduction) and hyperuricemia (14% risk reduction), but not in patients with heart failure (28% risk increase). Urate-lowering therapy reduces all-cause mortality among patients with hyperuricemia and chronic kidney disease, but it seems to increase mortality in patients with heart failure and should be avoided in this subgroup.

Association between hyperuricemia and the risk of mortality in patients with osteoarthritis: A study based on the National Health and Nutrition Examination Survey database.

BACKGROUND: The purpose of this study was to evaluate the relationship between hyperuricemia and the risks of all-cause mortality and cardiovascular disease (CVD) mortality in patients with osteoarthritis (OA). METHODS: A retrospective cohort study was performed on 3,971 patients using data from the National Health and Nutrition Examination Survey database between 1999 and 2018. OA was diagnosed through specific questions and responses. The weighted COX regression models were used to explore the factors associated with all-cause mortality/CVD mortality in OA patients. Subgroup analyses were conducted based on age, gender, hypertension, dyslipidemia, CVD, and chronic kidney disease (CKD). Hazard ratio (HR) and 95% confidence interval (95% CI) were measured as the evaluation indexes. RESULTS: During the duration of follow-up time (116.38 ± 2.19 months), 33.69% (1,338 patients) experienced all-cause mortality, and 11.36% (451 patients) died from CVD. Hyperuricemia was associated with higher risks of all-cause mortality (HR: 1.22, 95% CI: 1.06-1.41, P = 0.008) and CVD mortality (HR: 1.32, 95% CI: 1.02-1.72, P = 0.036) in OA patients. Subgroup analyses showed that hyperuricemia was related to the risk of all-cause mortality in OA patients aged >65 years (HR: 1.17, 95% CI: 1.01-1.36, P = 0.042), in all male patients (HR: 1.41, 95% CI: 1.10-1.80, P = 0.006), those diagnosed with hypertension (HR: 1.17, 95% CI: 1.01-1.37, P = 0.049), dyslipidemia (HR: 1.18, 95% CI: 1.01-1.39, P = 0.041), CVD (HR: 1.30, 95% CI: 1.09-1.55, P = 0.004), and CKD (HR: 1.31, 95% CI: 1.01-1.70, P = 0.046). The association between hyperuricemia and a higher risk of CVD mortality was found in OA patients aged ≤ 65 years (HR: 1.90, 95% CI: 1.06-3.41, P = 0.032), who did not suffer from diabetes (HR: 1.36, 95% CI: 1.01-1.86, P = 0.048), who did not suffer from hypertension (HR: 2.56, 95% CI: 1.12-5.86, P = 0.026), and who did not suffer from dyslipidemia (HR: 2.39, 95% CI: 1.15-4.97, P = 0.020). CONCLUSION: These findings emphasize the importance of monitoring serum uric acid levels in OA patients for potentially reducing mortality associated with the disease.

Higher Dietary Inflammatory Index and Increased Mortality Rate of Adults With Hyperuricemia: Findings From the National Health and Nutritional Examination Survey (2001-2018).

OBJECTIVE: This study aimed to assess the association between Dietary Inflammatory Index (DII) score and death among adults with hyperuricemia. METHODS: We collected data from the 2001 to 2018 cohorts of the National Health and Nutritional Examination Survey. Death information was obtained based on death certificate records from the National Death Index through December 31, 2019. The associations between DII score and all-cause, cardiovascular disease (CVD), and cancer death were investigated by using Cox proportional hazards regression models. RESULTS: We enrolled 7,786 participants with hyperuricemia in this study. The DII score ranged from -4.42 to 4.61. Higher DII score was significantly associated with higher levels of body mass index, glycohemoglobin, glucose, low-density lipoprotein-cholesterol, and C-reactive protein (all P < 0.05). During 67,851 person-years of follow-up, deaths of 1,456 participants were identified, including 532 CVD deaths and 246 cancer deaths. After adjusting for potential variables, significant higher risk of all-cause (hazard ratio [HR] 1.18, 95% confidence interval [95% CI] 1.03-1.36, P = 0.01) and CVD (HR 1.30, 95% CI 1.03-1.63, P = 0.02) death was observed for individuals with higher DII scores. Considering the DII score as a continuous variable, the risk of all-cause and CVD death increases 5% (HR 1.05, 95% CI 1.01-1.08) and 8% (HR 1.08, 95% CI 1.02-1.15) with each one-unit increment in DII score, respectively. Subgroup analysis indicated that the association between DII score and all-cause death among participants with hyperuricemia was more significant in males. CONCLUSION: DII score is found to be positively associated with all-cause and CVD death of adults with hyperuricemia. Controlling the intake of proinflammatory food might be a potential strategy to reduce the mortality rate.

Impact of hyperuricemia and chronic kidney disease on the prevalence and mortality of cardiovascular disease in cancer survivors.

BACKGROUND: The risks of cardiovascular disease (CVD) and CVD mortality are prevalent among cancer survivors (CS) population. The 2022 ESC Guidelines on cardio-oncology have recommended that modifying cardiovascular risk factors (CVRF) could potentially improve long-term outcomes in CS. OBJECTIVES: To identify the independent and joint chronic kidney disease (CKD) associations of hyperuricemia with the incidence of CVD and mortality outcomes among CS. METHODS: Utilizing data from the US National Health and Nutrition Examination Survey spanning 2005-2018, we assessed the risk of CVD through weighted multivariable logistic regression and restricted cubic spline (RCS) regression. Additionally, all-cause and CVD-related mortality were evaluated using weighted multivariable Cox regression and Kaplan-Meier analysis. Subgroup analysis was conducted to further elucidate the interplay between hyperuricemia, CKD, and mortality within the CS population. RESULTS: A total of 3276 CS participants were enrolled in this study. Results showed that hyperuricemia was positively related to the incidence of CVD (OR [95% CI] = 1.86 [1.24, 2.81], p = 0.004). RCS analysis further demonstrated that uric acid levels ≥345 µmol/L positively correlated with CVD incidence (p value for nonlinearity = 0.0013). However, the association between hyperuricemia and CVD mortality, as well as all-cause mortality did not reach statistical significance in the fully adjusted model (HR = 1.48, 95% CI: 0.92-2.39, p = 0.11; HR = 1.11, 95% CI:0.92, 1.34, p = 0.28, respectively). Among CS participants with CKD, hyperuricemia could increase risks of all-cause (HR [95% CI] = 1.39 [1.08, 1.11], p = 0.02) and CVD mortality (HR [95% CI] =2.17 [1.29, 3.66], p = 0.004) after adjusting for sex, age, and ethnicity. CONCLUSIONS: In the CS population, hyperuricemia was positively associated with the incidence of CVD. In addition, CKD might be an intermediate variable among the CS population that mediated the effects of hyperuricemia on mortality.

Association of serum uric acid with all-cause and cardiovascular mortality in chronic kidney disease stages 3-5.

BACKGROUND AND AIMS: The role of serum uric acid (SUA) in the prognosis of chronic kidney disease (CKD) is inconclusive. To explore the association of SUA level with all-cause and cardiovascular disease (CVD) mortality in patients with CKD. METHODS AND RESULTS: Leveraging data from the National Health and Nutritional Examination Survey (NHANES) and linked national death records up to December 31 2019, we explored the association of SUA with all-cause and CVD mortality using weighted cox proportional hazards regression models and restricted cubic spline (RCS) models in patients with CKD stages 3-5. The study finally included 2644 patients with CKD stages 3-5, with a median SUA level of 6.5 mg/dL. After a median follow-up of 55 months, a total of 763 deaths were recorded, with 279 of them attributed to CVD. In the fully adjusted model, per 1 mg/dL increment in SUA concentration was found to be associated with increased HRs (95% CIs) of 1.07 (1.00, 1.14) for all-cause mortality and 1.11 (1.00, 1.24) for CVD mortality. Compared to Q2 (reference), those in Q4 had adjusted HRs of 1.72 (1.36, 2.17) for all-cause mortality and 2.17 (1.38, 3.41) for CVD mortality, while those in Q1 had adjusted HRs of 1.49 (1.19, 1.85) for all-cause mortality and 1.93 (1.26, 2.98) for CVD mortality. CONCLUSIONS: Both higher and lower SUA levels were associated with increased risks of all-cause and CVD mortality in patients with CKD stages 3-5.

Impact of hyperuricemia on 5-year clinical outcomes following percutaneous transluminal angioplasty.

BACKGROUND: Although the correlation between hyperuricemia and cardiovascular disease (CVD) is well known, there have been limited data regarding the impact of hyperuricemia on long-term clinical outcomes in patients with peripheral arterial disease (PAD) after percutaneous transluminal angioplasty (PTA). METHODS: A total of 718 patients who underwent PTA for PAD were enrolled. The patients were divided into the hyperuricemia group (N = 168) and the normal group (N = 550). Hyperuricemia was defined as a uric acid level ≥ 7.0 mg/dL in men, and ≥ 6.5 mg/dL in women. The primary endpoint was major adverse cerebral and cardiovascular event (MACCE), including death, myocardial infarction (MI), any coronary revascularization, and stroke, up to 5 years. The secondary endpoint was major adverse limb event (MALE), including any repeated PTA, and target extremity surgery (TES). Inverse probability weighting (IPTW) analysis, derived from the logistic regression model, was performed to adjust potential confounders. RESULTS: After IPTW matching analysis, compared to the normal group, the hyperuricemia group was not associated with increased MACCE but was associated with an increased incidence of MI (2.6 % vs. 0.5 %, p = 0.001), and coronary revascularization (6.7 % vs. 3.9 %, p = 0.018). Also, the hyperuricemia group was associated with a higher incidence of MALE (45.3 % vs. 28.9 %, p < 0.001), including target extremity revascularization (TER; 25.1 % vs. 15.9 %, p < 0.001), non-TER (11.5 % vs. 5.6 %, p < 0.001), and TES (22.8 % vs. 16.2 %, p = 0.002). CONCLUSIONS: In the present study, hyperuricemia was associated with worse clinical outcomes in PAD patients following PTA during 5-year clinical follow-up. Further investigations should be made regarding the clinical benefit of controlling hyperuricemia on clinical outcomes.

Prognostic value of hyperuricemia for patients with sepsis in the intensive care unit.

This study evaluated the relationship between hyperuricemia at admission and the clinical prognosis of patients with sepsis. The data were obtained from the Intensive Care Medical Information Database III. The patients were divided into a normal serum uric acid group and a hyperuricemia group. The main outcome was 90-day mortality, and the secondary outcomes were hospital mortality, 30-day mortality, and acute kidney injury. Propensity score matching was used to balance the baseline characteristics of the groups. Our study retrospectively included 954 patients. Before and after propensity score matching, the incidence of AKI, the 30-day and 90-day mortality rates were significantly higher in the hyperuricemia group. Cox regression analysis showed that hyperuricemia was significantly associated with 90-day mortality (HR 1.648, 95% CI 1.215-2.234, p = 0.006), and hyperuricemia was significantly associated with the incidence of AKI (HR 1.773, 95% CI 1.107-2.841, p = 0.017). The Kaplan-Meier survival curve showed that the 90-day survival rate was significantly lower in the hyperuricemia group. In patients with sepsis in the intensive care unit, hyperuricemia was significantly associated with increased risk 90-day all-cause mortality and the incidence of AKI.

The Prognostic Value of Serum Uric Acid in Hospitalized Patients with Acute Cerebral Infarction.

BACKGROUND: Previous studies reported that the level of serum uric acid (SUA) was an important risk factor for acute cerebral infarction (ACI). However, the prognostic value of SUA levels in hospitalized patients with ACI has not been fully elucidated. The aim of this study was to investigate whether the SUA level on admission was associated with subsequent mortality in hospitalized patients with ACI. METHODS: The clinical data of ACI patients obtained from December 2017 to December 2019 were retrospectively reviewed. χ 2 and Kaplan-Meier methods were used to compare the clinical differences and overall survival between patients with or without hyperuricemia, respectively. Univariate and multivariate analyses were used to identify independent prognoses. RESULTS: In the total population, the in-hospital mortality of the hyperuricemia group was significantly higher than that of the normal uric acid group (P = 0.006). In the abnormal renal function group, the in-hospital mortality among the hyperuricemia group was significantly higher than the normal uric acid group (P = 0.002). However, there was no statistical difference of in-hospital mortality between the two groups in the normal renal function group (P = 0.321). Univariate and multivariate analyses showed that a previous history of diabetes (P = 0.018), hyperuricemia (P = 0.001), and National Institutes of Health Stroke Scale (NIHSS) score on admission (P ≤ 0.001) were independent factors for all samples. The hyperuricemia (P = 0.003) on admission were independent factors for patients with abnormal renal function. CONCLUSIONS: In ACI patients with abnormal renal function, hyperuricemia may be associated with higher in-hospital mortality than patients with normal uric acid, and hyperuricemia may be an independent associated factor for in-hospital death in the subgroup patients.

Cumulative Serum Uric Acid and Its Time Course Are Associated With Risk of Myocardial Infarction and All-Cause Mortality.

Background Serum uric acid (SUA) has been demonstrated as a risk factor for myocardial infarction (MI) and all-cause mortality; however, the impact of cumulative SUA (cumSUA) remains unclear. We aimed to investigate the association of cumSUA with MI risk and all-cause mortality, and to further explore the effects of SUA accumulation time course. Methods and Results The study enrolled 53 463 participants without a history of MI, and these participants underwent 3 examinations during 2006 to 2010. cumSUA from baseline to the third examination was calculated, multiplying mean values between consecutive examinations by time intervals between visits. Cox models estimated hazard ratios (HRs) and 95% CIs of MI and all-cause mortality for cumSUA quartiles, hyperuricemia exposure duration, and SUA accumulation time course. During a median follow-up of 7.04 years, 476 incident MIs and 2692 deaths occurred. In the fully adjusted model, a higher MI risk was observed in the highest cumSUA quartile (HR, 1.48; 95% CI, 1.10-1.99), in participants with longer hyperuricemia exposure duration (HR, 1.71; 95% CI, 1.06-2.73), and in participants with cumSUA≥median and a negative slope (HR, 1.58; 95% CI, 1.18-2.11). Similar associations persisted for all-cause mortality. Conclusions The risk of MI and all-cause mortality increased with higher cumSUA and was affected by the SUA accumulation time course. Early SUA accumulation contributed more to MI risk and all-cause mortality than later SUA accumulation with the same overall cumulative exposure, emphasizing the importance of optimal SUA control early in life.

Possible burden of hyperuricaemia on mortality in a community-based population: a large-scale cohort study.

Hyperuricaemia is a risk for premature death. This study evaluated the burden of hyperuricaemia (serum urate > 7 mg/dL) for all-cause and cardiovascular mortality in 515,979 health checkup participants using an index of population attributable fraction (PAF). Prevalence of hyperuricaemia at baseline was 10.8% in total subjects (21.8% for men and 2.5% for women). During 9-year follow-up, 5952 deaths were noted, including 1164 cardiovascular deaths. In the Cox proportional hazard analysis adjusted for confounding factors, hyperuricaemia was independently associated with all-cause and cardiovascular mortality (adjusted hazard ratios [95% confidence interval]; 1.36 [1.25-1.49] and 1.69 [1.41-2.01], respectively). Adjusted PAFs of hyperuricaemia for all-cause and cardiovascular deaths were 2.9% and 4.4% (approximately 1 in 34 all-cause deaths and 1 in 23 cardiovascular deaths), respectively. In the subgroup analysis, the association between hyperuricaemia and death was stronger in men, smokers, and subjects with renal insufficiency. Adjusted PAFs for all-cause and cardiovascular deaths were 5.3% and 8.1% in men; 5.8% and 7.5% in smokers; and 5.5% and 7.3% in subjects with renal insufficiency. These results disclosed that a substantial number of all-cause and cardiovascular deaths were statistically relevant to hyperuricaemia in the community-based population, especially men, smokers, and subjects with renal insufficiency.

Early onset of hyperuricemia is associated with increased cardiovascular disease and mortality risk.

BACKGROUND: Hyperuricemia is associated with cardiovascular mortality, but the association of the age at hyperuricemia onset with cardiovascular disease (CVD) and mortality is still unclear. OBJECTIVE: The purpose of this study was to examine the associations of hyperuricemia onset age with CVD and all-cause mortality. METHODS: A total of 82,219 participants free of hyperuricemia and CVD from 2006 to 2015 in the Kailuan study were included. The analysis cohort comprised 18,311 new-onset hyperuricemia patients and controls matched for age and sex from the general population. Adjusted associations were estimated using Cox models for CVD and all-cause mortality across a range of ages. RESULTS: There were 1,021 incident cases of CVD (including 215 myocardial infarctions, 814 strokes) and 1459 deaths during an average of 5.2 years of follow-up. Patients with hyperuricemia onset at an age < 45 years had the highest hazard ratios (HRs) (1.78 (1.14-2.78) for CVD and 1.64 (1.04-2.61) for all-cause mortality relative to controls). The HRs of CVD and all-cause mortality were 1.32 (1.05-1.65) and 1.40 (1.08-1.81) for the 45-54 years age group, 1.23 (0.97-1.56) and 1.37 (1.11 to 1.72) for the 55-64 years age group, and 1.10 (0.88-1.39) and 0.88 (0.76-1.01) for the ≥ 65 years age group, respectively. CONCLUSIONS: The age at hyperuricemia onset was identified as an important predictor of CVD and all-cause mortality risk, and the prediction was more powerful in those with a younger age of hyperuricemia onset. Early onset of hyperuricemia is associated with increased cardiovascular disease and mortality risk.

Changes in serum uric acid and the risk of cardiovascular disease and all-cause mortality in the general population.

BACKGROUND AND AIM: Longitudinal evidence on change in serum (SUA) with risk of cardiovascular disease (CVD) and all-cause mortality is limited, as many prior studies focused on baseline SUA. Further, the optimal threshold range of SUA change is unclear. METHODS AND RESULTS: A total of 63,127 participants without history of CVD were enrolled. Change in SUA was determined by the difference of SUA levels between 2006 and 2010, which divided by baseline SUA was percent change in SUA. Multivariable Cox proportional hazards models were used to calculated the hazard ratios (HRs) and 95% confidence intervals (CIs). Our analysis also included restricted cubic spline model and three-piecewise Cox proportion hazards model to address the non-linearity between percent change in SUA and outcomes. During a median follow-up of 7.04 years, 3341 CVD and 3238 deaths occurred. We did not observed a significant association between changes in SUA and CVD. However, changes in SUA at extreme were associated with higher risk of all-cause mortality, the HRs (95% CIs) were 1.15 (1.02-1.29) and 1.20 (1.06-1.35) in the first and fifth quintile group, compared with the third quintile group. We further found a U-shaped association between percent change in SUA and all-cause mortality, and the optimal range was within 20%. CONCLUSIONS: Changes in SUA at extreme were risk factors for all-cause mortality, but not for CVD in the general population. The findings are relevant for role of SUA in the management of CVD risk and may contribute to improve identification of patients at higher risk.

Elevated serum uric acid and risk of cardiovascular or all-cause mortality in maintenance hemodialysis patients: A meta-analysis.

BACKGROUND AND AIMS: Studies have shown inconsistent results about the association between serum uric acid (SUA) levels and mortality in hemodialysis patients. We performed this meta-analysis to determine whether higher SUA values comprised a risk factor of cardiovascular or all-cause mortality in maintenance hemodialysis patients. METHODS AND RESULTS: Pubmed, Embase and the Cochrane library were searched up to August 31, 2020 for the longitudinal studies that investigated the association between the elevated SUA and cardiovascular or all-cause mortality risk in maintenance hemodialysis patients. Pooled adjusted hazard ratios (HR) and corresponding 95% confidence interval (CI) were calculated using a random-effects model. We included 10 studies with an overall sample of 264,571 patients with hemodialysis in this meta-analysis. Patients with the highest SUA were associated with a decreased risk of cardiovascular mortality (HR = 0.72, 95% CI 0.59-0.87) compared with patients with the lowest SUA after adjustment for potential confounders in a random effects model. Moreover, for each increase of 1 mg/dl of SUA, the overall risks of all-cause and cardiovascular mortality decreased by 6% and 9%, respectively (HR = 0.94, 95% CI 0.90-0.99; HR = 0.91, 95% CI 0.89-0.94). CONCLUSION: Elevated SUA levels are strongly and independently associated with lower risk of cardiovascular mortality in maintenance hemodialysis patients. More designed studies, especially randomized controlled trials, should be conducted to determine whether high SUA levels is an independent risk factor of all-cause mortality in hemodialysis patients.

Elevated serum uric acid is associated with a greater inflammatory response and with short- and long-term mortality in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

BACKGROUND AND AIMS: Despite elevated serum uric acid (eSUA) has been identified as independent risk factor for cardiovascular diseases, its prognostic value in the setting of ST-segment elevation myocardial infarction (STEMI) is still controversial. Although the mechanisms of this possible relationship are unsettled it has been suggested that eSUA could trigger the inflammatory response. This study sought to investigate the association between eSUA with short- and long-term mortality and with inflammatory response in patients with STEMI treated with primary percutaneous coronary intervention (pPCI). METHODS AND RESULTS: Blood samples were collected on admission and at 24 and 48 h after pPCI: the inflammatory biomarkers C-reactive protein (CRP), neutrophil count and neutrophil to lymphocytes ratio (NLR) were considered. Baseline eSUA was defined as ≥6.8 mg/dl. Cumulative 30-days and 1-year mortalities were estimated using the Kaplan-Meyer analysis. Multivariable analyses were performed by Cox proportional hazard models. In the 2369 patients with STEMI considered, 30-day mortality was 5.8% among patients with eSUA and 2% among patient with normal SUA level (p < 0.001); 1-year mortality was 8.5% vs 4%, respectively (p < 0.001). At multivariable analyses eSUA was an independent predictor of 30-day mortality (HR 1.196, 95%CI 1.006-1.321, p = 0.042) and 1-year mortality (HR 1.178, 95%CI 1.052-1.320, p = 0.005). eSUA patients presented higher values in on admission CRP (p < 0.001) and in neutrophil count and NLR at 24 h (respectively, p = 0.020 and p < 0.001) and at 48 h (p = 0.018 and p < 0.001) compared to patients with normal SUA levels. CONCLUSIONS: Elevated serum uric acid is associated with higher short- and long-term mortality and with a greater inflammatory response after reperfusion in patients with STEMI treated with primary PCI.

Evaluation of the safety and efficacy of low-dose rasburicase in critically ill children with haematological malignancies.

Background The recommended dose of rasburicase is quite expensive, thus limiting its use. Whether a lower dose of rasburicase would be equally effective for critically ill children, who often have more complicated situations and a higher risk of hospital death, is still unknown. Objective To explore the safety and efficacy of low-dose rasburicase in critically ill children with haematological malignancies who are at high risk of tumour lysis syndrome. Setting A single-centre retrospective cohort study. Method Children with haematological malignancies who had a history of rasburicase exposure during an intensive care unit stay were enrolled. Patients were divided into two groups according to the initial dosage of rasburicase: the standard-dose group (> 0.1 mg/kg/day) and the low-dose group (≤ 0.1 mg/kg/day). The adverse events and short-term prognosis of the two groups were compared. Results Thirty-seven children were selected, 22 in the standard-dose group and 15 in the low-dose group. The most common tumour type was Burkitt's lymphoma (81%), followed by acute lymphoblastic leukaemia (11%). All patients were at high risk of tumour lysis syndrome, and 73% of them had 3 or more tumour lysis syndrome risk factors. The uric acid levels of 90% of patients with hyperuricaemia returned to the normal range within 12 h (100% in the standard-dose group and 75% in the low-dose group, P = 0.083). Eighty-four percent of patients presented serious complications, including tumour lysis syndrome (73%), acute kidney injury (59%), renal replacement treatment (24%), respiratory failure (24%), disseminated intravascular coagulation (16%) and heart failure (11%). There was no significant difference in the incidence of serious complications between the two groups. The overall 7-day and 28-day survival rates after intensive care unit admission were 86% and 84%, respectively. The average length of stay in the intensive care unit was 9.92 ± 5.13 days. Neither the short-term mortality nor the length of stay in the intensive care unit were significantly different between the two groups. Conclusion Low-dose rasburicase is effective and may be an acceptable choice for critically ill children with haematological malignancies.

Increased serum uric acid levels are associated to renal arteriolopathy and predict poor outcome in IgA nephropathy.

BACKGROUND AND AIMS: IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and a leading cause of end stage renal disease (ESRD). In addition to classical progression factors, other atherosclerosis-related factors, including hyperuricemia (HU), have been associated to the renal progression of IgAN. Increased serum uric acid (SUA) levels are well known to be concomitant of cardiovascular and kidney diseases, and have been proposed to be implicated in the development of arteriolar damage (AD). The aim of the present study was to explore the correlation between SUA levels, renal damage and its implication for outcome in IgAN patients. METHODS AND RESULTS: Clinical, laboratory and histologic data of 145 patients with biopsy proven IgAN were collected and retrospectively analyzed to determine the correlation between SUA levels, renal damage and the primary outcome (death or ESRD). Biopsy-proven AD was defined by the presence of arteriolar hyalinosis and/or intimal thickening. HU, defined as the highest SUA gender-specific tertile, was >7.7 mg/dl for males and >6.2 mg/dl for females. The prevalence of AD increased with the increase in the SUA level tertiles (p = 0.02). At logistic regression analysis SUA was independently related to the presence of AD (OR 1.75 [95%CI 1.10-2.93], p = 0.03). HU and AD had a synergic impact on progression of IgAN. Patients having both AD and HU, showed a reduced survival free from the primary outcome as compared to those having only one risk factor or neither (p = 0.01). CONCLUSIONS: SUA levels are independently associated with AD and poor prognosis in patients with IgAN.