Jing Li

BACKGROUND: Observational studies of the relationship between hyperuricemia and the incidence of hypertension are controversial. We conducted a systematic review and meta-analysis to assess the association and consistency between uric acid levels and the risk of hypertension development. METHODS: We searched MEDLINE, EMBASE, CBM (Chinese Biomedicine Database) through September 2013 and reference lists of retrieved studies to identify cohort studies and nested case-control studies with uric acid levels as exposure and incident hypertension as outcome variables. Two reviewers independently extracted data and assessed study quality using Newcastle-Ottawa Scale. Extracted information included study design, population, definition of hyperuricemia and hypertension, number of incident hypertension, effect sizes, and adjusted confounders. Pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs) for the association between hyperuricemia and risk of hypertension were calculated using a random-effects model. RESULTS: We included 25 studies with 97,824 participants assessing the association between uric acid and incident hypertension in our meta-analysis. The quality of included studies is moderate to high. Random-effects meta-analysis showed that hyperuricemia was associated with a higher risk of incident hypertension, regardless of whether the effect size was adjusted or not, whether the data were categorical or continuous as 1 SD/1 mg/dl increase in uric acid level (unadjusted: RR = 1.73, 95% CI 1.46∼2.06 for categorical data, RR = 1.22, 95% CI 1.03∼1.45 for a 1 SD increase; adjusted: RR = 1.48, 95% CI 1.33∼1.65 for categorical data, RR = 1.15, 95% CI 1.06∼1.26 for a 1 mg/dl increase), and the risk is consistent in subgroup analyses and have a dose-response relationship. CONCLUSIONS: Hyperuricemia may modestly increase the risk of hypertension incidence, consistent with a dose-response relationship.

AIMS: We aimed to perform a systematic review and meta-analysis to assess the association between serum uric acid and incident heart failure (HF)/prognosis of HF patients. METHODS AND RESULTS: A systematic electronic literature search was conducted in Embase (Ovid SP, from 1974 to May 2013), Medline (Ovid SP, from 1946 to May 2013), and the Chinese Biomedical Literature Database (CBM, from 1978 to May 2013) to identify studies reporting on the association between serum uric acid and HF. Either a random effects model or a fixed effects model was used for pooling data. Five studies reporting on incident HF and 28 studies reporting on the adverse outcomes of HF patients were included. The results showed that hyperuricaemia was associated with an increased risk of incident HF [hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.41-1.94], and the risk of all-cause mortality (HR 2.15, 95% CI 1.64-2.83), cardiovascular mortality (HR 1.45, 95% CI 1.18-1.78), and the composite of death or cardiac events (HR 1.39, 95% CI 1.18-1.63) in HF patients. For every 1 mg/dL increase in serum uric acid, the odds of development of HF increased by 19% (HR 1.19, 95% CI 1.17-1.21), and the risk of all-cause mortality and the composite endpoint in HF patients increased by 4% (HR 1.04, 95% CI 1.02-1.06) and 28% (HR 1.28, 95% CI 0.97-1.70), respectively. Subgroup analyses supported the positive association between serum uric acid and HF. CONCLUSIONS: Elevated serum uric acid is associated with an increased risk of incident HF and adverse outcomes in HF patients.

Exercise intolerance is an important comorbidity in patients with CKD. Anaerobic threshold (AT) determines the upper limits of aerobic exercise and is a measure of cardiovascular reserve. This study investigated the prognostic capacity of AT on survival in patients with advanced CKD and the effect of kidney transplantation on survival in those with reduced cardiovascular reserve. Using cardiopulmonary exercise testing, cardiovascular reserve was evaluated in 240 patients who were waitlisted for kidney transplantation between 2008 and 2010, and patients were followed for ≤5 years. Survival time was the primary endpoint. Cumulative survival for the entire cohort was 72.6% (24 deaths), with cardiovascular events being the most common cause of death (54.2%). According to Kaplan–Meier estimates, patients with AT &lt;40% of predicted peak VO₂ had a significantly reduced 5-year cumulative overall survival rate compared with those with AT ≥40% (<i>P</i>&lt;0.001). Regarding the cohort with AT &lt;40%, patients who underwent kidney transplantation (6 deaths) had significantly better survival compared with nontransplanted patients (17 deaths) (hazard ratio, 4.48; 95% confidence interval, 1.78 to 11.38; <i>P</i>=0.002). Survival did not differ significantly among patients with AT ≥40%, with one death in the nontransplanted group and no deaths in the transplanted group. In summary, this is the first prospective study to demonstrate a significant association of AT, as the objective index of cardiovascular reserve, with survival in patients with advanced CKD. High-risk patients with reduced cardiovascular reserve had a better survival rate after receiving a kidney transplant.

Overexpression of soluble urokinase receptor (suPAR) causes pathology in animal models similar to primary FSGS, and one recent study demonstrated elevated levels of serum suPAR in patients with the disease. Here, we analyzed circulating suPAR levels in two cohorts of children and adults with biopsy-proven primary FSGS: 70 patients from the North America-based FSGS clinical trial (CT) and 94 patients from PodoNet, the Europe-based consortium studying steroid-resistant nephrotic syndrome. Circulating suPAR levels were elevated in 84.3% and 55.3% of patients with FSGS patients in the CT and PodoNet cohorts, respectively, compared with 6% of controls (P<0.0001); inflammation did not account for this difference. Multiple regression analysis suggested that lower suPAR levels associated with higher estimated GFR, male sex, and treatment with mycophenolate mofetil. In the CT cohort, there was a positive association between the relative reduction of suPAR after 26 weeks of treatment and reduction of proteinuria, with higher odds for complete remission (P=0.04). In the PodoNet cohort, patients with an NPHS2 mutation had higher suPAR levels than those without a mutation. In conclusion, suPAR levels are elevated in geographically and ethnically diverse patients with FSGS and do not reflect a nonspecific proinflammatory milieu. The associations between a change in circulating suPAR with different therapeutic regimens and with remission support the role of suPAR in the pathogenesis of FSGS.