A Genetic Deconstruction of Neurocognitive Traits in Schizophrenia and Bipolar Disorder

Background

Impairments in cognitive functions are common in patients suffering from psychiatric disorders, such as schizophrenia and bipolar disorder. Cognitive traits have been proposed as useful for understanding the biological and genetic mechanisms implicated in cognitive function in healthy individuals and in the dysfunction observed in psychiatric disorders.

Methods

Sets of genes associated with a range of cognitive functions often impaired in schizophrenia and bipolar disorder were generated from a genome-wide association study (GWAS) on a sample comprising 670 healthy Norwegian adults who were phenotyped for a broad battery of cognitive tests. These gene sets were then tested for enrichment of association in GWASs of schizophrenia and bipolar disorder. The GWAS data was derived from three independent single-centre schizophrenia samples, three independent single-centre bipolar disorder samples, and the multi-centre schizophrenia and bipolar disorder samples from the Psychiatric Genomics Consortium.

Results

The strongest enrichments were observed for visuospatial attention and verbal abilities sets in bipolar disorder. Delayed verbal memory was also enriched in one sample of bipolar disorder. For schizophrenia, the strongest evidence of enrichment was observed for the sets of genes associated with performance in a colour-word interference test and for sets associated with memory learning slope.

Conclusions

Our results are consistent with the increasing evidence that cognitive functions share genetic factors with schizophrenia and bipolar disorder. Our data provides evidence that genetic studies using polygenic and pleiotropic models can be used to link specific cognitive functions with psychiatric disorders.     

Association of Angiopoietin-2 with Renal Outcome in Chronic Kidney Disease

Background

The pathophysiological mechanisms of renal function progression in chronic kidney disease (CKD) have still not been completely explored. In addition to well-known traditional risk factors, non-traditional risk factors, such as endothelial dysfunction, have gradually attracted physicians'' attention. Angiopoietin-2 (Ang-2) impairs endothelial function through preventing angiopoietin-1 from binding to Tie2 receptor. Whether Ang-2 is associated with renal function progression in CKD is unknown.

Methods

This study enrolled 621 patients with stages 3–5 CKD to assess the association of circulating Ang-2 with commencing dialysis, doubling creatinine and rapid decline in renal function (the slope of estimated glomerular filtration rate (eGFR) greater than 5 ml/min per 1.73 m²/y) over follow-up of more than 3 years.

Results

Of all patients, 224 patients (36.1%) progressed to commencing dialysis and 165 (26.6%) reached doubling creatinine. 85 subjects (13.9%) had rapid decline in renal function. Ang-2 quartile was divided at 1494.1, 1948.8, and 2593.1 pg/ml. The adjusted HR of composite outcomes, either commencing dialysis or doubling creatinine was 1.53 (95% CI: 1.06–2.23) for subjects of quartile 4 compared with those of quartile 1. The adjusted OR for rapid decline in renal function was 2.96 (95% CI: 1.13–7.76) for subjects of quartile 4 compared with those of quartile 1. The linear mixed-effects model shows a more rapid decrease in eGFR over time in patients with quartile 3 or more of Ang-2 than those with the lowest quartile of Ang-2.

Conclusions

Ang-2 is an independent predictor of adverse renal outcome in CKD. Further study is needed to identify the pathogenic role of Ang-2 in CKD progression.     

Urinary Calprotectin and Posttransplant Renal Allograft Injury

Objective

Current methods do not predict the acute renal allograft injury immediately after kidney transplantation. We evaluated the diagnostic performance of urinary calprotectin for predicting immediate posttransplant allograft injury.

Methods

In a multicenter, prospective-cohort study of 144 incipient renal transplant recipients, we postoperatively measured urinary calprotectin using an enzyme-linked immunosorbent assay and estimated glomerular filtration rate (eGFR) after 4 weeks, 6 months, and 12 months.

Results

We observed a significant inverse association of urinary calprotectin concentrations and eGFR 4 weeks after transplantation (Spearman r = −0.33; P<0.001). Compared to the lowest quartile, patients in the highest quartile of urinary calprotectin had an increased risk for an eGFR less than 30 mL/min/1.73 m² four weeks after transplantation (relative risk, 4.3; P<0.001; sensitivity, 0.92; 95% CI, 0.77 to 0.98; specificity, 0.48; 95% CI, 0.31 to 0.66). Higher urinary calprotectin concentrations predicted impaired kidney function 4 weeks after transplantation, as well as 6 months and 12 months after transplantation. When data were analyzed using the urinary calprotectin/creatinine-ratio similar results were obtained. Urinary calprotectin was superior to current use of absolute change of plasma creatinine to predict allograft function 12 months after transplantation. Urinary calprotectin predicted an increased risk both in transplants from living and deceased donors. Multivariate linear regression showed that higher urinary calprotectin concentrations and older donor age predicted lower eGFR four weeks, 6 months, and 12 months after transplantation.

Conclusions

Urinary calprotectin is an early, noninvasive predictor of immediate renal allograft injury after kidney transplantation.     

Associations between Skeletal Growth in Childhood and Cognitive Function in Mid-Life in a 53-Year Prospective Birth Cohort Study

Background

Several studies have found that shorter stature (height and limb length) in late life is associated with dementia and cognitive impairment. The extent to which childhood environment and early life cognitive function accounts for these associations is not clear.

Methods

We investigated associations of adult trunk height and leg length with cognitive function in middle age, analysing data from the MRC National Survey of Health and Development: a cohort followed from birth to age 53, 1677 of whom had data on all covariates. The four cognitive tests measured verbal ability, word list memory, verbal fluency and speed/concentration. Early life environmental measures included parental education, poverty, parental divorce, physical health, cognitive ability at age 15, own education and own adult social class.

Results

After adjusting for gender, shorter trunk length was associated with lower cognitive function on all four tests and shorter leg length with lower verbal intelligence and word list memory. These associations were only partially attenuated following adjustment for childhood adversity/health but were substantially accounted for by cognitive ability at age 15.

Conclusions

Shorter stature was associated with lower cognitive function at age 53, the majority of this association being accounted for by cognitive function at age 15. Reduced cognitive reserve may well account for later associations between anthropometric measures and dementia.     

Ecstasy Exposure & Gender: Examining Components of Verbal Memory Functioning

Objective

Studies have demonstrated verbal memory deficits associated with past year ecstasy use, although specific underlying components of these deficits are less understood. Further, prior research suggests potential gender differences in ecstasy-induced serotonergic changes. Therefore, the current study investigated whether gender moderated the relationship between ecstasy exposure and components of verbal memory after controlling for polydrug use and confounding variables.

Method

Data were collected from 65 polydrug users with a wide range of ecstasy exposure (ages 18–35; 48 ecstasy and 17 marijuana users; 0–2310 ecstasy tablets). Participants completed a verbal learning and memory task, psychological questionnaires, and a drug use interview.

Results

Increased past year ecstasy exposure predicted poorer short and long delayed free and cued recalls, retention, and recall discrimination. Male ecstasy users were more susceptible to dose-dependent deficits in retention than female users.

Conclusion

Past year ecstasy consumption was associated with verbal memory retrieval, retention, and discrimination deficits in a dose-dependent manner in a sample of healthy young adult polydrug users. Male ecstasy users were at particular risk for deficits in retention following a long delay. Gender difference may be reflective of different patterns of polydrug use as well as increased hippocampal sensitivity. Future research examining neuronal correlates of verbal memory deficits in ecstasy users are needed.     

Triglyceride Levels Are Closely Associated with Mild Declines in Estimated Glomerular Filtration Rates in Middle-Aged and Elderly Chinese with Normal Serum Lipid Levels

Objective

To investigate the relationship between lipid profiles [including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C)] and a mild decline in the estimated glomerular filtration rate (eGFR) in subjects with normal serum lipid levels.

Design and Methods

In this study, we included 2647 participants who were ≥40 years old and had normal serum lipid levels. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used to estimate the GFR. A mildly reduced eGFR was defined as 60–90 mL/min/1.73 m². First, multiple linear regression analysis was used to estimate the association of lipid profiles with the eGFR. Then, the levels of each lipid component were divided into four groups, using the 25th, 50th and 75th percentiles as cut-off points. Finally, multiple logistic regression analysis was used to investigate the association of different lipid components with the risk of mildly reduced eGFR.

Results

In the group with a mildly reduced eGFR, TG and LDL-C levels were significantly increased, but HDL-C levels were significantly decreased. After adjusting for age, gender, body mass index (BMI), systolic blood pressure (SBP), glycated hemoglobin (HbA_1c), smoking and drinking, only TC and TG were independently related to the eGFR. Additionally, only TG showed a linear relationship with an increased risk of a mildly reduced eGFR, with the highest quartile group (TG: 108–150 mg/dl [1.22–1.70 mmol/L]) having a significantly increased risk after adjusting for the above factors.

Conclusions

Triglyceride levels are closely associated with a mildly reduced eGFR in subjects with normal serum lipid levels. Dyslipidemia with lower TG levels could be used as new diagnostic criteria for subjects with mildly reduced renal function.     

Cross-Sectional and Longitudinal Associations of Different Sedentary Behaviors with Cognitive Performance in Older Adults

Background

The deleterious health effects of sedentary behaviors, independent of physical activity, are increasingly being recognized. However, associations with cognitive performance are not known.

Purpose

To estimate the associations between different sedentary behaviors and cognitive performance in healthy older adults.

Methods

Computer use, time spent watching television (TV), time spent reading and habitual physical activity levels were self-reported twice (in 2001 and 2007) by participants in the SUpplémentation en Vitamines et MinérauX (SU.VI.MAX and SU.VI.MAX2) study. Cognitive performance was assessed at follow-up (in 2007–2009) via a battery of 6 neuropsychological tests used to derive verbal memory and executive functioning scores. Analyses (ANCOVA) were performed among 1425 men and 1154 women aged 65.6±4.5 at the time of the neuropsychological evaluation. We estimated mean differences with 95% confidence intervals (95%CI) in cognitive performance across categories of each type of sedentary behavior.

Results

In multivariable cross-sectional models, compared to non-users, participants using the computer for >1 h/day displayed better verbal memory (mean difference = 1.86; 95%CI: 0.95, 2.77) and executive functioning (mean difference = 2.15; 95%CI: 1.22, 3.08). A negative association was also observed between TV viewing and executive functioning. Additionally, participants who increased their computer use by more than 30 min between 2001 and 2007 showed better performance on both verbal memory (mean difference = 1.41; 95%CI: 0.55, 2.27) and executive functioning (mean difference = 1.41; 95%CI: 0.53, 2.28) compared to those who decreased their computer use during that period.

Conclusion

Specific sedentary behaviors are differentially associated with cognitive performance. In contrast to TV viewing, regular computer use may help maintain cognitive function during the aging process.

Clinical Trial Registration

clinicaltrial.gov (number {"type":"clinical-trial","attrs":{"text":"NCT00272428","term_id":"NCT00272428"}}NCT00272428).     

Differentiating the Cognitive Profile of Schizophrenia from That of Alzheimer Disease and Depression in Late Life

Background

To compare the cognitive profile of older patients with schizophrenia to those with other neuropsychiatric disorders assessed in a hospital-based memory clinic.

Methods

Demographic, clinical, and cognitive data of all patients referred to the memory clinic at the Centre for Addiction and Mental Health between April 1, 2006 and August 15, 2008 were reviewed. We then identified four groups of older patients with: (1) late-life schizophrenia (LLS) and no dementia or depression (DEP); (2) Alzheimer''s disease (AD); (3) DEP and no dementia or LLS; (4) normal cognition (NC) and no DEP or LLS.

Results

The four groups did not differ in demographic data except that patients with AD were about 12 years older than those with LLS. However, they differed on cognitive tests even after controlling for age. Patients with LLS were impaired on most cognitive tests in comparison with patients with NC but not on recalling newly learned verbal information at a short delay. They experienced equivalent performance on learning new verbal information in comparison with patients with AD, but better performance on all other tests of memory, including the ability to recall newly learned verbal information. Finally, they were more impaired than patients with DEP in overall memory.

Conclusions

Patients with LLS have a different cognitive profile than patients with AD or DEP. Particularly, memory impairment in LLS seems to be more pronounced in learning than recall. These findings suggest that cognitive and psychosocial interventions designed to compensate for learning deficits may be beneficial in LLS.     

Cognitive Functions in Middle Aged Individuals Are Related to Metabolic Disturbances and Aerobic Capacity: A Cross-Sectional Study

Aims

Metabolic disturbances may contribute to cognitive dysfunction in patients with type 2 diabetes. We investigated the relation between cognitive impairment and metabolic deteriorations, low physical fitness, low-grade inflammation and abdominal obesity in middle aged individuals.

Methods

We conducted a cross-sectional study including 40 to 65 year-old patients with type 2 diabetes and limited co morbidity (N = 56), age-matched individuals with impaired glucose tolerance (N = 56) as well as age-matched controls with normal glucose tolerance (N = 72). Specific cognitive functions were assessed with focus on verbal memory, processing speed, executive functions, and a composite overall mean score. Oral glucose tolerance test, VO₂max test, systemic inflammation, DXA scanning and abdominal MRI were measured.

Results

Multiple linear regression analyses adjusting for age, gender and verbal intelligence demonstrated that a low score in processing speed, executive functions and overall cognitive function were related to high fasting C-peptide, as well as low insulin sensitivity, beta-cell function and VO₂max. Measurements of blood glucose, obesity and inflammation were not associated with cognitive function.

Conclusion

Low cognitive scores are seen in middle aged individuals with hyperinsulinemia, low insulin sensitivity, beta-cell function and low aerobic capacity. These findings emphasize the importance of appropriate lifestyle and not only blood glucose control in prevention of cognitive disability.     

Cognitive Decline in Patients with Alzheimer’s Disease and Its Related Factors in a Memory Clinic Setting,Shanghai, China

Objectives

Progressive cognitive decline is a characteristic hallmark of AD. It is important to identify prognostic markers to improve patient care and long-term planning. We aimed to identify the characteristics of disease progression in AD patients, focusing on cognitive decline and its related factors.

Methods

Clinically diagnosed AD patients in a memory clinic were followed. The mini–mental state examination (MMSE) and a battery of other neuropsychological tests were performed to assess the rate of cognitive decline and to analyze the related factors.

Results

A total of 165 AD patients were analyzed for cognitive changes. The MMSE scores declined at a rate of 1.52 points per year. Most neuropsychological test scores deteriorated significantly over time. Younger and early-onset AD patients deteriorated more rapidly than older and late-onset patients in global cognition and executive function. Men declined faster in memory but slower in attention than women. Higher education was associated with more rapid deterioration in visuo-spatial ability. Family history, hypertension and cerebral vascular disease were also associated with disease progression.

Conclusion

Attention, executive and visuo-spatial functions deteriorate at faster rates than other cognitive functions in AD patients. Age and age at onset were the main factors that associated with deterioration.     

Complex Prospective Memory in Adults with Attention Deficit Hyperactivity Disorder

Objectives

Attention deficit hyperactivity disorder (ADHD) in adults has been associated with disturbances of attention and executive functions. Furthermore, impairments of verbal and figural retrospective memory were reported. However, little is known about the effects of ADHD on prospective memory, the execution of delayed intentions in the future.

Methods

The present study compared the performance of 45 adult patients with ADHD not treated with stimulant medication with the performance of 45 matched healthy individuals on a paradigm of complex prospective memory which measured task planning, plan recall, self-initiation and execution. Furthermore, the contribution of other cognitive functions to prospective memory functioning was assessed, including measures of attention, executive functions and memory.

Results

A large-scale impairment could be observed in task planning abilities in patients with ADHD. Only negligible to small effects were found for plan recall, self-initiation and execution. Inhibition was identified to contribute significantly to performance on task planning.

Conclusions

The present findings suggest that four cognitive components contribute to the performance of prospective memory. Impairments of prospective memory mainly emerged from deficient planning abilities in adults with ADHD. Implications on behavioral based intervention strategies are discussed.     

Neuropsychological Sequelae of Carotid Angioplasty with Stent Placement: Correlation with Ischemic Lesions in Diffusion Weighted Imaging

Background and Purpose

Few studies investigated the neuropsychological outcome after carotid angioplasty with stent placement (CAS), yielding partially inconsistent results. The present investigation evaluated the effect of CAS in patients with high-grade stenosis and assessed the predictive value of ischemic lesion number for postinterventional cognitive deterioration.

Methods

22 patients were tested neuropsychologically before and six weeks after CAS. Cerebral ischemic changes were assessed with diffusion weighted imaging (DWI) prior to and after angioplasty.

Results

Pre- to postinterventional cognitive performance improved significantly in terms of verbal memory (t = −2.30; p<0.05), whereas significant deterioration was noted regarding verbal memory span (t = 2.31; p<0.05). 8 (36%) persons conformed to the criteria of cognitive improvement. 6 patients (27%) were postinterventionally classified as having deficits. Analysis yielded no statistically significant correlations between lesion quantity and cognitive change.

Conclusion

Both improvement and deterioration of cognitive functioning was observed in our collective of patients, leaving the neuropsychological outcome after percutaneous transluminal angioplasty unpredictable in individual cases. The presence of acute ischemic lesions on DWI was found to be not tightly associated with cognitive dysfunction after CAS.     

LORETA Current Source Density for Duration Mismatch Negativity and Neuropsychological Assessment in Early Schizophrenia

Introduction

Patients with schizophrenia elicit cognitive decline from the early phase of the illness. Mismatch negativity (MMN) has been shown to be associated with cognitive function. We investigated the current source density of duration mismatch negativity (dMMN), by using low-resolution brain electromagnetic tomography (LORETA), and neuropsychological performance in subjects with early schizophrenia.

Methods

Data were obtained from 20 patients meeting DSM-IV criteria for schizophrenia or schizophreniform disorder, and 20 healthy control (HC) subjects. An auditory odd-ball paradigm was used to measure dMMN. Neuropsychological performance was evaluated by the brief assessment of cognition in schizophrenia Japanese version (BACS-J).

Results

Patients showed smaller dMMN amplitudes than those in the HC subjects. LORETA current density for dMMN was significantly lower in patients compared to HC subjects, especially in the temporal lobes. dMMN current density in the frontal lobe was positively correlated with working memory performance in patients.

Conclusions

This is the first study to identify brain regions showing smaller dMMN current density in early schizophrenia. Further, poor working memory was associated with decreased dMMN current density in patients. These results are likely to help understand the neural basis for cognitive impairment of schizophrenia.     

Association of High-Density Lipoprotein Cholesterol with the Estimated Glomerular Filtration Rate in a Community-Based Population

Background

Reduced kidney function is independently associated with low high-density lipoprotein cholesterol (HDL-C) levels in patients with end-stage renal disease (ESRD), those on hemodialysis, and those with stage 3–5 chronic kidney disease (CKD). However, epidemiological data investigating the relationship between HDL-C levels and kidney function in the general population with roughly normal kidney function are limited, and the results are also inconsistent. The aim of this study was to evaluate the relationship between HDL-C levels and the estimated glomerular filtration rate (eGFR) in a community-based population in China.

Methods

This was a community-based cross-sectional survey. In total, 4925 participants (age range, 18–96 years; mean, 51.30±11.98 years) were recruited during routine health status examinations. A questionnaire was used to ascertain age, smoking status, and the history of hypertension and diabetes mellitus for each participant. We measured the body mass index, waist circumference, systolic and diastolic blood pressure, and fasting glucose, total cholesterol, triglyceride, HDL-C, low-density lipoprotein cholesterol, uric acid, and serum creatinine level of each participant. eGFR was evaluated using the Chinese modified Modification of Diet in Renal Disease equation.

Results

The HDL-C level was higher in the first quartile (lowest quartile) of eGFR than in the fourth quartile (the highest quartile). Additionally, HDL-C levels decreased as eGFR decreased. Pearson’s correlation analysis revealed that HDL-C levels were associated with eGFR (r=0.16). After adjustment for some confounders, HDL-C was independently associated with all quartiles of eGFR in the participants.

Conclusions

HDL-C was independently associated with kidney function in a community-dwelling general population. The association between low HDL-C levels and a decreased eGFR gradually strengthened as eGFR declined.     

Grey Matter Changes in Cognitively Impaired Parkinson's Disease Patients

Background

Cortical changes associated with cognitive decline in Parkinson''s disease (PD) are not fully explored and require investigations with established diagnostic classification criteria.

Objective

We used MRI source-based morphometry to evaluate specific differences in grey matter volume patterns across 4 groups of subjects: healthy controls (HC), PD with normal cognition (PD-NC), PD with mild cognitive impairment (MCI-PD) and PD with dementia (PDD).

Methods

We examined 151 consecutive subjects: 25 HC, 75 PD-NC, 29 MCI-PD, and 22 PDD at an Italian and Czech movement disorder centre. Operational diagnostic criteria were applied to classify MCI-PD and PDD. All structural MRI images were processed together in the Czech centre. The spatial independent component analysis was used to assess group differences of local grey matter volume.

Results

We identified two independent patterns of grey matter volume deviations: a) Reductions in the hippocampus and temporal lobes; b) Decreases in fronto-parietal regions and increases in the midbrain/cerebellum. Both patterns differentiated PDD from all other groups and correlated with visuospatial deficits and letter verbal fluency, respectively. Only the second pattern additionally differentiated PD-NC from HC.

Conclusion

Grey matter changes in PDD involve areas associated with Alzheimer-like pathology while fronto-parietal abnormalities are possibly an early marker of PD cognitive decline. These findings are consistent with a non-linear cognitive progression in PD.     

Area-Based Socioeconomic Position and Adult Glioma: A Hierarchical Analysis of Surveillance Epidemiology and End Results Data

Background

Glioma rates vary by demographic factors and geo-political boundaries and this variation suggests higher glioma rates in groups of higher socioeconomic position. The primary goal of this analysis is to investigate the relationship between glioma and county socioeconomic position using U.S. Surveillance Epidemiology and End Results (SEER) data.

Methods

Cases were individuals 25+ years diagnosed with glioma between 2000 and 2006 and residing within the SEER-17 catchment area. County-, sex-, race-, age-specific rates were created in order to investigate individual-level associations (population data from U.S. Census 2000). A Bayesian hierarchical Poisson spatial conditionally autoregressive (CAR) model was utilized to simultaneously estimate individual- and county-level associations while controlling for county spatial dependence.

Results

Those residing in counties of the second, third, and fourth highest quartiles of socioeconomic position have glioma incidence rates that are 1.10 (95% CI: 1.02,1.19), 1.11 (95% CI: 1.02,1.20), 1.14 (95% CI: 1.05,1.23) times that of the first quartile, respectively. A CAR model properly controlled for error spatial dependence. Investigated lag times suggest year 2000 census data yields superior model fit.

Conclusion

Demographically adjusted rates of glioma are elevated in counties of higher socioeconomic position. More well-grounded theory concerning the glioma-socioeconomic position association along with socioeconomic data collected at multiple levels is recommended for future studies investigating this relationship.     

Inflammation and Renal Function after a Four-Year Follow-Up in Subjects with Unimpaired Glomerular Filtration Rate: Results from the Observational,Population-Based CARLA Cohort

Background

There is evidence that chronic inflammation is associated with the progression/development of chronic renal failure; however, relations in subjects with preserved renal function remain insufficiently understood.

Objective

To examine the association of inflammation with the development of renal failure in a cohort of the elderly general population.

Methods

After excluding subjects with reduced estimated glomerular filtration rate (eGFR<60 mL/min/1.73 m²) and missing data, the cohort incorporated 785 men and 659 women (aged 45–83 years). Follow-up was performed four years after baseline. Covariate adjusted linear and logistic regression models were used to assess the association of plasma/serum concentrations of soluble tumour necrosis factor receptor 1 (sTNF-R1), C-reactive protein (CRP), and interleukin 6 (IL-6) with change in eGFR/creatinine. The areas under the curve (AUCs) from receiver operating characteristics (ROCs) were estimated.

Results

In adjusted models sTNF-R1 was distinctively associated with a decline in eGFR in men (0.6 mL/min/1.73 m² per 100 pg/mL sTNF-R1; 95% CI: 0.4–0.8), but not in women. A similar association could not be found for CRP or IL-6. Estimates of sTNF-R1 in the cross-sectional analyses were similar between sexes, while CRP and IL-6 were not relevantly associated with eGFR/creatinine.

Conclusion

In the elderly male general population with preserved renal function sTNF-R1 predicts the development of renal failure.     

Serum Uric Acid and Chronic Kidney Disease: The Role of Hypertension

Background

There are inconsistent findings on the role of hyperuricemia as an independent risk factor for chronic kidney disease (CKD). Hypertension has been implicated as a factor influencing the association between serum uric acid and CKD. In this population-based study we investigated the association between serum uric acid and decline in renal function and tested whether hypertension moderates this association.

Methods

We included 2601 subjects aged 55 years and over from the Rotterdam Study. Serum uric acid and estimated glomerular filtration rate (eGFR) were assessed at baseline. After average 6.5 years of follow-up, second eGFR was assessed. CKD was defined as eGFR<60 ml/min/1.73 m². All associations were corrected for socio-demographic and cardiovascular factors.

Results

Each unit (mg/dL) increase in serum uric acid was associated with 0.19 ml/min per 1.73 m² faster annual decline in eGFR. While the association between serum uric acid and incidence of CKD was not significant in our study population (Hazard Ratio: 1.12, 95% confidence interval [CI]: 0.98–1.28), incorporating our results in a meta-analysis with eleven published studies revealed a significant association (Relative Risk: 1.18, 95%CI: 1.15–1.22). In the stratified analyses, we observed that the associations of serum uric acid with eGFR decline and incident CKD were stronger in hypertensive subjects (P for interaction = 0.046 and 0.024, respectively).

Conclusions

Our findings suggest that hyperuricemia is independently associated with a decline in renal function. Stronger association in hypertensive individuals may indicate that hypertension mediates the association between serum uric acid and CKD.