Uric Acid and Risk of Cardiovascular Disease and Mortality: A Longitudinal Cohort Study.

BACKGROUND: This study aimed to examine the association of serum uric acid levels with incident cardiovascular disease and mortality in Korean adults without gout. METHODS: This large longitudinal cohort study included adults aged > 19 years who had serum uric acid levels measured at least once at the National Health Insurance Service Ilsan Hospital from January 1, 2006 to December 31, 2015. Longitudinal data on person-level cardiovascular disease and cardiovascular mortality were linked to the National Health Insurance Service claims database and National Death Index. RESULTS: Among a total of 92,454 study participants with a median follow-up of 4.7 years, 7,670 (8.3%) composite events of cardiovascular disease or cardiovascular mortality were observed. Multivariable Cox proportional-hazards models revealed that each 1 mg/dL increment in uric acid level was associated with a 6% higher risk of composite outcomes. Compared with that for the uric acid level category of 4.0 to < 5.0 mg/dL, adjusted hazard ratios (95% confidence interval) for uric acid level categories of 5.0 to < 6.0, 6.0 to < 7.0, and ≥ 7.0 mg/dL were 1.10 (1.04-1.18), 1.20 (1.11-1.30), and 1.36 (1.25-1.47), respectively. In the secondary analyses for cardiovascular disease or cardiovascular mortality examined separately, a higher uric acid level was similarly associated with a higher risk of each adverse outcome. These associations were generally consistent across clinically relevant subgroups. CONCLUSION: A graded association was noted between serum uric acid levels and cardiovascular risk, suggesting that higher uric acid levels may adversely affect cardiovascular health and survival in individuals without gout.

THYROID HORMONE REPLACEMENT REDUCES THE RISK OF CARDIOVASCULAR DISEASES IN DIABETIC NEPHROPATHY PATIENTS WITH SUBCLINICAL HYPOTHYROIDISM.

OBJECTIVE: Patients with diabetic nephropathy (DMN) have an increased risk of cardiovascular disease (CVD). However, strategies to reduce this risk are limited. Thyroid hormone replacement therapy (THRT) in patients with hypothyroidism has been shown to reduce several surrogate markers of CVD. Therefore, we performed a study to determine if THRT would reduce CVD risk in patients with subclinical hypothyroidism (SCH) and DMN. METHODS: This was a retrospective, nonrandomized study of patients with type 2 diabetes, DMN, and SCH. Those with known thyroid dysfunction or taking THRT at baseline were excluded. Patients receiving THRT for at least 180 days were included in the THRT group, while the remaining patients were assigned to the non-THRT group. The primary outcome was CVD events, which included coronary syndrome, cerebrovascular events, and peripheral artery diseases. RESULTS: Among the 257 patients, 83 (32.3%) were in the THRT group. The mean ages were 62.7 ± 12.3 and 66.8 ± 12.4 years in the THRT and non-THRT groups, respectively. The corresponding numbers of male patients were 32 (40.0%) and 94 (53.1%). During a mean follow-up of 38.0 ± 29.2 months, 98 CVD events were observed. Acute coronary syndrome and cerebrovascular event prevalence rates were lower in the THRT group than the non-THRT group, but there was no difference for peripheral artery diseases. Multivariate Cox analysis revealed that THRT was independently associated with a decreased CVD event risk. CONCLUSION: THRT may decrease the risk of CVD in DMN patients with SCH. Randomized trials are needed to verify this finding. ABBREVIATIONS: CV = cardiovascular DMN = diabetic nephropathy eGFR = estimated glomerular filtration rate fT4 = free thyroxine HbA1c = glycosylated hemoglobin HR = hazard ratio hs-CRP = high-sensitivity C-reactive protein LDL-C = low-density lipoprotein cholesterol SCH = subclinical hypothyroidism T2DM = type 2 diabetes THRT = thyroid hormone replacement therapy TSH = thyroid-stimulating hormone.

Update of aristolochic acid nephropathy in Korea.

BACKGROUND/AIMS: The true incidence of aristolochic acid nephropathy (AAN) is thought to be underestimated because numerous ingredients known or suspected to contain aristolochic acid (AA) are used in traditional medicine in Korea. METHODS: We collected data on cases of AAN since 1996 via a database in Korea. We evaluated the year of AAN development, route to obtaining AA-containing herbal medicine, gender, reason for taking AA-containing herbal medicine, clinical manifestations, histological findings, phytochemical analysis, and prognosis of patients with AAN. RESULTS: Data on 16 cases of AAN were collected. Thirteen cases developed AAN before and three cases after the prohibition of AA-containing herbal medicine by the Korea Food and Drug Administration. Patients were prescribed AA-containing herbal medicine from oriental clinics or had purchased it from traditional markets. AAN was distributed in all age groups. Young females were most commonly exposed to AA-containing herbal medicine for slimming purposes and postpartum health promotion, while older adults took AA-containing compounds for the treatment of chronic diseases. The most common symptoms presented at hospitalization were nausea and vomiting, and acute kidney injury was accompanied by Fanconi syndrome in almost half of the patients. Phytochemical analysis of AA in herbal medicine was available in six cases. Progression to end stage renal disease (ESRD) was observed in seven patients (43.8%), and five patients (31.3%) had progressed to ESRD within 6 months of diagnosis. CONCLUSION: Our report shows that patients were still exposed to AA-containing herbal medicine and that there is a possibility of underdiagnosis of AAN in Korea. A stronger national supervision system of herbal ingredients and remedies in oriental medicine is needed to prevent AAN.

High and low sodium intakes are associated with incident chronic kidney disease in patients with normal renal function and hypertension.

The association between salt intake and renal outcome in subjects with preserved kidney function remains unclear. Here we evaluated the effect of sodium intake on the development of chronic kidney disease (CKD) in a prospective cohort of people with normal renal function. Data were obtained from the Korean Genome and Epidemiology Study, a prospective community-based cohort study while sodium intake was estimated by a 24-hour dietary recall Food Frequency Questionnaire. A total of 3,106 individuals with and 4,871 patients without hypertension were analyzed with a primary end point of CKD development [a composite of estimated glomerular filtration rate (eGFR) under 60 mL/min/1.73 m2 and/or development of proteinuria during follow-up]. The median ages were 55 and 47 years, the proportions of males 50.9% and 46.3%, and the median eGFR 92 and 96 mL/min/1.73 m2 in individuals with and without hypertension, respectively. During a median follow-up of 123 months in individuals with hypertension and 140 months in those without hypertension, CKD developed in 27.8% and 16.5%, respectively. After adjusting for confounders, multiple Cox models indicated that the risk of CKD development was significantly higher in people with hypertension who consumed less than 2.08 g/day or over 4.03 g/day sodium than in those who consumed between 2.93-4.03 g/day sodium. However, there was no significant difference in the incident CKD risk among each quartile of people without hypertension. Thus, both high and low sodium intakes were associated with increased risk for CKD, but this relationship was only observed in people with hypertension.

High dietary phosphorus density is a risk factor for incident chronic kidney disease development in diabetic subjects: a community-based prospective cohort study.

Background: High serum phosphorus concentrations are associated with an increased risk of cardiovascular disease and progression of chronic kidney disease (CKD). However, the relation between dietary phosphorus intake and CKD development has not been well evaluated.Objective: In this study, we investigated the impact of dietary phosphorus density on the development of incident CKD in a cohort of subjects with normal renal function.Design: Data were retrieved from the Korean Genome and Epidemiology Study, a prospective community-based cohort study. The study cohort consisted of subjects aged 40-69 y, who were followed up biennially from 2001 to 2014. A total of 873 subjects with diabetes mellitus (DM) and 5846 subjects without DM (non-DM) were included in the final analysis. The primary endpoint was incident CKD, defined as a composite of estimated glomerular filtration rate <60 mL · min-1 · 1.73 m-2 and/or the development of proteinuria.Results: In the DM and non-DM groups, the mean ages of the participants were 55.6 ± 8.7 and 51.4 ± 8.6 y, the numbers of male subjects were 454 (52.0%) and 2784 (47.6%), and the mean estimated glomerular filtration rates were 91.6 ± 14.0 and 94.5 ± 14.0 mL · min-1 · 1.73 m-2, respectively. The mean values of dietary phosphorus density, defined as the ratio of a single-day dietary phosphorus amount to the total daily calorie intake, were 0.51 ± 0.08 mg/kcal in the DM group and 0.51 ± 0.07 mg/kcal in the non-DM group. During the follow-up, CKD newly developed in 283 (32.4%) and 792 subjects (13.5%) in the DM and non-DM groups, respectively. When the subjects were divided into quartiles according to the dietary phosphorus density in each group, the highest quartile was significantly associated with the development of incident CKD by multiple Cox proportional hazard analysis in the DM group (P = 0.02) but not in the non-DM group (P = 0.72).Conclusions: High dietary phosphorus density is associated with an increased risk of CKD development in DM patients with normal renal function. The causality in this association needs to be tested in a randomized controlled trial.

Body mass index is inversely associated with mortality in patients with acute kidney injury undergoing continuous renal replacement therapy.

BACKGROUND: Many epidemiologic studies have reported on the controversial concept of the obesity paradox. The presence of acute kidney injury (AKI) can accelerate energy-consuming processes, particularly in patients requiring continuous renal replacement therapy (CRRT). Thus, we aimed to investigate whether obesity can provide a survival benefit in this highly catabolic condition. METHODS: We conducted an observational study in 212 patients who had undergone CRRT owing to various causes of AKI between 2010 and 2014. The study end point was defined as death that occurred within 30 days after the initiation of CRRT. RESULTS: Patients were categorized into three groups according to tertiles of body mass index (BMI). During ≥30 days after the initiation of CRRT, 39 patients (57.4%) in the highest tertile died, as compared with 58 patients (78.4%) in the lowest tertile (P = 0.02). In a multivariable analysis adjusted for cofounding factors, the highest tertile of BMI was significantly associated with a decreased risk of death (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.37-0.87; P = 0.01). This significant association remained unaltered for 60-day (HR, 0.64; 95% CI, 0.43-0.94; P = 0.03) and 90-day mortality (HR, 0.66; 95% CI, 0.44-0.97; P = 0.03). CONCLUSION: This study showed that a higher BMI confer a survival benefit over a lower BMI in AKI patients undergoing CRRT.

Neck circumference predicts renal function decline in overweight women: A community-based prospective cohort study.

Chronic kidney disease (CKD) is characterized by increased risks of morbidity and mortality. Upper-body subcutaneous fat, which is commonly estimated from the neck circumference (NC), was revealed to be the main reservoir of circulating nonesterified fatty acids in overweight patients. Despite a close association between NC and metabolic complications, the relationship of NC with renal function has not been fully investigated. In this study, the impact of NC on the development of incident CKD was elucidated.The data were retrieved from the Korean Genome and Epidemiology Study cohort. The subjects were followed at 2-year intervals from 2003 to 2011. Overweight was defined as a body mass index of ≥23 kg/m. A total of 4298 cohort subjects were screened. After exclusion, 2268 overweight subjects were included for the final analysis. The primary end point was incident CKD, which was defined as a composite of estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m or the development of proteinuria.The mean patient age was 36.3 ±â€Š3.0 years, and 1285 (56.7%) were men. They were divided into 2 groups according to the median NC in male and female subjects, separately. In both sexes, hypertension (men, P < 0.001; women, P = 0.009) and diabetes (men, P = 0.002; women, P < 0.001) were significantly more prevalent in the big NC group than in the small NC group. In contrast, eGFR was significantly lower only in male subjects of the big NC group (P < 0.001), whereas it was comparable between the small and big NC groups (P = 0.167). In multivariate Cox proportional hazards regression analysis, NC values were independently associated with incident CKD development in female subjects after adjusting for multiple confounding factors (per 1 cm increase, hazard ratio [95% confidence interval] = 1.159 [1.024-1.310], P = 0.019) but not in male subjects.NC is independently associated with the development of CKD in overweight female subjects, suggesting that it could be a practical risk factor for CKD.

Low Dentin Matrix Protein 1 Is Associated With Incident Cardiovascular Events in Peritoneal Dialysis Patients.

Recent reports demonstrated that dentin matrix protein 1 (DMP1) acts as an inhibitor of vascular calcification and might be a potential biomarker for chronic kidney disease-mineral and bone disorder; however, no clinical investigations regarding DMP1 have been performed in dialysis patients. We investigated the prognostic value of DMP1 on cardiovascular outcomes in prevalent peritoneal dialysis patients. We recruited 223 prevalent peritoneal dialysis patients and divided them into high and low DMP1 groups according to log-transformed plasma DMP1 levels. Lateral lumbar spine radiographs were used for measurement of vascular calcification. Major cardiovascular events were compared between the two groups. A Cox proportional hazards analysis determined DMP1 was independently associated with cardiovascular outcomes. In vitro mouse osteocytes were cultured in media containing indoxyl sulfate (IS), and the expressions of DMP1 were examined. The mean age was 52.1 ± 11.8 years, and 116 (52.0%) patients were male. The median value of log DMP1 was 0.91 (0.32-2.81 ng/mL). The multiple logistic regression analysis indicated that DMP1 levels were independently associated with the presence of vascular calcification after adjustment for multiple confounding factors (odds ratio = 0.719; 95% confidence interval [CI] 0.522-0.989; p = 0.043). During a mean follow-up duration of 34.6 months, incident cardiovascular events were observed in 41 (18.4%) patients. A Kaplan-Meier plot showed that the low DMP1 group had a significantly higher rate of incident cardiovascular events compared with the high DMP1 group (log-rank test, p = 0.026). In addition, multiple Cox analysis showed that low DMP1 was significantly associated with incident cardiovascular events (log 1 increase: hazard ratio = 0.855; 95% CI 0.743-0.984; p = 0.029) after adjustment for multiple confounding factors. In IS-stimulated osteocytes, mRNA and protein expression levels of DMP1 were significantly decreased compared with control osteocytes. We showed that low DMP1 levels were significantly associated with presence of vascular calcification and were independently associated with the incident cardiovascular events in prevalent peritoneal dialysis patients. DMP1 might be a potential factor contributing to cardiovascular complications in dialysis patients. © 2016 American Society for Bone and Mineral Research.