Hyoungnae Kim

The clinical and immunogenetic characteristics of adult-onset type 1 diabetes mellitus in Korea.

Although the HLA class II alleles and immunological abnormalities are associated with type 1 diabetes mellitus (T1DM) in all racial groups, there are considerable variations in the genotypes and the prevalence of autoantibodies. In order to investigate the characteristics of the immunogenetic patterns and to use these as an early diagnostic tool and guideline for a therapeutic plan, we examined the clinical characteristics and the patterns of anti-GAD antibody (GADA), IA-2 antibody (IA-2A), HLA-DR and HLA-DQ in Korean adult-onset T1DM patients. Adult-onset patients had higher serum C-peptide levels than child-onset patients. In adult-onset patients, the prevalence of GADA and IA-2A were 59.5% and 15.3% respectively, and increased frequencies of HLADR4 and-DR9 were found. The frequencies of HLADQA1,-DQB1 and-DQ heterodimers were similar to those of the control, but child-onset patients had high frequencies of the HLA-DR3,-DR4,-DR9, DQA1*0301, DQA1*0501 and DQB1*0201 genotypes. In conclusion, Korean adult-onset T1DM patients had a lower prevalence of GADA, which was comparable to that found in Caucasian patients. The detection of GADA might help to predict the insulin dependency of adult-onset diabetes. Difference in the frequencies of diabetes associated with HLA type suggests that there might be a heterogeneity in the pathogenesis of diabetes according to the age of onset.

Electrolyte and mineral disturbances in septic acute kidney injury patients undergoing continuous renal replacement therapy.

AbstractElectrolyte and mineral disturbances remain a major concern in patients undergoing continuous renal replacement therapy (CRRT); however, it is not clear whether those imbalances are associated with adverse outcomes in patients with septic acute kidney injury (AKI) undergoing CRRT. We conducted a post-hoc analysis of data from a prospective randomized controlled trial. A total of 210 patients with a mean age of 62.2 years (136 [64.8%] males) in 2 hospitals were enrolled. Levels of sodium, potassium, calcium, and phosphate measured before (0 hour) and 24 hours after CRRT initiation. Before starting CRRT, at least 1 deficiency and excess in electrolytes or minerals were observed in 126 (60.0%) and 188 (67.6%) patients, respectively. The excess in these parameters was greatly improved, whereas hypokalemia and hypophosphatemia became more prevalent at 24 hours after CRRT. However, 1 and 2 or more deficiencies in those parameters at the 2 time points were not associated with mortality. However, during 28 days, 89 (71.2%) deaths occurred in patients with phosphate levels at 0 hour of ≥4.5 mg/dL as compared with 49 (57.6%) in patients with phosphate levels <4.5 mg/dL. The 90-day mortality was also significantly higher in patients with hyperphosphatemia. Similarly, in 184 patients who survived at 24 hours after CRRT, hyperphosphatemia conferred a 2.2-fold and 2.6-fold increased risk of 28- and 90-day mortality, respectively. The results remained unaltered when the serum phosphate level was analyzed as a continuous variable. Electrolyte and mineral disturbances are common, and hyperphosphatemia may predict poor prognosis in septic AKI patients undergoing CRRT.

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.

Warfarin Use in Patients with Atrial Fibrillation Undergoing Hemodialysis: A Nationwide Population-Based Study

Background and Purpose— The aim of this study is to elucidate the effects of warfarin use in patients with atrial fibrillation undergoing dialysis using a population-based Korean registry. Methods— Data were extracted from the Health Insurance Review and Assessment Service, which is a nationwide, mandatory social insurance database of all Korean citizens enrolled in the National Health Information Service between 2009 and 2013. Thromboembolic and hemorrhagic outcomes were analyzed according to warfarin use. Overall and propensity score–matched cohorts were analyzed by Cox proportional hazards models. Results— Among 9974 hemodialysis patients with atrial fibrillation, the mean age was 66.6±12.2 years, 5806 (58.2%) were men, and 2921 (29.3%) used warfarin. After propensity score matching to adjust for all described baseline differences, 5548 subjects remained, and differences in baseline variables were distributed equally between warfarin users and nonusers. During a mean follow-up duration of 15.9±11.1 months, ischemic and hemorrhagic stroke occurred in 678 (6.8%) and 227 (2.3%) patients, respectively. In a multiple Cox model, warfarin use was significantly associated with an increased risk of hemorrhagic stroke (hazard ratio, 1.44; 95% confidence interval, 1.09–1.91; P=0.010) in the overall cohort. Furthermore, a significant relationship between warfarin use and hemorrhagic stroke was found in propensity-matched subjects (hazard ratio, 1.56; 95% confidence interval, 1.10–2.22; P=0.013). However, the ratios for ischemic stroke were not significantly different in either the propensity-matched (hazard ratio, 0.95; 95% confidence interval, 0.78–1.15; P=0.569) or overall cohort (hazard ratio, 1.06; 95% confidence interval, 0.90–1.26; P=0.470). Conclusions— Our findings suggest that warfarin should be used carefully in hemodialysis patients, given the higher risk of hemorrhagic events and the lack of ability to prevent thromboembolic complications.

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.

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.

Vitamin D deficiency is significantly associated with depression in patients with chronic kidney disease

Background Depression is reported to be the most common psychological problem in patients with chronic kidney disease (CKD). Several studies have reported that lower levels of serum vitamin D are significantly associated with depression. Both vitamin D deficiency and depression are prevalent in patients with CKD, yet the relationship between these two factors remains poorly understood. This study aimed to investigate the association between vitamin D levels and depression among CKD patients. Methods Totally, 21,257 individuals who participated in the Korean National Health and Nutrition Examination Survey (KNHANES V, VI) from 2010–2014 were screened for the study; 533 CKD patients were included. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D3 [25(OH)D3] ≤10 ng/mL. Patients were divided into vitamin D deficient or sufficient groups. Depression was screened for using the Korean version of the WHO Composite International Diagnostic Interview-Short Form. The association between vitamin D deficiency and depression was evaluated by multivariate logistic regression analysis. Results The mean participant age was 70.1±9.4 years; 262 patients (49.2%) were male. The median 25(OH)D3 level was 19.1±6.9 ng/mL. The prevalence of depression was higher in CKD patients than in the general population (14.3 vs. 11.1%, P = 0.03). Additionally, the prevalence of depression was significantly higher in CKD patients with (vs. without) vitamin D deficiency (32.5% vs. 50.0%, P<0.001). Multivariate logistic regression analysis showed that vitamin D deficiency was a significant independent predictor of depression after adjusting for confounding factors (adjusted odds ratio, 6.15; 95% confidence interval, 2.02–8.75; P = 0.001). Conclusion Depression was highly prevalent in CKD patients, in whom vitamin D deficiency was a significant independent predictor of depression. Therefore, management of vitamin D deficiency might help prevent depression in CKD patients.

Tissue-specific regulation of malonyl-CoA decarboxylase activity in OLETF rats.

Aim:  The intracellular concentration of malonyl‐CoA, a key regulator of fatty acid oxidation, is determined both from its synthesis by acetyl‐CoA carboxylase and from its degradation by malonyl‐CoA decarboxylase (MCD). The aim of our study was to investigate the activity and mRNA expression of MCD under insulin resistance and after treatment with insulin sensitizers in different tissues.

Effects of Coffee Intake on Incident Chronic Kidney Disease: Community-Based Prospective Cohort Study

BACKGROUND Drinking coffee can raise public health problems, but the association between coffee and kidney disease is unknown. We studied whether coffee intake can affect the development of chronic kidney disease in the general population. METHODS We analyzed 8717 subjects with normal renal function recruited from the Korean Genome and Epidemiology Study (KoGES) cohort. Based on a food frequency questionnaire, coffee consumption was categorized into 5 groups: 0 per week, <1 cup per week, 1-6 cups per week, 1 cup per day, and ≥2 cups per day. The primary outcome was incident chronic kidney disease, defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2. RESULTS The mean age (standard deviation) of study subjects was 52.0 (8.8) years, and 47.8% were male. Among the subjects, 52.8% were daily coffee consumers. During a mean follow-up of 11.3 (range, 5.9-11.5) years, 9.5% of participants developed chronic kidney disease. The incident chronic kidney disease occurred less in daily coffee consumers. Unadjusted hazard ratios (HRs) was significantly lower in daily coffee consumers. In multivariable Cox model even after adjustment of blood pressure, hypertension, cardiovascular disease, diabetes, and amount of daily intake for caffeine-containing foods such as tea and chocolate, coffee consumers with 1 cup per day (HR, 0.76; 95% confidence interval, 0.63-0.92) and ≥2 cups per day (HR, 0.80; 95% confidence interval, 0.65-0.98) were associated with a lower risk of chronic kidney disease development than nondrinkers. Time-averaged and time-varying Cox models yielded similar results. The rates of decline in glomerular filtration were lower in daily coffee consumers. CONCLUSIONS Our findings suggest that daily coffee intake is associated with decreased risk of the development of chronic kidney disease.

Baseline Cardiovascular Characteristics of Adult Patients with Chronic Kidney Disease from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD)

Cardiovascular disease (CVD) is the most common cause of death in patients with chronic kidney disease (CKD). We report the baseline cardiovascular characteristics of 2,238 participants by using the data of the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) study. The cohort comprises 5 subcohorts according to the cause of CKD: glomerulonephritis (GN), diabetic nephropathy (DN), hypertensive nephropathy (HTN), polycystic kidney disease (PKD), and unclassified. The average estimated glomerular filtration rate (eGFR) was 50.5 ± 30.3 mL/min−1/1.73 m−2 and lowest in the DN subcohort. The overall prevalence of previous CVD was 14.4% in all patients, and was highest in the DN followed by that in the HTN subcohort. The DN subcohort had more adverse cardiovascular risk profiles (higher systolic blood pressure [SBP], and higher levels of cardiac troponin T, left ventricular mass index [LVMI], coronary calcium score, and brachial-ankle pulse wave velocity [baPWV]) than the other subcohorts. The HTN subcohort exhibited less severe cardiovascular risk profiles than the DN subcohort, but had more severe cardiovascular risk features than the GN and PKD subcohorts. All these cardiovascular risk profiles were inversely correlated with eGFR. In conclusion, this study shows that the KNOW-CKD cohort exhibits high cardiovascular burden, as other CKD cohorts in previous studies. Among the subcohorts, the DN subcohort had the highest risk for CVD. The ongoing long-term follow-up study up to 10 years will further delineate cardiovascular characteristics and outcomes of each subcohort exposed to different risk profiles.