Dapagliflozin Reduces Urinary Kidney Injury Biomarkers in Chronic Kidney Disease Irrespective of Albuminuria Level.

The beneficial effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with chronic kidney disease (CKD) with low albuminuria levels have not been established. This study aimed to compare the effects of dapagliflozin on kidney injury biomarkers in patients with CKD stratified by albuminuria level. We prospectively enrolled healthy volunteers (HVs; n = 20) and patients with CKD (n = 54) with and without diabetes mellitus. Patients with CKD were divided into two age-matched and sex-matched subgroups according to urinary albumin-creatinine ratio (uACR) levels (<300 mg/g and ≥300 mg/g). The CKD group received dapagliflozin (10 mg/day). Urine samples were collected before treatment and after 3 and 6 months of dapagliflozin. Urinary kidney injury molecule-1 (KIM-1), interleukin-1ß (IL-1ß), and mitochondrial DNA nicotinamide adenine dinucleotide dehydrogenase subunit-1 (mtND1) copy number were measured. The estimated glomerular filtration rate (eGFR) of patients with CKD was lower than that of HVs (P < 0.001). During the study period, eGFR decreased and uACR did not change in the CKD group. Kidney injury markers were significantly elevated in patients with CKD compared with those in HVs. Dapagliflozin reduced urinary KIM-1, IL-1ß, and mtDNA copy number in patients with CKD after 6 months of treatment. In further, the levels of urinary KIM-1 and IL-1ß, patients with CKD decreased after 6 months of dapagliflozin treatment regardless of albuminuria level. Dapagliflozin reduced urinary kidney injury biomarkers in patients with CKD, regardless of albuminuria level. These findings suggest that SGLT2 inhibitors may also attenuate the progression of low albuminuric CKD.

MicroRNA-5010-5p ameliorates high-glucose induced inflammation in renal tubular epithelial cells by modulating the expression of PPP2R2D.

INTRODUCTION: We previously reported the significant upregulation of eight circulating exosomal microRNAs (miRNAs) in patients with diabetic kidney disease (DKD). However, their specific roles and molecular mechanisms in the kidney remain unknown. Among the eight miRNAs, we evaluated the effects of miR-5010-5p on renal tubular epithelial cells under diabetic conditions in this study. RESEARCH DESIGN AND METHODS: We transfected the renal tubular epithelial cell line, HK-2, with an miR-5010-5p mimic using recombinant plasmids. The target gene of hsa-miR-5010-5p was identified using a dual-luciferase assay. Cell viability was assessed via the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. Moreover, mRNA and protein expression levels were determined via real-time PCR and western blotting, respectively. RESULTS: High glucose levels did not significantly affect the intracellular expression of miR-5010-5p in HK-2 cells. Transfection of the miR-5010-5p mimic caused no change in cell viability. However, miR-5010-5p-transfected HK-2 cells exhibited significantly decreased expression levels of inflammatory cytokines, such as the monocyte chemoattractant protein-1, interleukin-1ß, and tumor necrosis factor-ɑ, under high-glucose conditions. These changes were accompanied by the restored expression of phosphorylated AMP-activated protein kinase (AMPK) and decreased phosphorylation of nuclear factor-kappa B. Dual-luciferase assay revealed that miR-5010-5p targeted the gene, protein phosphatase 2 regulatory subunit B delta (PPP2R2D), a subunit of protein phosphatase 2A, which modulates AMPK phosphorylation. CONCLUSIONS: Our findings suggest that increased miR-5010-5p expression reduces high glucose-induced inflammatory responses in renal tubular epithelial cells via the regulation of the target gene, PPP2R2D, which modulates AMPK phosphorylation. Therefore, miR-5010-5p may be a promising therapeutic target for DKD.

The clinical relevance of a polygenic risk score for type 2 diabetes mellitus in the Korean population.

The clinical utility of a type 2 diabetes mellitus (T2DM) polygenic risk score (PRS) in the East Asian population remains underexplored. We aimed to examine the potential prognostic value of a T2DM PRS and assess its viability as a clinical instrument. We first established a T2DM PRS for 5490 Korean individuals using East Asian Biobank data (269,487 samples). Subsequently, we assessed the predictive capability of this T2DM PRS in a prospective longitudinal study with baseline data and data from seven additional follow-ups. Our analysis showed that the T2DM PRS could predict the transition of glucose tolerance stages from normal glucose tolerance to prediabetes and from prediabetes to T2DM. Moreover, T2DM patients in the top-decile PRS group were more likely to be treated with insulin (hazard ratio = 1.69, p value = 2.31E-02) than were those in the remaining PRS groups. T2DM PRS values were significantly high in the severe diabetes subgroup, characterized by insulin resistance and ß -cell dysfunction (p value = 0.0012). The prediction models with the T2DM PRS had significantly greater Harrel's C-indices than did corresponding models without it. By utilizing prospective longitudinal study data and extensive clinical risk factor information, our analysis provides valuable insights into the multifaceted clinical utility of the T2DM PRS.

Euglycemic diabetic ketoacidosis following traumatic brain injury.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors lower glucose levels by reducing glucose reabsorption in the kidneys, which can lead to ketogenesis. Euglycemic diabetic ketoacidosis (DKA) is a rare but potentially life-threatening complication of SGLT2 inhibitors that can be triggered by trauma. However, the absence of significant hyperglycemia can delay its diagnosis and treatment, which may lead to detrimental consequences. Herein, we report a case of euglycemic DKA following traumatic brain injury in a patient with type 2 diabetes who was taking an SGLT2 inhibitor. Delayed recognition of euglycemic DKA in this case led to progressive metabolic deterioration. This report emphasizes the importance of promptly suspecting, diagnosing, and treating euglycemic DKA in patients with traumatic injuries who exhibit high anion-gap metabolic acidosis, ketonuria, and glucosuria-even if they do not have significant hyperglycemia.

Dietary cholesterol intake is not associated with the development of chronic kidney disease: Results from two Korean cohort studies.

BACKGROUND AND AIMS: Although dyslipidemia is a major risk factor for chronic kidney disease (CKD), the relationship between dietary cholesterol and CKD remains unknown. We investigated the association between cholesterol intake and CKD risk. METHODS AND RESULTS: The Korea National Health and Nutrition Examination Survey (KNHANES) 2019-2021 (n = 13,769) and the Korean Genome and Epidemiology Study (KoGES) (n = 9225) data were used for this study. Cholesterol intake was assessed using a 24-h recall food frequency questionnaire, and participants were categorized into three groups (T1, T2, and T3) based on cholesterol intake. Primary outcomes were prevalence and incidence of CKD. Higher cholesterol intake was modestly associated with increased serum levels of total, low-density lipoprotein, and high-density lipoprotein cholesterol in the KNHANES. However, we found no significant association between cholesterol intake and CKD prevalence in the KNHANES, regardless of a history of hypercholesterolemia. In the KoGES, during a median follow-up of 11.4 years, cholesterol intake was not associated with incident CKD in participants without hypercholesterolemia (hazard ratio [HR] per 10 mg increase, 1.00; 95 % confidence interval [CI], 0.99-1.01) and in those with hypercholesterolemia (HR, 1.01; 95 % CI, 0.98-1.04). Egg consumption also showed no significant association with the risk of incident CKD. Additionally, cholesterol intake had no significant interaction on the relationships between serum cholesterol levels and incident CKD. CONCLUSION: Although cholesterol intake was associated with increased serum cholesterol levels, it was not associated with CKD prevalence and incidence. Our findings suggest that reducing cholesterol intake alone may not be sufficient to prevent CKD.

Complement C3 Reduces Apoptosis via Interaction with the Intrinsic Apoptotic Pathway.

Myocardial ischemia/reperfusion (I/R) elicits an acute inflammatory response involving complement factors. Recently, we reported that myocardial necrosis was decreased in complement C3-/- mice after heart I/R. The current study used the same heart model to test the effect of C3 on myocardial apoptosis and investigated if C3 regulation of apoptosis occurred in human cardiomyocytes. Comparative proteomics analyses found that cytochrome c was present in the myocardial C3 complex of WT mice following I/R. Incubation of exogenous human C3 reduced apoptosis in a cell culture system of human cardiomyocytes that did not inherently express C3. In addition, human C3 inhibited the intrinsic apoptosis pathway in a cell-free apoptosis system. Finally, human pro-C3 was found to bind with an apoptotic factor, pro-caspase 3, in a cell-free system. Thus, we present firsthand evidence showing that C3 readily reduces myocardial apoptosis via interaction with the intrinsic apoptotic pathway.

Co-inhibition of glutaminolysis and one-carbon metabolism promotes ROS accumulation leading to enhancement of chemotherapeutic efficacy in anaplastic thyroid cancer.

Anaplastic thyroid cancer (ATC) is one of the most aggressive tumors with an extremely poor prognosis. Based on the several biological features related to glutamine metabolism in ATC, we hypothesized glutaminolysis inhibition induces cell death in ATC cells. However, glutamine metabolism inhibition triggered cell growth arrest independent of cell death in ATC, suggesting that other signaling pathways avoid glutamine metabolism inhibition-induced stress exist. To investigate the functional mechanism against glutamine metabolism inhibition, we conducted mRNA and ATAC-Sequencing data analysis and found that glutamine deprivation increased ATF4-mediated one-carbon metabolism. When we inhibited PHGDH, the first rate-limiting enzyme for one-carbon metabolism, cell growth arrest was promoted upon glutamine metabolism inhibition by accumulating intracellular ROS. We next observed that the co-inhibition of glutamine and one-carbon metabolism could augment the anticancer effects of drugs used in patients with ATC. Finally, single-cell RNA sequencing analysis revealed that one-carbon metabolism was strengthened through the evolutionary process from PTC to ATC. Collectively, our data demonstrate that one-carbon metabolism has a potential role of modulation of cell fate in metabolic stress and can be a therapeutic target for enhancing antitumor effects in ATC.

Epigenomic landscape exhibits interferon signaling suppression in the patient of myocarditis after BNT162b2 vaccination.

After the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, a novel mRNA vaccine (BNT162b2) was developed at an unprecedented speed. Although most countries have achieved widespread immunity from vaccines and infections, yet people, even who have recovered from SARS-CoV-2 infection, are recommended to receive vaccination due to their effectiveness in lowering the risk of recurrent infection. However, the BNT162b2 vaccine has been reported to increase the risk of myocarditis. To our knowledge, for the first time in this study, we tracked changes in the chromatin dynamics of peripheral blood mononuclear cells (PBMCs) in the patient who underwent myocarditis after BNT162b2 vaccination. A longitudinal study of chromatin accessibility using concurrent analysis of single-cell assays for transposase-accessible chromatin with sequencing and single-cell RNA sequencing showed downregulation of interferon signaling and upregulated RUNX2/3 activity in PBMCs. Considering BNT162b2 vaccination increases the level of interferon-α/γ in serum, our data highlight the immune responses different from the conventional responses to the vaccination, which is possibly the key to understanding the side effects of BNT162b2 vaccination.

Association between abdominal perivascular adipose tissue quantity and quality assessed by CT and cardiometabolic risk.

BACKGROUND & AIMS: Changes in the perivascular adipose tissue (PVAT) are associated with the risk of metabolic syndrome (MetS). We hypothesized that the quantity and quality of PVAT measured by computed tomography (CT) are associated with cardiometabolic risk. METHODS: This study analyzed the data of 505 participants (men, 72.7%) who underwent general health checkups, including abdominal and pelvic CT. We measured the volume and fat attenuation index (FAI) of the abdominal periaortic (APA) and renal sinus (RS) adipose tissues. Participants were categorized into three groups according to the number of MetS components they had based on the modified ATP III criteria (0, 1-2, and ≥3). RESULTS: Moving stepwise from the no MetS component group to the 1-2 components group to the ≥3 components group, all PVAT volumes increased and all PVAT FAIs decreased consistently. Greater PVAT volume was independently associated with greater prevalence of MetS components in the ≥3 components group (P = 0.002 for right RS, P = 0.027 for left RS, and P = 0.001 for APA), whereas lower FAI in all PVATs was associated with greater prevalence of MetS components in the 1-2 components group after adjusting for the corresponding adipose tissue volumes (P = 0.007 for right RS, P = 0.002 for left RS, and P = 0.001 for APA). CONCLUSION: Higher abdominal PVAT volume was independently associated with prevalent MetS. Moreover, lower abdominal PVAT FAI was associated with mild metabolic derangement. Image-based assessment of abdominal PVAT may be a potential biomarker for cardiometabolic risk.

Association of glomerular hyperfiltration with carotid artery plaque in the general population.

BACKGROUND AND AIMS: Glomerular hyperfiltration (GHF) is a hemodynamic change of the kidney as an adaptive response to nephron loss. Although GHF is associated with metabolic risk factors and cardiovascular disease (CVD), the mechanisms that explain these relationships remain largely unknown. This is partially caused by a non-unified definition of GHF based on pathophysiologic vascular changes. Thus, the objective of this study was to evaluate the association between various definitions of GHF and carotid plaque in a health checkup cohort. METHODS: A total of 4493 individuals without history of CVD who had carotid ultrasonography (USG) results available between January 2016 and June 2018 were enrolled. GHF was defined as >90th percentile of eGFR residuals after adjusting for confounding factors. Carotid plaque score was calculated based on carotid USG results. RESULTS: Of 4493 individuals (mean age, 52.3 ± 10.1 years; 3224 [71.8%] males), 449 subjects were included in the GHF group (mean eGFR, 107.0 ± 7.1 ml/min/1.73 m2) and 4044 subjects were included in the non-GHF group (mean eGFR, 92.5 ± 12.3 ml/min/1.73 m2). When the GHF group was compared to the non-GHF group, GHF was associated with the presence of significant carotid plaque (carotid plaque score ≥2) (adjusted OR: 1.46; 95% CI: 1.16 to 1.83; p = 0.001). GHF defined in this study showed higher sensitivity to the presence of carotid plaque than other definitions of GHF. CONCLUSIONS: GHF status was associated with risk of carotid plaque in individuals without history of CVD. Presence of subclinical carotid plaque was associated with risk of future CVD. Therefore, GHF based on creatinine could be a useful surrogate marker for surveillance of CVD in asymptomatic individuals.

The role of complement C3 in the outcome of regional myocardial infarction.

Coronary heart disease leading to myocardial ischemia is a major cause of heart failure. A hallmark of heart failure is myocardial fibrosis. Using a murine model of myocardial ischemia/reperfusion injury (IRI), we showed that, following IRI, in mice genetically deficient in the central factor of complement system, C3, myocardial necrosis was reduced compared with WT mice. Four weeks after the ischemic period, the C3-/- mice had significantly less cardiac fibrosis and better cardiac function than the WT controls. Overall, our results suggest that innate immune response through complement C3 plays an important role in necrotic cell death, which contributes to the cardiac fibrosis that underlies post-infarction heart failure.

Changes in abdominal fat depots after bariatric surgery are associated with improved metabolic profile.

BACKGROUND AND AIMS: Obesity associated with a change in the quantity and quality of fat depots. Using computed tomography (CT), we analyzed abdominal fat depots in patients with obesity after bariatric surgery according to their metabolic health status. METHODS AND RESULTS: We recruited 79 individuals with metabolically unhealthy obesity before bariatric surgery and compared them with age-sex matched healthy controls. The volume and fat attenuation index (FAI) of fat depots were measured using CT scans that were conducted prior to and a year after bariatric surgery. 'Metabolically healthy' was defined as having no hypertension, normal fasting glucose and a waist-to-hip ratio of <1.05 for men and <0.95 for women. Individuals who achieved a metabolic health status conversion (MHC) (n = 29, 37%)-from unhealthy to healthy-were younger (p < 0.001) as compared to individuals without MHC. Pre-surgery BMI and reduction of BMI did not differ between the two groups (p = 0.099, p = 0.5730). Bariatric surgery reduced the volume and increased the FAI of fat depots. Baseline lower abdominal periaortic adipose tissue (AT) volume (p = 0.014) and great percent reduction in renal sinus AT volume after surgery (p = 0.019) were associated with MHC after surgery. Increased intraperitoneal AT FAI (p = 0.031) was also associated with MHC. CONCLUSION: MHC was not associated with improvement in general obesity, based on indicators such as reduction of BMI after surgery. Weight reduction induced specific abdominal fat depot changes measured by CT are positively associated with MHC.

Empagliflozin suppresses urinary mitochondrial DNA copy numbers and interleukin-1ß in type 2 diabetes patients.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors improve cardiovascular and renal outcomes in type 2 diabetes mellitus (T2DM) patients. However, the mechanisms by which SGLT2 inhibitors improve the clinical outcomes remain elusive. We evaluated whether empagliflozin, an SGLT2 inhibitor, ameliorates mitochondrial dysfunction and inflammatory milieu of the kidneys in T2DM patients. We prospectively measured copy numbers of urinary and serum mitochondrial DNA (mtDNA) nicotinamide adenine dinucleotide dehydrogenase subunit-1 (mtND-1) and cytochrome-c oxidase 3 (mtCOX-3) and urinary interleukin-1ß (IL-1ß) in healthy volunteers (n = 22), in SGLT2 inhibitor-naïve T2DM patients (n = 21) at baseline, and in T2DM patients after 3 months of treatment with empagliflozin (10 mg, n = 17 or 25 mg, n = 4). Both urinary mtDNA copy numbers and IL-1ß levels were higher in the T2DM group than in healthy volunteers. Baseline copy numbers of serum mtCOX-3 in the T2DM group were lower than those in healthy volunteers. Empagliflozin induced marked reduction in both urinary and serum mtND-1 and mtCOX-3 copy numbers, as well as in urinary IL-1ß. Empagliflozin could attenuate mitochondrial damage and inhibit inflammatory response in T2DM patients. This would explain the beneficial effects of SGLT2 inhibitors on cardiovascular and renal outcomes.

Circulating miRNAs in extracellular vesicles related to treatment response in patients with idiopathic membranous nephropathy.

BACKGROUND: Extracellular vesicle (EV)-microRNAs (miRNAs) are potential biomarkers for various renal diseases. This study attempted to identify the circulating EV-miRNA signature not only for discriminating idiopathic membranous nephropathy (IMN) from idiopathic nephrotic syndrome (INS), but also to predict the treatment response of patients with IMN. METHODS: We prospectively enrolled 60 participants, including those with IMN (n = 19) and INS (n = 21) and healthy volunteers (HVs; n = 20) in this study. Using RNA sequencing, we assessed the serum EV-miRNA profiles of all participants. To identify the EV-miRNAs predictive of treatment response in IMN, we also analyzed EV-miRNAs among patients with IMN with and without clinical remission. RESULTS: The expression levels of 3 miRNAs differed between IMN patients, INS patients and HVs. In addition, compared to HVs, RNA sequencing revealed differential expression of 77 and 44 EV-miRNAs in patients with IMN without and with remission, respectively. We also identified statistically significant (|fold change ≥ 2, p < 0.05) differences in the expression levels of 23 miRNAs in IMN without remission. Biological pathway analysis of miRNAs in IMN without remission indicated that they are likely involved in various pathways, including renal fibrosis. CONCLUSION: Our study identified EV-miRNAs associated with IMN as well as those associations with therapeutic response. Therefore, these circulating EV-miRNAs may be used as potential markers for the diagnosis and prediction of treatment response in patients with IMN.

Weight Change Alters the Small RNA Profile of Urinary Extracellular Vesicles in Obesity.

INTRODUCTION: Various kidney diseases reportedly show different urinary extracellular vesicle (EV) RNA profiles. Although obesity is one of the main causes of chronic kidney disease, the expression pattern of urinary EV RNA in obesity is uncertain. Our aim was to sequence the small RNA profiles of urinary EVs in obese patients before and after weight reduction and compare them to those of healthy volunteers (HVs). METHODS: We recruited age-sex-matched obese patients and HVs. The small RNA profiles of urinary EVs were analyzed using RNA sequencing. To evaluate the effect of weight reduction, small RNA profiles of urinary EVs 6 months after bariatric surgery were also analyzed. RESULTS: The proportion of urinary EVs transfer RNA and microRNA of obese patients differed from that of HVs. Obese patients showed differential expression of 1,343 small RNAs in urinary EVs compared to HVs (fold change ≥2 and p value <0.05). Among those, 61 small RNAs were upregulated in obese patients and downregulated after weight reduction, whereas 167 small RNAs were downregulated in obese patients and upregulated after weight reduction. RNA sequencing revealed the correlation between the specific urinary EV small RNAs and clinical parameters including body weight, low-density lipoprotein cholesterol, triglyceride, high-density lipoprotein cholesterol, serum glucose, estimated glomerular filtration rate, and albuminuria. CONCLUSION: Obese patients showed distinct urinary EV small RNA profiles compared to HVs. Weight reduction altered urinary EV small-RNA profiles in obese patients.

Association between blood pressure and the risk of chronic kidney disease in treatment-naïve hypertensive patients.

BACKGROUND: Although hypertension is a well-known risk factor for chronic kidney disease (CKD), the blood pressure (BP) at which antihypertensive interventions should be initiated remains to be determined. Therefore, we investigated the association between BP and CKD in treatment-naïve individuals. METHODS: This prospective cohort study considered 7,343 individuals in the Korean Genome and Epidemiology Study who were not taking antihypertensive medications. Subjects were categorized into six groups according to their systolic BP (SBP) and five groups according to their diastolic BP (DBP). The primary outcome was incident CKD, which was defined as an estimated glomerular filtration rate of <60 mL/min/1.73 m2 or the development of proteinuria. The secondary outcome was incident cardiovascular disease (CVD). RESULTS: In the time-varying Cox models, the hazard ratios (95% confidence interval [CI]) for CKD were 1.39 (1.10-1.77) with SBP 130-139 mmHg, 1.79 (1.40-2.28) with SBP 140-159 mmHg, and 3.22 (2.35-4.40) with SBP ≥ 160 mmHg, compared with SBP 100-119 mmHg. In addition, the hazard ratios (95% CI) for CKD were 1.88 (1.48-2.37) with DBP 90-99 mmHg and 4.30 (3.20-5.76) with DBP ≥ 100 mmHg, compared with DBP 70-79 mmHg. A significantly increased CVD risk was also observed in subjects with SBP ≥ 130 mmHg or DBP ≥ 90 mmHg. CONCLUSION: Our findings indicate that SBP ≥ 130 mmHg and DBP ≥ 90 mmHg are associated with an increased risk of CKD. Therefore, BP-lowering strategies should be considered starting at those thresholds to prevent CKD development.

Epicardial adipose tissue radiodensity is associated with all-cause mortality in patients undergoing hemodialysis.

The radiodensity and volume of epicardial adipose tissue (EAT) on computed tomography angiography (CTA) may provide information regarding cardiovascular risk and long-term outcomes. EAT volume is associated with mortality in patients undergoing incident hemodialysis. However, the relationship between EAT radiodensity/volume and all-cause mortality in patients with end-stage renal disease (ESRD) undergoing maintenance hemodialysis remains elusive. In this retrospective study, EAT radiodensity (in Hounsfield units) and volume (in cm3) on coronary CTA were quantified for patients with ESRD using automatic, quantitative measurement software between January 2012 and December 2018. All-cause mortality data (up to December 2019) were obtained from the Korean National Statistical Office. The prognostic values of EAT radiodensity and volume for predicting long-term mortality were assessed using multivariable Cox regression models, which were adjusted for potential confounders. A total of 221 patients (mean age: 64.88 ± 11.09 years; 114 women and 107 men) with ESRD were included. The median follow-up duration (interquartile range) after coronary CTA was 29.63 (range 16.67-44.7) months. During follow-up, 82 (37.1%) deaths occurred. In the multivariable analysis, EAT radiodensity (hazard ratio [HR] 1.055; 95% confidence interval [CI] 1.015-1.095; p = 0.006) was an independent predictor of all-cause mortality in patients with ESRD. However, EAT volume was not associated with mortality. Higher EAT radiodensity on CTA is associated with higher long-term all-cause mortality in patients undergoing prevalent hemodialysis, highlighting its potential as a prognostic imaging biomarker in patients undergoing hemodialysis.

Relationship between carbohydrate-to-fat intake ratio and the development of chronic kidney disease: A community-based prospective cohort study.

BACKGROUND & AIMS: It is well-known that high protein intake is associated with renal hyperfiltration and faster renal function decline, but the association of other macronutrients, carbohydrate and fat, with development of chronic kidney disease (CKD) is still inconclusive. Therefore, we aimed to examine the relationship between fat-to-carbohydrate intake ratio (F/C ratio) and incident CKD. METHODS: We included 9226 subjects from the Korean Genome and Epidemiology Study. The subjects were divided into two groups depending on 1 g protein intake per ideal body weight per day. Primary exposure was the F/C ratio defined as calorie intake of fat/calorie intake of fat and carbohydrate. The primary outcome was the development of CKD, which was defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2 and/or proteinuria (≥1+). RESULTS: During a median follow-up duration of 11.4 years, 778 (8.4%) CKD events occurred. Subjects in the lowest F/C ratio tertile had faster eGFR decline rate than other tertiles. In multivariable Cox analysis, a significantly higher CKD risk was observed in the lowest tertile when protein intake > 1 g/kg/day (hazard ratio [HR] for T1 (<16.1%) vs. T3 (>21.5%), 1.38; 95% confidence interval [CI], 1.03-1.84; P = 0.031). In sensitivity analysis, subjects maintained low F/C ratio diet (<16.1%) during 4 years showed higher risk of subsequent CKD development than those maintained high F/C ratio diet (≥16.1%; HR, 1.70; 95% CI, 1.10-2.63; P = 0.018). In cubic spline analysis, CKD risk was sharply increased in F/C ratio <16.1%, but the risk was nearly constant in F/C ratio ≥16.1%. CONCLUSIONS: A diet with a low F/C ratio was associated with increased risk of CKD in the general population. Therefore, it is necessary to limit excessive high carbohydrate and low fat intake to prevent CKD development in this population.

Community-Based Aerobic Exercise Program for Primary Prevention of Cardiovascular Disease in Adults With Visual or Auditory Impairments: A Feasibility Study.

OBJECTIVE: To investigate the feasibility of a public health center-based aerobic and resistance training program for primary prevention of cardiovascular disease in people with visual, auditory, or physical/brain impairments. METHODS: The study included 25 adults aged >40 years who lived in Cheorwon-gun in South Korea, had a disability registered for visual, auditory, or physical/brain impairments under the Disability Welfare Act, and had either known cardiovascular disease or two or more risk factors for cardiovascular disease. The program comprised four education sessions and 12 weeks of customized aerobic and strengthening exercises performed twice a week at moderate intensity, with each exercise session lasting for 1 hour. The body mass index (BMI), percent body fat, 6-minute walk distance (6MWD), and 30-second sit-to-stand test results were measured at baseline and on program completion. RESULTS: Seventeen subjects (68%) completed the program. There were significant decreases in BMI and percent body fat (both p<0.05), with a significant increase in 30-second sit-to-stand strength (p<0.05) but no changes in the 6MWD. In subjects with visual or auditory impairments, BMI and percent body fat were significantly decreased after the program; however, there was no significant change in the results of the 30-second sit-to-stand strength test or the 6MWD. CONCLUSION: In people with disabilities, a 3-month community-based exercise program can decrease body mass index and percent body fat and increase sit-to-stand strength. The 30-second sit-to-stand test may be a useful measure of the strength and endurance of the lower extremities in people with disabilities.

Reversible pH Responsive Aggregation Behavior of Size-Controlled Calcium Carbonate Composite Nanoparticles by Phytic Acid in Aqueous Solution.

Composite colloidal nanoparticles were prepared by a carbonate controlled-addition method in the presence of phytic acid, in which an aqueous ammonium carbonate solution was added into an aqueous solution of phytic acid and CaCl2. The number-average particle size of the colloidal particles was 76 ± 18 nm formed by using the molar ratio [phytic acid]/[Ca2+] = 0.5 from the complexation time of 1 h. The composite nanoparticles were stable for more than 5 days in the suspension under the quiescent condition. After isolation of the nanoparticles by ultrafiltration, the dried samples could be redispersed in water. Effects of the complexation times of the aqueous solution of phytic acid and CaCl2 and the molar ratio ([phytic acid]/[Ca2+]) were studied. Increasing the concentration of the calcium reagents as well as increasing the complexation times increased the particle sizes. The minimum and maximum average particle sizes of 29 and 142 nm were obtained. The plot of the transmittance at 350 nm of the aqueous solution of the dispersion against pH values after addition of 0.05 M HCl for 6 h showed that, by gradually increasing turbidity with decreasing pH from 9.6 to 7.3, precipitates were recognized at below pH 7.5, and turbidity decreased with further decreasing pH beyond 7.2. Dynamic light scattering analysis showed that the particle diameters increased from 90 to 200 nm with decreasing pH from 9.6 to 7.2. When increasing the pH from 6.2, the precipitate was redispersed and the turbidity increased to a pH of 7.4. No precipitates were observed above a pH of 7.4. These results suggest that the present phytic acid stabilized nanoparticles exhibit pH-dependent reversible precipitation and redispersion without degradation under slightly acidic conditions.