Publications by authors named "Joongyub Lee"

139 Publications

The difference between cystatin C- and creatinine-based eGFR is associated with adverse cardiovascular outcome in patients with chronic kidney disease.

Atherosclerosis 2021 Oct 27;335:53-61. Epub 2021 Aug 27.

Yonsei University, Institute of Kidney Disease Research, College of Medicine, Department of Internal Medicine, Seoul, South Korea. Electronic address:

Background And Aims: Decreased kidney function is an important risk factor for cardiovascular disease (CVD). However, assessing risk of CVD may be difficult when there is a gap between creatinine- and cystatin C-based estimated glomerular filtration rate (eGFR). We studied the association of the difference in eGFRs with major adverse cardiovascular events (MACE) in patients with chronic kidney disease (CKD).

Methods: This prospective cohort study was conducted in 2076 patients with CKD stages based on the KDIGO guideline (eGFR categories of G1: ≥90; G 2: 60-89; G3: 30-59; G4: 15-29; G5: <15 mL/min/1.73 m without kidney replacement therapy). The difference in eGFR (eGFR) was calculated by subtracting the cystatin C-based eGFR (eGFR) from the creatinine-based eGFR (eGFR). The primary outcome was MACE, defined as non-fatal acute myocardial infarction and unstable angina, stroke, congestive heart failure, symptomatic arrhythmia, and cardiac death.

Results: During a median follow-up of 4.1 years, MACE occurred in 147 patients (incidence rate, 15.0 per 1000 patient-years). When patients were categorized into baseline eGFR tertiles, the highest tertile was associated with a significantly higher risk of MACE (hazard ratio, 2.12; 95% confidence interval [CI], 1.28-3.51) than the lowest tertile when adjusted for eGFR, eGFR, or eGFR based on both creatinine and cystatin C. Patients in the highest tertile had more baseline coronary artery calcification (CAC) than those in the lowest tertile (odds ratio [OR], 1.38; 95% CI, 1.03-1.86). In addition, 978 patients had data for both baseline and follow-up CAC at year 4. In this subgroup, baseline eGFR was significantly associated with accelerated CAC progression (≥50/year) (OR, 1.03; 95% CI, 1.01-1.05).

Conclusions: A large positive difference between eGFR and eGFR was associated with a higher risk of MACE and faster CAC progression in patients with CKD. Therefore, careful monitoring of CVD is needed for patients with a higher eGFR.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.08.036DOI Listing
October 2021

mHealth Interventions for Lifestyle and Risk Factor Modification in Coronary Heart Disease: Randomized Controlled Trial.

JMIR Mhealth Uhealth 2021 Sep 24;9(9):e29928. Epub 2021 Sep 24.

Department of Prevention and Management, School of Medicine, Inha University Hospital, Inha University, Incheon, Republic of Korea.

Background: Self-management of lifestyle and cardiovascular disease risk factors is challenging in older patients with coronary heart disease (CHD). SMS text messaging could be a potential support tool for self-management and the most affordable and accessible method through a mobile phone. High-quality evidence had been lacking, and previous studies evaluated the effects of SMS text messaging on the subjective measures of short-term outcomes. Recently, a large-sized randomized controlled trial in Australia reported promising findings on the objective measures upon 6-month follow-up. However, an examination of the effectiveness of such interventions in an Asian population with unique demographic characteristics would be worthwhile.

Objective: This study examined the effectiveness of a 1-way SMS text messaging program to modify the lifestyle and cardiovascular disease risk factors of patients who underwent the first percutaneous coronary intervention (PCI).

Methods: A parallel, single-blinded, 1:1 random allocation clinical trial was conducted with 879 patients treated through PCI. They were recruited during hospital admission from April 2017 to May 2020 at 2 university hospitals in the Republic of Korea. In addition to standard care, the intervention group received access to a supporting website and 4 SMS text messages per week for 6 months regarding a healthy diet, physical activity, smoking cessation, and cardiovascular health. Random allocation upon study enrollment and SMS text messaging after hospital discharge were performed automatically using a computer program. The coprimary outcomes were low-density-lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP), and BMI. The secondary outcomes were change in lifestyle and adherence to the recommended health behaviors.

Results: Of the eligible population, 440 and 439 patients who underwent PCI were assigned to the intervention and control groups, respectively. The 1-way SMS text messaging program significantly enhanced physical activity (P=.02), healthy diet (P<.01), and medication adherence (P<.04) among patients with CHD. Hence, more people were likely to control their cardiovascular disease risk factors per the recommendations. The intervention group was more likely to control all 5 risk factors by 62% (relative risk 1.62, 95% CI 1.05-2.50) per the recommendations. On the other hand, physiological measures of the primary outcomes, including LDL-C levels, SBP, and BMI, were not significant. Most participants found the SMS text messaging program useful and helpful in motivating lifestyle changes.

Conclusions: Lifestyle-focused SMS text messages were effective in the self-management of a healthy diet, exercise, and medication adherence, but their influence on the physiological measures was not significant. One-way SMS text messages can be used as an affordable adjuvant method for lifestyle modification to help prevent the recurrence of cardiovascular disease.

Trial Registration: Clinical Research Information Service (CRiS) KCT0005087; https://cris.nih.go.kr/cris/search/detailSearch.do/19282.
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http://dx.doi.org/10.2196/29928DOI Listing
September 2021

All-cause and cause-specific mortality of patients with rheumatoid arthritis in Korea: A nation-wide population-based study.

Joint Bone Spine 2021 Oct 6;89(1):105269. Epub 2021 Oct 6.

Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea. Electronic address:

Objective: To compare all-cause and cause-specific mortality between rheumatoid arthritis (RA) patients versus the general population of Korea.

Methods: A nationally representative RA population aged≥40 years was identified from Korea National Health Insurance Service (KNHIS) database. We estimated age- and sex-adjusted all-cause and cause-specific standardized mortality ratios (SMRs) with 95% confidence intervals (CIs), comparing RA patients to the general population. Subgroup analyses were done by sex, age group, calendar year, and biologics use.

Results: We identified 79,352 RA patients with 6404 deaths during 2011-2016. The all-cause SMR [95% CI] of RA patients compared to the general population was 1.53 [1.49-1.56]. The top five causes of death were cancer (19.5%), respiratory disease (19.1%), cardiovascular disease (18.8%), systemic rheumatic diseases (9.5%, 9.1% due to RA), and infection (6.1%). Cause-specific SMRs [95% CI] were 0.95 [0.90-1.01] for cancer, 3.34 [3.15-3.52] for respiratory disease, 1.26 [1.18-1.33] for cardiovascular disease, 3.41 [3.08-3.75] for infection, and 4.88 [3.10-6.65] for non-RA systemic rheumatic disease. The SMR of RA population was slightly higher among men than women, and highest in their 60s and 70s. The yearly SMR increased from 1.10 [1.01-1.18] in 2011 to 1.85 [1.75-1.95] in 2016 due to population aging and comorbidity accumulation. Users of biologics showed a higher SMR than non-users (1.82 [1.69-1.96] vs. 1.50 [1.46-1.54]), due to higher RA activity, and more comorbidities despite a younger mean age.

Conclusion: RA patients in Korea experienced 1.5-fold increase in all-cause mortality compared to the general population. Except for cancer, the top five causes of death were associated with excess mortality among RA patients. RA-associated mortality was largely determined by age, RA activity, and comorbidity status.
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http://dx.doi.org/10.1016/j.jbspin.2021.105269DOI Listing
October 2021

Effects of blood urea nitrogen independent of the estimated glomerular filtration rate on the development of anemia in non-dialysis chronic kidney disease: The results of the KNOW-CKD study.

PLoS One 2021 10;16(9):e0257305. Epub 2021 Sep 10.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnamsi, Gyeonggi-do, Korea.

Background: Anemia is a common complication of chronic kidney disease (CKD). Blood urea nitrogen (BUN) in CKD represents nitrogenous uremic toxin accumulation which could be involved in anemia of CKD. We investigated the effects of BUN independent of estimated glomerular filtration rate (eGFR) on anemia in non-dialysis CKD (NDCKD).

Methods: This prospective study included 2,196 subjects enrolled in the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD) cohort with BUN and hemoglobin level data. Initially, we investigated the association between BUN and hemoglobin level. To examine the impact of baseline BUN on the incident anemia, a longitudinal study was performed on 1,169 patients without anemia at study enrollment. BUN residuals were obtained from the fitted curve between BUN and eGFR. Anemia was defined as a hemoglobin level of <13.0 g/dL for men and <12.0 g/dL for women.

Results: BUN residuals were not related to eGFR but to daily protein intake (DPI), while BUN was related to both eGFR and DPI. BUN was inversely associated with hemoglobin level (β -0.03; 95% confidence interval [CI] -0.04, -0.03; P <0.001) in the multivariable linear regression analysis adjusted for multiple confounders including eGFR, and BUN residual used instead of BUN was also inversely associated with hemoglobin level (β -0.03; 95% CI -0.04, -0.02; P <0.001). Among the 1,169 subjects without anemia at baseline, 414 (35.4%) subjects newly developed anemia during the follow-up period of 37.5 ± 22.1 months. In the multivariable Cox regression analysis with adjustment, both high BUN level (Hazard ratio [HR] 1.02; 95% CI 1.01, 1.04; P = 0.002) and BUN residual used instead of BUN (HR 1.02; 95% CI 1.00, 1.04; P = 0.031) increased the risk of anemia development. Moreover, BUN, rather than eGFR, increased the risk of anemia development in patients with CKD stage 3 in the multivariable Cox regression.

Conclusion: Higher BUN levels derived from inappropriately high protein intake relative to renal function were associated with low hemoglobin levels and the increased risk of anemia independent of eGFR in NDCKD patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0257305PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432877PMC
September 2021

Association Between Longitudinal Blood Pressure Trajectory and the Progression of Chronic Kidney Disease: Results From the KNOW-CKD.

Hypertension 2021 Nov 15;78(5):1355-1364. Epub 2021 Aug 15.

Department of Internal Medicine, Institute of Kidney Disease Research (Y.S.J., H.W.K., K.H.N., J.Y.L., J.T.P., T.-H.Y., S.-W.K., S.H.H.), College of Medicine, Yonsei University, Seoul, Republic of Korea.

[Figure: see text].
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.17542DOI Listing
November 2021

Metabolic Acidosis Is an Independent Risk Factor of Renal Progression in Korean Chronic Kidney Disease Patients: The KNOW-CKD Study Results.

Front Med (Lausanne) 2021 29;8:707588. Epub 2021 Jul 29.

Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.

We aimed to evaluate serum bicarbonate as a risk factor for renal progression, cardiovascular events, and mortality in Korean CKD patients. We analyzed 1,808 participants from a Korean CKD cohort whose serum bicarbonate levels were measured at enrollment. Serum bicarbonate levels were categorized as low, lower normal, higher normal, and high (total carbon dioxide <22, 22-26, 26.1-29.9, and ≥30 mmol/L, respectively) groups. Metabolic acidosis was defined as a serum bicarbonate level <22 mmol/L. The primary outcome was renal events defined as doubling of serum creatinine, 50% reduction of eGFR from the baseline values, or development of end-stage kidney disease. The secondary outcome consisted of cardiovascular events and death. In addition, patients whose eGFR values were measured more than three times during the follow-up period were analyzed for eGFR decline. The rapid decline in eGFR was defined as lower than the median value of the eGFR slope. The mean serum bicarbonate level was 25.7 ± 3.7 mmol/L and 240 (13.2%) patients had metabolic acidosis. During the follow-up period of 55.2 ± 24.1 months, 545 (30.9%) patients developed renal events and 187 (10.6%) patients developed a composite of cardiovascular events and death. After adjustment, the low serum bicarbonate group experienced 1.27 times more renal events than the lower normal bicarbonate group [hazard ratio (HR): 1.27; 95% CI: 1.01-1.60, = 0.043]. There was no significant association between the bicarbonate groups and the composite outcome of cardiovascular events and death. The low bicarbonate group showed a significantly rapid decline in eGFR [odds ratio (OR): 2.12; 95% CI: 1.39-3.22, < 0.001] compared to the lower normal bicarbonate group. Metabolic acidosis was significantly associated with increased renal events and a rapid decline in renal function in Korean predialysis CKD patients.
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http://dx.doi.org/10.3389/fmed.2021.707588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358180PMC
July 2021

Inflammation Alters Relationship Between High-Density Lipoprotein Cholesterol and Cardiovascular Risk in Patients With Chronic Kidney Disease: Results From KNOW-CKD.

J Am Heart Assoc 2021 08 7;10(16):e021731. Epub 2021 Aug 7.

Department of Internal Medicine College of Medicine Institute of Kidney Disease Research Yonsei University Seoul Korea.

Background The function of high-density lipoprotein can change from protective to proatherosclerotic under inflammatory conditions. Herein, we studied whether inflammation could modify the relationship between high-density lipoprotein level and risk of adverse outcomes in patients with chronic kidney disease . Methods and Results In total, 1864 patients from the prospective KNOW-CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease) were enrolled. The main predictor was high-density lipoprotein cholesterol (HDL-C) level. Presence of inflammation was defined by hs-CRP (high-sensitivity C-reactive protein) level of ≥1.0 mg/L. The primary outcome was extended major adverse cardiovascular events. During 9231.2 person-years of follow-up, overall incidence of the primary outcome was 15.8 per 1000 person-years. In multivariable Cox analysis after adjusting for confounders, HDL-C level was not associated with the primary outcome. There was a significant interaction between the inflammatory status and HDL-C for risk of extended major adverse cardiovascular events (=0.003). In patients without inflammation, the hazard ratios (HRs) (95% CIs) for HDL-C levels <40, 50 to 59, and ≥60 mg/dL were 1.10 (0.50-1.82), 0.95 (0.50-1.82), and 0.42 (0.19-0.95), respectively, compared with HDL-C of 40 to 49 mg/dL. However, the significant association for HDL-C ≥60 mg/dL was not seen after Bonferroni correction. In patients with inflammation, we observed a trend toward increased risk of extended major adverse cardiovascular events in higher HDL-C groups (HRs [95% CIs], 0.73 [0.37-1.43], 1.24 [0.59-2.61], and 1.56 [0.71-3.45], respectively), but without statistical significance. Conclusions The association between HDL-C level and adverse cardiovascular outcomes showed reverse trends based on inflammation status in Korean patients with chronic kidney disease. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01630486.
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http://dx.doi.org/10.1161/JAHA.120.021731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475026PMC
August 2021

Moderate-Vigorous Physical Activity and Clinical Outcomes in Adults with Nondialysis Chronic Kidney Disease.

J Clin Med 2021 Jul 29;10(15). Epub 2021 Jul 29.

Department of Internal Medicine, National Medical Center, Seoul 04564, Korea.

The health benefits of physical activity (PA) are well known. However, the association between an adequate amount of moderate-vigorous PA (MVPA) and clinical outcomes has limited evidence in chronic kidney disease (CKD). We assessed PA using a self-administered questionnaire. The amount of MVPA was categorized into four groups: none, low, moderate, and high (0, <7.5, 7.5-14.9, and 15.0-29.9 metabolic equivalent-hours/week, respectively). We analyzed the association between the amount of MVPA and clinical outcomes. Among a total of 1909 adults with CKD, adults with MVPA showed various beneficial outcomes compared to those with no MVPA in a Kaplan-Meier curve followed over a median of 5.9 years. In multivariable-adjusted Cox proportional hazard models, a low and a moderate amount of MVPA was associated with a lower risk of all-cause death. A moderate amount of MVPA was associated with a lower risk of cardiovascular events. A high amount of MVPA was associated with a lower risk of end-stage kidney disease in ESKD in 1324 adults with eGFR <60 mL/min/1.73 m. Age and sex modified the relationships between MVPA and clinical outcomes. MVPA is associated with various beneficial outcomes across the amount of MVPA. PA plans should be tailored for individual adults with CKD.
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http://dx.doi.org/10.3390/jcm10153365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8347400PMC
July 2021

Association between Influenza Vaccination and the Risk of Bell's Palsy in the Korean Elderly.

Vaccines (Basel) 2021 Jul 6;9(7). Epub 2021 Jul 6.

Department of Health Convergence, Ewha Womans University, Seoul 03760, Korea.

Previous studies have shown controversial results on the risk of Bell's palsy after influenza vaccination. Since the antigenic components of influenza vaccine can vary from season to season, continuous safety monitoring is required. The aim of the present study was to determine whether there was an increased risk of Bell's palsy in the elderly after influenza vaccination between the 2015/2016 and 2017/2018 flu seasons. This study included the elderly who received influenza vaccinations for three flu seasons using a large-linked database of vaccination registration data from the Korea Disease Control and Prevention Agency and the National Health Insurance Service claims data. We used a self-controlled risk interval design with a risk interval of 1 to 42 days and a control interval of 57 to 98 days postvaccination and calculated the incidence rate ratio. To ensure the robustness of the results, sensitivity analyses were also carried out with different risk and control intervals. Of 4,653,440 elderly people who received the influenza vaccine, there was no statistically significant increase in the risk of Bell's palsy (IRR: 0.99, 95% CI: 0.92-1.07). Similar results were found in analysis results for each season and the results of the sensitivity analyses excluding the 2017/2018 season. In conclusion, we found no evidence of an increased risk of Bell's palsy after influenza vaccination. The results of our study provide reassurance about the safety of the influenza vaccine NIP program. However, it is necessary to continuously monitor the risk of Bell's palsy during future flu seasons.
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http://dx.doi.org/10.3390/vaccines9070746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310133PMC
July 2021

Did inter-hospital transfer reduce mortality in patients with acute myocardial infarction in the real world? A nationwide patient cohort study.

PLoS One 2021 5;16(8):e0255839. Epub 2021 Aug 5.

Department of Prevention and Management, Inha University Hospital, School of Medicine, Inha University, Incheon, Korea.

Introduction: Inter-hospital transfer (IHT) and primary percutaneous coronary intervention (PCI) are preferred over onsite thrombolysis when provided expeditiously. On the other hand, its benefit has not been evaluated in a real-world situation. This study examined the effects of IHT on the short- and long-term mortality in patients with acute myocardial infarction (AMI) and compared the reperfusion treatments and resources between the referring and receiving hospitals.

Methods: Patients newly diagnosed with AMI and admitted to hospital were selected from the national health insurance database from 2004 to 2018. The 30-day and one-year mortality in the transferred and non-transferred patients were estimated and compared using stabilized inverse probability of treatment weighting to account for confounding bias.

Results: Of the 258,291 participants, 10,158 were transferred to one or more hospitals. IHT was more likely to occur to older or more comorbid people, patients in rural areas, and those whose insurance was medical aid. The 30-day and one-year mortality of the non-IHT group was 9.7% and 15.8%, respectively, whereas the figure was 11.4% and 20.5% in the IHT group. After balancing the baseline characteristics, the transferred patients were 1.12 (95% CI: 1.06-1.20) and 1.25 (95% CI: 1.20-1.31) times more likely to die during the subsequent 30 days and one year, respectively, than those treated solely at the presenting hospital. In ST-segment elevation myocardial infarction (STEMI), the hazard ratios of the 30-day and 1-year mortality were 1.14 (95% CI: 0.97-1.35) and 1.31 (95% CI: 1.15-1.49) in the transferred patients after balancing cardiogenic shock and cardiac arrest. On-site thrombolysis was rarely performed in the referring hospitals.

Conclusion: Patients transferred for the treatment of AMI experienced higher short- and long-term mortality. Therefore, onsite thrombolysis and the estimated time delay to PCI should be considered in regional hospitals to reduce mortality with the organization of STEMI treatment networks.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255839PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341481PMC
August 2021

Machine learning enhances the performance of short and long-term mortality prediction model in non-ST-segment elevation myocardial infarction.

Sci Rep 2021 06 18;11(1):12886. Epub 2021 Jun 18.

Department of Prevention and Management, School of Medicine, Inha University Hospital, Inha University, 27 Inhang-Ro, Jung-Gu, Incheon, Republic of Korea.

Machine learning (ML) has been suggested to improve the performance of prediction models. Nevertheless, research on predicting the risk in patients with acute myocardial infarction (AMI) has been limited and showed inconsistency in the performance of ML models versus traditional models (TMs). This study developed ML-based models (logistic regression with regularization, random forest, support vector machine, and extreme gradient boosting) and compared their performance in predicting the short- and long-term mortality of patients with AMI with those of TMs with comparable predictors. The endpoints were the in-hospital mortality of 14,183 participants and the three- and 12-month mortality in patients who survived at discharge. The performance of the ML models in predicting the mortality of patients with an ST-segment elevation myocardial infarction (STEMI) was comparable to the TMs. In contrast, the areas under the curves (AUC) of the ML models for non-STEMI (NSTEMI) in predicting the in-hospital, 3-month, and 12-month mortality were 0.889, 0.849, and 0.860, respectively, which were superior to the TMs, which had corresponding AUCs of 0.873, 0.795, and 0.808. Overall, the performance of the predictive model could be improved, particularly for long-term mortality in NSTEMI, from the ML algorithm rather than using more clinical predictors.
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http://dx.doi.org/10.1038/s41598-021-92362-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213755PMC
June 2021

Sex disparities and adverse cardiovascular and kidney outcomes in patients with chronic kidney disease: results from the KNOW-CKD.

Clin Res Cardiol 2021 Jul 18;110(7):1116-1127. Epub 2021 May 18.

Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Yonsei-ro 50, Seodaemun-gu, Seoul, Republic of Korea.

Aims: Longitudinal studies of the association between sex and adverse clinical outcomes in patients with chronic kidney disease (CKD) are scarce. We assessed whether major outcomes may differ by sex among CKD patients.

Methods: We analyzed a total of 1780 participants with non-dialysis CKD G1-5 from the KoreaN cohort study for Outcome in patients with Chronic Kidney Disease (KNOW-CKD). The primary outcome was a composite of non-fatal cardiovascular events or all-cause mortality. Secondary outcomes included fatal and non-fatal cardiovascular events, all-cause mortality, and a composite kidney outcome of ≥ 50% decline in estimated glomerular filtration rate from baseline or the onset of end-stage kidney disease.

Results: There were 1088 (61%) men and 692 (39%) women in the study cohort. The proportion of smokers was significantly higher in men (24% vs. 3%). During 8430 person-years of follow-up, 201 primary outcome events occurred: 144 (13%) in men and 57 (8%) in women, with corresponding incidence rates of 2.9 and 1.7 per 100 person-years, respectively. In multivariable Cox models, men were associated with a 1.58-fold (95% CI 1.06-2.35) higher risk of composite outcome. Propensity score matching analysis revealed similar findings (HR 1.81; 95% CI 1.14-2.91). Risk of all-cause mortality was significantly higher in men of the matched cohort. However, there was no difference in the risk of CKD progression. In the subgroup with coronary artery calcium (CAC) measurements, men had a higher likelihood of CAC progression.

Conclusions: In Korean CKD patients, men were more likely to experience adverse cardiovascular events and death than women.
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http://dx.doi.org/10.1007/s00392-021-01872-5DOI Listing
July 2021

Low-dose aspirin was associated with an increased risk of cardiovascular events in patients with chronic kidney disease patients and low bodyweight: results from KNOW-CKD study.

Sci Rep 2021 03 23;11(1):6691. Epub 2021 Mar 23.

Department of Internal Medicine, Graduate School of Medicine, Gachon University, Incheon, Republic of Korea.

The benefits and risks of aspirin therapy for patients with chronic kidney disease (CKD) who have a high burden of cardiovascular events (CVE) are controversial. To examine the effects of low-dose aspirin on major clinical outcomes in patients with CKD. As a prospective observational cohort study, using propensity score matching, 531 aspirin recipients and non-recipients were paired for analysis from 2070 patients and fulfilled the inclusion criteria among 2238 patients with CKD. The primary outcome was the first occurrence of major CVE. The secondary outcomes were kidney events defined as a > 50% reduction of estimated glomerular filtration rate from baseline, doubling of serum creatinine, or onset of kidney failure with replacement therapy, the all-cause mortality, and bleeding event. The incidence of CVE was significantly greater in low-dose aspirin users than in non-users (HR 1.798; P = 0.011). A significant association between aspirin use and an increased risk of CVE was observed only in the lowest quartile of body weight (HR 4.014; P = 0.019) (Q1 < 60.0 kg). Secondary outcomes were not significantly different between aspirin users and non-users. It needs to be individualized of prescribing low-dose aspirin for the prevention of cardiovascular events in patients with chronic kidney disease, particularly patients with low bodyweight (< 60 kg).
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http://dx.doi.org/10.1038/s41598-021-86192-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988000PMC
March 2021

Association between the transtubular potassium gradient and progression of chronic kidney disease: results from KNOW-CKD.

J Nephrol 2021 Mar 23. Epub 2021 Mar 23.

Department of Internal Medicine, Institute of Kidney Disease Research, College of Medicine, Yonsei University, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea.

Background: The transtubular potassium gradient which reflects potassium secretion by the kidney through the cortical collecting duct, has not yet been tested as a surrogate marker of kidney function decline. Here, we investigate the relationship between the transtubular potassium gradient and chronic kidney disease (CKD) progression.

Methods: We studied 1672 patients from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD) cohort. The transtubular potassium gradient was calculated using a standard equation. The study endpoint was CKD progression, defined as a composite of a ≥ 50% decrease in estimated glomerular filtration rate (eGFR) from baseline values or end-stage kidney disease.

Results: During a median follow-up of 4.1 years (7149 person-years), 441 participants reached the endpoint. In cause-specific competing risk analysis, the highest tertile was associated with a significantly lower risk of an adverse kidney outcome compared with the lowest tertile [hazard ratio (HR), 0.73; 95% confidence interval (CI), 0.55-0.97]. When the transtubular potassium gradient was treated as a continuous variable, an increase of 1 in the transtubular potassium gradient was associated with a 6% lower risk of CKD progression (95% CI, 0.90-0.99). This association was particularly evident in patients with an eGFR ≥ 45 mL/min/1.73 m. A time-updated transtubular potassium gradient model showed similar results. The predictive performance of the transtubular potassium gradient was significantly less than that of the eGFR, but similar to that of proteinuria, serum bicarbonate, and urine osmolality.

Conclusions: A higher transtubular potassium gradient is associated with a significantly lower risk of CKD progression, suggesting that it may offer insights into the prognosis of CKD.
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http://dx.doi.org/10.1007/s40620-021-01019-9DOI Listing
March 2021

Association of Blood Pressure With the Progression of CKD: Findings From KNOW-CKD Study.

Am J Kidney Dis 2021 08 11;78(2):236-245. Epub 2021 Jan 11.

Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Republic of Korea. Electronic address:

Rationale & Objective: Optimal blood pressure (BP) control is a major therapeutic strategy in the management of chronic kidney disease (CKD). We studied the association between BP and adverse kidney outcomes within a diverse cohort of Koreans with CKD.

Study Design: Prospective observational cohort study.

Setting & Participants: 2,044 participants from the Korean Cohort Study for Outcomes in Patients With CKD (KNOW-CKD).

Exposures: Baseline and time-updated systolic BP (SBP) and diastolic BP (DBP).

Outcome: A composite kidney outcome of a≥50% decline in estimated glomerular filtration rate (eGFR) from the baseline value or incident kidney replacement therapy.

Analytical Approach: Multivariate cause-specific hazards models and marginal structural models were fitted for baseline and time-updated BP, respectively.

Results: During 7,472 person-years of follow-up, the primary composite kidney outcome occurred in 473 participants (23.1%), an incidence rate of 63.3 per 1,000 patient-years. Compared with baseline SBP<120mm Hg, the hazard ratios (HRs) for 120-129, 130-139, and≥140mm Hg were 1.10 (95% CI, 0.83-1.44), 1.20 (95% CI, 0.93-1.59), and 1.43 (95% CI, 1.07-1.91), respectively. This association was more evident in the model with time-updated SBP, for which the corresponding HRs were 1.31 (95% CI, 0.98-1.75), 1.59 (95% CI, 1.16-2.16), and 2.29 (95% CI, 1.69-3.11), respectively. In the analyses of DBP, we observed that time-updated DBP but not baseline DBP was significantly associated with the composite kidney outcome. Compared to patients with SBP<120mm Hg, patients with higher SBP had steeper slopes of eGFR decline. In the model including both SBP and DBP, only SBP was significantly associated with the composite kidney outcome.

Limitations: Observational design, unmeasured confounders, and use of office BPs only.

Conclusions: In patients with CKD, higher SBP and DBP levels were associated with a higher risk of a composite kidney outcome reflecting CKD progression. SBP had a greater association with adverse kidney outcomes than DBP.
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http://dx.doi.org/10.1053/j.ajkd.2020.12.013DOI Listing
August 2021

Incidence of cardiovascular events and mortality in Korean patients with chronic kidney disease.

Sci Rep 2021 01 13;11(1):1131. Epub 2021 Jan 13.

Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.

Few studies have investigated the incidence of cardiovascular disease (CVD) in the Asian chronic kidney disease (CKD) population. This study assessed the incidence of CVD, death, and a composite outcome of CVD and death in a prospective Korean predialysis CKD cohort. From a total of 2179 patients, incidence rates were analyzed, and competing risk analyses were conducted according to CKD stage. Additionally, incidence was compared to the general population. During a median 4.1 years of follow-up, the incidence of CVD, all-cause death, and the composite outcome was 17.2, 9.6, and 24.5 per 1000 person-years, respectively. These values were higher in diabetic vs. non-diabetic subjects (P < 0.001). For all outcomes, incidence rates increased with increasing CKD stage (CVD, P = 0.001; death, P < 0.001; and composite, P < 0.001). Additionally, CKD stage G4 [hazard ratio (HR) 2.8, P = 0.008] and G5 (HR 5.0, P < 0.001) were significant risk factors for the composite outcome compared to stage G1 after adjustment. Compared to the general population, the total cohort population (stages G1-G5) showed significantly higher risk of CVD (HR 2.4, P < 0.001) and the composite outcome (HR 1.7, P < 0.001). The results clearly demonstrate that CKD is a risk factor for CVD in an Asian population.
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http://dx.doi.org/10.1038/s41598-020-80877-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806882PMC
January 2021

Development and Validation of a Symptom-Focused Quality of Life Questionnaire (KOQUSS-40) for Gastric Cancer Patients after Gastrectomy.

Cancer Res Treat 2021 Jul 29;53(3):763-772. Epub 2020 Dec 29.

Department of Surgery, Dongnam Institute of Radiological and Medical Sciences, Busan, Korea.

Purpose: Patients who have undergone gastrectomy have unique symptoms that are not appropriately assessed using currently available tools. This study developed and validated a symptom-focused quality of life (QoL) questionnaire for patients who have received gastrectomy for gastric cancer.

Materials And Methods: Based on a literature review, patient interviews, and expert consultation by the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS), the initial item pool was developed. Two large-scale developmental studies were then sequentially conducted for exploratory factor analyses for content validity and item reduction. The final item pool was validated in a separate cohort of patients and assessed for internal consistency, test-retest reliability, construct validity, and clinical validity.

Results: The initial questionnaire consisted of 46-items in 12 domains. Data from 465 patients at 11 institutions, followed by 499 patients at 13 institutions, were used to conduct item reduction and exploratory factor analyses. The final questionnaire (KOQUSS-40) comprised 40 items within 11 domains. Validation of KOQUSS-40 was conducted on 413 patients from 12 hospitals. KOQUSS-40 was found to have good model fit. The mean summary score of the KOQUSS-40 was correlated with the EORTC QLQ-C30 and STO22 (correlation coefficients, 0.821 and 0.778, respectively). The KOQUSS-40 score was also correlated with clinical factors, and had acceptable internal consistency (> 0.7). Test-retest reliability was greater than 0.8.

Conclusion: The KOQUSS-40 can be used to assess QoL of gastric cancer patients after gastrectomy and allows for a robust comparison of surgical techniques in clinical trials.
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http://dx.doi.org/10.4143/crt.2020.1270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291178PMC
July 2021

Effectiveness of bystander cardiopulmonary resuscitation in improving the survival and neurological recovery of patients with out-of-hospital cardiac arrest: A nationwide patient cohort study.

PLoS One 2020 16;15(12):e0243757. Epub 2020 Dec 16.

Department of Prevention and Management, Inha University Hospital, School of Medicine, Inha University, Incheon, South Korea.

Introduction: Few studies have focused on enhancing causality and yielding unbiased estimates on the effectiveness of bystander cardiopulmonary resuscitation (BCPR) on the outcomes of out-of-hospital cardiac arrest (OHCA) in a real-world setting. Therefore, this study evaluated the effect of BCPR on the outcomes of OHCA and its differences according to the characteristics of OHCA.

Methods: This study enrolled all patients with OHCA of cardiac etiology treated by emergency medical services (EMS) in Korea from 2012 to 2015. The endpoints were survival and neurological recovery at discharge, and the main exposure was BCPR conducted by a layperson. The effect of BCPR was analyzed after adjusting for confounders, determined using a directed acyclic graph, by inverse probability of treatment weighting (IPTW) and model-based standardization (STR). Moreover, differences in subgroups and time trends were evaluated.

Results: Among 10,505 eligible patients after excluding those with missing data on BCPR, 7,721 patients received BCPR, accounting for 74.3% of EMS-treated OHCA patients. BCPR increased the odds of survival and good neurological recovery at discharge by 1.67- (95% confidence interval (CI): 1.44-1.93) and 1.93- (95% CI: 1.56-2.39) fold, respectively, in the IPTW analysis. These findings were comparable to those obtained with STR. The odds ratios were 2.39 (95% CI: 1.91-2.94) and 2.70 (95% CI: 1.94-3.41), respectively, in the sensitivity analysis of the missing BCPR information considering confounders and the outcome variable. However, the effect of qualified BCPR was not evenly distributed, and it did not increase with time. BCPR was likely to be more effective in male patients aged <65 years, those who experienced an OHCA in a private place or non-capital region, and those with shockable rhythm at the scene.

Conclusion: Based on data from a nationwide registry, the estimated effect of BCPR on survival and neurological recovery was moderate and did not improve from 2012 to 2015.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243757PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744051PMC
January 2021

Clinical outcomes of prolonged dual antiplatelet therapy after coronary drug-eluting stent implantation in dialysis patients.

Clin Kidney J 2020 Oct 3;13(5):803-812. Epub 2020 May 3.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

Background: End-stage renal disease yields susceptibility to both ischemia and bleeding. The optimal duration of dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation is not established in dialysis patients, who are usually excluded from randomized studies. Since recent studies implied the benefits of prolonged DAPT >12 months in chronic kidney disease, we investigated the effectiveness and safety of prolonged DAPT in dialysis patients with higher cardiovascular risks.

Methods: In this nationwide population-based study, we analyzed dialysis patients who underwent DES implantation from 2008 to 2015. Continued DAPT was compared with discontinued DAPT using landmark analyses, including free-of-event participants at 12 ( = 2246), 15 ( = 1925) and 18 months ( = 1692) after DES implantation. The primary outcome was major adverse cardiovascular events (MACEs): a composite of mortality, nonfatal myocardial infarction, coronary revascularization and stroke. Major bleeding was a safety outcome. Inverse probability of treatment weighting Cox regression was performed.

Results: Mean follow-up periods were 278.3-292.4 days, depending on landmarks. Overall, incidences of major bleeding were far lower than those of MACE. Continued DAPT groups showed lower incidences of MACE and higher incidences of major bleeding, compared with discontinued DAPT groups. In Cox analyses, continued DAPT reduced the hazards of MACE at the 12- [hazard ratio (HR) = 0.74, 95% confidence interval (CI) 0.61-0.90; P=0.003], 15- (HR = 0.78, 95% CI 0.64-0.96; P=0.019) and 18-month landmarks (HR = 0.79, 95% CI 0.63-0.99; P=0.041), but without a significant increase in major bleeding at 12 (HR = 1.39, 95% CI 0.90-2.16; P=0.14), 15 (HR = 1.13, 95% CI 0.75-1.70; P=0.55) or 18 months (HR = 1.27, 95% CI 0.83-1.95; P=0.27).

Conclusions: Prolonged DAPT reduced MACE without significantly increasing major bleeding in patients who were event-free at 12 months after DES implantation. In deciding on DAPT duration, prolonged DAPT should be considered in dialysis patients.
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http://dx.doi.org/10.1093/ckj/sfaa037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577762PMC
October 2020

The tacrolimus metabolism affect post-transplant outcome mediating acute rejection and delayed graft function: analysis from Korean Organ Transplantation Registry data.

Transpl Int 2021 01 9;34(1):163-174. Epub 2020 Nov 9.

Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

Tacrolimus is a key drug in kidney transplantation (KT) with a narrow therapeutic index. The association between the tacrolimus metabolism rate and KT outcomes have not been investigated in large-scale multi-center studies. The Korean Organ Transplantation Registry (KOTRY) datasets were used. A total of 3456 KT recipients were analyzed. The tacrolimus metabolism rate was defined as blood trough concentration of tacrolimus (C ) divided by the daily dose (D). The patients were grouped into fast, intermediate, or slow metabolizers by the C /D measured 6 months after transplantation. The slow metabolism group was associated with a 2.7 ml/min/1.73 m higher adjusted estimated glomerular filtration rate (eGFR) at 6 months [95% confidence interval (C.I.) 1.2-4.3, P = 0.001], less acute rejection (AR) within 6 months [Odds ratio (OR) 0.744, 95% C.I. 0.585-0.947, P = 0.016], and less interstitial fibrosis and tubular atrophy [OR 0.606, 95% C.I. 0.390-0.940, P = 0.025]. Fast tacrolimus metabolism affected the 6-month post-KT eGFR through mediation of AR [natural indirect effect (NIE) -0.434, 95% C.I. -0.856 to -0.012, P = 0.044) and delayed graft function (DGF; NIE -0.119, 95% C.I. -0.231 to -0.007, P = 0.038). Slow tacrolimus metabolism was associated with better post-KT eGFR. AR and DGF were found to be significant mediators.
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http://dx.doi.org/10.1111/tri.13777DOI Listing
January 2021

Low High-Sensitivity C-Reactive Protein Level in Korean Patients With Chronic Kidney Disease and Its Predictive Significance for Cardiovascular Events, Mortality, and Adverse Kidney Outcomes: Results From KNOW-CKD.

J Am Heart Assoc 2020 11 23;9(21):e017980. Epub 2020 Oct 23.

Department of Internal Medicine College of Medicine Institute of Kidney Disease Research Yonsei University College of Medicine Seoul Korea.

Background Inflammation levels are lower in East Asians than in Western people. We studied the association between high-sensitivity hs-CRP (C-reactive protein) and adverse outcomes in Korean patients with chronic kidney disease. Methods and Results We included 2018 participants from the KNOW-CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease) between April 2011 and February 2016. The primary outcome was a composite of extended major cardiovascular events (eMACE) or all-cause mortality. The secondary end points were separate outcomes of eMACE, all-cause death, and adverse kidney outcome. We also evaluated predictive ability of hs-CRP for the primary outcome. The median hs-CRP level was 0.60 mg/L. During the mean follow-up of 3.9 years, there were 125 (6.2%) eMACEs and 80 (4.0%) deaths. In multivariable Cox analysis after adjustment of confounders, there was a graded association of hs-CRP with the primary outcome. The hazard ratios for hs-CRPs of 1.0 to 2.99 and ≥3.0 mg/L were 1.33 (95% CI, 0.87-2.03) and 2.08 (95% CI, 1.30-3.33) compared with the hs-CRP of <1.0 mg/L. In secondary outcomes, this association was consistent for eMACE and all-cause death; however, hs-CRP was not associated with adverse kidney outcomes. Finally, prediction models failed to show improvement of predictive performance of hs-CRP compared with conventional factors. Conclusions In Korean patients with chronic kidney disease, the hs-CRP level was low and significantly associated with higher risks of eMACEs and mortality. However, hs-CRP did not associate with adverse kidney outcome, and the predictive performance of hs-CRP was not strong. Registration URL: http://www.clinicaltrials.gov; Unique identifier: NCT01630486.
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http://dx.doi.org/10.1161/JAHA.120.017980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763415PMC
November 2020

Patterns of percutaneous transthoracic needle biopsy (PTNB) of the lung and risk of PTNB-related severe pneumothorax: A nationwide population-based study.

PLoS One 2020 10;15(7):e0235599. Epub 2020 Jul 10.

School of Medicine, Inha University, Incheon, Republic of Korea.

Background: As percutaneous transthoracic needle biopsy (PTNB) of the lung is a well-established diagnostic method for the evaluating pulmonary lesions, evidence of safety based on representative data is limited. This study investigated the practice patterns of PTNB of the lung and assessed the incidence and risk factors of PTNB-related severe pneumothorax in Korea.

Methods: We used a national-level health insurance database between January 1, 2007 and December 31, 2015. Patients who underwent PTNB of the lung were identified using procedure codes for organ biopsy, fluoroscopy, computed tomography, chest radiography, and lung-related diagnosis codes. The annual age-/sex-standardized rate of PTNB and the incidence of PTNB-related severe pneumothorax were calculated. We defined severe pneumothorax as the pneumothorax requiring intervention. The odds ratios of risk factors were assessed by a generalized estimating equation model with exchangeable working correlation matrix to address clustering effect within institution.

Results: A total of 66,754 patients were identified between 2007 and 2015. The annual age-/sex-standardized rate of PTNB per 100,000 population was 19.6 in 2007 and 22.4 in 2015, and it showed an increasing trend. The incidence of severe pneumothorax was 2.4% overall: 2.5% in men and 1.2% in women, and 2.6%, 2.7%, 2.1%, 2.1%, 1.9%, 2.4%, and 2.4% from 2009 to 2015. Older age (≥60), male sex, presence of chronic obstructive pulmonary disease, receiving treatment in an urban or rural area versus a metropolitan area, and receiving treatment at a general hospital were significantly associated with the risk of severe pneumothorax.

Conclusions: Considering the increasing trend of PTNB, more attention needs to be paid to patients with risk factors for severe pneumothorax.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235599PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351186PMC
September 2020

Urinary Angiotensinogen in addition to Imaging Classification in the Prediction of Renal Outcome in Autosomal Dominant Polycystic Kidney Disease.

J Korean Med Sci 2020 Jun 8;35(22):e165. Epub 2020 Jun 8.

Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.

Background: Intrarenal renin-angiotensin system (RAS) is known to play the major role in the development of hypertension and renal progression in autosomal dominant polycystic kidney disease (ADPKD). Urinary angiotensinogen to creatinine ratio (AGT/Cr) was suggested as a novel biomarker to reflect intrarenal RAS activity. This study was performed to evaluate urinary AGT/Cr as a predictive biomarker for renal function decline in addition to imaging classification in a prospective ADPKD cohort.

Methods: From 2011 to 2016, a total of 364 ADPKD patients were enrolled in the prospective cohort called the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD). Among them, a total of 207 subjects in chronic kidney disease stage 1-4 with baseline urinary AGT and total kidney volume and subsequent renal function follow-up data over more than 1 year were included in the analysis. Patients were defined as slow progressors (SP) if they are classified as 1A or 1B by imaging classification whereas rapid progressors (RP) if they are classified as 1C-1E. Patients were divided according to AGT/Cr quartiles and annual estimated glomerular filtration rate (eGFR) slope was compared among highest quartile (hAGT group) and the rest of quartiles (lAGT group). Patients were divided into 4 groups to evaluate the predictive value of urinary AGT/Cr in addition to imaging classification: SP/lAGT, SP/hAGT, RP/lAGT, and RP/hAGT. The Cox regression model was used to evaluate the hazard ratio (HR) between groups.

Results: The mean age was 45.9 years and 88.9% had hypertension. Baseline eGFR was 79.0 ± 28.4 mL/min/1.73 m² and median height-adjusted total kidney volume was 788.2 (471.2; 1,205.2) mL/m. The patients in the hAGT group showed lower eGFR (72.4 ± 24.8 vs. 81.1 ± 29.2 mL/min/1.73 m², = 0.039), lower plasma hemoglobin (13.0 ± 1.4 vs. 13.7 ± 1.6 g/dL, = 0.007), higher urinary protein to creatinine ratio (0.14 [0.09, 0.38] vs. 0.07 [0.04, 0.12] g/g, = 0.007) compared to the lAGT group. The hAGT group was an independent risk factor for faster eGFR decline after adjusting for gender, RP, baseline eGFR, and other known risk factors. During median follow-up duration of 4.6 years, a total of 29 renal events (14.0%) occurred. The SP/hAGT group showed significantly higher risk of developing renal outcome compared to SP/lAGT group (HR, 13.4; 95% confidence interval, 1.282-139.324; = 0.03).

Conclusion: Urinary AGT/Cr can be a useful predictive marker in the patients with relatively small ADPKD. Various biomarkers should be considered to define RP when implementing novel treatment in the patients with ADPKD.
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http://dx.doi.org/10.3346/jkms.2020.35.e165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279941PMC
June 2020

Infection, antibiotic exposure and development of atopic dermatitis: A nationwide case-control study.

J Dermatol 2020 Jul 22;47(7):707-713. Epub 2020 May 22.

Laboratory of Cutaneous Aging and Hair Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.

Previous studies suggest an association between atopic dermatitis (AD) and exposure to microorganisms and antibiotics. However, these studies have limitations, and the sole influence on the development of AD was elusive. We performed a nationwide population-based case-control study in a Korean population to investigate the association between AD and early-life infection or antibiotic exposure. A total of 244 805 children with AD from the 2 283 601 children born between January 2010 and December 2014 and an equal number of sex- and age-matched healthy children were enrolled. A conditional logistic regression analysis showed that the episode of infection and antibiotic exposure were associated with an increased risk of AD (odds ratio [OR], 1.60; 95% confidence interval [CI], 1.58-1.63 for infection; and OR, 1.11; 95% CI, 1.09-1.13 for antibiotic exposure). A dose-dependent relationship was observed between risk for AD, the number of infection episodes and antibiotic cycles and the duration of antibiotic exposure. On further analysis using a conditional logistic model, the risk of AD was less when the antibiotics were used during the infection episode than that without the use of antibiotics, especially if the duration of the infection was short. Although our study could not consider the effect of cause or severity of infection, class of antibiotics and genetic or environmental factors of enrolled subjects, our results suggested that infection and antibiotic exposure were associated with an increased risk of AD. In addition, the results also implied that the use of antibiotics during an infection episode can decrease the risk of AD induced by the infection and that appropriate management of infections can minimize the risk of AD induced by infection or antibiotics.
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http://dx.doi.org/10.1111/1346-8138.15387DOI Listing
July 2020

Indexation of left ventricular mass to predict adverse clinical outcomes in pre-dialysis patients with chronic kidney disease: KoreaN cohort study of the outcome in patients with chronic kidney disease.

PLoS One 2020 19;15(5):e0233310. Epub 2020 May 19.

Department of Internal Medicine, Nowon Eulji Medical Center, Eulji University, Seoul, Republic of Korea.

Background: No study has compared the clinical impact of indexation of left ventricular mass (LVM) on adverse clinical outcomes in pre-dialysis patients with chronic kidney disease (CKD).

Methods: We reviewed 2,101 patients from a large-scale multi-center prospective study that gathered anthropometric and echocardiographic measurements and clinical outcomes. The LVM was indexed as body surface area (LVMI-BSA) and height raised to the power of 2.7 (LVMI-H2.7). The main outcomes were composite renal and cardiovascular events and all-cause mortality. Left ventricular hypertrophy (LVH) was defined as the highest sex-specific quartile of LVMI-BSA or LVMI-H2.7.

Results: During a mean period of 3.5 years, 692 patients developed composite outcomes (32.9%). The area under the curve at 5 year of LVM (60.6%) for composite outcome was smaller than that for LVMI-BSA (63.2%, P <0.001) and LVMI-H2.7 (63.4%, P <0.001). The hazard ratio (HR) and 95% confidence interval (CI) per one unit increase in LVM (g), LVMI-BSA (g/m2), and LVMI-H2.7 (g/m2.7) for composite outcomes were 1.004 (1.002-1.005, P <0.001), 1.011 (1.006-1.016, P <0.001), and 1.023 (1.012-1.035, P <0.001), respectively. Patients with LVH determined by LVMI-BSA and LVMI-H2.7 (HR 1.352, 95% CI 1.123-1.626, P = 0.001) and LVH determined by only LVMI-BSA (HR 1.908, 95% CI 1.233-2.953, P = 0.004) showed an independent increase in the risk of composite-outcome development, when compared with patients without LVH, according to LVMI-BSA and LVMI-H2.7.

Conclusion: Indexation of LVM improved the prediction of adverse outcomes. BSA may be as useful as height2.7 in indexing of LVM for predicting adverse outcomes in pre-dialysis patients with CKD.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0233310PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236996PMC
August 2020

Optimal Prediction of the Central Venous Catheter Insertion Depth Targeting the Cavoatrial Junction.

World J Surg 2020 07;44(7):2170-2174

Department of Surgery, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.

Background: Central venous catheters should be positioned at the cavoatrial junction or the right atrium. If catheters are inserted to a depth derived by adding the length between the needle insertion point and the clavicular notch and the length between the clavicular notch and the carina, the catheter tip can be placed near the carina. Based on this, we aim to make a formula to place a catheter tip near the cavoatrial junction.

Methods: This prospective nonrandomized interventional study included patients who needed a central venous catheter from June 2017 to July 2018. The location of the cavoatrial junction was identified using a fluoroscopic technique. The following variables were measured: L1, the length between the needle insertion point and the clavicular notch; L2, the length between the clavicular notch and the carina; and α, the length between the carina and the cavoatrial junction.

Results: A total of 70 patients were enrolled. The mean age was 65.5 ± 11.6 years, and 62.9% were male. The mean L1 and L2 were 7.6 ± 1.4 and 7.0 ± 1.4 cm, respectively. The mean α was 4.4 ± 1.5 cm (95% CI 4.1-4.8), and it was not affected by demographic factors, such as sex, age, height or weight.

Conclusions: Central venous catheters in adult patients can be placed near the cavoatrial junction using a simple formula: the distance between the insertion point and the clavicular notch + the distance between the clavicular notch to the carina + 4.4 cm.
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http://dx.doi.org/10.1007/s00268-020-05449-7DOI Listing
July 2020

Granulocyte Colony-Stimulating Factor Attenuates Renal Ischemia-Reperfusion Injury by Inducing Myeloid-Derived Suppressor Cells.

J Am Soc Nephrol 2020 04 4;31(4):731-746. Epub 2020 Mar 4.

Biomedical Research Institute and

Background: Granulocyte colony-stimulating factor (G-CSF) can increase populations of myeloid-derived suppressor cells, innate immune suppressors that play an immunoregulatory role in antitumor immunity. However, the roles of myeloid-derived suppressor cells and G-CSF in renal ischemia-reperfusion injury remain unclear.

Methods: We used mouse models of ischemia-reperfusion injury to investigate whether G-CSF can attenuate renal injury by increasing infiltration of myeloid-derived suppressor cells into kidney tissue.

Results: G-CSF treatment before ischemia-reperfusion injury subsequently attenuated acute renal dysfunction, tissue injury, and tubular apoptosis. Additionally, G-CSF treatment suppressed renal infiltration of macrophages and T cells as well as renal levels of IL-6, MCP-1, IL-12, TNF-, and IFN-, but it increased levels of IL-10, arginase-1, and reactive oxygen species. Moreover, administering G-CSF after ischemia-reperfusion injury improved the recovery of renal function and attenuated renal fibrosis on day 28. G-CSF treatment increased renal infiltration of myeloid-derived suppressor cells (F4/80CD11bGr-1), especially the granulocytic myeloid-derived suppressor cell population (CD11bLy6GiLy6C); splenic F4/80CD11bGr-1 cells sorted from G-CSF-treated mice displayed higher levels of arginase-1, IL-10, and reactive oxygen species relative to those from control mice. Furthermore, these splenic cells effectively suppressed T cell activation mainly through arginase-1 and reactive oxygen species, and their adoptive transfer attenuated renal injury. Combined treatment with anti-Gr-1 and G-CSF showed better renoprotective effects than G-CSF alone, whereas preferential depletion of myeloid-derived suppressor cells by pep-G3 or gemcitabine abrogated the beneficial effects of G-CSF against renal injury.

Conclusions: G-CSF induced renal myeloid-derived suppressor cells, thereby attenuating acute renal injury and chronic renal fibrosis after ischemia-reperfusion injury. These results suggest therapeutic potential of myeloid-derived suppressor cells and G-CSF in renal ischemia-reperfusion injury.
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http://dx.doi.org/10.1681/ASN.2019060601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191933PMC
April 2020

Cardiovascular risk of nonsteroidal anti-inflammatory drugs in dialysis patients: a nationwide population-based study.

Nephrol Dial Transplant 2021 04;36(5):909-917

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

Background: Given the cardiovascular risk of nonsteroidal anti-inflammatory drugs (NSAIDs), it is essential to identify the relationship between NSAIDs and cardiovascular outcomes in dialysis patients who have elevated cardiovascular risk.

Methods: A case-crossover study was conducted to assess the association of NSAIDs with major adverse cardiac and cerebrovascular events (MACCEs) and mortality using the Korean Health Insurance dataset. The case period was defined as 1-30 days prior to the event date and the control periods were defined as 61-90 days and 91-120 days prior to the event date.

Results: There were 3433 and 8524 incident dialysis patients who experienced MACCEs and mortality, respectively, after exposure to NSAIDs within 120 days before each event. NSAIDs significantly increased the risk of MACCEs {adjusted odds ratio [aOR] 1.37 [95% confidence interval (CI) 1.26-1.50]} and mortality [aOR 1.29 (95% CI 1.22-1.36)]. Nonselective NSAIDs, but not selective cyclooxygenase-2 inhibitors, significantly increased the risk of MACCEs and mortality. However, the MACCE and mortality risk did not increase in a dose-dependent manner in the analysis according to the cumulative defined daily dosage of NSAIDs. The incidence of MACCEs in the case period tended to be more common in patients who had recent exposure to NSAIDs than in patients who did not have recent exposure to NSAIDs.

Conclusions: Clinicians should be particularly cautious when prescribing NSAIDs to dialysis patients considering the associations of NSAIDs with cardiovascular outcomes and mortality, which might occur independent of the dose and duration of exposure.
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http://dx.doi.org/10.1093/ndt/gfz276DOI Listing
April 2021

Alcohol Consumption and Progression of Chronic Kidney Disease: Results From the Korean Cohort Study for Outcome in Patients with Chronic Kidney Disease.

Mayo Clin Proc 2020 02 26;95(2):293-305. Epub 2019 Dec 26.

Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Republic of Korea. Electronic address:

Objective: To assess the association of alcohol consumption with chronic kidney disease (CKD) progression in patients with CKD.

Patients And Methods: The KoreaN cohort study for Outcome in patients with CKD (KNOW-CKD) is a prospective observational study that included detailed questionnaires regarding alcohol consumption. The 1883 individuals with CKD were enrolled from April 1, 2011, through February 28, 2016, and followed until May 31, 2017. Using a questionnaire, alcohol consumption pattern was classified according to the amount of alcohol per occasion (none, moderate, or binge) or drinking frequency (none, occasional, or regular). The primary endpoint was a composite of 50% or greater decline in estimated glomerular filtration rate (eGFR) from the baseline level or end-stage renal disease.

Results: During a follow-up of 5555 person-years (median, 2.95 years), the primary outcome occurred in 419 patients. Unadjusted cause-specific hazards model showed that the risk of the primary outcome was lower in drinkers than in non-drinkers. However, a fully adjusted model including eGFR and proteinuria yielded a reverse association. Compared with non-drinking, regular and occasional binge drinking were associated with a 2.2-fold (95% CI, 1.38-3.46) and a 2.0-fold (95% CI, 1.33-2.98) higher risk of CKD progression, respectively. This association was particularly evident in patients who had decreased kidney function and proteinuria. There was a significant interaction between alcohol consumption and eGFR for CKD progression. The slopes of eGFR decline were steeper in binge drinkers among patients with eGFR less than 60 mL/min/1.73 m.

Conclusions: Heavy alcohol consumption was associated with faster progression of CKD.
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http://dx.doi.org/10.1016/j.mayocp.2019.06.014DOI Listing
February 2020
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