Publications by authors named "Jung Pyo Lee"

190 Publications

Exposure to phthalates and environmental phenols in association with chronic kidney disease (CKD) among the general US population participating in multi-cycle NHANES (2005-2016).

Sci Total Environ 2021 Jun 8;791:148343. Epub 2021 Jun 8.

Department of Environmental Health Sciences, School of Public Health, Seoul National University, Seoul, Republic of Korea; Institute of Health and Environmental, Seoul National University, Seoul, Republic of Korea. Electronic address:

Exposure to consumer chemicals has been associated with chronic kidney disease (CKD) among humans, but their associations with estimated glomerular filtration rate (eGFR) are inconsistent. Such observations may be due to potential bias caused by the method of urine dilution adjustment and lack of consideration for multiple chemical exposure in the association models. This study aimed to identify major urinary chemicals associated with CKD by applying an alternative adjustment method of urine dilution ('novel' covariate-adjusted creatinine adjustment vs 'traditional' creatinine adjustment) and with a mixture exposure concept in the association model. For this purpose, the adult participants of US National Health and Nutrition Examination Survey (NHANES) 2005-2016 (n = 9008) were used, and the associations of urinary exposure biomarkers of major consumer chemicals, e.g., phthalates, bisphenol A, benzophenone-3, and parabens, with CKD related parameters of eGFR and albumin-to-creatinine ratio (ACR), were assessed. The use of the novel covariate-adjusted creatinine standardization resulted in significant inverse associations with eGFR for most measured chemicals, unlike the results with the use of the conventional creatinine adjustment. Phthalate metabolites, such as monobutyl phthalate (MBP) and mono-benzyl phthalate (MBzP), were positively associated with ACR. Even in mixture exposure models using weighted quantile sum (WQS) regression, MBzP, metabolites of di-(2-ethylhexyl) phthalate (DEHP), and bisphenol A (BPA) were revealed as major drivers of the association with eGFR or ACR. Results of sensitivity analyses with the subpopulation with normal eGFR range (n = 7041) were generally similar. Our observation suggests that exposure to benzyl butyl phthalate (BBP), DEHP, and BPA may be responsible for declined eGFR and increased ACR even at the exposure levels occurring among general adults.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148343DOI Listing
June 2021

Evaluation of the Prognosis of COVID-19 Patients According to the Presence of Underlying Diseases and Drug Treatment.

Int J Environ Res Public Health 2021 05 17;18(10). Epub 2021 May 17.

Department of Public Health Sciences, Institute of Health and Environment and Graduate School of Public Health, Seoul National University, Seoul 08826, Korea.

Certain underlying diseases such as diabetic mellitus and hypertension are a risk factor for the severity and mortality of coronavirus disease (COVID-19) patients. Furthermore, both angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) are controversial at role in the process of COVID-19 cases. The aim of the study was to investigate whether underlying diseases and taking ACEi/ARBs, affect the duration of hospitalization and mortality in patients with confirmed COVID-19. Medical usage claims data for the past three years until 15 May 2020, from the "CORONA-19 International Cooperation Research" project was used. We analyzed the medical insurance claims data for all 7590 coronavirus (COVID-19) patients confirmed by RT-PCR tests nationwide up to 15 May 2020. Among the comorbidities, a history of hypertension (hazard ratio [HR], 1.51; 95% confidence interval [CI], 1.056-2.158) and diabetes (HR, 1.867; 95% CI, 1.408-2.475) were associated significantly with mortality. Furthermore, heart failure (HR, 1.391; 95% CI, 1.027-1.884), chronic obstructive pulmonary disease (HR, 1.615; 95% CI, 1.185-2.202), chronic kidney disease (HR, 1.451; 95% CI, 1.018-2.069), mental disorder (HR, 1.61; 95% CI, 1.106-2.343), end stage renal disease (HR, 5.353; 95% CI, 2.185-13.12) were also associated significantly with mortality. The underlying disease has increased the risk of mortality in patients with COVID-19. Diabetes, hypertension, cancer, chronic kidney disease, heart failure, and mental disorders increased mortality. Controversial whether taking ACEi/ARBs would benefit COVID-19 patients, in our study, patients taking ACEi/ARBs had a higher risk of mortality.
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http://dx.doi.org/10.3390/ijerph18105342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157012PMC
May 2021

cMet agonistic antibody prevents acute kidney injury to chronic kidney disease transition by suppressing Smurf1 and activating Smad7.

Clin Sci (Lond) 2021 Jun;135(11):1427-1444

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

We aimed to investigate the role of cMet agonistic antibody (cMet Ab) in preventing kidney fibrosis during acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Additionally, we explored the effect of cMet Ab on TGF-β1/Smad pathway during the pathogenesis of kidney fibrosis. A unilateral ischemia-reperfusion injury (UIRI) mouse model was established to induce AKI-to-CKD transition. Furthermore, we incubated human proximal tubular epithelial cells (hPTECs) under hypoxic conditions as in vitro model of kidney fibrosis. We analyzed the soluble plasma cMet level in patients with AKI requiring dialysis. Patients who did not recover kidney function and progressed to CKD presented a higher increase in the cMet level. The kidneys of mice treated with cMet Ab showed fewer contractions and weighed more than the controls. The mice in the cMet Ab-treated group showed reduced fibrosis and significantly decreased expression of fibronectin and α-smooth muscle actin. cMet Ab treatment decreased inflammatory markers (MCP-1, TNF-α, and IL-1β) expression, reduced Smurf1 and Smad2/3 level, and increased Smad7 expressions. cMet Ab treatment increased cMet expression and reduced the hypoxia-induced increase in collagen-1 and ICAM-1 expression, thereby reducing apoptosis in the in vitro cell model. After cMet Ab treatment, hypoxia-induced expression of Smurf1, Smad2/3, and TGF-β1 was reduced, and suppressed Smad7 was activated. Down-regulation of Smurf1 resulted in suppression of hypoxia-induced fibronectin expression, whereas treatment with cMet Ab showed synergistic effects. cMet Ab can successfully prevent fibrosis response in UIRI models of kidney fibrosis by decreasing inflammatory response and inhibiting the TGF-β1/Smad pathway.
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http://dx.doi.org/10.1042/CS20210013DOI Listing
June 2021

Causal effect of alcohol use on the risk of end-stage kidney disease and related comorbidities: a Mendelian randomization study.

Kidney Res Clin Pract 2021 Apr 20. Epub 2021 Apr 20.

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

Background: An inverse observational association between alcohol use and the risk of chronic kidney disease (CKD) or end-stage kidney disease (ESKD) has been reported. The causal effect of alcohol use on the risk of ESKD warrants additional investigation.

Methods: The study was an observational cohort study investigating the UK Biobank and performed Mendelian randomization (MR) analysis. Amounts of alcohol use were collected using a touchscreen questionnaire. In the observational analysis, 212,133 participants without prevalent ESKD were studied, and the association between alcohol use and the risk of prevalent CKD or incident ESKD was investigated. The genetic analysis included 337,138 participants of white British ancestry. For one-sample MR, an analysis based on a polygenic risk score (PRS) was conducted with genetically predicted alcohol intake. The MR analysis investigated ESKD outcome and related comorbidities.

Results: Lower alcohol use was observationally associated with a higher risk of prevalent CKD or incident ESKD. However, the genetic risk of CKD was significantly associated with lower alcohol use, suggesting reverse causation. A higher PRS for alcohol use was significantly associated with a higher risk of ESKD (per units of one phenotypical alcohol drink; adjusted odds ratio of 1.16 [95% confidence interval, 1.02-1.31]) and related comorbidities, including hypertension, diabetes mellitus, obesity, and central obesity.

Conclusion: The inverse observational association between alcohol use and the risk of CKD or ESKD may have been affected by reverse causation. Our study supports a causal effect of alcohol use on a higher risk of ESKD and related predisposing comorbidities.
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http://dx.doi.org/10.23876/j.krcp.20.186DOI Listing
April 2021

Atrial fibrillation and kidney function: a bidirectional Mendelian randomization study.

Eur Heart J 2021 May 23. Epub 2021 May 23.

Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea.

Aims: The aim of this study was to investigate the causal effects between atrial fibrillation (AF) and kidney function.

Methods And Results: We performed a bidirectional summary-level Mendelian randomization (MR) analysis implementing the results from a large-scale genome-wide association study for estimated glomerular filtration rate (eGFR) by the CKDGen (N = 765 348) and AF (N = 588 190) to identify genetic instruments. The inverse variance weighted method was the main MR method used. For replication, an allele score-based MR was performed by individual-level data within a UK Biobank cohort of white British ancestry individuals (N = 337 138). A genetic predisposition to AF was significantly associated with decreased eGFR [for log-eGFR, beta -0.003 (standard error, 0.0005), P < 0.001] and increased risk of chronic kidney disease [beta 0.059 (0.0126), P < 0.001]. The significance remained in MR sensitivity analyses and the causal estimates were consistent when we limited the analysis to individuals of European ancestry. Genetically predicted eGFR did not show a significant association with the risk of AF [beta -0.366 (0.275), P = 0.183]. The results were similar in allele score-based MR, as allele score for AF was significantly associated with reduced eGFR [for continuous eGFR, beta -0.079 (0.021), P < 0.001], but allele score for eGFR did not show a significant association with risk of AF [beta -0.005 (0.008), P = 0.530].

Conclusions: Our study supports that AF is a causal risk factor for kidney function impairment. However, an effect of kidney function on AF was not identified in this study.
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http://dx.doi.org/10.1093/eurheartj/ehab291DOI Listing
May 2021

Clinical outcomes associated with long-term exposure to airborne particulate pollution in kidney transplant recipients.

Environ Health 2021 May 15;20(1):61. Epub 2021 May 15.

Department of Public Health Science, Institute of Sustainable Development, Institute of Health and Environment, Graduate School of Public Health, Seoul National University, Room 708, Building 220, Gwanak-Ro Gwanak-Gu, Seoul, 08826, Republic of Korea.

Background: Researchers have yet to investigate the specific association between 10-μm particulate matter (PM10) levels and the risk of graft failure, kidney disease, or the functional decline of transplanted kidneys, in kidney transplant recipients (KTRs). Furthermore, we know very little about the association between PM10 levels and the development of allograft rejection in transplanted kidneys. Identification of air pollution as a potential contributor to kidney disease could help reduce future disease burden, stimulate policy discussions on the importance of reducing air pollution with respect to health and disease, and increase public awareness of the hazards of air pollution. We aimed to evaluate the relationship of PM10 with the risk of graft failure, mortality, and decline of graft function in KTRs.

Methods: Air pollutant data were obtained from the Korean National Institute of Environmental Research. We then investigated potential associations between these data and the clinical outcomes of 1532 KTRs who underwent kidney transplantation in a tertiary hospital between 2001 and 2015. Survival models were used to evaluate the association between PM10 concentrations and the risk of death-censored graft failure (DCGF), all-cause mortality, and biopsy-proven rejection (BPR), over a median follow-up period of 6.31 years.

Results: The annual mean PM10 exposure after kidney transplantation was 27.1 ± 8.0 μg/m. Based on 1-year baseline exposure, 1 μg/m increase in PM10 concentration was associated with an increased risk of DCGF (hazard ratio (HR): 1.049; 95% confidence interval (CI): 1.014-1.084) and BPR (HR: 1.053; 95% CI: 1.042-1.063). Fully adjusted models showed that all-cause mortality was significantly associated with 1-year average PM10 concentrations (HR, 1.09; 95% CI, 1.043 to 1.140).

Conclusions: Long-term PM10 exposure is significantly associated with BPR, DCGF, and all-cause mortality in KTRs.
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http://dx.doi.org/10.1186/s12940-021-00741-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126074PMC
May 2021

Effects of air pollution on mortality of patients with chronic kidney disease: A large observational cohort study.

Sci Total Environ 2021 Sep 30;786:147471. Epub 2021 Apr 30.

Institute of Health and Environment, Seoul National University, South Korea; Department of Public Health Science, School of Public Health, Seoul National University, South Korea. Electronic address:

Due to industrialization, the burden of diseases associated with air pollution is increasing. Although the risk associated with air pollution in the general population has been actively investigated, few studies have been conducted on the effects of exposure to air pollution in patients with chronic kidney disease (CKD) in East Asia. A total of 29,602 patients with CKD in Seoul participated in a retrospective cohort at three medical centers. We assessed the association of individualized exposure to five types of air pollutants (PM, PM, NO, SO, and CO) using inverse distance weighting (IDW) on mortality in CKD patients in the Cox proportional hazard model that was adjusted for sex, age, eGFR, hemoglobin, hypertension, diabetes, and area-level characteristics. During the 6.14 ± 3.96 years, 3863 deaths (13%) were observed. We confirmed the significant effects of PM (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.07-0.29) and CO (HR 1.17, 95% CI 1.00-1.38) on mortality in CKD patients. Different associations were found when stratified by age, body mass index, smoking, and drinking status. Long-term exposure to air pollutants had negative effects on mortality in patients with CKD. These effects were prominent in patients aged over 65 years, patients with a lean body, and those who did not drink alcohol.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147471DOI Listing
September 2021

The minimum-mortality estimated glomerular filtration rate percentile shifts upward in the aged population: a nationwide population-based study.

Clin Kidney J 2021 May 29;14(5):1356-1363. Epub 2020 Dec 29.

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

Background: The estimated glomerular filtration rate (eGFR) is a biomarker not only for kidney function, but also for major clinical outcomes. We aimed to evaluate the patterns of mortality across the entire eGFR percentile spectrum using a population-based dataset.

Methods: We retrospectively reviewed the National Health Insurance Service (NHIS) database for people who received nationwide health check-ups from 2009 to 2012. Subjects who were ≥45 years old and had one or more serum creatinine values available were included in the study. The primary outcome was all-cause mortality as a function of eGFR percentile.

Results: The middle-aged group (45-64 years) showed a U-shaped pattern of association between eGFR percentile and all-cause mortality. The minimum-mortality eGFR percentile was shifted upward in the elderly group (≥65 years). Specifically, the minimum-mortality eGFR percentiles were the 28th percentile (83.8 mL/min/1.73 m) for middle-aged males, the 63rd percentile (86.2 mL/min/1.73 m) for elderly males, the 42nd percentile (102.8 mL/min/1.73 m) for middle-aged females and the 75th percentile (90.1 mL/min/1.73 m) for elderly females. Diabetes and hypertension shifted the minimum-mortality eGFR percentile upward in the middle-aged group. This pattern was attenuated in the elderly group.

Conclusions: The eGFR percentile showing minimum mortality moves upward in the aged population as well as patients with diabetes and hypertension, which might reduce the clinical significance of hyperfiltration. Risk stratification for mortality should be approached differently according to the specific conditions of the patient group.
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http://dx.doi.org/10.1093/ckj/sfaa238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087142PMC
May 2021

Kidney function and obstructive lung disease: a bidirectional Mendelian randomisation study.

Eur Respir J 2021 May 6. Epub 2021 May 6.

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

Background: Additional study is warranted to investigate the causal effects between kidney function and obstructive lung disease.

Methods: This study was a bidirectional two-sample Mendelian randomisation (MR) analysis. The CKDGen genome-wide association study (GWAS) meta-analysis for estimated glomerular filtration rate (eGFR) including individuals of European ancestry (N=567 460) provided the genetic instrument for kidney function and outcome summary statistics. A GWAS for FEV1/FVC including individuals of European ancestry from the UK Biobank (N=321 047) provided the genetic instrument for FEV1/FVC and outcome data. A polygenic score (PGS) analysis was performed to test the causal estimates from kidney function to binary obstructive lung disease outcomes, including chronic obstructive pulmonary disease (COPD), asthma, and FEV1/FVC<70%, and to perform non-linear MR with individual-level UK Biobank data.

Results: The causal estimates by summary-level MR indicated that genetically predicted increased kidney function was significantly associated with increased FEV1/FVC Z scores [10% increase in eGFR, beta 0.055 (0.024, 0.086)]. The PGS for increased eGFR showed a significant association with a reduced risk of FEV1/FVC<70% [OR 0.93 (0.87, 0.99)], COPD [OR 0.93 (0.87, 0.99)] and late-onset (≥50 years old) asthma [OR 0.93 (0.88, 0.99)]. The non-linear MR demonstrated that the causal effect from eGFR to FEV1/FVC was apparent in eGFR ranges lower than 60 mL/min/1.73 m. On the other hand, genetically predicted FEV1/FVC showed nonsignificant causal estimates of eGFR change [beta 0.568% (-0.458, 1.605%)].

Conclusion: This study supports kidney function impairment would be a causative factor for obstructive lung disease.
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http://dx.doi.org/10.1183/13993003.00848-2021DOI Listing
May 2021

Comprehensive metabolomic profiling in early IgA nephropathy patients reveals urine glycine as a prognostic biomarker.

J Cell Mol Med 2021 Jun 3;25(11):5177-5190. Epub 2021 May 3.

Kidney Research Institute, Seoul National University, Seoul, Korea.

Identification of a urinary metabolite biomarker with diagnostic or prognostic significance for early immunoglobulin A nephropathy (IgAN) is needed. We performed nuclear magnetic resonance-based metabolomic profiling and identified 26 metabolites in urine samples. We collected urine samples from 201, 77, 47, 36 and 136 patients with IgAN, patients with membranous nephropathy, patients with minimal change disease, patients with lupus nephritis and healthy controls, respectively. We determined whether a metabolite level is associated with the prognosis of IgAN through Cox regression and continuous net reclassification improvement (cNRI). Finally, in vitro experiments with human kidney tubular epithelial cells (hTECs) were performed for experimental validation. As the results, the urinary glycine level was higher in the IgAN group than the control groups. A higher urinary glycine level was associated with lower risk of eGFR 30% decline in IgAN patients. The addition of glycine to a predictive model including clinicopathologic information significantly improved the predictive power for the prognosis of IgAN [cNRI 0.72 (0.28-0.82)]. In hTECs, the addition of glycine ameliorated inflammatory signals induced by tumour necrosis factor-α. Our study demonstrates that urinary glycine may have diagnostic and prognostic value for IgAN and indicates that urinary glycine is a protective biomarker for IgAN.
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http://dx.doi.org/10.1111/jcmm.16520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178259PMC
June 2021

Causal effects of physical activity or sedentary behaviors on kidney function: an integrated population-scale observational analysis and Mendelian randomization study.

Nephrol Dial Transplant 2021 Apr 7. Epub 2021 Apr 7.

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

Background: An investigation for the causality of the effects of physical activity and specific sedentary activities on kidney function in the general population is warranted.

Methods: In this observational cohort study, first, the clinical associations of the prevalence of stages 3-5 chronic kidney disease (CKD) and the eGFR with physical activity, determined by self-report or objective wrist-band accelerometer results, and sedentary activities (watching television, using a computer, and driving) were investigated in 329,758 UK Biobank participants. To assess causality, a two-sample Mendelian randomization (MR) analysis was performed to investigate the associations of a genetic predisposition to physical activity and a sedentary lifestyle with the risk of kidney function impairment in an independent CKDGen genome-wide association study (N = 567,460). The findings were replicated with the 321,024 UK white British Biobank participants in the allele-score-based one-sample MR.

Results: A higher degree of self-reported or accelerometer-determined moderate-to-vigorous physical activity was associated with a higher eGFR, while a longer time spent watching television was significantly associated with a lower eGFR and a higher prevalence of CKD. The two-sample MR demonstrated that the genetic predisposition to a higher degree of physical activity was associated with a lower risk of CKD and a higher eGFR, while the genetically predicted television watching duration was associated with a higher risk of CKD and a lower eGFR. The other sedentary behaviors yielded inconsistent results. The findings were similarly replicated in the one-sample MR.

Conclusion: Physical activity and television watching causally affect kidney function in the general population.
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http://dx.doi.org/10.1093/ndt/gfab153DOI Listing
April 2021

Causal Effects of Homocysteine, Folate, and Cobalamin on Kidney Function: A Mendelian Randomization Study.

Nutrients 2021 Mar 11;13(3). Epub 2021 Mar 11.

Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea.

Blood homocysteine level and related vitamin levels are associated with various health outcomes. We aimed to assess causal effects of blood homocysteine, folate, and cobalamin on kidney function in the general population by performing Mendelian randomization (MR) analysis. Genetic instruments for blood homocysteine, folate, and cobalamin levels were introduced from a previous genome-wide association (GWAS) meta-analysis of European individuals. Summary-level MR analysis was performed for the estimated glomerular filtration rate (eGFR) from the CKDGen consortium GWAS that included 567,460 European ancestry individuals. For replication, allele-score-based MR was performed with an independent U.K. Biobank cohort of 337,138 individuals of white British ancestry. In summary-level MR for the CKDGen data, high genetically predicted homocysteine levels were significantly associated with low eGFR (per 1 standard deviation, beta for eGFR change -0.95 (-1.21, -0.69) %), supported by pleiotropy-robust MR sensitivity analysis. Genetically predicted high folate levels were significantly associated with high eGFR change (0.86 (0.30, 1.42) %); however, causal estimates from cobalamin were nonsignificant (-0.11 (-0.33, 0.11) %). In the U.K. Biobank data, the results were consistently identified. Therefore, a high blood homocysteine level causally decreases eGFR. Future trials with appropriate homocysteine-lowering interventions may be helpful for the primary prevention of kidney function impairment.
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http://dx.doi.org/10.3390/nu13030906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001564PMC
March 2021

Causal Effects of Positive Affect, Life Satisfaction, Depressive Symptoms, and Neuroticism on Kidney Function: A Mendelian Randomization Study.

J Am Soc Nephrol 2021 Jun 30;32(6):1484-1496. Epub 2021 Mar 30.

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

Background: Further investigation of the causal effects of psychologic wellbeing on kidney function is warranted.

Methods: In this Mendelian randomization (MR) study, genetic instruments for positive affect, life satisfaction, depressive symptoms, and neuroticism were introduced from a previous genome-wide association study meta-analysis of European individuals. Summary-level MR was performed using the CKDGen data of European ancestry (=567,460), and additional allele score-based MR was performed in the individual-level data of White British UK Biobank participants (=321,024).

Results: In summary-level MR with the CKDGen data, depressive symptoms were a significant causative factor for kidney function impairment (CKD OR, 1.45; 95% confidence interval, 1.07 to 1.96; eGFR change [%] beta -2.18; 95% confidence interval, -3.61 to -0.72) and pleiotropy-robust sensitivity analysis results supported the causal estimates. A genetic predisposition for positive affect was significantly associated with better kidney function (CKD OR, 0.69; 95% confidence interval, 0.52 to 0.91), eGFR change [%] beta 1.50; 95% confidence interval, 0.09 to 2.93) and sensitivity MR analysis results supported the finding for CKD outcome, but was nonsignificant for eGFR. Life satisfaction and neuroticism exposures showed nonsignificant causal estimates. In the UK Biobank with covariate-adjusted allele score MR analysis, allele scores for positive affect and life satisfaction were causally associated with reduced risk of CKD and higher eGFR. In contrast, neuroticism allele score was associated with increased risk of CKD and lower eGFR, and depressive symptoms allele score was associated with lower eGFR, but showed nonsignificant association with CKD.

Conclusions: Health care providers in the nephrology field should be aware of the causal linkage between psychologic wellbeing and kidney function.
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http://dx.doi.org/10.1681/ASN.2020071086DOI Listing
June 2021

Changes in renal function and predictors affecting renal outcome of living kidney donors: a nationwide prospective cohort study.

Nephrology (Carlton) 2021 Jun 15;26(6):541-548. Epub 2021 Apr 15.

Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, South Korea.

Aim: The safety of donors is an important issue in living donor kidney transplantation. We investigated serial changes in renal function and predictors affecting the renal outcome of living kidney donors.

Methods: We obtained the data of 456 kidney donors registered to the Korean Organ Transplantation Registry from 2014 to 2016. The estimated glomerular filtration rate (eGFR) changes according to the development of incident chronic kidney disease (CKD) and factors related to CKD were analysed. CKD was defined as an eGFR <60 ml/min/1.73 m or the presence of proteinuria or albuminuria. The change in eGFR over time was analysed using a linear mixed model.

Results: At 2 years after kidney donation, 21.7% of the donors (99/456) developed CKD. Annual eGFR changes after nephrectomy were 2.2 ml/min/1.73 m /year in donors without CKD, and - 0.4 ml/min/1.73 m /year in donors with CKD. Higher systolic blood pressure was associated with higher risk of CKD (odds ratio [OR] 1.322 per 10 mmHg increment, 95% confidence interval [CI] 1.036-1.686, p = .025). Higher pre-donation eGFR (OR 0.906 per 1 ml/min/1.73 m increment, 95% CI 0.876-0.936, p < .001) and higher ratio of eGFR at discharge to pre-donation (OR 0.603 per 0.1 increment, 95% CI 0.426-0.849, p = .004) were related to lower risk of CKD.

Conclusion: Kidney donors without incident CKD at 2 years after donation showed gradual increases in eGFR, whereas donors with CKD had relatively constant eGFR. A low ratio of eGFR at discharge after nephrectomy to baseline was a risk factor of CKD.
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http://dx.doi.org/10.1111/nep.13880DOI Listing
June 2021

NK1.1 natural killer T cells upregulate interleukin-17 expression in experimental lupus nephritis.

Am J Physiol Renal Physiol 2021 05 15;320(5):F772-F788. Epub 2021 Mar 15.

Kidney Research Institute, Seoul National University, Seoul, Korea.

Interleukin (IL)-17-secreting invariant natural killer T (NKT) cells are involved in several inflammatory diseases. However, their role in lupus nephritis (LN) has not been fully characterized. Samples from patients with LN or glomerulonephritis and healthy controls were obtained, and elevated IL-17 NKT cell numbers and IL-17 expression were observed in blood cells and kidneys, respectively, in patients with LN. Comparison of a mouse model of experimental autoimmune LN with the parental strain (NKT-deficient mice) revealed improved proteinuria, disease severity, and histopathology and decreased levels of chemokine (C-X-C motif) ligand 16 and T cell receptor-α variable 14 expression. Spleens and kidneys of mice also showed downregulation of inflammatory markers and IL-17. In coculture with renal mesangial and NKT cells, inflammatory markers and IL-17 were upregulated following α-galactosylceramide treatment and downregulated after treatment with IL-17-blocking antibodies. This was most prominent with killer cell lectin-like receptor subfamily B member 1 C (NK1.1) NKT cells. Thus, IL-17 is upregulated in LN. Activation of NKT cells regulates IL-17-related immune responses systemically and in the kidneys, primarily via NK1.1 NKT cells. IL-17-secreting NK1.1 NKT cells could serve as diagnostic and therapeutic targets for LN. This study makes a significant contribution to the literature because our results indicate that IL-17 is upregulated in lupus nephritis and that natural killer T (NKT) cells are involved in its pathogenesis. Activation of NKT cells regulates IL-17-related immune responses, both systemically and in the kidney, and this mainly involves NK1.1 NKT cells. Furthermore, IL-17-secreting NK1.1 NKT cells could serve as a diagnostic and therapeutic target for lupus nephritis.
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http://dx.doi.org/10.1152/ajprenal.00252.2020DOI Listing
May 2021

Observational or Genetically Predicted Higher Vegetable Intake and Kidney Function Impairment: An Integrated Population-Scale Cross-Sectional Analysis and Mendelian Randomization Study.

J Nutr 2021 May;151(5):1167-1174

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

Background: Further exploration of the possible effects of vegetable intake on kidney function is warranted.

Objective: We aimed to study the causality of the association between vegetable intake and kidney function by implementing Mendelian randomization (MR) analysis.

Methods: This study comprised a cross-sectional dietary investigation using UK Biobank data and MR analysis. For the cross-sectional investigation, 432,732 participants aged 40-69 y from the UK Biobank cohort were included. Self-reported vegetable intake was the exposure, and the outcomes were the estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD). Next, we included 337,138 participants of white British ancestry in the UK Biobank, and a genome-wide association study (GWAS) was performed to generate a genetic instrument. For MR, we first performed polygenic score (PGS)-based 1-sample MR. In addition, 2-sample MR was performed with CKDGen GWAS for kidney function traits, and the inverse variance weighted method was the main MR method.

Results: Higher vegetable intake was cross-sectionally associated with a higher eGFR (per heaped tablespoon increase; β: 0.154; 95% CI: 0.144, 0.165) and lower odds of CKD (OR: 0.975; 95% CI: 0.968, 0.982). A PGS for vegetable intake was significantly associated with a higher eGFR [per ordinal category increase (0, 1-3, 4-6, ≥7 tablespoons per day); β: 4.435; 95% CI: 2.337, 6.533], but the association with CKD remained nonsignificant (OR: 0.468; 95% CI: 0.143, 1.535). In the 2-sample MR, the causal estimates indicated that a higher genetically predicted vegetable intake was associated with a higher eGFR (percent change; β: 3.071; 95% CI: 0.602, 0.560) but nonsignificantly associated with the risk of CKD (OR: 0.560; 95% CI: 0.289, 1.083) in the European ancestry data from the CKDGen.

Conclusions: This study suggests that higher vegetable intake may have a causal effect on higher eGFRs in the European population.
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http://dx.doi.org/10.1093/jn/nxaa452DOI Listing
May 2021

Causal effects of relative fat, protein, and carbohydrate intake on chronic kidney disease: a Mendelian randomization study.

Am J Clin Nutr 2021 04;113(4):1023-1031

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

Background: The effects of specific macronutrients on kidney function independent of total calorie intake have rarely been studied, although the composition of macronutrient intake has been reported to affect health outcomes.

Objectives: We aimed to investigate the effects of macronutrient intake ratios on the risk of chronic kidney disease (CKD) by Mendelian randomization (MR) analysis.

Methods: The study was an observational cohort study mainly based on the UK Biobank and including MR analysis. First, we evaluated the relative baseline macronutrient composition-that is, the number of calories from each macronutrient divided by total calorie intake-of the diets of UK Biobank participants, and we used Cox regression to assess the incidence of end-stage kidney disease (ESKD) in 65,164 participants with normal kidney function [estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2]. We implemented a genetic instrument for relative fat, protein, and carbohydrate intake developed by a previous genome-wide association study (GWAS) and performed MR analysis. Two-sample MR was performed with the summary statistics from independent CKDGen GWAS for kidney function traits (n = 567,460), including CKD (eGFR <60 mL/min/1.73 m2) and log-transformed eGFR.

Results: The median relative macronutrient intake composition at baseline was 35% fats, 15% protein, and 50% carbohydrates. Higher relative protein intake in subjects with normal kidney function was significantly associated with a lower risk of incident ESKD (HR: 0.54; 95% CI: 0.30, 0.95) in the observational investigation. Two-sample MR indicated that increased relative fat intake causally increased the risk of kidney function impairment [CKD (OR: 1.94; 95% CI: 1.39, 2.71); log eGFR (β: -0.036; 95% CI: -0.048, -0.024)] and that higher relative protein intake was causally linked to a lower CKD risk [CKD (OR: 0.50; 95% CI: 0.35, 0.72); log eGFR (β: 0.044; 95% CI: 0.030, 0.058)].

Conclusions: A desirable macronutrient composition, including high relative protein intake and low relative fat intake, may causally reduce the risk of CKD in the general population.
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http://dx.doi.org/10.1093/ajcn/nqaa379DOI Listing
April 2021

Low serum total CO and its association with mortality in patients being followed up in the nephrology outpatients clinic.

Sci Rep 2021 Jan 18;11(1):1711. Epub 2021 Jan 18.

Department of Internal Medicine, Seoul National University Boramae Medical Center, 20, Boramae-ro 5-gil, Dongjak-gu, Seoul, 07061, Korea.

Large-scale studies have not been conducted to assess whether serum hypobicarbonatemia increases the risk for kidney function deterioration and mortality among East-Asians. We aimed to determine the association between serum total CO (TCO) concentrations measured at the first outpatient visit and clinical outcomes. In this multicenter cohort study, a total of 42,231 adult nephrology outpatients from 2001 to 2016 were included. End-stage renal disease (ESRD) patients on dialysis within 3 months of the first visit were excluded. Instrumental variable (IV) was used to define regions based on the proportion of patients with serum TCO < 22 mEq/L. The crude mortality rate was 12.2% during a median 77.0-month follow-up period. The Cox-proportional hazard regression model adjusted for initial kidney function, alkali supplementation, and the use of diuretics demonstrated that low TCO concentration was not associated with progression to ESRD, but significantly increased the risk of death. The IV analysis also confirmed a significant association between initial TCO concentration and mortality (HR 0.56; 95% CI 0.49-0.64). This result was consistently significant regardless of the underlying renal function. In conclusion, low TCO levels are significantly associated with mortality but not with progression to ESRD in patients with ambulatory care.
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http://dx.doi.org/10.1038/s41598-021-81332-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814051PMC
January 2021

Smoking, development of or recovery from metabolic syndrome, and major adverse cardiovascular events: A nationwide population-based cohort study including 6 million people.

PLoS One 2021 12;16(1):e0241623. Epub 2021 Jan 12.

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

Smoking, metabolic syndrome (MetS), and major adverse cardiovascular events (MACEs) are important global health problems. We aimed to investigate the association between smoking, alteration in MetS status, and the consequent risk of MACE. We performed a nationwide observational cohort study based on the claims database of Korea. We included people with ≥ 3 national health screenings from 2009 to 2013. Total 6,099,717 people, including 3,576,236 nonsmokers, 862,210 ex-smokers, 949,586 light-to-moderate smokers, and 711,685 heavy smokers, at the first health screening, were investigated. First, we performed a logistic regression analysis using smoking status at the first screening as the exposure variable and MetS development or recovery as the outcome variable. Second, we performed a Poisson regression using smoking status at the third screening as the exposure variable and the outcome was risk of incident MACEs. Among those previously free from MetS (N = 4,889,493), 347,678 people developed MetS, and among those who had previous MetS (N = 1,210,224), 347,627 people recovered from MetS. Smoking was related to a higher risk of MetS development [for heavy smokers: adjusted OR 1.71 (1.69 to 1.73)] and a lower probability of MetS recovery [for heavy smokers: adjusted OR 0.68 (0.67 to 0.69)]. Elevated triglycerides was the MetS component with the most prominent association with smoking. The risk for incident MACEs (78,640 events during a median follow-up of 4.28 years) was the highest for heavy smokers, followed in order by light-to-moderate, ex-smokers and nonsmokers, for every MetS status. Therefore, smoking may promote MetS or even hinder recovery from MetS. Smoking cessation should be emphasized to reduce MACE risk even for those without MetS.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241623PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802921PMC
April 2021

Cardiovascular or mortality risk of controlled hypertension and importance of physical activity.

Heart 2021 Jan 5. Epub 2021 Jan 5.

Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea (the Republic of)

Objective: To investigate the risk of major adverse cardiac and cerebrovascular events (MACCEs) and all-cause death of patients with controlled hypertension and suggest the benefits of physical activity in their prognosis.

Methods: People aged 40-69 years from the prospective UK Biobank cohort (UKB, n=220 026) and the retrospective Korean National Health Insurance Service cohort (KNHIS, n=3 593 202) were included in this observational cohort study, excluding those with previous cerebrocardiovascular diseases or hypertension without treatment. The study groups were stratified into normotension, controlled hypertension (patients with hypertension with systolic blood pressure <140 mm Hg and diastolic blood pressure <90 mm Hg) and uncontrolled hypertension groups. The outcomes were MACCEs and all-cause mortality, analysed by Cox regression analysis.

Results: We included 161 405/18 844/39 777 and 3 122 890/383 828/86 484 individuals with normotension/controlled hypertension/uncontrolled hypertension state from the UKB and KNHIS cohorts, respectively. The controlled hypertension group showed significantly higher risk of MACCEs (UKB: adjusted HR 1.73 (95% CI 1.55 to 1.92); KNHIS: 1.46 (95% CI 1.43 to 1.49)) and all-cause mortality (UKB: adjusted HR 1.28 (95% CI 1.18 to 1.39); KNHIS: 1.29 (95% CI 1.26 to 1.32)) than individuals with normotension. The controlled hypertension group not involved in any moderate or moderate-to-vigorous physical activity showed high risk of adverse outcomes, which was comparable with or even higher than the risk of patients with uncontrolled hypertension who were engaged in physical activity.

Conclusions: Controlled hypertension is associated with residual risks of adverse outcomes. Clinicians may encourage physical activity for patients with controlled hypertension, not being reassured by their achieved target blood pressure values.
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http://dx.doi.org/10.1136/heartjnl-2020-318193DOI Listing
January 2021

Impact of variability in estimated glomerular filtration rate on major clinical outcomes: A nationwide population-based study.

PLoS One 2020 17;15(12):e0244156. Epub 2020 Dec 17.

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

Background: The estimated glomerular filtration rate (eGFR), commonly estimated using the serum creatinine value, often fluctuates throughout the serial measurement. The clinical significance of GFR variation among the general population with normal renal function has not yet been demonstrated. Thus, we explored the impact of GFR variability on adverse clinical outcomes.

Methods: A nationwide retrospective cohort study using the Korean National Health Insurance System database was performed. National health screening examinees who underwent creatinine measurement ≥3 times between 2012 and 2016 were considered. Those with eGFR under 60 mL/min/m2 were excluded. The fluctuation of eGFR was represented with variability independent of the mean (VIM) index; which was calculated by the standard deviation divided by the exponent of the regression coefficient of the mean. Then, the risks of myocardial infarction (MI), stroke and death were assessed according to the quartiles of the VIM.

Results: Of total 3,538,500 participants, 0.29% of myocardial infarction (MI), 0.14% of stroke, 0.36% of deaths were observed during the median follow up of 3.27 years. Participants with the highest VIM index, which represents the highest eGFR variability, were significantly associated with an increased risk of MI (hazard ratio [HR]; 1.10, 95% confidence interval [95% CI]; 1.04-1.16), stroke (HR: 1.16; 95% CI 1.09-1.23), and death (HR: 1.18; 95% CI 1.12-1.24). The elevated risk of adverse events was consistent after the multivariate adjustment with potential confounding factors, except the risk of MI (HR 1.06; 95% 1.00-1.06).

Conclusions: Increased eGFR variability exhibited an association with major clinical outcomes, indicating that monitoring eGFR variability might be a useful parameter for predicting the adverse outcomes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244156PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746294PMC
March 2021

Cumulative fluid balance and mortality in elderly patients with acute kidney injury requiring continuous renal-replacement therapy: a multicenter prospective cohort study.

Kidney Res Clin Pract 2020 Dec;39(4):414-425

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

Background: The effect of fluid balance on outcomes in elderly patients with acute kidney injury (AKI) requiring continuous renal-replacement therapy (CRRT) is not explained well. We investigated outcomes according to cumulative fluid balance (CFB) in elderly patients with AKI undergoing CRRT.

Methods: A total of 607 patients aged 65 years or older who started CRRT due to AKI were enrolled and stratified into two groups (fluid overload [FO] vs. no fluid overload [NFO]) based on the median CFB value for 72 hours before CRRT initiation. Propensity score-matching analysis was performed.

Results: The median age of included patients was 73.0 years and 60.0% of the population was male. The median 72-hour CFB value was 2,839.0 mL. The overall cumulative survival and 28-day survival rates were lower in the FO group than in the NFO group (P < 0.001 for both) and remained so after propensity score-matching. Furthermore, patients in the FO group demonstrated a higher overall mortality risk after adjustment for age, sex, systolic blood pressure, Charlson comorbidity index, Acute Physiology and Chronic Health Evaluation II score, serum albumin, creatinine, diuretic use, and mechanical ventilation status (hazard ratio, 1.38; 95% confidence interval, 1.13 to 1.89; < 0.001). Among survivors, both the duration of CRRT and the total duration of hospitalization from CRRT initiation showed no difference between the FO and NFO groups.

Conclusion: A higher CFB value is associated with an increased risk of mortality in elderly patients with AKI requiring CRRT.
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http://dx.doi.org/10.23876/j.krcp.20.089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770993PMC
December 2020

Impact of health-related quality of life on survival after dialysis initiation: a prospective cohort study in Korea.

Kidney Res Clin Pract 2020 Dec;39(4):426-440

Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea.

Background: The effect of each health-related quality of life (HRQOL) component on hemodialysis prognosis has not been well studied. We aimed to investigate the clinical factors associated with HRQOL and the effect of HRQOL after dialysis initiation on long-term survival in an Asian population.

Methods: A total of 568 hemodialysis patients were included from a nationwide prospective cohort study. HRQOL was evaluated using the Kidney Disease Quality of Life (KDQOL) Short FormTM 1.3 at 3 months after dialysis initiation. The effect of each KDQOL item score on mortality was analyzed. Multivariable Cox analysis was performed after adjusting for age, sex, modified Charlson comorbidity index, and causes of primary kidney disease.

Results: Old age, diabetes mellitus, high comorbidities, and low serum albumin levels were associated with poor physical health status. Decreased urine output was associated with both poor physical and mental health status. The scores of 3 indices in the kidney disease domain (effect of kidney disease, social support, and dialysis staff encouragement) showed significant associations with mortality, as did the 3 indices (physical function, physical role limitation, and body pain) in the physical health domain. Neither the 4 indices in the mental health domain nor the mental composite score showed a significant association with mortality. However, a high physical composite score was associated with decreased overall patient mortality ( = 0.003). The effect of physical composite score on survival was prominent among young or middle-aged groups.

Conclusion: Poor physical health status 3 months after hemodialysis start correlates significantly with overall mortality.
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http://dx.doi.org/10.23876/j.krcp.20.065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770988PMC
December 2020

Association of the Serum Osteoprotegerin Level With Target Organ Damage in Patients at High Risk of Coronary Artery Disease.

Circ J 2020 12 28;85(1):69-76. Epub 2020 Nov 28.

Division of Cardiology, Department of Internal Medicine, Seoul National University College of Medicine, Boramae Medical Center.

Background: There is little data as to whether osteoprotegerin (OPG) is associated with target organ damage (TOD), so we evaluated the association in patients at high risk of coronary artery disease (CAD).Methods and Results:A total of 349 patients who underwent invasive coronary angiography (ICA) for suspected CAD were prospectively recruited. During the index admission, 6 TOD parameters were collected: extent of CAD, glomerular filtration rate (GFR), left ventricular mass index (LVMI), E/e', brachial-ankle pulse wave velocity (baPWV), and ankle-brachial index (ABI). Serum OPG levels were measured using enzyme-linked immunosorbent assay. The OPG level was significantly higher in patients with ≥1 TOD parameter than in those without (314±186 vs. 202±74 pg/mL, P<0.001). For each TOD parameter, the serum OPG level was significantly higher in patients with TOD than in those without (P<0.05 for each) except for ABI. In correlation analysis, OPG was significantly associated with GFR, LVMI, E/e', baPWV and ABI (P<0.05 for each). The OPG concentration increased proportionally with increasing TOD (P<0.001). Higher OPG concentrations (≥198 pg/mL) was significantly associated with the presence of TOD (odds ratio 3.22; 95% confidence interval 1.51-6.85; P=0.002) even after controlling for potential confounders.

Conclusions: Serum OPG level was significantly associated with a variety of TOD in patients undergoing ICA. OPG may be a useful marker for TOD and in the risk stratification of patients at high risk of CAD.
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http://dx.doi.org/10.1253/circj.CJ-20-0675DOI Listing
December 2020

Variability of urinary creatinine, specific gravity, and osmolality over the course of pregnancy: Implications in exposure assessment among pregnant women.

Environ Res 2021 07 13;198:110473. Epub 2020 Nov 13.

School of Public Health, Seoul National University, Seoul, Republic of Korea; Institute of Health and Environment, Seoul National University, Seoul, Republic of Korea. Electronic address:

Due to dilution status of the urine, chemical concentrations measured in spot urine are frequently adjusted using correction factors, such as creatinine, specific gravity (SG), or osmolarity of the urine. Urinary correction factors, however, can be influenced dramatically by physiological changes such as pregnancy. Details about the variation of urine dilution over the course of pregnancy are not well characterized. In the present study, we investigated the variation of urine correction factors over time among the pregnant women of Korea (n = 69) and Thailand (n = 102). Creatinine, SG, and osmolality were determined in the urine samples obtained in each trimester of the participating women, and were compared by sampling time and by nationality. Implication of the variation in these correction factors was studied using phthalate metabolites measured in the urine samples as model chemicals. Urinary correction factors significantly varied across the trimesters especially in Korean pregnant women: urinary creatinine and osmolality were significantly lower in the third trimester (T3) urine than the first trimester (T1) urine. Urinary creatinine and SG of the T3 urine of Korean pregnant women were also significantly lower than those reported from the non-pregnant women who participated in Korean National Environmental Health Survey (KoNEHS) 2015-2017. Among Thai women, however, these correction factors were rather stable across the pregnancy. Differences in ethnicity, or in behavior such as water consumption amount may partly explain the differences. Temporal changes in these urine correction factors influenced the urinary phthalate metabolite concentrations adjusted for dilution, in both Korean and Thai pregnant women. The present observations show that the variations of urinary correction factors should be considered in exposure assessment of urinary chemicals for pregnant women, in order to circumvent potential bias due to physiological changes occurring during pregnancy, and to reduce errors in exposure classification and association.
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http://dx.doi.org/10.1016/j.envres.2020.110473DOI Listing
July 2021

Association Between Moderate-to-Vigorous Physical Activity and the Risk of Major Adverse Cardiovascular Events or Mortality in People With Various Metabolic Syndrome Status: A Nationwide Population-Based Cohort Study Including 6 Million People.

J Am Heart Assoc 2020 11 6;9(22):e016806. Epub 2020 Nov 6.

Department of Internal Medicine Seoul National University Hospital Seoul Korea.

Background A population-scale evidence for the association between moderate-to-vigorous physical activity (MV-PA) and risks of major adverse cardiovascular event (MACE) or all-cause mortality in people with various metabolic syndrome (MetS) status is warranted. Methods and Results We performed a nationwide retrospective cohort study based on the claims database of South Korea. We included people who received ≥3 national health screenings from 2009 to 2013 without a previous MACE history. We determined the MetS status of 6 108 077 people: MetS-chronic (N=864 063), MetS-developed (N=348 163), MetS-recovery (N=348 313), and MetS-free (N=4 547 538). The exposure was self-reported MV-PA frequencies. The outcome was incident MACEs or all-cause mortality. The incidence rate ratios (IRR) were calculated with adjustments for clinical/demographic characteristics. During the median follow-up of 4.28 years, 78 770 and 51 840 people experienced MACEs or died, respectively. Those who engaged in MV-PA had a significantly lower risk of MACEs or all-cause mortality than those not engaged in MV-PA in every spectrum of MetS. Even among those who were free from MetS (for MACEs, IRR 0.94 [0.92-0.97], for all-cause mortality, IRR 0.85 [0.82-0.87]) or who had already recovered from MetS (for MACEs, IRR 0.89 [0.84-0.95], for all-cause mortality, IRR 0.74 [0.68-0.81]), 1 to 2 days per week of MV-PA were significantly associated with lower risk of the adverse outcomes when compared with not being engaged in MV-PA. Those who were engaged in MV-PA more frequently also had significantly lower risks of MACEs or all-cause mortality. Conclusions This nationwide study suggests that MV-PA may be recommended to the general population regardless of recent MetS status.
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http://dx.doi.org/10.1161/JAHA.120.016806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763708PMC
November 2020

Effect of the similarity of gut microbiota composition between donor and recipient on graft function after living donor kidney transplantation.

Sci Rep 2020 11 3;10(1):18881. Epub 2020 Nov 3.

Department of Internal Medicine, Seoul National University Hospital, 103 Daehakro, Jongno-gu, Seoul, 03080, Republic of Korea.

Graft outcomes of unrelated donor kidney transplant are comparable with those of related donor kidney transplant despite their genetic distance. This study aimed to identify whether the similarity of donor-recipient gut microbiota composition affects early transplant outcomes. Stool samples from 67 pairs of kidney transplant recipients and donors were collected. Gut microbiota differences between donors and recipients were determined using weighted UniFrac distance. Among the donor-recipient pairs, 30 (44.8%) pairs were related, while 37 (55.2%) were unrelated. The unrelated pairs, especially spousal pairs, had similar microbial composition, and they more frequently shared their meals than related pairs did. The weighted UniFrac distance showed an inverse correlation with the 6-month allograft function (p = 0.034); the correlation was significant in the unrelated pairs (p = 0.003). In the unrelated pairs, the microbial distance showed an excellent accuracy in predicting the estimated glomerular filtration rate of < 60 mL/min/1.73 m at 6-months post-transplantation and was better than human leukocyte antigen incompatibility and rejection. The incidence of infection within 6 months post-transplantation increased in the recipients having dissimilar microbiota with donors compared to the other recipients. Thus, pre-transplantation microbial similarity in unrelated donors and recipients may be associated with 6-month allograft function.
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http://dx.doi.org/10.1038/s41598-020-76072-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641223PMC
November 2020

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

Response to Comment on Kwon et al. The Long-term Effects of Metformin on Patients With Type 2 Diabetic Kidney Disease. Diabetes Care 2020;43:948-955.

Diabetes Care 2020 11;43(11):e191

Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea

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http://dx.doi.org/10.2337/dci20-0040DOI Listing
November 2020

Comparative analysis of the tonsillar microbiota in IgA nephropathy and other glomerular diseases.

Sci Rep 2020 10 1;10(1):16206. Epub 2020 Oct 1.

Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, Republic of Korea.

Immunoglobulin A nephropathy (IgAN) involves repeated events of gross haematuria with concurrent upper airway infections. The mucosal immune system, especially the tonsil, is considered the initial site of inflammation, although the role of the tonsillar microbiota has not been established in IgAN. In this study, we compared the tonsillar microbiota of patients with IgAN (n = 21) and other glomerular diseases (n = 36) as well as, healthy controls (n = 23) from three medical centres in Korea. The microbiota was analysed from tonsil swabs using the Illumina MiSeq system based on 16S rRNA gene. Tonsillar bacterial diversity was higher in IgAN than in other glomerular diseases, although it did not differ from that of healthy controls. Principal coordinates analysis revealed differences between the tonsillar microbiota of IgAN and both healthy and disease controls. The proportions of Rahnella, Ruminococcus_g2, and Clostridium_g21 were significantly higher in patients with IgAN than in healthy controls (corrected p < 0.05). The relative abundances of several taxa were correlated with the estimated glomerular filtration rate, blood urea nitrogen, haemoglobin, and serum albumin levels. Based on our findings, tonsillar microbiota may be associated with clinical features and possible immunologic pathogenesis of IgAN.
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http://dx.doi.org/10.1038/s41598-020-73035-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530979PMC
October 2020