Publications by authors named "Yong Chul Kim"

346 Publications

Causal linkage between adult height and kidney function: An integrated population-scale observational analysis and Mendelian randomization study.

PLoS One 2021 29;16(7):e0254649. Epub 2021 Jul 29.

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

As adult height is linked to various health outcomes, further investigation of its causal effects on kidney function later in life is warranted. This study involved a cross-sectional observational analysis and summary-level Mendelian randomization (MR) analysis. First, the observational association between height and estimated GFR determined by creatinine (eGFRcreatinine) or cystatin C (eGFRcystatinC) was investigated in 467,182 individuals aged 40-69 using UK Biobank. Second, the genetic instrument for adult height, as reported by the GIANT consortium, was implemented, and summary-level MR of eGFRcreatinine and CKDcreatinine in a CKDGen genome-wide association study was performed (N = 567,460), with multivariable MR being adjusted for the effects of genetic predisposition on body mass index. To replicate the findings, additional two-sample MR using the summary statistics of eGFRcystatinC and CKDcystatinC in UK Biobank was performed (N = 321,405). In observational analysis, adult height was inversely associated with both eGFRcreatinine (per 1 SD, adjusted beta -1.039, standard error 0.129, P < 0.001) and eGFRcystatinC (adjusted beta -1.769, standard error 0.161, P < 0.001) in a multivariable model adjusted for clinicodemographic, anthropometric, metabolic, and social factors. Moreover, multivariable summary-level MR showed that a taller genetically predicted adult height was causally linked to a lower log-eGFRcreatinine (adjusted beta -0.007, standard error 0.001, P < 0.001) and a higher risk of CKDcreatinine (adjusted beta 0.083, standard error 0.019, P < 0.001). Other pleiotropy-robust sensitivity MR analysis results supported the findings. In addition, similar results were obtained by two-sample MR of eGFRcystatinC (adjusted beta -1.303, standard error 0.140, P < 0.001) and CKDcystatinC (adjusted beta 0.153, standard error 0.025, P < 0.001) in UK Biobank. In conclusion, the results of this study suggest that a taller adult height is causally linked to worse kidney function in middle-aged to elderly individuals, independent of the effect of body mass index.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254649PLOS
July 2021

Clinical and genetic characteristics of Korean autosomal dominant polycystic kidney disease patients.

Korean J Intern Med 2021 07 1;36(4):767-779. Epub 2021 Jul 1.

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

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. It is characterized by cyst growth in the kidneys, resulting in kidney enlargement and end-stage kidney disease. The polycystic kidney disease 1 (PKD1) and PKD2 have been identified as genes related to ADPKD and their significance in the molecular pathology of the disease has been studied. A disease-modifying drug has been approved; therefore, it has become important to identify patients at a high risk of kidney disease progression. Genetic tests, image analysis methods, and clinical factors for kidney disease progression prediction have been established. This review describes genetic and clinical characteristics, and discusses ongoing studies in Korean ADPKD patients.
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http://dx.doi.org/10.3904/kjim.2021.176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273813PMC
July 2021

Evolving outcomes of peritoneal dialysis: secular trends at a single large center over three decades.

Kidney Res Clin Pract 2021 Jul 1. Epub 2021 Jul 1.

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

Background: Peritoneal dialysis (PD) is improving as a renal replacement therapy for end-stage renal disease (ESRD) patients. We analyzed the main outcomes of PD over the last three decades at a single large-scale PD center with an established high-quality care system.

Methods: As a retrospective cohort study, we included participants (n = 1,203) who began PD between 1990 and 2019. Major PD-related outcomes were compared among the three 10-year cohorts.

Results: The 1,203 participants were 58.3% male with a mean age of 47.9 ± 13.8 years. The median PD treatment duration was 45 months (interquartile range, 19-77 months); 362 patients (30.1%) transferred to hemodialysis, 289 (24.0%) received kidney transplants, and 224 (18.6%) died. Overall, the 5- and 8-year adjust patient survival rates were 64% and 49%, respectively. Common causes of death included infection (n = 55), cardiac (n = 38), and cerebrovascular (n = 17) events. The 5- and 8-year technique survival rates were 77% and 62%, respectively, with common causes of technique failure being infection (42.3%) and solute/water clearance problems (22.7%). The 5-year patient survival significantly improved over time (64% for the 1990-1999 cohort vs. 93% for the 2010-2019 cohort). The peritonitis rate also substantially decreased over time, from 0.278 episodes/patient-year (2000-2004) to 0.162 episodes/patient-year (2015-2019).

Conclusion: PD is an effective treatment option for ESRD patients. There was a substantial improvement in the patient survival and peritonitis rates over time. Establishing adequate infrastructure and an effective system for high-quality PD therapy may be warranted to improve PD outcomes.
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http://dx.doi.org/10.23876/j.krcp.21.020DOI Listing
July 2021

Role of the IL-33/ST2 pathway in renal allograft rejection.

Exp Cell Res 2021 Jun 21;405(2):112705. Epub 2021 Jun 21.

Kidney Research Institute, Seoul National University College of Medicine, Seoul, South Korea; Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea. Electronic address:

The interleukin-33 (IL-33)/suppression of tumorigenicity 2 (ST2) pathway modulates immune response and inflammation, associated with allograft dysfunction and rejection. We hypothesized that IL-33/ST2 is a marker of renal allograft rejection and IL-33/ST2 expression may differ according to rejection type. IL-33/ST2 expression was measured in sera and kidney tissues from recipients with acute antibody-mediated rejection (AAMR), acute cell-mediated rejection (ACMR), chronic antibody-mediated rejection (CAMR), and healthy controls. The soluble ST2 and IL-33/ST2 expression levels were higher in participants with all three rejection types than in controls. Although the expression levels in recipients with AAMR and ACMR were significantly higher than those with CAMR, there was no significant difference between the expression levels in AAMR and ACMR. Although IL-33, IL-8, and fibronectin expression were significantly increased after the addition of the recipients' serum in primary cultured human renal proximal tubular epithelial cells, the levels decreased after treatment with an anti-ST2 antibody. Furthermore, the anti-ST2 antibody specifically suppressed the upregulation of the mixed lymphocyte reaction. Boyden chamber assays demonstrated that anti-ST2 antibody abrogated chemotaxis induced by recombinant IL-33. Thus, IL-33 and ST2 are potent mediators of rejection. Treatment with an anti-ST2 antibody ameliorates rejection and could be a potential therapeutic strategy for renal allograft rejection.
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http://dx.doi.org/10.1016/j.yexcr.2021.112705DOI Listing
June 2021

Effects of residential greenness on clinical outcomes of patients with chronic kidney disease: a large-scale observation study.

Kidney Res Clin Pract 2021 Jun 26;40(2):272-281. Epub 2021 May 26.

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

Background: As industrialization and urbanization are accelerating, the distribution of green areas is decreasing, particularly in developing countries. Since the 2000s, the effects of surrounding greenness on self-perceived health, including physical and mental health, longevity, and obesity have been reported. However, the effects of surrounding green space on chronic kidney disease are not well understood. Therefore, we investigated the impact of residential greenness on the mortality of chronic kidney disease patients and progression from chronic kidney disease to end-stage renal disease (ESRD).

Methods: Using a large-scale observational study, we recruited chronic kidney disease patients (n = 64,565; mean age, 54.0 years; 49.0% of male) who visited three Korean medical centers between January 2001 and December 2016. We investigated the hazard ratios of clinical outcomes per 0.1-point increment of exposure to greenness using various models.

Results: During the mean follow-up of 6.8 ± 4.6 years, 5,512 chronic kidney disease patients developed ESRD (8.5%) and 8,543 died (13.2%). In addition, a 0.1-point increase in greenness reduced all-cause mortality risk in chronic kidney disease and ESRD patients and progression of chronic kidney disease to ESRD in a fully adjusted model. The association between mortality in ESRD patients and the normalized difference vegetation index was negatively correlated in people aged >65 years, who had normal weight, were nonsmokers, and lived in a nonmetropolitan area.

Conclusion: Chronic kidney disease patients who live in areas with higher levels of greenness are at reduced risk of all-cause mortality and progression to ESRD.
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http://dx.doi.org/10.23876/j.krcp.20.224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237126PMC
June 2021

Deep Learning-Based Quantification of Visceral Fat Volumes Predicts Posttransplant Diabetes Mellitus in Kidney Transplant Recipients.

Front Med (Lausanne) 2021 25;8:632097. Epub 2021 May 25.

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

Because obesity is associated with the risk of posttransplant diabetes mellitus (PTDM), the precise estimation of visceral fat mass before transplantation may be helpful. Herein, we addressed whether a deep-learning based volumetric fat quantification on pretransplant computed tomographic images predicted the risk of PTDM more precisely than body mass index (BMI). We retrospectively included a total of 718 nondiabetic kidney recipients who underwent pretransplant abdominal computed tomography. The 2D (waist) and 3D (waist or abdominal) volumes of visceral, subcutaneous, and total fat masses were automatically quantified using the deep neural network. The predictability of the PTDM risk was estimated using a multivariate Cox model and compared among the fat parameters using the areas under the receiver operating characteristic curves (AUROCs). PTDM occurred in 179 patients (24.9%) during the median follow-up period of 5 years (interquartile range, 2.5-8.6 years). All the fat parameters predicted the risk of PTDM, but the visceral and total fat volumes from 2D and 3D evaluations had higher AUROC values than BMI did, and the best predictor of PTDM was the 3D abdominal visceral fat volumes [AUROC, 0.688 (0.636-0.741)]. The addition of the 3D abdominal VF volume to the model with clinical risk factors increased the predictability of PTDM, but BMI did not. A deep-learning based quantification of visceral fat volumes on computed tomographic images better predicts the risk of PTDM after kidney transplantation than BMI.
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http://dx.doi.org/10.3389/fmed.2021.632097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185023PMC
May 2021

Interplay among Conformation, Intramolecular Hydrogen Bonds, and Chameleonicity in the Membrane Permeability and Cyclophilin A Binding of Macrocyclic Peptide Cyclosporin O Derivatives.

J Med Chem 2021 Jun 7;64(12):8272-8286. Epub 2021 Jun 7.

Department of Chemistry, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea.

A macrocyclic peptide scaffold with well-established structure-property relationship is desirable for tackling undruggable targets. Here, we adopted a natural macrocycle, cyclosporin O () and its derivatives (-), and evaluated the impact of conformation on membrane permeability, cyclophilin A (CypA) binding, and the pharmacokinetic (PK) profile. In nonpolar media, showed a similar conformation to cyclosporin A (), a well-known chameleonic macrocycle, but less chameleonic behavior in a polar environment. The weak chameleonicity of resulted in decreased membrane permeability; however, the more rigid conformation of was not detrimental to its PK profile. exhibited a higher plasma concentration than , which resulted from minimal CypA binding and lower accumulation in red blood cells and moderate oral bioavailability ( = 12%). Our study aids understanding of , a macrocyclic peptide that is less explored than but with greater potential for diversity generation and rational design.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00211DOI Listing
June 2021

Impact of kidney transplantation on the risk of retinal vein occlusion in end-stage renal disease.

Sci Rep 2021 Jun 2;11(1):11583. Epub 2021 Jun 2.

Department of Ophthalmology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.

It has been known that retinal vein occlusion (RVO) is associated with chronic kidney disease, especially end-stage renal disease (ESRD). However, little is known about the effect of kidney transplantation (KT) on RVO incidence in ESRD patients. This study aimed to compare the incidence of RVO in KT recipients (n = 10,498), matched ESRD patients (n = 10,498), and healthy controls (HCs, n = 10,498), using a long-term population-based cohort. The incidence of RVO was 2.74, 5.68, and 1.02 per 1000 patient-years, for the KT group, the ESRD group, and the HCs group, respectively. Adjusted hazard ratios for RVO development compared to the HCs group, were 1.53 and 3.21, in the KT group and the ESRD group, respectively. In the KT group, multivariable regression analysis indicated that an age over 50, a Charlson Comorbidity Index score over 4, and a history of desensitization therapy were associated with an increased risk of RVO. In summary, KT recipients have a lower risk for development of RVO than ESRD patients treated with dialysis. However, the risk is still higher compared to healthy people who have normal kidney functions.
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http://dx.doi.org/10.1038/s41598-021-90765-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172893PMC
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

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 Jun 20;40(2):282-293. 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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237113PMC
June 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

Incident Parkinson's disease in kidney transplantation recipients: a nationwide population-based cohort study in Korea.

Sci Rep 2021 May 18;11(1):10541. Epub 2021 May 18.

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

This nation-wide population based retrospective cohort study evaluated risk of incident Parkinson' disease in kidney transplant (KT) recipients in Korea. From Korean National Health Insurance Service database, we identified incident KT recipients aged ≥ 40 years without any history of Parkinson's disease between 2007 and 2015. We established two control cohorts without a history of Parkinson' disease: (1) General population (GP) cohort of insured subjects without a history of kidney disease, (2) end-stage renal disease (ESRD) cohort of incident ESRD subjects, with frequency matched for age, sex, and inclusion year. Parkinson's disease data were obtained from baseline until December 2017. We followed 8372 KT recipients, ESRD patients, and GP for 45,723, 38,357, and 47,476 patient-years, respectively. Their mean age was 51.2 years and 60.1% were men. During follow-up period, 19 KT recipients, 53 ESRD patients, and 15 GP developed Parkinson' disease. Risk of incident Parkinson's disease in KT recipients was similar to that in GP (adjusted hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.35 to 2.13, P = 0.75) and significantly lower than that in ESRD patients (adjusted HR 0.31, 95% CI 0.18 to 0.52, P < 0.001). Older age was the strongest predictor for incident Parkinson's disease in KT recipients.
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http://dx.doi.org/10.1038/s41598-021-90130-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131700PMC
May 2021

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

Environ Health 2021 05 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

Impact of Sleep Duration on Mortality and Quality of Life in Chronic Kidney Disease: Results from the 2007-2015 KNHANES.

Am J Nephrol 2021 6;52(5):396-403. Epub 2021 May 6.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.

Introduction: In the general population, short and long sleep durations have been associated with adverse health outcomes. However, this association remains unclear in patients with chronic kidney disease (CKD). We examined the relationship of sleep duration to mortality and health-related quality of life (HRQOL) in individuals with CKD.

Methods: A total of 1,783 adults with CKD who participated in the 2007-2015 Korea National Health and Nutrition Examination Survey were analyzed. CKD was defined as an estimated glomerular filtration rate of <60 mL/min per 1.73 m2. Participants were categorized into 3 groups according to self-reported sleep duration: <6 h (short sleepers), 6-8 h, and >8 h (long sleepers). The outcome variables were all-cause mortality and HRQOL. HRQOL was assessed using the European Quality of Life-5 Dimensions (EQ-5D) index.

Results: During a median of 6.4 years, 481 (27%) deaths occurred. In unadjusted Cox regression analysis, long sleepers with CKD had an increased risk of death (hazard ratio [HR], 1.62; 95% confidence interval [CI]: 1.26-2.09). This significant association remained after adjusting for age, sex, and BMI (HR, 1.36; 95% CI: 1.05-1.75); however, it was lost after adjusting for CKD stage, social and lifestyle factors, and presence of comorbidities (HR, 1.15; 95% CI: 0.89-1.49). Compared with 6- to 8-h sleepers with CKD, long sleepers with CKD had significantly worse HRQOL in multivariable linear regression models. The adjusted means of the EQ-5D index were 0.80 (95% CI: 0.77-0.82) for short sleepers, 0.81 (95% CI: 0.80-0.82) for 6- to 8-h sleepers, and 0.76 (95% CI: 0.73-0.79) for long sleepers (p = 0.01).

Discussion/conclusion: Long sleep duration is associated with poor HRQOL in Korean adults with CKD. The weak association between long sleep duration and mortality was attenuated after multivariable adjustment in this study.
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http://dx.doi.org/10.1159/000516096DOI Listing
May 2021

Risk of active tuberculosis infection in kidney transplantation recipients: A matched comparative nationwide cohort study.

Am J Transplant 2021 May 3. Epub 2021 May 3.

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

Large-scale evidence comparing the risk of Mycobacterium tuberculosis (TB) between kidney transplant (KT) recipients and dialysis patients is warranted. This is a nationwide retrospective cohort study based on the claims database of South Korea where a moderate prevalence of TB is reported. We included incident KT recipients from 2011 to 2015 and compared their active TB risks with 1:1 matched dialysis and general population control groups, respectively. The risk of incident active TB was assessed by multivariable Cox regression. Associations between active TB and posttransplant death or death-censored graft failure were investigated. The number of matched subjects included in each of the study groups was 7462. The KT group showed a significantly higher risk of active TB than the general population group (hazard ratio [HR] 3.39 [1.88-6.10]), whereas it showed a similar risk to that of the dialysis group (HR 0.98 [0.73-1.31]). In KT patients, active TB was a significant risk factor for both death (HR 2.33 [1.24-4.39]) and death-censored graft failure (HR 2.26 [1.39-3.67]). Although KT recipients may not have to burden the additional risk of active TB when compared with dialysis patients in recent medicine, active TB should not be overlooked as it is associated with a worse prognosis in posttransplant patients.
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http://dx.doi.org/10.1111/ajt.16627DOI Listing
May 2021

Discovery of Novel Pyrimidine-Based Capsid Assembly Modulators as Potent Anti-HBV Agents.

J Med Chem 2021 05 22;64(9):5500-5518. Epub 2021 Apr 22.

School of Life Science, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea.

Core assembly modulators of viral capsid proteins have been developed as an effective treatment of chronic hepatitis B virus (HBV) infection. In this study, we synthesized novel potent pyrimidine derivatives as core assembly modulators, and their antiviral effects were evaluated in in vitro and in vivo biological experiments. One of the synthesized derivatives, compound (R = MeSO, R = 1-piperidin-4-amine, R = 3-Cl-4-F-aniline) displayed potent inhibitory effects in the in vitro assays (52% inhibition in the protein-based assay at 100 nM and an IC value of 181 nM in the serum HBV DNA quantification assay). Moreover, treatment with compound for 5 weeks significantly decreased serum levels of HBV DNA levels (3.35 log reduction) in a human liver-chimeric uPA/SCID mouse model, and these effects were significantly increased when was combined with tenofovir, a nucleotide analogue inhibitor of reverse transcriptase used for the treatment of HBV infection.
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http://dx.doi.org/10.1021/acs.jmedchem.0c01938DOI Listing
May 2021

Real-Time Clinical Decision Support Based on Recurrent Neural Networks for In-Hospital Acute Kidney Injury: External Validation and Model Interpretation.

J Med Internet Res 2021 Apr 16;23(4):e24120. Epub 2021 Apr 16.

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

Background: Acute kidney injury (AKI) is commonly encountered in clinical practice and is associated with poor patient outcomes and increased health care costs. Despite it posing significant challenges for clinicians, effective measures for AKI prediction and prevention are lacking. Previously published AKI prediction models mostly have a simple design without external validation. Furthermore, little is known about the process of linking model output and clinical decisions due to the black-box nature of neural network models.

Objective: We aimed to present an externally validated recurrent neural network (RNN)-based continuous prediction model for in-hospital AKI and show applicable model interpretations in relation to clinical decision support.

Methods: Study populations were all patients aged 18 years or older who were hospitalized for more than 48 hours between 2013 and 2017 in 2 tertiary hospitals in Korea (Seoul National University Bundang Hospital and Seoul National University Hospital). All demographic data, laboratory values, vital signs, and clinical conditions of patients were obtained from electronic health records of each hospital. We developed 2-stage hierarchical prediction models (model 1 and model 2) using RNN algorithms. The outcome variable for model 1 was the occurrence of AKI within 7 days from the present. Model 2 predicted the future trajectory of creatinine values up to 72 hours. The performance of each developed model was evaluated using the internal and external validation data sets. For the explainability of our models, different model-agnostic interpretation methods were used, including Shapley Additive Explanations, partial dependence plots, individual conditional expectation, and accumulated local effects plots.

Results: We included 69,081 patients in the training, 7675 in the internal validation, and 72,352 in the external validation cohorts for model development after excluding cases with missing data and those with an estimated glomerular filtration rate less than 15 mL/min/1.73 m2 or end-stage kidney disease. Model 1 predicted any AKI development with an area under the receiver operating characteristic curve (AUC) of 0.88 (internal validation) and 0.84 (external validation), and stage 2 or higher AKI development with an AUC of 0.93 (internal validation) and 0.90 (external validation). Model 2 predicted the future creatinine values within 3 days with mean-squared errors of 0.04-0.09 for patients with higher risks of AKI and 0.03-0.08 for those with lower risks. Based on the developed models, we showed AKI probability according to feature values in total patients and each individual with partial dependence, accumulated local effects, and individual conditional expectation plots. We also estimated the effects of feature modifications such as nephrotoxic drug discontinuation on future creatinine levels.

Conclusions: We developed and externally validated a continuous AKI prediction model using RNN algorithms. Our model could provide real-time assessment of future AKI occurrences and individualized risk factors for AKI in general inpatient cohorts; thus, we suggest approaches to support clinical decisions based on prediction models for in-hospital AKI.
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http://dx.doi.org/10.2196/24120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087972PMC
April 2021

Deep Spinal Infection after Outpatient Epidural Injections for Pain: A Retrospective Sample Cohort Study Using a Claims Database in South Korea.

Anesthesiology 2021 06;134(6):925-936

Background: Deep spinal infection is a devastating complication after epidural injection. This study aimed to investigate the incidence of deep spinal infection primarily after outpatient single-shot epidural injection for pain. Secondarily, this study assessed the national trends of the procedure and risk factors for said infection.

Methods: Using South Korea's National Health Insurance Service sample cohort database, the 10-yr national trend of single-shot epidural injections for pain and the incidence rate of deep spinal infection after the procedure with its risk factors were determined. New-onset deep spinal infections were defined as those occurring within 90 days of the most recent outpatient single-shot epidural injection for pain, needing hospitalization for at least 1 night, and receiving at least a 4-week course of antibiotics.

Results: The number of outpatient single-shot epidural injections per 1,000 persons in pain practice doubled from 40.8 in 2006 to 84.4 in 2015 in South Korea. Among the 501,509 injections performed between 2007 and 2015, 52 cases of deep spinal infections were detected within 90 days postprocedurally (0.01% per injection). In multivariable analysis, age of 65 yr or more (odds ratio, 2.91; 95% CI, 1.62 to 5.5; P = 0.001), living in a rural area (odds ratio, 2.85; 95% CI, 1.57 to 5.0; P < 0.001), complicated diabetes (odds ratio, 3.18; 95% CI, 1.30 to 6.7; P = 0.005), multiple epidural injections (three times or more) within the previous 90 days (odds ratio, 2.34; 95% CI, 1.22 to 4.2; P = 0.007), and recent use of immunosuppressants (odds ratio, 2.90; 95% CI, 1.00 to 6.7; P = 0.025) were significant risk factors of the infection postprocedurally.

Conclusions: The incidence of deep spinal infection after outpatient single-shot epidural injections for pain is very rare within 90 days of the procedure (0.01%). The data identify high-risk patients and procedure characteristics that may inform healthcare provider decision-making.

Editor’s Perspective:
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http://dx.doi.org/10.1097/ALN.0000000000003770DOI Listing
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

Nationwide Glaucoma incidence in end stage renal disease patients and kidney transplant recipients.

Sci Rep 2021 Apr 1;11(1):7418. Epub 2021 Apr 1.

Department of Ophthalmology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.

Glaucoma shares common risk factors with chronic kidney disease (CKD) but previous cross-sectional studies have demonstrated discrepancies in the risk of glaucoma in CKD patients. This study enrolled kidney transplantation recipients (KTRs) (n = 10,955), end stage renal disease (ESRD) patients (n = 10,955) and healthy controls (n = 10,955) from National Health Insurance Service database of the Republic of Korea. A Cox proportional hazard regression model was used to calculate the hazard ratios (HR) for primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG) incidences. The incidence of POAG was higher in ESRD patients (3.36/1,000 person-years, P < 0.0001) and KTRs (3.22 /1,000 person-years, P < 0.0001), than in healthy controls (1.20/1,000 person-years). However, POAG risk showed no significant increase in either ESRD patients (P = 0.07) or KTRs (P = 0.08) when adjusted for the confounding factors. The incidence of PACG was significantly higher in ESRD patients (0.41/1,000 person-years) than in healthy controls (0.14/1,000 person-years, P = 0.008). The PACG incidence was significantly lower in KTRs than in ESRD patients (HR = 0.35, P = 0.015). In conclusion, this nationwide cohort study demonstrated that kidney transplantation can reduce the risk of PACG but not POAG in ESRD patients.
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http://dx.doi.org/10.1038/s41598-021-86846-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017003PMC
April 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

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

Deep Learning Model for Real-Time Prediction of Intradialytic Hypotension.

Clin J Am Soc Nephrol 2021 03 11;16(3):396-406. Epub 2021 Feb 11.

Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea

Background And Objectives: Intradialytic hypotension has high clinical significance. However, predicting it using conventional statistical models may be difficult because several factors have interactive and complex effects on the risk. Herein, we applied a deep learning model (recurrent neural network) to predict the risk of intradialytic hypotension using a timestamp-bearing dataset.

Design, Setting, Participants, & Measurements: We obtained 261,647 hemodialysis sessions with 1,600,531 independent timestamps (., time-varying vital signs) and randomly divided them into training (70%), validation (5%), calibration (5%), and testing (20%) sets. Intradialytic hypotension was defined when nadir systolic BP was <90 mm Hg (termed intradialytic hypotension 1) or when a decrease in systolic BP ≥20 mm Hg and/or a decrease in mean arterial pressure ≥10 mm Hg on the basis of the initial BPs (termed intradialytic hypotension 2) or prediction time BPs (termed intradialytic hypotension 3) occurred within 1 hour. The area under the receiver operating characteristic curves, the area under the precision-recall curves, and F1 scores obtained using the recurrent neural network model were compared with those obtained using multilayer perceptron, Light Gradient Boosting Machine, and logistic regression models.

Results: The recurrent neural network model for predicting intradialytic hypotension 1 achieved an area under the receiver operating characteristic curve of 0.94 (95% confidence intervals, 0.94 to 0.94), which was higher than those obtained using the other models (<0.001). The recurrent neural network model for predicting intradialytic hypotension 2 and intradialytic hypotension 3 achieved area under the receiver operating characteristic curves of 0.87 (interquartile range, 0.87-0.87) and 0.79 (interquartile range, 0.79-0.79), respectively, which were also higher than those obtained using the other models (≤0.001). The area under the precision-recall curve and F1 score were higher using the recurrent neural network model than they were using the other models. The recurrent neural network models for intradialytic hypotension were highly calibrated.

Conclusions: Our deep learning model can be used to predict the real-time risk of intradialytic hypotension.
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http://dx.doi.org/10.2215/CJN.09280620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011016PMC
March 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
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