Publications by authors named "Dong-Ki Kim"

289 Publications

A Mendelian randomization study found causal linkage between telomere attrition and chronic kidney disease.

Kidney Int 2021 Jul 30. Epub 2021 Jul 30.

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

Chronic kidney disease (CKD) is highly prevalent in the elderly population. However, it is rarely investigated whether kidney function is causally linked to biological aging itself. In this Mendelian randomization study, genetic instruments for telomere attrition were applied to a CKDGen genome wide association study results for 41,395 cases of CKD among 480,698 individuals as summary-level Mendelian randomization. A replicative analysis was performed by polygenic score analysis using independent United Kingdom Biobank data for 8,118 cases of CKD among 321,024 white individuals of British ancestry. Reverse-direction Mendelian randomization analysis was performed utilizing genetic instruments for log-estimated glomerular filtration rate change with Z-standardized telomere length outcome data for 326,075 participants in the UK Biobank. Genetic predisposition toward telomere attrition (one Z score decrease in length) was found to be a causative factor for a higher CKD risk [Odds Ratio 1.20 (95% confidence interval 1.08‒1.33)], as supported by pleiotropy-robust Mendelian randomization sensitivity analyses implemented using the CKDGen data. Based on United Kingdom Biobank data, the polygenic score for telomere attrition was significantly associated with a higher risk of CKD [1.20 (1.04‒1.39)]. In reverse-direction Mendelian randomization, the genetically predicted kidney function decrease was significantly associated with a higher degree of telomere attrition [beta 0.039 (0.009‒0.069)]. Thus, our study supports the causal linkage between telomere attrition and kidney function impairment.
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http://dx.doi.org/10.1016/j.kint.2021.06.041DOI Listing
July 2021

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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321232PMC
July 2021

Water Temperature Variability Is Associated with Neurologic Outcomes in Out-of-Hospital Cardiac Arrest Survivors Who Underwent Targeted Temperature Management at 33°C.

Ther Hypothermia Temp Manag 2021 Jul 16. Epub 2021 Jul 16.

Department of Emergency Medicine, Chonnam National University, Chonnam National University Hospital, Gwangju, Republic of Korea.

We examined the association between variability in body temperature (BT) and water temperature (WT) during the maintenance period of targeted temperature management (TTM) and neurologic outcomes in out-of-hospital cardiac arrest (OHCA) survivors. Adult (≥18 years), comatose OHCA survivors who underwent TTM at 33°C between October 2015 and December 2019 were included. We collected data on BT and WT recorded every minute during the TTM maintenance period. Temperature variability was measured as the standard deviation of BT and WT during the 33°C maintenance period. The primary outcome was a poor neurologic outcome, defined as a cerebral performance category scale 3-5 at 6 months. Of the 154 included patients, 96 (62.3%) had poor outcomes. The BT variability in the poor outcome group was lower than that in the good outcome group (0.16°C [0.13-0.27°C] vs. 0.13°C [0.11-0.18°C]). In addition, the WT variability during the maintenance period in the poor outcome group was lower than that in the good outcome group (2.24°C [1.80-3.96°C] vs. 1.77°C [1.26-2.32°C]). In the multivariate analysis, WT variability (odds ratio 0.508; 95% confidence interval, 0.295-0.874;  = 0.014) was independently associated with poor neurologic outcome. BT variability and cooling beyond 33.0°C ± 1.0°C were not associated with poor neurologic outcomes. WT variability during the maintenance period was independently associated with neurologic outcomes in OHCA survivors who underwent TTM at 33°C. In addition, overcooling or undercooling during the maintenance period was not associated with neurologic outcomes.
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http://dx.doi.org/10.1089/ther.2021.0011DOI Listing
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

Mortality predictors in critically ill patients with acute kidney injury requiring continuous renal replacement therapy.

Kidney Res Clin Pract 2021 Jul 5. Epub 2021 Jul 5.

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

Background: Because of high cost of continuous renal replacement therapy (CRRT) and the high mortality rate among severe acute kidney injury patients, careful identification of patients who will benefit from CRRT is warranted. This study determined factors associated with mortality among critically ill patients requiring CRRT.

Methods: This was a retrospective observational study of 414 patients admitted to the intensive care unit of four hospitals in South Korea who received CRRT from June 2017 to September 2018. Patients were divided according to degree of fluid overload (FO) and disease severity. The Cox proportional hazards model was used to explore the effect of relevant variables on mortality.

Results: In-hospital mortality rate was 57.2%. Ninety-day mortality rate was 58.5%. Lower creatinine and blood pH were significant predictors of mortality. A one-unit increase in the Sequential Organ Failure Assessment (SOFA) score was associated with increased risk of and 90-day mortality (hazard ratio [HR], 1.07; p < 0.001). The risk of 90-day mortality in FO patients was 57.2% (p < 0.001) higher than in those without FO. High SOFA score was associated with increased risk for 90-day mortality (HR, 1.79; p = 0.03 and HR, 3.05; p = 0.001) in patients without FO and with FO ≤ 10%, respectively. The highest mortality rates were in patients with FO > 10%, independent of disease severity.

Conclusion: FO increases the risk of mortality independent of other factors, including severity of acute illness. Prevention of FO should be a priority, especially when managing the critically ill.
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http://dx.doi.org/10.23876/j.krcp.20.205DOI Listing
July 2021

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

Exp Cell Res 2021 Aug 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
August 2021

Increasing prescription of renin-angiotensin-aldosterone system blockers associated with improved kidney prognosis in Korean IgA nephropathy patients.

Clin Kidney J 2021 Jun 11;14(6):1673-1680. Epub 2020 Dec 11.

Korean GlomeruloNEphritis sTudy (KoGNET) Group, Korean Society of Nephrology, Seoul, Korea.

Background: We aimed to describe the characteristics of immunoglobulin A nephropathy (IgAN) in Korea with assessment for time trends.

Methods: We performed a multicenter retrospective observational cohort study including biopsy-confirmed native IgAN cases from four tertiary hospitals in Korea. Time eras of diagnosis were stratified into 1979-2003, 2004-9 and 2010-17. The prognostic variable was progression to end-stage kidney disease (ESKD) analyzed by multivariable Cox regression analysis.

Results: We included 1366 (from 1979 to 2003), 1636 (from 2004 to 2009) and 1442 (from 2010 to 2017) IgAN patients in this study. In the recent periods, IgAN had relatively better clinical characteristics, as patients had higher estimated glomerular filtration rates and lower baseline blood pressures than before. The use of renin-angiotensin-aldosterone system (RAAS) blockers increased from 57.7% in 1979-2003 to 80.0% in 2010-17. During a median follow-up duration of 11.3 years, 722 patients progressed to ESKD with an incidence rate of 12.5 per 1000 person-years. The 10-year risk of progression to ESKD was lower in 2010-17 compared with that of 1979-2003 [adjusted hazard ratio 0.692 (95% confidence interval 0.523-0.915)], even after adjustment for multiple clinicopathologic characteristics. The use of RAAS blockers was a significant mediator (P < 0.001) for the association between time trends and lower 10-year ESKD risk.

Conclusions: Clinicopathologic characteristics of IgAN in Korea have changed over time. Although the limitation of a retrospective observational study remains, the result showed that the prognosis of IgAN has improved over the study period, possibly related to increased prescription of RAAS blockers.
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http://dx.doi.org/10.1093/ckj/sfaa204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162855PMC
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

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

Cardiovascular Risk Comparison between Expanded Hemodialysis Using Theranova and Online Hemodiafiltration (CARTOON): A Multicenter Randomized Controlled Trial.

Sci Rep 2021 May 24;11(1):10807. Epub 2021 May 24.

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

Expanded hemodialysis (HDx) with medium cutoff (MCO) membranes, which remove middle-to-large molecules well, may be a good option to replace online hemodiafiltration (online-HDF). To provide more evidence, this randomized controlled trial compared several cardiovascular parameters between patients undergoing HDx and online-HDF. Eighty patients undergoing thrice-weekly hemodialysis were randomly assigned to receive either HDx with a Theranova membrane (n = 43) or online-HDF (n = 37). The primary endpoints were changes in brachial-ankle pulse wave velocity (baPWV), echocardiographic parameters, and coronary artery calcium (CAC) scores over 1 year, and the secondary endpoints included blood cardiovascular biomarkers, mortality, and patient-reported outcomes. A linear mixed model and log-rank test were used to estimate the group differences. 65 patients had completed the trial. The changes in baPWV and echocardiographic parameters did not differ between the two groups. The CAC scores remained stable in the online-HDF group, whereas an increasing trend was shown in the HDx group (P = 0.012). Other endpoints, including cardiovascular and all-cause mortalities, were similar between the two groups. The changes in cardiovascular parameters did not differ between HDx with an MCO membrane and online-HDF. However, attention may be needed in patients with high CAC scores or scores with an increasing tendency when online-HDF is replaced with HDx with an MCO membrane.
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http://dx.doi.org/10.1038/s41598-021-90311-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144214PMC
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 Jul;42(29):2816-2823

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
July 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

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

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

Performance of Modified Early Warning Score (MEWS) for Predicting In-Hospital Mortality in Traumatic Brain Injury Patients.

J Clin Med 2021 Apr 28;10(9). Epub 2021 Apr 28.

Department of Emergency Medicine, Chonnam National University Medical School, 160 Baekseo-ro, Dong-gu, Gwangju 61469, Korea.

The present study aimed to analyze and compare the prognostic performances of the Revised Trauma Score (RTS), Injury Severity Score (ISS), Shock Index (SI), and Modified Early Warning Score (MEWS) for in-hospital mortality in patients with traumatic brain injury (TBI). This retrospective observational study included severe trauma patients with TBI who visited the emergency department between January 2018 and December 2020. TBI was considered when the Abbreviated Injury Scale was 3 or higher. The primary outcome was in-hospital mortality. In total, 1108 patients were included, and the in-hospital mortality was 183 patients (16.3% of the cohort). Receiver operating characteristic curve analyses were performed for the ISS, RTS, SI, and MEWS with respect to the prediction of in-hospital mortality. The area under the curves (AUCs) of the ISS, RTS, SI, and MEWS were 0.638 (95% confidence interval (CI), 0.603-0.672), 0.742 (95% CI, 0.709-0.772), 0.524 (95% CI, 0.489-0.560), and 0.799 (95% CI, 0.769-0.827), respectively. The AUC of MEWS was significantly different from the AUCs of ISS, RTS, and SI. In multivariate analysis, age (odds ratio (OR), 1.012; 95% CI, 1.000-1.023), the ISS (OR, 1.040; 95% CI, 1.013-1.069), the Glasgow Coma Scale (GCS) score (OR, 0.793; 95% CI, 0.761-0.826), and body temperature (BT) (OR, 0.465; 95% CI, 0.329-0.655) were independently associated with in-hospital mortality after adjustment for confounders. In the present study, the MEWS showed fair performance for predicting in-hospital mortality in patients with TBI. The GCS score and BT seemed to have a significant role in the discrimination ability of the MEWS. The MEWS may be a useful tool for predicting in-hospital mortality in patients with TBI.
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http://dx.doi.org/10.3390/jcm10091915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124302PMC
April 2021

Effectiveness of Clinical Pharmacist Service on Drug-Related Problems and Patient Outcomes for Hospitalized Patients with Chronic Kidney Disease: A Randomized Controlled Trial.

J Clin Med 2021 Apr 20;10(8). Epub 2021 Apr 20.

College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Korea.

(1) Background: The study aimed to analyze the effectiveness of clinical pharmacist services on drug-related problems (DRPs) and patient outcomes in inpatients with chronic kidney disease (CKD). (2) Methods: In a randomized controlled trial, the participants in the intervention group received pharmacist services, including medication reconciliation, medication evaluation and management, and discharge pharmaceutical care transition services. Participants in the control group received usual care. The primary outcome was the number of DRPs per patient at discharge. (3) Results: The baseline characteristics of 100 participants included the following: mean age, 52.5 years; median eGFR, 9.2 mL/min/1.73 m. The number of DRPs in the intervention group during hospitalization increased significantly with decreasing eGFR (PR, 0.970; 95% CI, 0.951-0.989) and an increasing number of unintentional medication discrepancies at admission (PR, 1.294; 95% CI, 1.034-1.620). At discharge, the number of DRPs per patient was 0.94 ± 1.03 and 1.96 ± 1.25 in the intervention and control groups, respectively ( < 0.001). The service had a significant effect on the reduction of the unintentional discrepancies at discharge ( < 0.001). (4) Conclusion: Hospital pharmacists play an important role in the prevention of DRPs at discharge and unintentional medication discrepancies in inpatients with CKD.
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http://dx.doi.org/10.3390/jcm10081788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072770PMC
April 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

Histopathologic and clinicopathologic classifications of antineutrophil cytoplasmic antibody-associated glomerulonephritis: a validation study in a Korean cohort.

Kidney Res Clin Pract 2021 Mar 24;40(1):77-88. Epub 2021 Mar 24.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.

Background: Antineutrophil cytoplasmic antibodies (ANCA)-associated glomerulonephritis (AAGN) is a common cause of rapidly progressive glomerulonephritis and requires prompt and proper immunosuppressive therapy to improve renal prognosis. This study aimed to evaluate the predictive value of two different classifications for renal outcomes in Korean AAGN patients.

Methods: Ninety-two patients who were diagnosed with AAGN at two tertiary hospitals between 2004 and 2018 were retrospectively analyzed retrospectively. The histopathologic classification according to glomerular pathology and the clinicopathologic classification according to normal glomeruli ratio, degree of interstitial fibrosis/tubular atrophy, and baseline renal function were evaluated using the Cox proportional hazards model.

Results: Forty-five patients (48.9%) progressed to end-stage kidney disease (ESKD) during the observation period. The mean age was 61.0 ± 15.3 years, and most patients had myeloperoxidase-ANCA (93.5%). In the histopathologic classification, the best renal survival occurred in the focal class, whereas the sclerotic class had the worst renal survival (sclerotic class vs. focal class; adjusted hazard ratio [aHR], 5.05; 95% confidence interval [CI], 1.32-19.31; p = 0.018). The mixed class had intermediate renal outcomes (mixed class vs. focal class; aHR, 4.23; 95% CI, 1.23-14.58; p = 0.022). In the clinicopathologic classification, the high-risk group had poor renal outcomes compared with the low-risk group (aHR, 6.56; 95% CI, 1.25-34.26; p = 0.026), but renal outcomes did not differ between the low- and medium-risk groups.

Conclusion: In Korean AAGN patients, histopathologic and clinicopathologic classifications had predictive value for renal outcomes, especially in the sclerotic class or the high-risk group with higher risk of progression to ESRD despite treatment.
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http://dx.doi.org/10.23876/j.krcp.20.184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041633PMC
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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259638PMC
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

Apolipoprotein B is a risk factor for end-stage renal disease.

Clin Kidney J 2021 Feb 11;14(2):617-623. Epub 2020 Feb 11.

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

Background: Apolipoprotein B (ApoB), a constituent of lipid particles, is known to increase the risk of cardiovascular diseases. However, the association between ApoB and end-stage renal disease (ESRD) remains to be resolved. Our objective was to determine whether the ApoB concentration has an association with the risk of ESRD.

Methods: Serum ApoB, ApoA1, conventional lipid parameters and lipid subfractions were analyzed in 9403 subjects. The hazard ratio (HR) for the risk of ESRD was calculated using tertiles of ApoB concentration.

Results: ESRD developed in 110 patients (1.2%) during 10 years of follow-up. Several lipid parameters were compared for their association with the risk of ESRD, of which ApoB was best and its relationship was also independent of other clinical parameters. Individuals in the second and third ApoB tertiles had a higher risk of ESRD than those in the first tertile, with HRs of 1.5 [95% confidence interval (CI) 0.89-2.61] and 2.6 (1.56-4.20), respectively. A high ApoB:ApoA1 ratio was associated with a higher risk of ESRD, but ApoA1 had no independent association. Even after adjusting the competing risk for all-cause death, high ApoB concentrations had an association with the risk of ESRD.

Conclusions: High ApoB concentration is associated with a higher risk of ESRD, despite adjustment for other lipid and clinical parameters. Accordingly, the monitoring of ApoB may be helpful for the prediction of ESRD.
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http://dx.doi.org/10.1093/ckj/sfz186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886579PMC
February 2021

Author Correction: Immune cell composition in normal human kidneys.

Sci Rep 2021 Feb 16;11(1):4313. Epub 2021 Feb 16.

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

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http://dx.doi.org/10.1038/s41598-021-83841-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887186PMC
February 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
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