Publications by authors named "Tae-Hyun Yoo"

269 Publications

Increased Risk of Chronic Kidney Disease Associated With Weight Gain in Healthy Adults: Insight From Metabolic Profiles and Body Composition.

Front Med (Lausanne) 2021 28;8:705881. Epub 2021 Sep 28.

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

Obesity is an established risk factor for kidney damage. In this study, we explored the long-term association of changes in body mass index (BMI) over time with incident chronic kidney disease (CKD). For this analysis, 5,393 middle-aged adults without comorbidities in the Korean Genome and Epidemiology Study (KoGES) were included. Group-based trajectory modeling was used to determine the patterns of BMI change (decreasing, stable, and increasing BMI) between baseline and year 4. The primary outcome was the subsequent development of CKD from year 4. A multivariable Cox proportional hazards model was constructed to determine the risk of incident CKD according to BMI trajectories. During 55,327 person-years, incident CKD occurred in 354 (6.5%) participants; 6.0, 6.1, and 7.8 per 1,000 person-years across the trajectories, respectively ( = 0.005). In the multivariable-adjusted Cox proportional hazards model, the increasing BMI trajectory was associated with a 1.4-fold [hazard ratio (HR), 1.41; 95% CI, 1.06-1.87] a higher risk of incident CKD compared with stable BMI trajectory. This association was stronger for overweight and obese individuals. The HRs for CKD development in these two groups were 1.6 (95% CI, 1.06-1.87) and 2.2 (95% CI, 1.40-3.48), respectively. While the increasing BMI group was gaining weight, there were concomitant increases in blood pressure, insulin resistance, serum concentrations of total cholesterol, triglyceride, and high-sensitivity C-reactive protein (hs-CRP), and fat mass, but high-density lipoprotein (HDL)-cholesterol level and muscle-to-fat (MF) ratio decreased. Weight gain is associated with an increased risk of incident CKD in healthy adults. This association is attributed to worsening metabolic profiles and increasing fat mass.
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http://dx.doi.org/10.3389/fmed.2021.705881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508617PMC
September 2021

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

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

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

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

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

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

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

Synergic association of diabetes mellitus and chronic kidney disease with muscle loss and cachexia: results of a 16-year longitudinal follow-up of a community-based prospective cohort study.

Aging (Albany NY) 2021 Sep 16;13(18):21941-21961. Epub 2021 Sep 16.

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

Muscle loss is a serious complication in patients with diabetes mellitus (DM) and chronic kidney disease (CKD). However, studies on a long-term change in muscle mass presence or absence of DM and CKD are scarce. We included 6247 middle-aged adults from the Korean Genome and Epidemiology Study (KoGES) between 2001 and 2016. Bioimpedance analysis (BIA) was performed biennially. Patients were classified into four groups according to the presence or absence of DM and CKD. The primary outcome was muscle depletion, which was defined as a decline in fat-free mass index (FFMI) below the 10th percentile of all subjects. The secondary outcomes included the occurrence of cachexia, all-cause mortality, and the slopes of changes in fat-free mass and weight. During 73,059 person-years of follow-up, muscle depletion and cachexia occurred in 460 (7.4%) and 210 (3.4%), respectively. In the multivariable cause-specific hazards model, the risk of muscle depletion was significantly higher in subjects with DM alone than in those without DM and CKD (HR, 1.37; 95% CI, 1.04-1.80) and was strongly pronounced in subjects with both conditions (HR, 3.38; 95% CI, 1.30-8.75). The secondary outcome analysis showed consistent results. The annual decline rates in FFMI, fat mass, and body mass index (BMI) were the steepest in subjects with DM and CKD among the four groups. DM and CKD are synergically associated with muscle loss over time. In addition, the mortality risk is higher in individuals with muscle loss.
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http://dx.doi.org/10.18632/aging.203539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507303PMC
September 2021

Erythropoiesis stimulating agent recommendation model using recurrent neural networks for patient with kidney failure with replacement therapy.

Comput Biol Med 2021 10 31;137:104718. Epub 2021 Jul 31.

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

In patients with kidney failure with replacement therapy (KFRT), optimizing anemia management in these patients is a challenging problem because of the complexities of the underlying diseases and heterogeneous responses to erythropoiesis-stimulating agents (ESAs). Therefore, we propose a ESA dose recommendation model based on sequential awareness neural networks. Data from 466 KFRT patients (12,907 dialysis sessions) in seven tertiary-care general hospitals were included in the experiment. First, a Hb prediction model was developed to simulate longitudinal heterogeneous ESA and Hb interactions. Based on the prediction model as a prospective study simulator, we built an ESA dose recommendation model to predict the required amount of ESA dose to reach a target hemoglobin level after 30 days. Each model's performance was evaluated in the mean absolute error (MAE). The MAEs presenting the best results of the prediction and recommendation model were 0.59 (95% confidence interval: 0.56-0.62) g/dL and 43.2 μg (ESAs dose), respectively. Compared to the results in the real-world clinical data, the recommendation model achieved a reduction of ESA dose (Algorithm: 140 vs. Human: 150 μg/month, P < 0.001), a more stable monthly Hb difference (Algorithm: 0.6 vs. Human: 0.8 g/dL, P < 0.001), and an improved target Hb success rate (Algorithm: 79.5% vs. Human: 62.9% for previous month's Hb < 10.0 g/dL; Algorithm: 95.7% vs. Human:73.0% for previous month's Hb 10.0-12.0 g/dL). We developed an ESA dose recommendation model for optimizing anemia management in patients with KFRT and showed its potential effectiveness in a simulated prospective study.
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http://dx.doi.org/10.1016/j.compbiomed.2021.104718DOI Listing
October 2021

Association of Blood Pressure with Cardiovascular Outcome and Mortality: Results from the KNOW-CKD Study.

Nephrol Dial Transplant 2021 Sep 2. Epub 2021 Sep 2.

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

Background: Optimal BP control is a major therapeutic strategy to reduce adverse cardiovascular events and mortality in patients with CKD. We studied the association of BP with adverse cardiovascular outcome and all-cause death in patients with CKD.

Methods: Among 2,238 participants from the KoreaN cohort study for Outcome in patients With CKD, 2,226 patients with baseline BP measurements were enrolled. Main predictor was SBP categorized by 5 levels: <110, 110-119, 120-129, 130-139, and ≥140 mmHg. Primary endpoint was a composite outcome of all-cause death or incident cardiovascular events. We primarily used marginal structural models using averaged and the most recent time-updated SBPs.

Results: During a median follow-up of 10233.79 person-years (median 4.60 years), the primary composite outcome occurred in 240 (10.8%) participants, with a corresponding incidence rate of 23.5 (95% CI, 20.7-26.6) per 1,000 patient-years. Marginal structural models with averaged SBP showed a U-shaped relationship with the primary outcome. Compared to time-updated SBP of 110-119 mmHg, hazard ratios (95% CI) for <110, 120-129, 130-139, and ≥140 mmHg were 2.47 (1.48-4.11), 1.29 (0.80-2.08), 2.15 (1.26-3.69), and 2.19 (1.19-4.01), respectively. Marginal structural models with the most recent SBP also showed similar findings.

Conclusions: In Korean patients with CKD, there was a U-shaped association of SBP with the risk of adverse clinical outcome. Our findings highlight the importance of BP control and suggest a potential hazard of SBP <110 mmHg.
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http://dx.doi.org/10.1093/ndt/gfab257DOI Listing
September 2021

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

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

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

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

Mixed- versus predilution hemodiafiltration effects on convection volume and small and middle molecule clearance in hemodialysis patients: a prospective randomized controlled trial.

Kidney Res Clin Pract 2021 Sep 30;40(3):445-456. Epub 2021 Jul 30.

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

Background: The use of newly developed mixed-dilution hemodiafiltration (HDF) can supplement the weaknesses of pre- and postdilution HDF. However, it is unclear whether mixed-HDF performs well compared to predilution HDF.

Methods: We conducted a prospective, open-labeled, randomized controlled trial from two hemodialysis centers in Korea. Between January 2017 and September 2019, 60 patients who underwent chronic hemodialysis were randomly assigned at a 1:1 ratio to receive either predilution HDF (n = 30) or mixed-HDF (n = 30) for 6 months. We compared convection volume, changes in small- and medium-sized molecule clearance, high-sensitive C-reactive protein (hs-CRP) level, and dialysis-related parameters between the two dialysis modalities.

Results: A mean effective convection volume of 41.0 ± 10.3 L/session in the predilution HDF group and 51.5 ± 9.0 L/session in the mixed-HDF group was obtained by averaging values of three time-points. The difference in effective convection volume between the groups was 10.5 ± 1.3 L/session. This met the preset noninferiority criteria, suggesting that mixed-HDF was noninferior to predilution HDF. Moreover, the β2-microglobulin reduction rate was greater in the mixed-HDF group than in the predilution HDF group, while mixed-HDF provided greater transmembrane pressure. There were no significant between-group differences in Kt/V urea levels, changes in predialysis hs-CRP levels, proportions of overhydration, or blood pressure values. Symptomatic intradialytic hypotension episodes and other adverse events occurred similarly in the two groups.

Conclusion: Use of mixed-HDF was comparable to predilution HDF in terms of delivered convection volume and clinical parameters. Moreover, mixed-HDF provided better β2-microglobulin clearance than predilution HDF.
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http://dx.doi.org/10.23876/j.krcp.21.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476308PMC
September 2021

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

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

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

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

Increased risk of acute kidney injury in coronavirus disease patients with renin-angiotensin-aldosterone-system blockade use: a systematic review and meta-analysis.

Sci Rep 2021 06 30;11(1):13588. Epub 2021 Jun 30.

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

Acute kidney injury (AKI) is a severe complication of coronavirus disease (COVID-19) that negatively affects its outcome. Concern had been raised about the potential effect of renin-angiotensin-aldosterone system (RAAS) blockades on renal outcomes in COVID-19 patients. However, the association between RAAS blockade use and incident AKI in COVID-19 patients has not been fully understood. We investigated the association between RAAS blockade exposure and COVID-19-related AKI in hospitalized patients through meta-analysis. Electronic databases were searched up to 24th December 2020. Summary estimates of pooled odds ratio (OR) of COVID-19-related AKI depending on RAAS blockade exposure were obtained through random-effects model. The random-effect meta-analysis on fourteen studies (17,876 patients) showed that RAAS blockade use was significantly associated with increased risk of incident AKI in hospitalized COVID-19 patients (OR 1.68; 95% confidence interval 1.19-2.36). Additional analysis showed that the association of RAAS blockade use on COVID-19-related AKI remains significant even after stratification by drug class and AKI severity. RAAS blockade use is significantly associated with the incident AKI in hospitalized COVID-19 patients. Therefore, careful monitoring of renal complications is recommended for COVID-19 patients with recent RAAS blockade use due to the potential risk of AKI.
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http://dx.doi.org/10.1038/s41598-021-92323-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245570PMC
June 2021

Exosome-based delivery of super-repressor IκBα ameliorates kidney ischemia-reperfusion injury.

Kidney Int 2021 09 27;100(3):570-584. Epub 2021 May 27.

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

Ischemia-reperfusion injury is a major cause of acute kidney injury. Recent studies on the pathophysiology of ischemia-reperfusion-induced acute kidney injury showed that immunologic responses significantly affect kidney ischemia-reperfusion injury and repair. Nuclear factor (NF)-ĸB signaling, which controls cytokine production and cell survival, is significantly involved in ischemia-reperfusion-induced acute kidney injury, and its inhibition can ameliorate ischemic acute kidney injury. Using EXPLOR, a novel, optogenetically engineered exosome technology, we successfully delivered the exosomal super-repressor inhibitor of NF-ĸB (Exo-srIĸB) into B6 wild type mice before/after kidney ischemia-reperfusion surgery, and compared outcomes with those of a control exosome (Exo-Naïve)-injected group. Exo-srIĸB treatment resulted in lower levels of serum blood urea nitrogen, creatinine, and neutrophil gelatinase-associated lipocalin in post-ischemic mice than in the Exo-Naïve treatment group. Systemic delivery of Exo-srIĸB decreased NF-ĸB activity in post-ischemic kidneys and reduced apoptosis. Post-ischemic kidneys showed decreased gene expression of pro-inflammatory cytokines and adhesion molecules with Exo-srIĸB treatment as compared with the control. Intravital imaging confirmed the uptake of exosomes in neutrophils and macrophages. Exo-srIĸB treatment also significantly affected post-ischemic kidney immune cell populations, lowering neutrophil, monocyte/macrophage, and T cell frequencies than those in the control. Thus, modulation of NF-ĸB signaling through exosomal delivery can be used as a novel therapeutic method for ischemia-reperfusion-induced acute kidney injury.
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http://dx.doi.org/10.1016/j.kint.2021.04.039DOI Listing
September 2021

Glomerular subepithelial microparticles - a footprint for podocyte injury.

Ultrastruct Pathol 2021 May 20;45(3):236-242. Epub 2021 May 20.

Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea.

The aim of this study was to clarify the nature and clinical significance of glomerular subepithelial microparticles (SMPs), located between the basal surface of the podocytes and the glomerular basement membrane. Ultrastructural morphology of 79 renal biopsy samples (obtained from 25 native and 54 transplanted kidneys), showing SMPs in the last 3 years, was reevaluated with regard to the podocyte changes and clinical condition of the patients. One hundred and nine SMPs were identified, with 32.9% of the samples having two or more per glomerulus. Overall, they were most frequently located in the open capillary loops (55%). However, in the native kidney samples with mesangial deposits, 64.3% of SMPs were present in the mesangium-bound areas. Each vesicle ranged from 46.9 to 87.1 nm, and vesicles were admixed with curved strands in larger SMPs. Diffuse effacement of the foot processes and condensation of the actin filaments were present in 56.0% and 62.4% of the samples, respectively. SMPs were associated with hematuria, proteinuria of ≥ 1 gm, and immune complex deposition in the patients with native kidneys, whereas they were related to hyperglycemia and elevated serum creatinine levels in the patients with renal allografts. Patients with native and transplanted kidneys most commonly presented with IgA nephropathy and allograft rejection, respectively. Finding SMPs in the renal biopsy samples is not rare and they may act as a footprint of podocyte injury caused by diverse etiologies. Considering their size, podocyte exosomes could be a possible source of SMPs.
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http://dx.doi.org/10.1080/01913123.2021.1929625DOI Listing
May 2021

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

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

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

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

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

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

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

Urinary angiotensinogen as a marker of elevated blood pressure in patients with chronic kidney disease.

Korean J Intern Med 2021 05 30;36(3):541-543. Epub 2021 Apr 30.

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

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http://dx.doi.org/10.3904/kjim.2021.188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137407PMC
May 2021

Smoking Cessation and Coronary Artery Calcification in CKD.

Clin J Am Soc Nephrol 2021 06 20;16(6):870-879. Epub 2021 Apr 20.

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

Background And Objectives: Smoking is associated with vascular calcification and a higher risk of cardiovascular disease. In this study, we investigated the association of smoking dose and cessation with coronary artery calcification (CAC) in patients with CKD.

Design, Setting, Participants, & Measurements: From a nationwide, prospective cohort of Korean patients with CKD, 1914 participants were included. Prevalent CAC was defined as an Agatston score >0, using computed tomography. CAC progression was defined as ≥30%/yr increase in Agatston score at the 4-year follow-up examination in patients with baseline CAC.

Results: Prevalent CAC was observed in 952 (50%) patients. Compared with never smokers, former smokers had a similar prevalence ratio for CAC, but current smokers had a 1.25-fold higher prevalence ratio (95% confidence interval [95% CI], 1.10 to 1.42). Among former smokers, a lower smoking load of <10 pack-years (prevalence ratio, 0.77; 95% CI, 0.65 to 0.90) and longer duration of smoking cessation (prevalence ratio for 10 to <20 years, 0.85; 95% CI, 0.73 to 0.98: prevalence ratio for ≥20 years, 0.83; 95% CI, 0.73 to 0.96) were associated with lower risk of prevalent CAC compared with current smoking. The prevalence ratios did not differ between never smoking and long-term cessation. However, short-term cessation with heavy smoking load was associated with a higher risk of prevalent CAC (prevalence ratio, 1.21; 95% CI, 1.03 to 1.40) compared with never smoking. CAC progression was observed in 111 (33%) patients with baseline CAC. Compared with never smokers, former smokers showed a similar risk of CAC progression, but current smokers had a higher risk (relative risk, 1.92; 95% CI, 1.30 to 2.86).

Conclusions: In CKD, former smoking with a lower smoking load and long-term cessation were associated with a lower risk of prevalent CAC than current smoking. CAC progression was more pronounced in current smokers.
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http://dx.doi.org/10.2215/CJN.15751020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216611PMC
June 2021

Extracellular vesicles in kidneys and their clinical potential in renal diseases.

Kidney Res Clin Pract 2021 Jun 13;40(2):194-207. Epub 2021 Apr 13.

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

Extracellular vesicles (EVs), such as exosomes and microvesicles, are cell-derived lipid bilayer membrane particles, which deliver information from host cells to recipient cells. EVs are involved in various biological processes including the modulation of the immune response, cell-to-cell communications, thrombosis, and tissue regeneration. Different types of kidney cells are known to release EVs under physiologic as well as pathologic conditions, and recent studies have found that EVs have a pathophysiologic role in different renal diseases. Given the recent advancement in EV isolation and analysis techniques, many studies have shown the diagnostic and therapeutic potential of EVs in various renal diseases, such as acute kidney injury, polycystic kidney disease, chronic kidney disease, kidney transplantation, and renal cell carcinoma. This review updates recent clinical and experimental findings on the role of EVs in renal diseases and highlights the potential clinical applicability of EVs as novel diagnostics and therapeutics.
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http://dx.doi.org/10.23876/j.krcp.20.209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237124PMC
June 2021

A new opportunity for Kidney Research and Clinical Practice to make a great leap forward as a Science Citation Index Expanded journal.

Kidney Res Clin Pract 2021 Mar 30;40(1):1-5. Epub 2021 Mar 30.

Editorial Board of Kidney Research and Clinical Practice, Official Journal of the Korean Society of Nephrology, Seoul, Republic of Korea.

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http://dx.doi.org/10.23876/j.krcp.21.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041634PMC
March 2021

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

J Nephrol 2021 Mar 23. Epub 2021 Mar 23.

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

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

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

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

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

Reduction in proteinuria after immunosuppressive therapy and long-term kidney outcomes in patients with immunoglobulin A nephropathy.

Korean J Intern Med 2021 Sep 10;36(5):1169-1180. Epub 2021 Feb 10.

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

Background/aims: Despite controversy regarding the benefits of immunosuppressive therapy in immunoglobulin A nephropathy (IgAN), clinical outcomes may vary depending on the patient's responsiveness to this therapy. This study evaluated long-term kidney outcomes according to the extent of proteinuria reduction after immunosuppression in IgAN patients.

Methods: Among 927 patients with biopsy-proven IgAN, 127 patients underwent immunosuppression. Time-averaged urine protein-creatinine ratio before and within 1 year after start of immunosuppression were calculated, and responsiveness to immunosuppression was assessed as the reduction of proteinuria between the two periods. Patients were classified into tertiles according to the extent of proteinuria reduction. We compared the slopes of estimated glomerular filtration rate (eGFR) decline using a linear mixed model, and estimated hazard ratios (HRs) for disease progression (defined as development of a ≥ 30% decline in eGFR or end-stage renal disease) using a Cox proportional hazard model.

Results: Median extent of proteinuria reduction was -2.1, -0.9, and -0.2 g/gCr in the first, second, and third tertiles, respectively. There were concomitant changes in the slopes of annual eGFR decline: -2.03, -2.44, and -4.62 mL/min/1.73 m2 among the first, second, and third tertiles, respectively. In multivariable Cox analysis, the HRs (95% confidence intervals) for disease progression were 0.30 (0.12 to 0.74) in the first tertile and 0.70 (0.34 to 1.45) in the second tertile compared with the thirdtertile.

Conclusion: This study showed that greater proteinuria reduction after immunosuppression was associated with a lower risk of disease progression in patients with IgAN, suggesting that responsiveness to immunosuppression may be an important determinant of kidney outcomes.
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http://dx.doi.org/10.3904/kjim.2020.240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435500PMC
September 2021

Association Between Nocturnal Blood Pressure Dipping and Chronic Kidney Disease Among Patients With Controlled Office Blood Pressure.

Am J Hypertens 2021 08;34(8):821-830

Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea.

Background: Although abnormal blood pressure (BP) patterns are associated with adverse cardiorenal outcomes, their associations are yet unquantified by nocturnal dipping status. We examined the association of nocturnal BP dipping pattern with albuminuria and kidney function among participants with controlled hypertension without prior advanced kidney disease.

Methods: Ambulatory BP (ABP) measurements were collected from 995 middle-aged, cardiology clinic patients with controlled office BP (OBP) (<140/90 mm Hg). The magnitude of dipping was calculated as the difference between daytime and nighttime systolic BP (SBP) divided by daytime SBP. Accordingly, the participants were categorized as extreme-dipper (≥20%), dipper (10% to <20%), non-dipper (0% to <10%), or reverse-dipper (<0%). We analyzed the cross-sectional associations of dipping with albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g) and decreased estimated glomerular filtration rate (<60 ml/min/1.73 m2), adjusting for OBP/ABP, antihypertensive class, body mass index, total cholesterol, fasting glucose, socioeconomic status, and health behavior.

Results: The participants (mean age 60.2 years; 52.9% male) consisted of 13.5% extreme-dippers, 43.1% dippers, 34.7% non-dippers, and 8.7% reverse-dippers. In reference to dippers, odds ratios [95% confidence interval] for albuminuria were 1.73 [1.04-2.60] in reverse-dippers, 1.67 [1.20-2.32] in non-dippers, and 0.62 [0.38-1.04] in extreme-dippers. Likewise, abnormal dipping profile was associated with decreased kidney function: reverse-dipping, 2.02 [1.06-3.84]; non-dipping, 1.98 [1.07-3.08]; extreme-dipping, 0.69 [0.20-1.17]. The associations persisted among participants with more conservatively controlled OBP (<130/80 mm Hg).

Conclusions: Monitoring diurnal and nocturnal BP may identify chronic kidney disease otherwise overlooked based on OBP.
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http://dx.doi.org/10.1093/ajh/hpab031DOI Listing
August 2021

Characterization of ferroptosis in kidney tubular cell death under diabetic conditions.

Cell Death Dis 2021 02 8;12(2):160. Epub 2021 Feb 8.

Institute of Kidney Disease Research, College of Medicine, Yonsei University, Seoul, South Korea.

Kidney tubular cell death induced by transforming growth factor-β1 (TGF-β1) is known to contribute to diabetic nephropathy, a major complication of diabetes. Caspase-3-dependent apoptosis and caspase-1-dependent pyroptosis are also involved in tubular cell death under diabetic conditions. Recently, ferroptosis, an atypical form of iron-dependent cell death, was reported to cause kidney disease, including acute kidney injury. Ferroptosis is primed by lipid peroxide accumulation through the cystine/glutamate antiporter system X (xCT) and glutathione peroxidase 4 (GPX4)-dependent mechanisms. The aim of this study was to evaluate the role of ferroptosis in diabetes-induced tubular injury. TGF-β1-stimulated proximal tubular epithelial cells and diabetic mice models were used for in vitro and in vivo experiments, respectively. xCT and GPX4 expression, cell viability, glutathione concentration, and lipid peroxidation were quantified to indicate ferroptosis. The effect of ferroptosis inhibition was also assessed. In kidney biopsy samples from diabetic patients, xCT and GPX4 mRNA expression was decreased compared to nondiabetic samples. In TGF-β1-stimulated tubular cells, intracellular glutathione concentration was reduced and lipid peroxidation was enhanced, both of which are related to ferroptosis-related cell death. Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, alleviated TGF-β1-induced ferroptosis. In diabetic mice, kidney mRNA and protein expressions of xCT and GPX4 were reduced compared to control. Kidney glutathione concentration was decreased, while lipid peroxidation was increased in these mice, and these changes were alleviated by Fer-1 treatment. Ferroptosis is involved in kidney tubular cell death under diabetic conditions. Ferroptosis inhibition could be a therapeutic option for diabetic nephropathy.
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http://dx.doi.org/10.1038/s41419-021-03452-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870666PMC
February 2021

Systolic blood pressure and chronic kidney disease progression in patients with primary glomerular disease.

J Nephrol 2021 08 8;34(4):1057-1067. Epub 2021 Feb 8.

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

Introduction: Many current guidelines on optimal target blood pressure (BP) for chronic kidney disease (CKD) patients are largely based on studies in diabetic and hypertensive patients. However, there have been few studies in patients with glomerular diseases.

Methods: We retrospectively studied the longitudinal association between BP and CKD progression in 1,066 biopsy-proven patients diagnosed with primary glomerular diseases, including IgA nephropathy, membranous nephropathy (MN), and focal segmental glomerulosclerosis (FSGS), between 2005 and 2017. The main predictor was time-updated systolic blood pressure (SBP) at every clinic visit. The primary outcome was a composite one including ≥ 50% decrease in estimated glomerular filtration rate (eGFR) from the baseline, and end-stage kidney disease (ESKD).

Results: During 5009 person-years of follow-up, the primary outcome occurred in 157 (14.7%) patients. In time-varying Cox model, the adjusted hazard ratios (HRs) (95% confidence interval (CI)) for the primary outcome were 1.48 (0.96-2.29), 2.07 (1.22-3.52), and 2.53 (1.13-5.65) for SBP of 120-129, 130-139, and ≥ 140 mmHg, respectively, compared with SBP < 120 mmHg. This association was particularly evident in patients with elevated proteinuria. However, there was no association between baseline SBP and adverse kidney outcomes. Finally, prediction models failed to show the improvement of predictive performance of SBP compared with that of remission status. Moreover, patients with remission and less controlled SBP had better kidney outcomes than those with non-remission and well-controlled SBP.

Conclusion: Among patients with glomerular disease, higher time-updated SBP was significantly associated with higher risk of CKD progression. However, the clinical significance of blood pressure was less powerful than remission status.
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http://dx.doi.org/10.1007/s40620-020-00930-xDOI Listing
August 2021

Effect of Psychosocial Distress on the Rate of Kidney Function Decline.

J Gen Intern Med 2021 Oct 19;36(10):2966-2974. Epub 2021 Jan 19.

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

Backgrounds: Chronic kidney disease is a growing global health problem. Psychosocial stress has been found to induce changes in biological processes and behavioral patterns that increase risks of cardiovascular and metabolic diseases. However, the association between psychosocial stress and kidney function is not well understood.

Objective: To evaluate the association between psychosocial stress and kidney function decline.

Design: In this prospective cohort study, psychosocial distress was assessed using the psychosocial well-being index short-form (PWI-SF).

Participants: Data of a total of 7246 participants were retrieved from a community-based cohort (Korean Genome and Epidemiology Study).

Main Measures: The rate of estimated glomerular filtration rate (eGFR) decline was calculated for each individual. Rapid eGFR decline was defined as a decrease of ≥ 3 mL/min/1.73 m per year. The presence of kidney disease was defined as eGFR < 60 mL/min/1.73 m at baseline or proteinuria of higher than trace levels from two consecutive urine test results.

Key Results: A total of 7246 participants were analyzed. The mean eGFR was 92.1 ± 14.0 mL/min/1.73 m. Rapid eGFR decline was observed in 941 (13.0%) participants during a median follow-up of 11.7 years. When the participants were categorized into tertiles according to PWI-SF score, rapid eGFR decline was more prevalent in the group with the highest PWI-SF score (15.8%) than in the group with the lowest score (12.2%). Multivariate logistic regression analysis revealed that the risk of rapid eGFR decline was significantly increased in the tertile group with the highest PWI-SF score compared to the lowest group (odds ratio, 1.35; 95% confidence interval, 1.15-1.59). This association was maintained even after adjusting for confounding variables and excluding participants with kidney disease.

Conclusions: Higher levels of psychosocial distress were closely associated with an increased risk of rapid kidney function decline.
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http://dx.doi.org/10.1007/s11606-020-06573-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481510PMC
October 2021

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

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

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

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

Study Design: Prospective observational cohort study.

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

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

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

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

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

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

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

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

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

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

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

Micellized Protein Transduction Domain-Bone Morphogenetic Protein-7 Efficiently Blocks Renal Fibrosis Via Inhibition of Transforming Growth Factor-Beta-Mediated Epithelial-Mesenchymal Transition.

Front Pharmacol 2020 19;11:591275. Epub 2020 Nov 19.

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

Tubulointerstitial renal fibrosis is a chronic disease process affecting chronic kidney disease (CKD). While the etiological role of transforming growth factor-beta (TGF-β) is well known for epithelial-mesenchymal transition (EMT) in chronic kidney disease, effective therapeutics for renal fibrosis are largely limited. As a member of the TGF-β superfamily, bone morphogenetic protein-7 (BMP-7) plays an important role as an endogenous antagonist of TGF-β, inhibiting fibrotic progression in many organs. However, soluble rhBMP-7 is hardly available for therapeutics due to its limited pharmacodynamic profile and rapid clearance in clinical settings. In this study, we have developed a novel therapeutic approach with protein transduction domain (PTD) fused BMP-7 in micelle (mPTD-BMP-7) for long-range signaling . Contrary to rhBMP-7 targeting its cognate receptors, the nano-sized mPTD-BMP-7 is transduced into cells through an endosomal pathway and secreted to the exosome having active BMP-7. Further, transduced mPTD-BMP-7 successfully activates SMAD1/5/8 and inhibits the TGF-β-mediated epithelial-mesenchymal transition process and in an unilateral ureter obstruction model. To determine the clinical relevance of our strategy, we also developed an intra-arterial administration of mPTD-BMP-7 through renal artery in pigs. Interestingly, mPTD-BMP-7 through renal artery intervention effectively delivered into Bowman's space and inhibits unilateral ureter obstruction-induced renal fibrosis in pigs. Our results provide a novel therapeutic targeting TGF-β-mediated renal fibrosis and other organs as well as a clinically available approach for kidney.
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http://dx.doi.org/10.3389/fphar.2020.591275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751754PMC
November 2020

Soluble Urokinase-Type Plasminogen Activator Receptor, Changes of 24-Hour Blood Pressure, and Progression of Chronic Kidney Disease.

J Am Heart Assoc 2021 01 16;10(1):e017225. Epub 2020 Dec 16.

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

Background Soluble urokinase-type plasminogen activator receptor (suPAR) is associated with cardiovascular risks and poor renal outcomes. However, whether elevated suPAR levels are associated with 24-hour blood pressure patterns or kidney disease progression in patients with chronic kidney disease (CKD) is unclear. Methods and Results A total of 751 patients with CKD stage 1 to 5 were recruited from CMERC-HI (Cardiovascular and Metabolic Disease Etiology Research Center-High Risk) cohort study (2013-2018). The relationship of serum suPAR levels to 24-hour blood pressure parameters and CKD progression was analyzed. The median serum suPAR level was 1439.0 (interquartile range, 1026.2-2150.1) pg/mL, and the mean estimated glomerular filtration rate was 52.8±28.5 mL/min per 1.73 m at baseline. Patients with higher suPAR levels had significantly higher levels of office, 24-hour, daytime, and nighttime systolic blood pressure and nighttime diastolic blood pressure than those with lower suPAR levels. The highest suPAR tertile was associated with an increased risk of a reverse dipping pattern (odds ratio, 2.93; 95% CI, 1.27-6.76; =0.01). During a follow-up of 43.2 (interquartile range, 27.0-55.6) months, the CKD progression occurred in 271 (36.1%) patients. The highest suPAR tertile was significantly associated with higher risk of CKD progression than the lowest tertile (hazard ratio [HR], 2.09; 95% CI, 1.37-3.21; =0.001). When the relationship was reevaluated with respect to each dipping pattern (dipper, extreme dipper, nondipper, and reverse dipper), this association was consistent only in reverse dippers in whom the risk of CKD progression increased (HR, 1.43; 95% CI, 1.02-2.01; =0.03) with every 1-unit increase in serum suPAR levels. Conclusions Elevated suPAR levels are independently associated with CKD progression, and this association is prominent in reverse dippers.
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http://dx.doi.org/10.1161/JAHA.120.017225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955457PMC
January 2021

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

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

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

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

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

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

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

Association of Reproductive Lifespan Duration and Chronic Kidney Disease in Postmenopausal Women.

Mayo Clin Proc 2020 12 6;95(12):2621-2632. Epub 2020 Nov 6.

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

Objective: To investigate the relationship between endogenous estrogen exposure and renal function, the association of female reproductive life span duration (RLD) and chronic kidney disease (CKD) was analyzed in postmenopausal women.

Patients And Methods: Data were retrieved from the Korean Genome and Epidemiology Study, which was constructed from May 1, 2001, through December 25, 2017. A total of 50,338 and 3155 postmenopausal women were each included in the cross-sectional and longitudinal analyses. The RLD was determined by subtracting the age at menarche from the age at menopause. Participants were grouped into RLD quartiles. Participants with estimated glomerular filtration rates less than 60 mL/min/1.73 m were regarded to have CKD.

Results: In the cross-sectional analysis, mean ± SD age and estimated glomerular filtration rate were 56.3±4.9 years and 93.1±13.6 mL/min/1.73 m, respectively. Mean ± SD RLD was 34.2±4.0 years. A total of 765 of 50,338 (1.52%) women were found to have CKD. Logistic regression analysis revealed that the odds ratio for CKD was lower in groups with longer RLDs as compared with the shortest RLD group. In longitudinal analysis, postmenopausal women with normal kidney function were followed up for 9.7 years and incident CKD occurred in 221 of 3155 (7.00%) participants. Cox analysis revealed that the risk for CKD development was significantly lower in longer RLD groups. This finding was significant even after adjustments for confounding factors.

Conclusion: The risk for CKD was lower in women with longer RLDs. The amount of endogenous estrogen exposure could be a determining factor for renal function in postmenopausal women.
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http://dx.doi.org/10.1016/j.mayocp.2020.02.034DOI Listing
December 2020
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