Publications by authors named "Curie Ahn"

342 Publications

The Impact of Recipient and Donor Smoking in Living-Donor Kidney Transplantation: A Prospective Multicenter Cohort Study.

Transpl Int 2021 Oct 12. Epub 2021 Oct 12.

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

The smoking status of kidney transplant recipients and living donors has not been explored concurrently in a prospective study, and the synergistic adverse impact on outcomes remains uncertain. The self-reported smoking status and frequency were obtained from recipients and donors at the time of kidney transplantation in a prospective multicenter longitudinal cohort study (NCT02042963). Smoking status was categorized as "ever smoker" (current and former smokers collectively) or "never smoker." Among 858 eligible kidney transplant recipients and the 858 living donors, 389 (45.3%) and 241 (28.1%) were considered ever smokers at the time of transplant. During the median follow-up period of 6 years, the rate of death-censored graft failure was significantly higher in ever-smoker recipients than in never-smoker recipients (adjusted HR, 2.82; 95% CI 1.01-7.87; p=0.048). A smoking history of >20 pack-years was associated with a significantly higher rate of death-censored graft failure than a history of ≤20 pack-years (adjusted HR, 2.83; 95% CI 1.19-6.78; p=0.019). No donor smoking effect was found in terms of graft survival. The smoking status of the recipients and donors or both did not affect the rate of biopsy-proven acute rejection, major adverse cardiac events, all-cause mortality, or posttransplant diabetes mellitus. Taken together, the recipient's smoking status before kidney transplantation is dose-dependently associated with impaired survival.
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http://dx.doi.org/10.1111/tri.14137DOI Listing
October 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

Association Between Intraoperative Arterial Hypotension and Postoperative Delirium After Noncardiac Surgery: A Retrospective Multicenter Cohort Study.

Anesth Analg 2021 Sep 13. Epub 2021 Sep 13.

Department of Anesthesiology, Montefiore Medical Center, Albert Einstein College of Medicine, New York, New York.

Background: It is unclear whether intraoperative arterial hypotension is associated with postoperative delirium. We hypothesized that intraoperative hypotension within a range frequently observed in clinical practice is associated with increased odds of delirium after surgery.

Methods: Adult noncardiac surgical patients undergoing general anesthesia at 2 academic medical centers between 2005 and 2017 were included in this retrospective cohort study. The primary exposure was intraoperative hypotension, defined as the cumulative duration of an intraoperative mean arterial pressure (MAP) <55 mm Hg, categorized into and short (<15 minutes; median [interquartile range {IQR}], 2 [1-4] minutes) and prolonged (≥15 minutes; median [IQR], 21 [17-31] minutes) durations of intraoperative hypotension. The primary outcome was a new diagnosis of delirium within 30 days after surgery. In secondary analyses, we assessed the association between a MAP decrease of >30% from baseline and postoperative delirium. Multivariable logistic regression adjusted for patient- and procedure-related factors, including demographics, comorbidities, and markers of procedural severity, was used.

Results: Among 316,717 included surgical patients, 2183 (0.7%) were diagnosed with delirium within 30 days after surgery; 41.7% and 2.6% of patients had a MAP <55 mm Hg for a short and a prolonged duration, respectively. A MAP <55 mm Hg was associated with postoperative delirium compared to no hypotension (short duration of MAP <55 mm Hg: adjusted odds ratio [ORadj], 1.22; 95% confidence interval [CI], 1.11-1.33; P < .001 and prolonged duration of MAP <55 mm Hg: ORadj, 1.57; 95% CI, 1.27-1.94; P < .001). Compared to a short duration of a MAP <55 mm Hg, a prolonged duration of a MAP <55 mm Hg was associated with greater odds of postoperative delirium (ORadj, 1.29; 95% CI, 1.05-1.58; P = .016). The association between intraoperative hypotension and postoperative delirium was duration-dependent (ORadj for every 10 cumulative minutes of MAP <55 mm Hg: 1.06; 95% CI, 1.02-1.09; P =.001) and magnified in patients who underwent surgeries of longer duration (P for interaction = .046; MAP <55 mm Hg versus no MAP <55 mm Hg in patients undergoing surgery of >3 hours: ORadj, 1.40; 95% CI, 1.23-1.61; P < .001). A MAP decrease of >30% from baseline was not associated with postoperative delirium compared to no hypotension, also when additionally adjusted for the cumulative duration of a MAP <55 mm Hg (short duration of MAP decrease >30%: ORadj, 1.13; 95% CI, 0.91-1.40; P = .262 and prolonged duration of MAP decrease >30%: ORadj, 1.19; 95% CI, 0.95-1.49; P = .141).

Conclusions: In patients undergoing noncardiac surgery, a MAP <55 mm Hg was associated with a duration-dependent increase in odds of postoperative delirium. This association was magnified in patients who underwent surgery of long duration.
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http://dx.doi.org/10.1213/ANE.0000000000005739DOI Listing
September 2021

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

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

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

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

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

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

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

Persistent Resistant Hypertension Has Worse Renal Outcomes in Chronic Kidney Disease than that Resolved in Two Years: Results from the KNOW-CKD Study.

J Clin Med 2021 Sep 3;10(17). Epub 2021 Sep 3.

Department of Internal Medicine, Chonnam National University Medical School, Gwangju 61469, Korea.

Apparent treatment-resistant hypertension (ATRH) is closely related to chronic kidney disease (CKD); however, the long-term outcomes and the effects of improvement in ATRH in patients with CKD are not well understood. We evaluated the relationship between the persistence of ATRH and the progression of CKD. This cohort study enrolled 1921 patients with CKD. ATRH was defined as blood pressure above 140/90 mmHg and intake of three different types of antihypertensive agents, including diuretics, or intake of four or more different types of antihypertensive agents, regardless of blood pressure. We defined ATRH subgroups according to the ATRH status at the index year and two years later. The prevalence of ATRH at baseline was 14.0%. The presence of ATRH at both time points was an independent risk factor for end-point renal outcome (HR, 1.41; 95% CI, 1.04-1.92; = 0.027). On the other hand, the presence of ATRH at any one of the time points was not statistically significant. In conclusion, persistent ATRH is more important for the prognosis of renal disease than the initial ATRH status. Continuous follow-up and appropriate treatment are important to improve the renal outcomes.
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http://dx.doi.org/10.3390/jcm10173998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432533PMC
September 2021

Greater adherence to the dietary approaches to stop hypertension dietary pattern is associated with preserved muscle strength in patients with autosomal dominant polycystic kidney disease: a single-center cross-sectional study.

Nutr Res 2021 09 25;93:99-110. Epub 2021 Jul 25.

Department of Internal Medicine, Seoul National University Hospital, Seoul, 03080, Republic of Korea. Electronic address:

The present study aimed to determine whether certain diets lower the risk of low muscle strength in patients with autosomal dominant polycystic kidney disease (ADPKD). In this cross-sectional study, outpatient ADPKD patients were enrolled from a tertiary care hospital. Muscle strength was assessed on the basis of handgrip strength (HGS), and dietary pattern indices were calculated using dietary intake data. Among the 68 participants included in this study, 19 (27.9%) had low HGS. Cystatin C concentrations were significantly higher in all participants, and in women in the low compared to the normal HGS group in the unadjusted analyses (P = 0.004). Among analyzed dietary pattern indices, the Dietary Approaches to Stop Hypertension (DASH) score was lower, for all participants and men, in the low compared to the normal HGS group (P < 0.05). Especially, the component score for whole grains of the DASH score was significantly lower in men in the low compared to the normal HGS group in unadjusted analyses. The DASH score was positively correlated with HGS in men (r = 0.387, P = 0.046). In addition, logistic regression analysis showed that the DASH score was negatively associated with low HGS, for all participants (odds ratio = 0.851, P = 0.049) and men (odds ratio = 0.716, P = 0.043), after adjusting for age, sex, and body weight. These findings suggest that the DASH dietary pattern may promote the preservation of muscle strength in ADPKD patients. The DASH diet can be considered as a nutritional strategy to maintain muscle strength and prevent sarcopenia in ADPKD patients.
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http://dx.doi.org/10.1016/j.nutres.2021.07.006DOI 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

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

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

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

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

Synergistic impact of pre-sensitization and delayed graft function on allograft rejection in deceased donor kidney transplantation.

Sci Rep 2021 08 9;11(1):16095. Epub 2021 Aug 9.

Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, Seoul, South Korea.

The aim of this study is to investigate whether or not delayed graft function (DGF) and pre-transplant sensitization have synergistic adverse effects on allograft outcome after deceased donor kidney transplantation (DDKT) using the Korean Organ Transplantation Registry (KOTRY) database, the nationwide prospective cohort. The study included 1359 cases between May 2014 and June 2019. The cases were divided into 4 subgroups according to pre-sensitization and the development of DGF post-transplant [non-pre-sensitized-DGF(-) (n = 1097), non-pre-sensitized-DGF(+) (n = 127), pre-sensitized-DGF(-) (n = 116), and pre-sensitized-DGF(+) (n = 19)]. We compared the incidence of biopsy-proven allograft rejection (BPAR), time-related change in allograft function, allograft or patient survival, and post-transplant complications across 4 subgroups. The incidence of acute antibody-mediated rejection (ABMR) was significantly higher in the pre-sensitized-DGF(+) subgroup than in other 3 subgroups. In addition, multivariable cox regression analysis demonstrated that pre-sensitization combined with DGF is an independent risk factor for the development of acute ABMR (hazard ratio 4.855, 95% confidence interval 1.499-15.727). Moreover, DGF and pre-sensitization showed significant interaction (p-value for interaction = 0.008). Pre-sensitization combined with DGF did not show significant impact on allograft function, and allograft or patient survival. In conclusion, the combination of pre-sensitization and DGF showed significant synergistic interaction on the development of allograft rejection after DDKT.
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http://dx.doi.org/10.1038/s41598-021-95327-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352860PMC
August 2021

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

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

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

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

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

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

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

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

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

Kidney Res Clin Pract 2021 Sep 1;40(3):472-483. 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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476299PMC
September 2021

Serum uric acid is associated with coronary artery calcification in early chronic kidney disease: a cross-sectional study.

BMC Nephrol 2021 Jul 4;22(1):247. Epub 2021 Jul 4.

Division of Nephrology, Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Chong No Gu, 03080, Seoul, Korea.

Background: Although uric acid (UA) is regarded as a risk factor for cardiovascular disease, whether UA is an independent risk factor contributing to coronary artery calcification in chronic kidney disease (CKD) is not well known. We evaluated whether UA level is associated with coronary artery calcium (CAC) score in a predialysis CKD cohort.

Methods: A total of 1,350 subjects who underwent coronary computed tomography as part of the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease were analysed. We conducted a logistic regression analysis to evaluate the association between UA and the presence of CAC.

Results: CAC was detected in 705 (52.2 %) patients, and the level of UA was significantly higher in CAC > 0 patients. UA showed a positive relationship with CAC > 0 in age- and sex-adjusted logistic regression analysis (Odds ratio (OR) 1.11, 95 % confidence interval (CI) 1.04-1.19, P = 0.003). However, UA showed no association with CAC > 0 in multivariate analysis. Further analysis showed that UA showed a positive association with CAC > 0 only in estimated glomerual filtration rate (eGFR) > 60 ml/min/1.73 m (OR 1.23, 95 % CI 1.02-1.49, P = 0.036) but not in eGFR 30-59 ml/min/1.73 m (OR 0.92, 95 % CI 0.78-1.08, P = 0.309) or < 30 ml/min/1.73 m (OR 0.92, 95 % CI 0.79-1.08, P = 0.426).

Conclusions: UA level was significantly associated with CAC in early CKD, but not in advanced CKD.
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http://dx.doi.org/10.1186/s12882-021-02463-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255010PMC
July 2021

Polypharmacy and the Progression of Chronic Kidney Disease: Korean Cohort Study for Outcome in Patients with Chronic Kidney Disease.

Kidney Blood Press Res 2021 4;46(4):460-468. Epub 2021 Jun 4.

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

Introduction: The renal hazard of polypharmacy has never been evaluated in predialysis chronic kidney disease (CKD) patients.

Objective: We aimed to analyze the renal hazard of polypharmacy in predialysis CKD patients with stage 1-5.

Method: The data of 2,238 patients from a large-scale multicenter prospective Korean study (2011-2016), excluding 325 patients with various missing data, were reviewed. Polypharmacy was defined as taking 6 or more medications at the time of enrollment; renal events were defined as a ≥50% decrease in kidney function from baseline values, doubling of the serum creatinine levels, or initiation of renal replacement treatment. Hazard ratio (HR) and 95% confidence interval (CI) were calculated using Cox proportional-hazard regression analysis.

Results: Of the 1,913 patients, the mean estimated glomerular filtration rate was 53.6 mL/min/1.73 m2. The mean medication count was 4.1, and the prevalence of polypharmacy was 27.1%. During the average period of 3.6 years, 520 patients developed renal events (27.2%). Although increased medication counts were associated with increased renal hazard with HR (95% CI) of 1.056 (1.007-1.107, p = 0.025), even after adjusting for various confounders, adding comorbidity score and kidney function nullified the statistical significance. In mediation analysis, 55.6% (p = 0.016) of renal hazard in increased medication counts was mediated by the kidney function, and there was no direct effect of medication counts on renal event development. In subgroup analysis, the renal hazard of the medication counts was evident only in stage 1-3 of CKD patients (p for interaction = 0.014).

Conclusions: We cannot identify the direct renal hazard of multiple medications, and most of the potential renal hazard was derived from intimate relationship with disease burden and kidney function.
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http://dx.doi.org/10.1159/000516029DOI Listing
June 2021

Low serum adiponectin level is associated with better physical health-related quality of life in chronic kidney disease.

Sci Rep 2021 05 25;11(1):10928. Epub 2021 May 25.

Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-Gu, Seoul, 03181, Republic of Korea.

Hyperadiponectemia is paradoxically associated with renal disease progression and mortality in chronic kidney disease (CKD). Its association with health-related quality of life (HR-QOL) is unknown. This study aimed to verify the association between adiponectin and HR-QOL in Korean pre-dialysis CKD cohort. This cross-sectional study analyzed 1551 pre-dialysis CKD patients from KNOW-CKD (KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease). Participants were categorized into three tertiles (T1-T3) according to adiponectin levels. HR-QOL was assessed using SF-36. High physical component summary (PCS) and mental component summary (MCS) were defined as highest quartile of each score. Multivariate logistic regression was used to analyze odds ratio (OR) and 95% confidence interval (CI) for high PCS and MCS. Prevalence of high PCS were 33.3%, 27.5%, and 17.0% and that of high MCS were 31.7%, 24.8%, and 21.3% for T1, T2, and T3 (both p for trend < 0.001). The adjusted OR [95% CI] of T1 and T2 in reference to T3 were 1.56 [1.09-2.23] and 1.19 [0.85-1.68] for high PCS and 1.19 [0.85-1.68] and 0.94 [0.68-1.29] for high MCS. Serum adiponectin level was inversely associated with physical HR-QOL in Korean pre-dialysis CKD patients. This relationship was independent of various cardiovascular risk factors.
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http://dx.doi.org/10.1038/s41598-021-90339-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149720PMC
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

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

Rapid Weight Change Over Time Is a Risk Factor for Adverse Outcomes in Patients With Predialysis Chronic Kidney Disease: A Prospective Cohort Study.

J Ren Nutr 2021 Mar 22. Epub 2021 Mar 22.

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

Objective: Both obesity and being underweight are risk factors for adverse outcomes in chronic kidney disease (CKD) patients. However, the effects of longitudinal weight changes on patients with predialysis CKD have not yet been studied. In this study, we analyzed the effects of weight change over time on the adverse outcomes in predialysis CKD population.

Methods: Longitudinal data from a multicenter prospective cohort study (KNOW-CKD) were analyzed. In a total of 2,022 patients, the percent weight change per year were calculated using regression analysis and the study subjects were classified into five categories: group 1, ≤ -5%/year; group 2, -5< to ≤ -2.5%/year; group 3, -2.5< to <2.5%/year; group 4, 2.5≤ < 5%/year; and group 5, ≥5%/year. The incidences of end-stage renal disease (ESRD) and the composite outcome of cardiovascular disease (CVD) and death were calculated in each group and compared to group 3 as reference.

Results: During a median 4.4 years of follow-up, 414 ESRD, and 188 composite of CVD and mortality events occurred. Both weight gain and loss were independent risk factors for adverse outcomes. There was a U-shaped correlation between the degree of longitudinal weight change and ESRD (hazard ratio 3.61, 2.15, 1.86 and 3.66, for group 1, 2, 4 and 5, respectively) and composite of CVD and death (hazard ratio 2.92, 2.15, 1.73 and 2.54, respectively), when compared to the reference group 3. The U-shape correlation was most prominent in the subgroup of estimated glomerular filtration rate <45 mL/min/1.73 m.

Conclusion: Both rapid weight gain and weight loss are associated with high risk of adverse outcomes, particularly in the advanced CKD.
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http://dx.doi.org/10.1053/j.jrn.2021.01.026DOI Listing
March 2021

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

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

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

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

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

J Nephrol 2021 Mar 23. Epub 2021 Mar 23.

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

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

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

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

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

Clinical Factors Associated with the Risk of Intracranial Aneurysm Rupture in Autosomal Dominant Polycystic Kidney Disease.

Cerebrovasc Dis 2021 11;50(3):339-346. Epub 2021 Mar 11.

Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea,

Background: The occurrence of intracranial aneurysms is higher in patients with autosomal dominant polycystic kidney disease (ADPKD) than in the healthy population. However, research concerning the factors related to the risk of intracranial aneurysm rupture in patients with ADPKD is still insufficient.

Objectives: The aim of the study was to investigate the prevalence of intracranial aneurysms and aneurysmal subarachnoid hemorrhage (SAH) and to analyze the systemic factors associated with high-risk aneurysms in patients with ADPKD.

Methods: We screened patients who underwent cerebral angiography between January 2007 and May 2017 in the ADPKD registry. Patients were examined for the presence of intracranial aneurysms and subsequently reclassified into 3 groups based on the risk of aneurysmal rupture: the aneurysm-negative (group 1), low-risk aneurysm (group 2), or high-risk aneurysm (group 3). Various systemic factors were compared, and independent factors associated with high-risk aneurysms were analyzed.

Results: Among the 926 patients, 148 (16.0%) had intracranial aneurysms and 11 (1.2%) had previous aneurysmal SAH. Patients with intracranial aneurysms were further classified into group 2 (low-risk aneurysms, 15.5%) or group 3 (high-risk aneurysms, 84.5%). Age (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01-1.05, p = 0.004), female sex (OR 3.13, 95% CI 1.94-5.0 6, p < 0.001), dolichoectasia (OR 8.57, 95% CI 1.53-48.17, p = 0.015), and mitral inflow deceleration time (DT) (OR 1.01, 95% CI 1.00-1.01, p = 0.046) were independently associated with high-risk aneurysms, whereas hypercholesterolemia (OR 0.46, 95% CI 0.29-0.72, p = 0.001) was negatively associated.

Conclusion: In the present study among patients with ADPKD, the prevalence of intracranial aneurysms and aneurysmal SAH was 16 and 1.2%, respectively. Age, female sex, dolichoectasia, and mitral inflow DT were positively associated with high-risk aneurysms, whereas hypercholesterolemia was negatively associated. A subsequent large-scaled longitudinal study is needed to define the plausibility of the clinical parameters.
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http://dx.doi.org/10.1159/000513709DOI Listing
August 2021

Presence of a survival benefit of HLA-incompatible living donor kidney transplantation compared to waiting or HLA-compatible deceased donor kidney transplantation with a long waiting time.

Kidney Int 2021 07 26;100(1):206-214. Epub 2021 Feb 26.

Transplantation Center, Seoul National University Hospital, Seoul, Republic of Korea; Department of Surgery, Seoul National University Hospital, Seoul, Republic of Korea. Electronic address:

HLA-incompatible living donor kidney transplantation (LDKT) is one of efforts to increase kidney transplantation opportunity for sensitized patients with kidney failure. However, there are conflicting reports for outcomes of HLA-incompatible kidney transplantation compared to patients who wait for HLA-compatible deceased donor kidney transplantation (DDKT) in the United States and United Kingdom. Waiting for an HLA-compatible DDKT is relatively disadvantageous in Korea, because the average waiting time is more than five years. To study this further, we compared outcomes of HLA-incompatible LDKT with those who wait for HLA-compatible DDKT in Korea. One hundred eighty nine patients underwent HLA-incompatible LDKT after desensitization between 2006 and 2018 in two Korean hospitals (42 with a positive complement-dependent cytotoxicity cross-match, 89 with a positive flow cytometric cross-match, and 58 with a positive donor-specific antibody with negative cross-match). The distribution of matched variables was comparable between the HLA-incompatible LDKT group and the matched control groups (waiting-list-only group; and the waiting-list-or-HLA-compatible-DDKT groups; 930 patients each). The HLA-incompatible LDKT group showed a significantly better patient survival rate compared to the waiting-list-only group and the waiting-list-or-HLA-compatible-DDKT groups. Furthermore, the HLA-incompatible LDKT group showed a significant survival benefit as compared with the matched groups at all strength of donor-specific antibodies. Thus, HLA-incompatible LDKT could have a survival benefit as compared with patients who were waitlisted for HLA-compatible DDKT or received HLA-compatible DDKT in Korea. This suggests that HLA-incompatible LDKT as a good option for sensitized patients with kidney failure in countries with prolonged waiting times for DDKT.
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http://dx.doi.org/10.1016/j.kint.2021.01.027DOI Listing
July 2021

Soluble α-klotho anchors TRPV5 to the distal tubular cell membrane independent of FGFR1 by binding TRPV5 and galectin-1 simultaneously.

Am J Physiol Renal Physiol 2021 04 22;320(4):F559-F568. Epub 2021 Feb 22.

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

Hypercalciuria is one of the early manifestations of diabetic nephropathy (DN). This is partially due to a decrease in the expression of renal transient receptor potential vanilloid type 5 (TRPV5), which is responsible for renal Ca reabsorption. Soluble klotho has been previously determined to increase TRPV5 by cleaving sialic acid, causing TRPV5 to bind to membrane protein galectin-1. However, a recent study showed that soluble klotho binds to α2-3-sialyllactose, where sialic acid is located, on TRPV5, rather than cleave it. Here, we report that soluble klotho tethers TRPV5 on the membrane by binding both TRPV5 and galectin-1, thereby protecting membrane TRPV5 from diabetes-induced endocytosis. In the present study, we injected recombinant soluble α-klotho protein (rKL) into and mice for 8 wk and collected urine and kidneys. We administered rKL, AZD4547 [fibroblast growth factor (FGF) receptor type 1 inhibitor], and OTX008 (galectin-1 inhibitor) to cultured mouse distal tubular cells with or without 30 mM high-glucose (HG) exposure. mice showed increased renal Ca excretion and decreased renal TRPV5 expression. rKL treatment reversed this change. In vitro, TRPV5 expression in distal tubular cells decreased under HG conditions, and rKL successfully upregulated TRPV5 with or without FGF23. Also, immunofluorescence showed colocalization of klotho, TRPV5, and galectin-1 in distal tubule cells, suggesting that klotho binds to both TRPV5 and galectin-1. Moreover, when both FGF receptor type 1 and galectin-1 were inhibited, rKL failed to increase TRPV5 under HG conditions. Our results indicate that soluble klotho prevents TRPV5 from degradation and subsequent diabetes-induced endocytosis by anchoring TRPV5 through binding with both TRPV5 and galectin-1. Soluble α-klotho anchors transient receptor potential vanilloid type 5 (TRPV5) on the apical membrane of the distal tubule by binding both TRPV5 and a membrane-abundant protein, galectin-1. This newly discovered mechanism works even when fibroblast growth factor (FGF)23 signaling is inhibited by treatment with FGF receptor type 1 inhibitor. Therefore, we identified how soluble α-klotho increases TRPV5 without FGF23. We confirmed this mechanism by observing that soluble α-klotho fails to enhance TRPV5 when both FGF receptor type 1 and galectin-1 are inhibited.
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http://dx.doi.org/10.1152/ajprenal.00044.2021DOI Listing
April 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

Genetic identification of inherited cystic kidney diseases for implementing precision medicine: a study protocol for a 3-year prospective multicenter cohort study.

BMC Nephrol 2021 01 6;22(1). Epub 2021 Jan 6.

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

Background: Inherited cystic kidney disease is a spectrum of disorders in which clusters of renal cysts develop as the result of genetic mutation. The exact methods and pipelines for defining genetic mutations of inherited cystic kidney disease are not clear at this point. This 3-year, prospective, multicenter, cohort study was designed to set up a cohort of Korean patients with inherited cystic kidney disease, establish a customized genetic analysis pipeline for each disease subtype, and identify modifying genes associated with the severity of the disease phenotype.

Methods/design: From May 2020 to May 2022, we aim to recruit 800 patients and their family members to identify pathogenic mutations. Patients with more than 3 renal cysts in both kidneys are eligible to be enrolled. Cases of simple renal cysts and acquired cystic kidney disease that involve cyst formation as the result of renal failure will be excluded from this study. Demographic, laboratory, and imaging data as well as family pedigree will be collected at baseline. Renal function and changes in total kidney volume will be monitored during the follow-up period. Genetic identification of each case of inherited cystic kidney disease will be performed using a targeted gene panel of cystogenesis-related genes, whole exome sequencing (WES) and/or family segregation studies. Genotype-phenotype correlation analysis will be performed to elucidate the genetic effect on the severity of the disease phenotype.

Discussion: This is the first nationwide cohort study on patients with inherited cystic kidney disease in Korea. We will build a multicenter cohort to describe the clinical characteristics of Korean patients with inherited cystic kidney disease, elucidate the genotype of each disease, and demonstrate the genetic effects on the severity of the disease phenotype.

Trial Registration: This cohort study was retrospectively registered at the Clinical Research Information Service ( KCT0005580 ) operated by the Korean Center for Disease Control and Prevention on November 5th, 2020.
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http://dx.doi.org/10.1186/s12882-020-02207-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786983PMC
January 2021

Epidemiology, risk factors, and clinical impact of early post-transplant infection in older kidney transplant recipients: the Korean organ transplantation registry study.

BMC Geriatr 2020 12 2;20(1):519. Epub 2020 Dec 2.

Division of Nephrology, Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul, Republic of Korea.

Background: As in younger recipients, post-transplant infection is a frequent and devastating complication after kidney transplantation (KT) in older recipients. However, few studies have analyzed characteristics of post-transplant infection in older kidney recipients. In this study of a nation-wide cohort of older kidney recipients, we investigated the current epidemiology, risk factors, and clinical impacts of early post-transplant infection, which was defined as infectious complications requiring hospitalization within the first 6 months after KT.

Methods: Three thousand seven hundred thirty-eight kidney recipients registered in the Korean Organ Transplantation Registry between 2014 and 2017 were enrolled. Recipients were divided into two groups, younger (n = 3081) and older (n = 657), with a cutoff age of 60 years. We observed characteristics of early post-transplant infection, and investigated risk factors for the development of infection. We also analyzed the association of early post-transplant infection with clinical outcomes including cardiac events, rejection, graft loss, and all-cause mortality.

Results: The incidence of early post-transplant infection was more frequent in older recipients (16.9% in younger group and 22.7% in older group). Bacteria were the most common causative pathogens of early post-transplant infection, and the most frequent site of infection was the urinary tract in both older and younger recipients. Older recipients experienced more mycobacterial infections, co-infections, and multiple site infections compared with younger recipients. In older recipients, female sex (HR 1.398, 95% CI 1.199-1.631), older donor age (HR 1.010, 95% CI 1.004-1.016), longer hospitalization after KT (HR 1.010, 95% CI 1.006-1.014), and experience of acute rejection (HR 2.907, 95% CI 2.471-3.419) were independent risk factors for the development of early post-transplant infection. Experiencing infection significantly increases the incidence of rejection, graft loss, and all-cause mortality.

Conclusion: Our results illustrate current trends, risk factors, and clinical impacts of early post-transplant infection after KT in older recipients. Considering the poor outcomes associated with early post-transplant infection, careful screening of recipients at high risk for infection and monitoring of recipients who experience infection are advised. In addition, since older recipients exhibit different clinical characteristics than younger recipients, further studies are needed to establish effective strategies for treating older recipients.
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http://dx.doi.org/10.1186/s12877-020-01859-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709316PMC
December 2020

Outcomes of ABO-incompatible kidney transplantation in older patients: a national cohort study.

Transpl Int 2021 02 31;34(2):290-301. Epub 2020 Dec 31.

Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea.

Background: Outcomes of ABO-incompatible living donor kidney transplantation (ABOi LDKT) in older individuals have not been established.

Methods: This multicentric observational study, using data from the Korean Organ Transplantation Registry database, included 634 older patients (≥60 years) undergoing kidney transplantation. We compared clinical outcomes of ABOi LDKT (n = 80) with those of ABO-compatible LDKT (ABOc LDKT, n = 222) and deceased donor kidney transplantation (DDKT, n = 332) in older patients.

Results: Death-censored graft survival was similar between the three groups (P = 0.141). Patient survival after ABOi LDKT was similar to that after ABOc LDKT (P = 0.489) but higher than that after DDKT (P = 0.038). In multivariable analysis, ABOi LDKT was not risk factor (hazard ratio [HR] 1.73, 95% confidence interval [CI] 0.29-10.38, P = 0.548), while DDKT was significant risk factor (HR 3.49, 95% CI 1.01-12.23, P = 0.049) for patient survival. Although ABOi LDKT showed higher biopsy-proven acute rejection than ABOc LDKT, the difference was not significant after adjustment with covariates. However, ABOi LDKT was significant risk factor for infection (HR 1.66, 95% CI 1.12-2.45, P = 0.012).

Conclusions: In older patients, ABOi LDKT was not inferior to ABOc LDKT and was superior to DDKT for patient survival. ABOi LDKT can be recommended for older patients, rather than waiting for DDKT.
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http://dx.doi.org/10.1111/tri.13794DOI Listing
February 2021
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