Potential benefits of hormone replacement therapy on cardiovascular and kidney outcomes in postmenopausal women with chronic kidney disease.

BACKGROUND: Hormone replacement therapy (HRT) is recommended for alleviating vasomotor symptoms or preventing bone loss in postmenopausal women. This study aimed to investigate the impact of hormone replacement therapy on major adverse cardiovascular events, kidney failure, and mortality in women with chronic kidney disease (CKD). METHODS: This population-based cohort study analyzed data from the National Cancer Screening Program and the national health examination of South Korea. Data on postmenopausal women were extracted from the 2009 National Cancer Screening Program. Among these postmenopausal women, those with CKD without kidney replacement therapy were selected through a national health examination from 2009 to 2013. The study outcomes were the risks of major adverse cardiovascular events, kidney failure, and all-cause mortality according to hormone replacement therapy. RESULTS: A total of 768,279 postmenopausal women with CKD were enrolled in this study; of these women, 13.8% (N = 106,052) had a history of hormone replacement therapy. The user and non-user groups differed with respect to baseline characteristics, with the latter being older and having risk factors for cardiovascular disease. After adjustment for confounding factors, the group exposed to hormone replacement therapy showed lower risks of major adverse cardiovascular events, kidney failure, and all-cause mortality. CONCLUSIONS: This study suggests the potential benefits of hormone replacement therapy in postmenopausal women with CKD and highlighted its potential advantages for cardiovascular and kidney outcomes.

Medical costs in the peridiagnosis period of various biopsy-confirmed kidney diseases in South Korea.

Background: In-depth investigation is imperative to scrutinize medical costs associated with the periods before and after biopsies for diverse kidney diseases in South Korea. Long-term epidemiological data, including follow-up information, is essential for comparing risks linked to various kidney diseases and their adverse outcomes. Methods: Patients diagnosed with glomerulonephritis (GN), tubulointerstitial nephritis (TIN), and acute tubular necrosis (ATN) at Seoul National University Hospital between 2012 and 2018 were included. We linked the prospective cohort data of biopsy-confirmed kidney disease patients (KORNERSTONE) from our study hospital to the national claims database of Korea, covering both medical events and insured costs. We analyzed medical costs during the periods before and after kidney biopsies, categorized by specific diagnoses, and delved into adverse prognostic outcomes. Results: Our study involved 1,390 patients with biopsy-confirmed GN, TIN, and ATN. After diagnosis, monthly average medical costs increased for most kidney diseases, excluding membranous nephropathy, Henoch-Schönlein purpura, and amyloidosis. The most substantial yearly average medical cost increase was observed in the ATN, acute TIN (ATIN), and chronic TIN (CTIN) groups. Costs rose for most kidney disease categories, except for amyloidosis. Higher myocardial infarction, stroke, and death rates were noted in CTIN, ATIN, and ATN compared to other types, with lupus nephritis displaying the highest end-stage kidney disease progression rate. Conclusion: In South Korea, medical costs for the majority of GN, TIN, and ATN patients increased following kidney biopsy diagnosis. This current data provides valuable epidemiological insights into the medical costs and prognosis of various kidney diseases in the country.

Recurrent and De Novo Focal Segmental Glomerulosclerosis After Kidney Transplantation: Comparison of Clinical Features and Transplant Outcomes.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a notable subtype of glomerulonephritis in kidney transplantation, often resulting in graft failure. Yet, research comparing transplant outcomes between de novo and recurrent FSGS is scarce. This study aims to compare clinical features and transplant outcomes between these two categories. METHODS: This retrospective study enrolled 773 kidney transplant recipients from two centers between January 2008 and October 2021. Patients diagnosed with FSGS through graft kidney biopsy were included. They were categorized into two groups based on the time of FSGS occurrence and results of native kidney biopsy: the recurrent FSGS group and the de novo FSGS group. RESULTS: Of 773 kidney transplant patients, 24 had primary FSGS-causing end-stage renal disease. During a median 65-month follow-up, 5 of these patients developed recurrent FSGS (incidence: 26.3%). Among 749 patients with other kidney diseases causing end-stage renal disease, 9 had de novo FSGS (incidence: 1.2%). In the recurrent FSGS group, 2 out of 5 patients experienced graft failure, with no deaths or acute rejections. Similarly, in the de novo FSGS group, 3 out of 9 patients experienced graft failure, with no deaths or acute rejections. Kaplan-Meier analysis showed slower graft loss in de novo FSGS, resulting in a higher graft survival rate compared to recurrent FSGS (probability of graft survival, 60% vs 33.3%, P = .036). CONCLUSIONS: Graft loss progresses more slowly in de novo FSGS compared to recurrent FSGS, resulting in a higher long-term graft survival rate in de novo FSGS than in recurrent FSGS.

Risk of mortality and cause of death according to kidney function parameters: a nationwide observational study in Korea.

BACKGROUND: Further study is warranted to determine the association between estimated glomerular filtration rate (eGFR) or albuminuria and the risk of death from diverse causes. METHODS: We screened >10 million general health screening examinees who received health examinations conducted in 2009 using the claims database of Korea. After the exclusion of those previously diagnosed with renal failure and those with missing data, 9,917,838 individuals with available baseline kidney function measurements were included. The primary outcome was mortality and cause-specific death between 2009 and 2019 identified through death certificates based on the diagnostic codes of International Classification of Diseases, 10th revision. Multivariable Cox regression analysis adjusted for various clinicodemographic and social characteristics was used to assess mortality risk. RESULTS: The hazard ratio of death was significantly high in both the eGFR <60 mL/min/1.73 m2 and in the eGFR ≥120 mL/ min/1.73 m2 groups in univariable and multivariable regression analyses when compared to those within the reference range (eGFR of 90-120 mL/min/1.73 m2). The results were similar for death by cardiovascular, cancer, infection, endocrine, respiratory, and digestive causes. We also found that albuminuria was associated with higher risk of death regardless of eGFR range, and those in the higher categories of dipstick albuminuria showed higher risk. CONCLUSION: We reconfirmed the significant association between eGFR, albuminuria, and mortality. Healthcare providers should keep in mind that albuminuria and decreased eGFR as well as kidney hyperfiltration are independent predictors of mortality.

Impact of nonspecific allograft biopsy findings in symptomatic kidney transplant recipients.

A for-cause biopsy is performed to diagnose the cause of allograft dysfunction in kidney transplantation. We occasionally encounter ambiguous biopsy results in symptomatic kidney transplant recipients. Yet, the allograft survival outcome in symptomatic recipients with nonspecific allograft biopsy findings remains unclear. The purpose of this study was to analyze the impact of nonspecific for-cause biopsy findings in symptomatic kidney transplant recipients. We retrospectively collected records from 773 kidney transplant recipients between January 2008 and October 2021. The characteristics of transplant recipients with nonspecific findings in the first for-cause biopsy were analyzed. Nonspecific allograft biopsy findings were defined as other biopsy findings excluding rejection, borderline rejection, calcineurin inhibitor toxicity, infection, glomerulonephritis, and diabetic nephropathy. The graft outcome was compared between recipients who had never undergone a for-cause biopsy and those who had a first for-cause biopsy with nonspecific findings. The graft survival in recipients with nonspecific for-cause biopsy findings was comparable to that in recipients who did not require the for-cause biopsy before and after propensity score matching. Even in symptomatic kidney transplant recipients, nonspecific allograft biopsy findings might not be a poor prognostic factor for allograft survival compared to recipients who did not require the for-cause biopsy.

Long-term ozone exposure and mortality in patients with chronic kidney disease: a large cohort study.

BACKGROUND: Epidemiologic studies on the effects of long-term exposure to ozone (O3) have shown inconclusive results. It is unclear whether to O3 has an effect on chronic kidney disease (CKD). We investigated the effects of O3 on mortality and renal outcome in CKD. METHODS: We included 61,073 participants and applied Cox proportional hazards models to examine the effects of ozone on the risk of end-stage renal disease (ESRD) and mortality in a two-pollutants model adjusted for socioeconomic status. We calculated the concentration of ozone exposure one year before enrollment and used inverse distance weighting (IDW) for interpolation, where the exposure was evenly distributed. RESULTS: In the single pollutant model, O3 was significantly associated with an increased risk of ESRD and all-cause mortality. Based on the O3 concentration from IDW interpolation, this moving O3 average was significantly associated with an increased risk of ESRD and all-cause mortality. In a two-pollutants model, even after we adjusted for other measured pollutants, nitrogen dioxide did not attenuate the result for O3. The hazard ratio (HR) value for the district-level assessment is 1.025 with a 95% confidence interval (CI) of 1.014-1.035, while for the point-level assessment, the HR value is 1.04 with a 95% CI of 1.035-1.045. The impact of ozone on ESRD, hazard ratio (HR) values are, 1.049(95%CI: 1.044-1.054) at the district unit and 1.04 (95%CI: 1.031-1.05) at the individual address of the exposure assessment. The ozone hazard ratio for all-cause mortality was 1.012 (95% confidence interval: 1.008-1.017) for administrative districts and 1.04 (95% confidence interval: 1.031-1.05) for individual addresses. CONCLUSIONS: This study suggests that long-term ambient O3 increases the risk of ESRD and mortality in CKD. The strategy to decrease O3 emissions will substantially benefit health and the environment.

Non-indicated initiation of proton pump inhibitor and risk of adverse outcomes in patients with underlying chronic kidney disease: a nationwide, retrospective, cohort study.

OBJECTIVE: Evidence related to the risk of kidney damage by proton pump inhibitor (PPI) initiation in patients with 'underlying' chronic kidney disease (CKD) remains scarce, although PPI use is generally associated with acute interstitial nephritis or incident CKD. We aimed to investigate the association between PPI initiation and the risk of adverse outcomes in patients with CKD in the absence of any deterministic indications for PPI usage. DESIGN: Retrospective observational study. SETTING: Korea National Health Insurance Service database from 2009 to 2017. PARTICIPANTS: A retrospective cohort of new PPI and histamine H2-receptor antagonists (H2RA) users among people with CKD. Patients with a history of gastrointestinal bleeding or those who had an endoscopic or image-based upper gastrointestinal tract evaluation were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: The study subjects were followed to ascertain clinical outcomes including mortality, end-stage kidney disease (ESKD), myocardial infarction and stroke. The HRs of outcomes were measured using a Cox regression model after adjusting for multiple variables. We applied an inverse probability of treatment weighting (IPTW) model to control for residual confounders. RESULTS: We included a total of 1038 PPI and 3090 H2RA users without deterministic indications for treatment. IPTW-weighted Cox regression analysis showed that PPI initiation was more significantly associated with a higher ESKD risk compared with that of H2RA initiation (adjusted HR 1.72 (95% CI 1.19 to 2.48)), whereas the risks of mortality or cardiovascular outcomes were similar between the two groups. In the subgroup analysis, multivariable Cox regression analysis showed that the association between PPI use and the progression to ESKD remained significant in non-diabetic and low estimated glomerular filtration rate (<60 mL/min/1.73 m2) groups (adjusted HR 1.72 (95% CI 1.19 to 2.48) and 1.63 (95% CI 1.09 to 2.43), respectively). CONCLUSIONS: Initiation of PPI administration may not be recommended in patients with CKD without deterministic indication, as their usage was associated with a higher risk of ESKD.

Associations of metabolic variabilities and cardiovascular outcomes according to estimated glomerular filtration rate in chronic kidney disease: a nationwide observational cohort study.

Background: The impact of baseline estimated glomerular filtration rate (eGFR) on the risk of adverse outcomes according to metabolic parameter variabilities in chronic kidney disease has rarely been investigated. Methods: We conducted a retrospective nationwide cohort study using the National Health Insurance System data in Korea from 2007 to 2013 to identify individuals with three or more health screenings. The metabolic components variability was defined as intraindividual variability between measurements using the variability independent of the mean. The metabolic variability score was defined as the total number of high-variability metabolic components. Multivariable-adjusted Cox regression analysis was conducted to evaluate the risks of all-cause mortality, myocardial infarction, and ischemic stroke. Results: During a mean follow-up of 6.0 ± 0.7 years, 223,531 deaths, 107,140 myocardial infarctions, and 116,182 ischemic strokes were identified in 9,971,562 patients. Low eGFR categories and higher metabolic variability scores were associated with a higher risk of adverse outcomes. The degree of association between metabolic variability and adverse outcomes was significantly larger in those with low eGFR categories than in those with preserved eGFR (p for interaction < 0.001). Representatively, those with high metabolic variability in the eGFR of <15 mL/min/1.73 m2 group showed a prominently higher risk for all-cause mortality (adjusted hazard ratio [aHR], 5.28; 95% confidence interval [CI], 4.02-6.94) when the degree was compared to the findings in those with preserved (eGFR of ≥60 mL/min/1.73 m2) kidney function (aHR, 2.55; 95% CI, 2.41-2.69). Conclusion: The degree of adverse association between metabolic variability and poor prognosis is accentuated in patients with impaired kidney function.

The association of time-updated ambulatory blood pressure and renal progression in hypertensive patients with chronic kidney disease: post hoc analysis of ACCURATE study.

OBJECTIVES: : This study aimed to evaluate the effect of time-updated ambulatory blood pressure on chronic kidney disease (CKD) progression in patients with hypertension. METHODS: : Among patients with hypertension and CKD stages 3 and 4, enrolled in a clinical trial in which hypertension was treated based on office or ambulatory blood pressure (BP), participants assigned to the ambulatory BP were included in this study. Ambulatory BP was measured at the start of the study and 3, 6, and 18 months. Renal events were defined as a decrease in the estimated glomerular filtration rate (eGFR) by at least 30%, dialysis, or transplantation. RESULTS: : A total of 21 cases of renal events were observed. For baseline BP, a multivariate Cox model revealed that neither office SBP nor any component of ambulatory SBP, including mean, day-time, night-time BPs was associated with the risk of renal events. For time-updated BP, a marginal structural model revealed that the office SBP was not associated with renal events [hazard ratio 1.03, 95% confidence interval (CI) 0.99-1.07, P  = 0.117], but higher ambulatory SBPs, including day-time (hazard ratio 1.05, 95% CI 1.01-1.10, P  = 0.014), night-time (hazard ratio 1.05, 95% CI 1.02-1.08, P  = 0.001), and mean (hazard ratio 1.06, 95% CI 1.02-1.10, P  = 0.002) ambulatory SBPs, were significantly associated with an increased risk of renal events. CONCLUSION: : A higher time-updated ambulatory BP was associated with an increased risk of renal events in patients with hypertension and CKD, whereas baseline office and ambulatory BP, and time-updated office BP were not.

Menopausal hormone therapy and risk for dementia in women with CKD: A nationwide observational cohort study.

AIM: The risk for dementia is increased in postmenopausal women. The incidences of premature menopause and dementia have increased in patients with chronic kidney disease (CKD). The potential benefits of hormone replacement therapy (HRT) on cognitive function may be a more critical issue for patients with CKD. METHODS: Women aged >40 years with or without HRT were identified using the 2009 National Health Screening Questionnaire. Women who were newly diagnosed with CKD between 2009 and 2013 were enrolled. HRT was used as an exposure variable, and participants were followed from the day CKD was diagnosed to December 2019. The hazard ratio (HR) for dementia was evaluated using Cox proportional hazards regression analysis. RESULTS: We included 755 426 postmenopausal women with CKD. The median follow-up period was 7.3 (IQR, 5.8-8.7) years. All-cause dementia, Alzheimer's disease, and vascular dementia occurred in 107 848 (14.3%), 87 833 (11.6%), and 10 245 (1.4%) women, respectively. HRT was significantly associated with a lower risk for dementia in the adjusted Cox regression model (all-cause dementia: HR 0.80; 95% confidence interval [CI] 0.78-0.82; p < 0.001; Alzheimer's disease: HR 0.80; 95% CI 0.77-0.82; p < 0.001; vascular dementia: HR 0.80; 95% CI 0.74-0.87; p < 0.001). CONCLUSIONS: HRT was significantly associated with a lower risk for CKD-related cognitive dysfunction in postmenopausal women. Prospective studies are needed to determine whether HRT lowers the risk for dementia in menopausal women with CKD.

Cardiovascular and Mortality Risks in Young Health Screening Examinees With Marginal Estimated GFR.

Introduction: Additional evidence is necessary to interpret kidney function parameters in young adults, particularly in those with marginal estimated glomerular filtration rate (eGFR) values. Therefore, we aimed to investigate the association between eGFR and adverse outcomes in general young adults. Methods: We performed a nationwide retrospective cohort study using the health-screening database of South Korea. We included young adults aged 20-39 years without a history of major adverse cardiovascular events (MACE) or kidney failure, who underwent nationwide health screening in 2012. The study exposure was eGFR categorized into 15 ml/min per 1.73 m2 intervals. The risks of all-cause mortality and MACE were calculated using Cox regression analysis, adjusted for various clinicodemographic characteristics. Results: In total, 3,132,409 young adults were included in this study. During a median follow-up of 7.3 years, marginal eGFR (60-75 ml/min per 1.73 m2) was not significantly associated with a higher risk of all-cause mortality (adjusted hazard ratio [aHR], 0.80 [0.74-0.87]). The results were similar for MACE outcomes (aHR, 0.94 [0.87-1.01]). Although the presence of dipstick albuminuria had a significant interaction with the association between eGFR categories and all-cause mortality (interaction term P = 0.028), the risks of all-cause mortality were not significantly higher (aHR, 0.98 [0.62, 1.55]) in those with albuminuria and eGFR 60-75 ml/min per 1.73 m2. Conclusion: Marginal eGFR was not associated with higher risks of all-cause mortality and MACE in general young adults. Additional clinical investigations for incidentally found marginal eGFR values may be discouraged in general young adults.

Impact of albuminuria on early-onset type 2 diabetes mellitus: a nationwide population-based study.

Background: Early-onset diabetes mellitus has a significant lifetime burden and is associated with higher morbidity and mortality. Since insulin resistance is one of the mechanisms of podocyte injury, we aimed to evaluate the effect of albuminuria on newly developed early-onset type 2 diabetes mellitus (T2DM). Methods: We screened 6,891,399 subjects aged ≥20 and <40 years without a history of prediabetes or diabetes from the Korean National Health Insurance Service database between 2009 and 2012. A multivariate Cox proportional hazard model was used to identify the impact of albuminuria on early-onset T2DM. Results: Among a total of 5,383,779 subjects, 62,148 subjects (1.2%) developed early-onset diabetes over 7.3 ± 1.2 years. Albuminuria was significantly associated with early-onset T2DM (adjusted hazard ratio [aHR], 1.62; 95% confidence interval [CI], 1.55-1.70) after adjustment for age, sex, anthropometric data, physical exercise status, serum glucose, and total cholesterol. The risk of early-onset T2DM increased more in subjects with more components of metabolic syndrome (MetS). Among each component of MetS, hypertriglyceridemia was prominently associated with early-onset T2DM (aHR, 2.02; 95% CI, 1.81-2.25) in subjects with albuminuria. Conclusion: Dipstick albuminuria was significantly associated with early-onset T2DM in young adult populations. Close monitoring of albuminuria is warranted for disease risk modification, especially in subjects with MetS.

Association between food insecurity and risk of chronic diseases affecting the kidney in older Korean patients.

AIMS: This study aimed to examine the association between food insecurity and the prevalence of chronic diseases among older adults in South Korea and to compare the findings with data from the United States (US). MATERIALS AND METHODS: We analyzed data from the Korea National Health and Nutrition Examination Survey (KNHANES) V (2010 - 2012) and VI (2013 - 2015) and 4 years (2012 - 2015) of food security questionnaire data. The data of 46,189 National Health and Nutrition Examination Survey participants (1999 - 2016) were subjected to propensity score-matched (PSM) analysis. RESULTS: We included 7,914 individuals from the KNHANES. In the older group (age > 65 years), no differences were observed in the prevalence of hypertension, diabetes, chronic kidney disease (CKD), and metabolic syndrome across the income groups. Income, education, and food security had no impact on hypertension, diabetes, and CKD prevalence in the multivariate logistic analysis after PSM. CKD was not associated with food insecurity (odds ratio (OR), 1.26; 95% confidence interval (CI), 0.94 - 1.26) in the final model using the KNHANES data; however, the U.S. NHANES data showed that an increased risk of hypertension was associated with food insecurity (OR, 1.27; 95% CI, 1.04 - 1.55). CONCLUSION: As per the U.S. NHANES data, food insecurity was associated with a high prevalence of hypertension, while as per the South Korean KNHANES data, food insecurity was not found to be associated with CKD, indicating divergent relationships between food insecurity and chronic diseases in the two countries. Further research is needed to explore these differences.

Intrinsic prefrontal functional connectivity according to cognitive impairment in patients with end-stage renal disease.

Background: This study aimed to investigate differences in intrinsic prefrontal functional connectivity according to the presence of cognitive impairment in patients with end-stage renal disease (ESRD) using functional near-infrared spectroscopy (fNIRS). Methods: We prospectively enrolled 37 patients with ESRD who had been undergoing hemodialysis for more than 6 months and had no history of neurological or psychiatric disorders. All patients with ESRD underwent the Korean version of the Montreal Cognitive Assessment (MoCA-K) to assess cognitive function. The NIRSIT Lite device (OBELAB Inc.) was used to acquire fNIRS data, and the NIRSIT Lite Analysis Tool program was used to process the data and generate a functional connectivity matrix. We obtained functional connectivity measures by applying graph theory to the connectivity matrix using the BRAPH (brain analysis using graph theory) program. Results: Of the 37 patients with ESRD, 23 had cognitive impairment, whereas 14 patients showed no cognitive impairment. Intrinsic prefrontal functional connectivity was significantly different between groups. Network measures of strength, global efficiency, and mean clustering coefficient were lower in ESRD patients with cognitive impairment than in those without cognitive impairment (4.458 vs. 5.129, p = 0.02; 0.397 vs. 0.437, p = 0.03; and 0.316 vs. 0.421, p = 0.003; respectively). There were no significant correlations between MoCA-K scores and clinical characteristics. Conclusion: We demonstrated a significant association between cognitive function and intrinsic prefrontal functional connectivity in patients with ESRD. ESRD patients with cognitive impairment have reduced connectivity and segregation in the prefrontal brain network compared to those without cognitive impairment.

Impact of albuminuria on the various causes of death in diabetic patients: a nationwide population-based study.

Diabetes mellitus (DM) is a well-known risk factor for mortality, and the risk is exacerbated by coexisting diabetic kidney disease (DKD). We aimed to explore the impact of DM on each cause of mortality according to kidney function and the presence of albuminuria. Data on subjects with DM were extracted from the Nationwide Health Insurance Database of South Korea between 2009 and 2012. Subjects were divided by eGFR and albuminuria into five groups. To evaluate the risk of diabetes, we used the Cox proportional hazards model. A total of 2,614,662 patients were enrolled in this study. Most causes of death showed a higher incidence in an advanced stage of DKD. In addition to all-cause mortality and cardiovascular death, the risk of death from neoplasms and diseases of the endocrine, respiratory, and digestive systems is increased by albuminuria. The synergistic effect of a reduced eGFR and the presence of albuminuria was prominent in death from circulatory diseases, and endocrine and metabolic diseases. The risk for mortality was different according to the stage of DKD. Even in patients with a favorable eGFR, the presence of albuminuria significantly increased the risk for mortality, especially that due to cardiovascular causes.

Evaluating the Safety and effectivenesS in adult KorEaN patients treated with Tolvaptan for management of autosomal domInAnt poLycystic kidney disease (ESSENTIAL): short-term outcomes during the titration period.

BACKGROUND: Tolvaptan reduces height-adjusted total kidney volume (htTKV) and renal function decline in autosomal dominant polycystic kidney disease (ADPKD). This study was aimed at investigating the efficacy and safety of tolvaptan in Korean patients with ADPKD during the titration period. METHODS: This study is a multicenter, single-arm, open-label phase 4 study. We enrolled 108 patients with ADPKD (age, 19-50 years) with an estimated glomerular filtration rate (eGFR) of >30 mL/min/1.73 m2 and factors defined as indicative of rapid disease progression. After tolvaptan titration, we evaluated efficacy and side effects and assessed factors associated with the effects. RESULTS: After titration for 4 weeks, eGFR and htTKV decreased by 6.4 ± 7.9 mL/min/1.73 m2 and 16 ± 45 mL/m, respectively. No serious adverse drug reactions were observed during the titration period. The greatest eGFR decline was observed in the first week, with a starting tolvaptan dose of 45 mg. Multivariate linear regression for htTKV decline showed that the greater the change in urine osmolality (Uosm), the greater the decrease in htTKV (ß, 0.436; p = 0.009) in the 1D group stratified by the Mayo Clinic image classification. Higher baseline eGFR was related to a higher htTKV reduction rate in the 1E group (ß, -0.642; p = 0.009). CONCLUSION: We observed short-term effects and safety during the tolvaptan titration period. The decline of htTKV can be predicted as a short-term effect of tolvaptan by observing Uosm changes from baseline to end of titration in 1D and baseline eGFR in 1E groups.

Association between homocysteinemia and mortality in CKD: A propensity-score matched analysis using NHANES-National Death Index.

Hyperhomocysteinemia (HHcy) is considered a risk factor for cardiovascular disease (CVD), including chronic kidney disease (CKD). In this study, we investigated the association between levels of serum homocysteine (Hcy) and mortality, inferred from the presence of CKD. Our study included data of 9895 participants from the 1999 to 2016 National Health and Nutrition Examination Surveys (NHANES). Multivariable-adjusted Cox proportional hazard models using propensity-score, were used to examine dose-response associations between Hcy level and mortality. A total of 9895 participants, 1025 (10.3%) participants were diagnosed with CKD. In a multivariate Cox regression analysis including all participants, Hcy level was significantly associated with all-cause mortality in the nonCKD group, compared to the 1st quartile in the fully adjusted model (2nd quartile: hazard ratio (HR) 1.75, 95% confidence interval (CI) 1.348-2.274, P < .001; 3rd quartile: HR 2.22, 95% CI 1.726-2.855, P < .001; 4th quartile: HR 3.77, 95% CI 2.952-4.830, P < .001). However, this finding was not observed in the CKD group. The observed pattern was similar after propensity score matching. In the nonCKD group, overall mortality increased in proportion to Hcy concentration (2nd quartile: HR 2.19, 95% CI 1.299-3.709, P = .003; 3rd quartile: HR 2.60, 95% CI 1.570-4.332, P < .001; 4th quartile: HR 3.72, 95% CI 2.254-6.139, P < .001). However, the risk of all-cause mortality according to the quartile of Hcy level, did not increase in the CKD group. This study found a correlation between the Hcy level and mortality rate only in the nonCKD group. These altered risk factor patterns may be attributed to protein-energy wasting or chronic inflammation status, that is accompanied by CKD.

Ambient carbon monoxide correlates with mortality risk of hemodialysis patients: comparing results of control selection in the case-crossover designs.

BACKGROUND: Growing evidence suggests that environmental air pollution adversely affects kidney health. To date, the association between carbon monoxide (CO) and mortality in patients with end-stage renal disease (ESRD) has not been examined. METHODS: Among 134,478 dialysis patients in the Korean ESRD cohort between 2001 and 2014, 8,130 deceased hemodialysis patients were enrolled, and data were analyzed using bidirectional, unidirectional, and time-stratified case-crossover design. We examined the association between short-term CO concentration and mortality in patients with ESRD. We used a two-pollutant model, adjusted for temperature as a climate factor and for nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and particulate matter less than 10 µm in diameter as air pollution variables other than CO. RESULTS: Characteristics of the study population included age (66.2 ± 12.1 years), sex (male, 59.1%; female, 40.9%), and comorbidities (diabetes, 55.6%; hypertension, 14.4%). Concentration of CO was significantly associated with all-cause mortality in the three case-crossover designs using the two-pollutant model adjusted for SO2. Patients with diabetes or age older than 75 years had a higher risk of mortality than patients without diabetes or those younger than 75 years. CONCLUSION: Findings presented here suggest that higher CO concentration is correlated with increased all-cause mortality in hemodialysis patients, especially in older high-risk patients.

Optimal target blood pressure for major adverse cardiovascular and cerebrovascular events in hypertensive patients: a nationwide population-based study.

BACKGROUND: Generalizing an 'optimal' blood pressure (BP) level for individuals with hypertension remains controversial due to the implementation of different medical guidelines. This study investigated the association of BP with major adverse cardiovascular and cerebrovascular events (MACCE) and determined the optimal BP for patients with hypertension. METHOD: A total of 934 179 individuals who received antihypertensive medications were selected from the National Health Insurance Service Examination Database between 2003 and 2011 in Korea. Their BP was measured at the index date, which was the first health examination. The study outcomes were MACCE, including acute myocardial infarction, heart failure, stroke, and all-cause mortality. The participants were monitored until in December, 2017. The hazard ratios were calculated using Cox proportional hazard models. The cumulative incidence of MACCE for each BP group was estimated using the Kaplan-Meier method. RESULTS: A lower risk of MACCE was observed at a SBP of 120-129 mmHg and a DBP of 80-89 mmHg. The endpoint-specific incidence rates and hazard ratios for acute myocardial infarction, heart failure, stroke, and all-cause mortality were the lowest at a SBP of 120-129 mmHg and a DBP of 80-89 mmHg. CONCLUSION: Even though this observational study did not support inference of a causal relationship, a SBP of 120-129 mmHg and a DBP of 80-89 mmHg may be safely recommended considering the possibility of MACCE in Korean patients with hypertension. In addition, the target BP should be tailored individually according to age, sex, and comorbidities.