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.

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.

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.

Factors affecting the long-term outcomes of idiopathic membranous nephropathy.

BACKGROUND: We attempted to describe the clinical features and determine the factors associated with renal survival in idiopathic membranous nephropathy (iMN) patients with nephrotic syndrome (NS) and to determine the factors associated with spontaneous complete remission (sCR) and progression to NS in iMN patients with subnephrotic proteinuria. METHODS: This retrospective study involved 166 iMN patients with NS and 65 patients with subnephrotic proteinuria. The primary end point was a doubling of serum creatinine or initiation of dialysis. In patients with subnephrotic proteinuria, we determined the factors associated with sCR and factors associated with progression to NS. RESULTS: Remission of NS was achieved in 125 out of 166 patients (75.3%). Of those who reached remission, 26 patients (20.8%) experienced relapse that was followed by second remission. The relapse or persistence of proteinuria was associated with the primary end points (hazard ratio [HR] = 12.40, P = 0.037, HR = 173, P < 0.001, respectively). In patients with subnephrotic proteinuria, sCR occurred in 35.4% of the patients. The patients with sCR had lower proteinuria and serum creatinine levels and higher serum albumin concentrations at baseline. The serum albumin level at diagnosis was a prognostic factor for progression to NS (Odds ratio [OR] = 0.015, P < 0.001). CONCLUSIONS: The occurrence of relapse or persistence of proteinuria had negative effects on renal survival in iMN patients with NS, and low serum albumin levels at baseline were associated with non-achievement of sCR and progression to NS.

Use of Preoperative MRI to Select Candidates for Local Excision of MRI-Staged T1 and T2 Rectal Cancer: Can MRI Select Patients With N0 Tumors?

BACKGROUND: To minimize the recurrence rate after local excision of rectal cancer, the false-negative rate of nodal staging should be minimized. OBJECTIVE: The purpose of this study was to develop a set of criteria using preoperative MRI that would minimize the false-negative rate for the diagnosis of regional lymph node metastasis. DESIGN: A prospectively maintained colorectal cancer database and MRI images were retrospectively reviewed. SETTINGS: This study was conducted at a multidisciplinary tertiary center. PATIENTS: A total of 246 consecutive patients who underwent MRI and curative-intent surgery for MRI-staged T1/T2 rectal cancer from January 2008 to July 2012 were included. MAIN OUTCOME MEASURES: MRI features significantly associated with lymph node metastasis were identified using a χ test. Five diagnostic criteria for lymph node metastasis were created based on these predictive MRI features, and their false-negative rates were compared using the generalized estimating equation method. RESULTS: Small size/homogeneity of lymph nodes and no visible tumor/partially involved muscular layer were significantly associated with lower risks of lymph node metastasis. When tumor invasion depth was not considered, the false-negative rate did not decrease below 10%, even when the strictest criterion for morphologic evaluation of lymph nodes (not visible or <3 mm) was used. Adding invasion depth to the diagnostic criteria significantly decreased the false-negative rate as low as 1.8%. LIMITATIONS: This study is limited by its small sample size and retrospective nature. CONCLUSIONS: Assessing both the depth of tumor invasion and lymph node morphology may reduce the false-negative rate and can be helpful to better identify candidates suitable for local excision of early stage rectal cancer. However, strict MRI criteria for oncologic safety might result in considerable false-positive cases and limit the application of local excision.

Preoperative chemoradiotherapy effects on anastomotic leakage after rectal cancer resection: a propensity score matching analysis.

OBJECTIVE: To assess the effects of preoperative chemoradiotherapy (CRT) on anastomotic leakage (AL) after rectal cancer resection, using propensity score matching. BACKGROUND: Conflicting data have emerged over the last decade regarding the effect of preoperative CRT on AL. METHODS: We reviewed 1437 consecutive patients with rectal cancer who underwent low anterior resection (LAR) at our institution between 2005 and 2012. AL evaluated as grade C was the primary endpoint, as proposed by the International Study Group of Rectal Cancer in 2010. The patients were treated with (n = 360) or without (n = 1077) preoperative CRT. The total radiation dose was 50.4 Gy in 28 fractions. Multivariate and propensity score matching analyses were used to compensate for the differences in some baseline characteristics. RESULTS: The preoperative CRT group contained more patients with the following characteristics, older age, male sex, smoker, advanced stage tumor, lower/mid rectal tumor location, ultra-LAR, and diverting stoma, than the non-preoperative CRT group (all Ps < 0.05). Postoperative AL occurred in 91 patients (6.3%). Before propensity score matching, the incidence of AL in patients with or without preoperative CRT was 7.5% and 5.9%, respectively (P = 0.293). After propensity score matching, the 2 groups were nearly balanced except for the initial stage and the length of the surgeon's career, and the incidence of AL in patients with or without preoperative CRT was 7.5% and 8.1%, respectively (P = 0.781). CONCLUSIONS: We did not observe that preoperative CRT increased the risk of postoperative AL after LAR in patients with rectal cancer, using propensity score matching analysis.

The magnetic resonance imaging-based approach for identification of high-risk patients with upper rectal cancer.

OBJECTIVE: To assess the efficacy of preoperative magnetic resonance imaging (MRI) in identifying upper rectal cancer patients who are at high risk for local recurrence. METHODS: 110 upper rectal cancer patients with locally advanced (pT3-4N0 or pTanyN+) tumors treated with tumor-specific mesorectal excision and no adjuvant radiotherapy were identified from an institutional database at a large academic medical center in Korea. Information on the extent of mesorectal invasion, sacral-side involvement was collected from preoperative MRI. RESULTS: At a median follow-up of 47 months, 5 patients (4.5%) experienced local recurrence (LR). LR rates for patients with intermediate risk (T1-2/N1, T3N0), moderately high risk (T1-2/N2, T3N1, T4N0), and high risk (T3N2, T4/N1-2) were 3%, 4.8%, and 8.7%, respectively. Patients who did not have sacral-side involvement or mesorectal invasion of 5 mm or less did not experience LR. The patients with sacral-side involvement and intermediate risk, moderately high risk, and high risk had an LR rate of 4.2%, 5.6%, and 10%, respectively, or 11.1%, 33.3%, and 18.2%, respectively, when combined with those with mesorectal invasion of greater than 5 mm. Multivariate analyses demonstrated the presence of both sacral-side location and mesorectal invasion of greater than 5 mm was significantly associated with adverse disease-free and overall survival (P < 0.05). CONCLUSIONS: Patients with mesorectal invasion of greater than 5 mm and sacral-side involvement identified on MRI were at an increased risk of local recurrence. The detection of these features on MRI provides prognostic information that is not available in conventional risk classification systems. Improved identification of a high-risk subset of upper rectal cancer patients may guide indications for preoperative chemoradiotherapy in this subset.

Hyperuricemia and deterioration of renal function in autosomal dominant polycystic kidney disease.

BACKGROUND: The role of hyperuricemia in disease progression of autosomal dominant polycystic kidney disease (ADPKD) has not been defined well. We investigated the association of serum uric acid (sUA) with renal function and the effect of hypouricemic treatment on the rate of renal function decline. METHODS: This is a single-center, retrospective, observational cohort study. A total of 365 patients with ADPKD who had estimated glomerular filtration rate (eGFR) ≥ 15 mL/min/1.73 m2 and who were followed up for > 1 year were included in our analysis. Hyperuricemia was defined by a sUA level of ≥ 7.0 mg/dL in male and ≥ 6.0 mg/dL in female or when hypouricemic medications were prescribed. RESULTS: Hyperuricemia was associated with reduced initial eGFR, independent of age, sex, hypertension, albuminuria, and total kidney volume. During a median follow-up period of over 6 years, patients with hyperuricemia showed a faster annual decline in eGFR (-6.3% per year vs. -0.9% per year, p = 0.008). However, after adjusting for age, sex, hypertension and initial eGFR, sUA was no longer associated with either annual eGFR decline or the development of ESRD. Among 53 patients who received hypouricemic treatment, the annual eGFR decline appeared to be attenuated after hypouricemic treatment (pretreatment vs. posttreatment: -5.3 ± 8. 2 vs. 0.2 ± 6.2 mL/min/1.73 m2 per year, p = 0.001 by Wilcoxon signed-rank test). CONCLUSIONS: Although hyperuricemia was associated with reduced eGFR, it was not an independent factor for renal progression in ADPKD. However, the correction of hyperuricemia may attenuate renal function decline in some patients with mild renal insufficiency.

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.

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.

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.

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.

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.

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.

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 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.

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.

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.