The role of PCSK9 in glomerular lipid accumulation and renal injury in diabetic kidney disease.

AIMS/HYPOTHESIS: Glomerular lipid accumulation is a defining feature of diabetic kidney disease (DKD); however, the precise underlying mechanism requires further elucidation. Recent evidence suggests a role for proprotein convertase subtilisin/kexin type 9 (PCSK9) in intracellular lipid homeostasis. Although PCSK9 is present in kidneys, its role within kidney cells and relevance to renal diseases remain largely unexplored. Therefore, we investigated the role of intracellular PCSK9 in regulating lipid accumulation and homeostasis in the glomeruli and podocytes under diabetic conditions. Furthermore, we aimed to identify the pathophysiological mechanisms responsible for the podocyte injury that is associated with intracellular PCSK9-induced lipid accumulation in DKD. METHODS: In this study, glomeruli were isolated from human kidney biopsy tissues, and glomerular gene-expression analysis was performed. Also, db/db and db/m mice were used to perform glomerular gene-expression profiling. We generated DKD models using a high-fat diet and low-dose intraperitoneal streptozocin injection in C57BL/6 and Pcsk9 knockout (KO) mice. We analysed cholesterol and triacylglycerol levels within the kidney cortex. Lipid droplets were evaluated using BODIPY staining. We induced upregulation and downregulation of PCSK9 expression in conditionally immortalised mouse podocytes using lentivirus and siRNA transfection techniques, respectively, under diabetic conditions. RESULTS: A significant reduction in transcription level of PCSK9 was observed in glomeruli of individuals with DKD. PCSK9 expression was also reduced in podocytes of animals under diabetic conditions. We observed significantly higher lipid accumulation in kidney tissues of Pcsk9 KO DKD mice compared with wild-type (WT) DKD mice. Additionally, Pcsk9 KO mouse models of DKD exhibited a significant reduction in mitochondria number vs WT models, coupled with a significant increase in mitochondrial size. Moreover, albuminuria and podocyte foot process effacement were observed in WT and Pcsk9 KO DKD mice, with KO DKD mice displaying more pronounced manifestations. Immortalised mouse podocytes exposed to diabetic stimuli exhibited heightened intracellular lipid accumulation, mitochondrial injury and apoptosis, which were ameliorated by Pcsk9 overexpression and aggravated by Pcsk9 knockdown in mouse podocytes. CONCLUSIONS/INTERPRETATION: The downregulation of PCSK9 in podocytes is associated with lipid accumulation, which leads to mitochondrial dysfunction, cell apoptosis and renal injury. This study sheds new light on the potential involvement of PCSK9 in the pathophysiology of glomerular lipid accumulation and podocyte injury in DKD.

High and low sodium intakes are associated with incident chronic kidney disease in patients with normal renal function and hypertension.

The association between salt intake and renal outcome in subjects with preserved kidney function remains unclear. Here we evaluated the effect of sodium intake on the development of chronic kidney disease (CKD) in a prospective cohort of people with normal renal function. Data were obtained from the Korean Genome and Epidemiology Study, a prospective community-based cohort study while sodium intake was estimated by a 24-hour dietary recall Food Frequency Questionnaire. A total of 3,106 individuals with and 4,871 patients without hypertension were analyzed with a primary end point of CKD development [a composite of estimated glomerular filtration rate (eGFR) under 60 mL/min/1.73 m2 and/or development of proteinuria during follow-up]. The median ages were 55 and 47 years, the proportions of males 50.9% and 46.3%, and the median eGFR 92 and 96 mL/min/1.73 m2 in individuals with and without hypertension, respectively. During a median follow-up of 123 months in individuals with hypertension and 140 months in those without hypertension, CKD developed in 27.8% and 16.5%, respectively. After adjusting for confounders, multiple Cox models indicated that the risk of CKD development was significantly higher in people with hypertension who consumed less than 2.08 g/day or over 4.03 g/day sodium than in those who consumed between 2.93-4.03 g/day sodium. However, there was no significant difference in the incident CKD risk among each quartile of people without hypertension. Thus, both high and low sodium intakes were associated with increased risk for CKD, but this relationship was only observed in people with hypertension.

Warfarin Use in Patients With Atrial Fibrillation Undergoing Hemodialysis: A Nationwide Population-Based Study.

BACKGROUND AND PURPOSE: The aim of this study is to elucidate the effects of warfarin use in patients with atrial fibrillation undergoing dialysis using a population-based Korean registry. METHODS: Data were extracted from the Health Insurance Review and Assessment Service, which is a nationwide, mandatory social insurance database of all Korean citizens enrolled in the National Health Information Service between 2009 and 2013. Thromboembolic and hemorrhagic outcomes were analyzed according to warfarin use. Overall and propensity score-matched cohorts were analyzed by Cox proportional hazards models. RESULTS: Among 9974 hemodialysis patients with atrial fibrillation, the mean age was 66.6±12.2 years, 5806 (58.2%) were men, and 2921 (29.3%) used warfarin. After propensity score matching to adjust for all described baseline differences, 5548 subjects remained, and differences in baseline variables were distributed equally between warfarin users and nonusers. During a mean follow-up duration of 15.9±11.1 months, ischemic and hemorrhagic stroke occurred in 678 (6.8%) and 227 (2.3%) patients, respectively. In a multiple Cox model, warfarin use was significantly associated with an increased risk of hemorrhagic stroke (hazard ratio, 1.44; 95% confidence interval, 1.09-1.91; P=0.010) in the overall cohort. Furthermore, a significant relationship between warfarin use and hemorrhagic stroke was found in propensity-matched subjects (hazard ratio, 1.56; 95% confidence interval, 1.10-2.22; P=0.013). However, the ratios for ischemic stroke were not significantly different in either the propensity-matched (hazard ratio, 0.95; 95% confidence interval, 0.78-1.15; P=0.569) or overall cohort (hazard ratio, 1.06; 95% confidence interval, 0.90-1.26; P=0.470). CONCLUSIONS: Our findings suggest that warfarin should be used carefully in hemodialysis patients, given the higher risk of hemorrhagic events and the lack of ability to prevent thromboembolic complications.

Circulating CD89-IgA complex does not predict deterioration of kidney function in Korean patients with IgA nephropathy.

BACKGROUND: Soluble CD89 (sCD89)-IgA complex plays a key role in the pathogenesis of IgA nephropathy (IgAN). However, there is a lack of evidence supporting this complex as a good biomarker for disease progression. This study aimed to evaluate the usefulness of sCD89-IgA complex for risk stratification of IgAN. METHODS: A total of 326 patients with biopsy-proven IgAN were included. sCD89-IgA complex was measured by sandwich-enzyme-linked immunosorbent assay. The study endpoints were a 30% decline in estimated glomerular filtration rate (eGFR). RESULTS: sCD89-IgA complex levels were inversely and weakly associated with eGFR at the time of biopsy (r=-0.12, p=0.03). However, the significance between the two factors was lost in the multivariate linear regression after adjustment of clinical factors (ß=0.35, p=0.75). In a multivariate Cox model, the highest (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.35-1.61; p=0.45) and middle (HR, 0.93; 95% CI, 0.46-1.89; p=0.84) tertiles of sCD89-IgA complex levels were not associated with an increased risk of developing a 30% decrease in eGFR. Furthermore, the decline rates in eGFR did not differ between groups and C-statistics revealed that the sCD89-IgA complex were not superior to clinical factors in predicting disease progression. CONCLUSIONS: This study found no association between sCD89-IgA complex levels and disease progression in IgAN. Although sCD89 can contribute to the formation of immune complexes, our findings suggest that the sCD89-IgA level is not a good predictor of adverse outcomes and has limited clinical utility as a biomarker for risk stratification in IgAN.

Delta neutrophil index is an independent predictor of mortality in septic acute kidney injury patients treated with continuous renal replacement therapy.

BACKGROUND: Delta neutrophil index (DNI), representing an elevated fraction of circulating immature granulocytes in acute infection, has been reported as a useful marker for predicting mortality in patients with sepsis. The aim of this study was to evaluate the prognostic value of DNI in predicting mortality in septic acute kidney injury (S-AKI) patients treated with continuous renal replacement therapy (CRRT). METHOD: This is a retrospective analysis of consecutively CRRT treated patients. We enrolled 286 S-AKI patients who underwent CRRT and divided them into three groups based on the tertiles of DNI at CRRT initiation (high, DNI > 12.0%; intermediate, 3.6-12.0%; low, < 3.6%). Patient survival was estimated with the Kaplan-Meier method and Cox proportional hazards models to determine the effect of DNI on the mortality of S-AKI patients. RESULTS: Patients in the highest tertile of DNI showed higher Acute Physiology and Chronic Health Evaluation II score (highest tertile, 27.9 ± 7.0; lowest tertile, 24.6 ± 8.3; P = 0.003) and Sequential Organ Failure Assessment score (highest tertile, 14.1 ± 3.0; lowest tertile, 12.1 ± 4.0; P = 0.001). The 28-day mortality rate was significantly higher in the highest tertile group than in the lower two tertile groups (P < 0.001). In the multiple Cox proportional hazard model, DNI was an independent predictor for mortality after adjusting multiple confounding factors (hazard ratio, 1.010; 95% confidence interval, 1.001-1.019; P = 0.036). CONCLUSION: This study suggests that DNI is independently associated with mortality of S-AKI patients on CRRT.

Trends in clinical outcomes of older hemodialysis patients: data from the 2023 Korean Renal Data System (KORDS).

With an increasing aging population, the mean age of patients with end-stage kidney disease (ESKD) is globally increasing. However, the current clinical status of elderly patients undergoing hemodialysis (HD) is rarely reported in Korea. The current study analyzed the clinical features and trends of older patients undergoing HD from the Korean Renal Data System (KORDS) database. The patients were divided into three groups according to age: <65 years (the young group), n = 50,591 (35.9%); 65-74 years (the younger-old group), n = 37,525 (26.6%); and ≥75 years (the older-old group), n = 52,856 (37.5%). The proportion of older-old group undergoing HD significantly increased in incidence and decreased in prevalence from 2013 to 2022. The median levels of hemoglobin, serum creatinine, albumin, calcium, phosphorus, and intact parathyroid hormone significantly decreased in the older-old group. The proportions of arteriovenous fistula creation and left forearm placement showed decreased trends with age. Although the utilization of low surface area dialyzers increased with age, the dialysis adequacy, including urea reduction ratio and Kt/V was within acceptable range in the older-old group on HD. Over the past 20 years, the mortality rate in the older-old group has increased, with cardiovascular diseases decreasing and infectious diseases increasing. The incidence of elderly patients undergoing HD has increased over time, but the high mortality of the older-old group needs to be solved. Therefore, it is imperative to develop holistic strategies based on age and individual needs for patients with ESKD.

Status and trends in epidemiologic characteristics of diabetic end-stage renal disease: an analysis of the 2021 Korean Renal Data System.

Korean Renal Data System (KORDS) is a nationwide end-stage renal disease (ESRD) registry database operated by the Korean Society of Nephrology (KSN). Diabetes mellitus is currently the leading cause of ESRD in Korea; this article provides an update on the trends and characteristics of diabetic ESRD patients. The KORDS Committee of KSN collects data on dialysis centers and patients through an online registry program. Here, we analyzed the status and trends in characteristics of diabetic chronic kidney disease stage 5D (CKD 5D) patients using data from 2001 to 2021. In 2021, the dialysis adequacy of hemodialysis (HD) was lower in diabetic CKD 5D patients than in nondiabetic CKD 5D patients, while that of peritoneal dialysis (PD) was similar. Diabetic CKD 5D patients had a higher proportion of cardiac and vascular diseases and were more frequently admitted to hospitals than nondiabetic CKD 5D patients, and the leading cause of death was cardiac disease. From 2001 to 2020, diabetic CKD 5D patients had a higher mortality rate than nondiabetic CKD 5D patients, but in 2021 this trend was reversed. Diabetic PD patients had the highest mortality rate over 20 years. The mortality rate of diabetic HD patients was higher than that of nondiabetic HD patients until 2019 but became lower starting in 2020. There was a decreasing trend in mortality rate in diabetic CKD 5D patients, but cardiac and vascular diseases were still prevalent in diabetic CKD 5D patients with frequent admissions to hospitals. More specialized care is needed to improve the clinical outcomes of diabetic CKD 5D patients.

Trends in epidemiologic characteristics of end-stage renal disease from 2019 Korean Renal Data System (KORDS).

BACKGROUND: The Korean Society of Nephrology (KSN) has maintained a nationwide end-stage renal disease (ESRD) registry data from Korean Renal Data System (KORDS) since 1985, as the representative registry of ESRD patients in Korea. This review is aimed to update the status of domestic ESRD and to provide evidence on the direction of dialysis therapy. METHODS: The KORDS Committee of KSN has collected data on dialysis centers and patients through an online registry program, and the data from 1986 to 2019 were analyzed. RESULTS: The incidence and prevalence of ESRD patients in Korea are increasing. The ESRD population numbered more than 100,000 in 2019, doubling during the 10 years since 2010. The proportion of diabetes mellitus as a major cause of ESRD seems to have reached a plateau. The increasing number of elderly dialysis patients is a constant trend, with more than half for the proportion of patients older than 65 years old in 2019. All-cause mortality decreased for the last approximately 20 years, regardless of sex, age, and cause of ESRD. The 5-year patient survival rate in both hemodialysis and peritoneal dialysis increased from 2001 to 2013. Since 2013, the patient survival rates in peritoneal dialysis were similar to those in hemodialysis. Cardiovascular complications were the leading cause of death in ESRD patients. CONCLUSIONS: The incidence and prevalence of Korean ESRD patients have increased over time, although patient survival has also steadily increased. The establishment of a surveillance method to address the major cause of mortality in ESRD patients will help improve outcomes.

Secondhand Smoke and CKD.

BACKGROUND AND OBJECTIVES: Active smoking is associated with higher risk of various diseases. However, the risk of CKD development in nonsmokers exposed to secondhand smoke is not well elucidated. We aimed to investigate the association between secondhand smoke exposure and the risk of CKD development among never-smokers. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 131,196 never-smokers with normal kidney function, who participated in the Korean Genome and Epidemiology Study from 2001 to 2014, were analyzed. The participants were classified into three groups on the basis of frequency of secondhand smoke exposure, assessed with survey questionnaires; no exposure, <3 days per week, and ≥3 days per week. The association between secondhand smoke and CKD, defined as eGFR<60 ml/min per 1.73 m2, was examined in the cross-sectional analysis. In addition, the risk of incident CKD development was analyzed in a longitudinal cohort of 1948 participants without CKD at baseline, which was a subset of the main cohort. RESULTS: The mean age of participants was 53 years, and 75% were women. Prevalent CKD was observed in 231 (1.8%), 64 (1.7%), and 2280 (2.0%) participants in the ≥3 days per week, <3 days per week, and no exposure groups. The odds ratio (OR) of prevalent CKD was significantly higher in the groups exposed to secondhand smoke than the no exposure group (<3 days per week: OR, 1.72; 95% confidence interval [95% CI], 1.30 to 2.27; and ≥3 days per week: OR, 1.44; 95% CI, 1.22 to 1.70). During a mean follow-up of 104 months, CKD occurred in 319 (16%) participants. Multivariable Cox analysis revealed that the risk for CKD development was higher in participants exposed to secondhand smoke than the no exposure group (<3 days per week: hazard ratio, 1.59; 95% CI, 0.96 to 2.65; and ≥3 days per week: hazard ratio, 1.66; 95% CI, 1.03 to 2.67). CONCLUSIONS: Exposure to secondhand smoke was associated with a higher prevalence of CKD as well as development of incident CKD.

Delta Neutrophil Index for the Prediction of the Development of Sepsis-Induced Acute Kidney Injury in the Emergency Department.

BACKGROUND AND PURPOSE: The early prediction of acute kidney injury (AKI) in sepsis and provision of timely treatment may improve outcomes. We investigated the efficacy of the delta neutrophil index (DNI)-which reflects the fraction of immature granulocytes-in predicting sepsis-induced AKI and 30-day mortality in cases of severe sepsis or septic shock. METHODS: This retrospective, observational cohort study was performed with patients prospectively integrated in a critical pathway of early-goal-directed therapy /SEPSIS. We analyzed adult sepsis patients admitted to the emergency department with normal kidney function or stage 1 disease, based on the Acute Kidney Injury Network classification, between January 1, 2014 and September 30, 2017. The outcomes were the development of sepsis-induced severe AKI within 7 days and 30-day mortality. RESULTS: A total of 346 patients were enrolled. An increase in the DNI values at Time-0 (odds ratio [OR], 1.060; P < 0.001) and Time-12 (OR, 1.086; P < 0.001) were strong independent predictors of severe AKI development. The increasing predictability of AKI was closely associated with a DNI ≥14.0% at Time-0 (OR, 7.238; P < 0.001) and ≥13.3% at Time-12 (OR, 18.089; P < 0.001). The development of severe AKI was an independent predictor of 30-day mortality (hazard ratio: 25.2, P < 0.001). CONCLUSION: Higher DNI values are independent predictors of severe AKI development and 30-day mortality in sepsis. Physicians can use the DNI to quickly determine the severity of sepsis and initial treatment strategies without additional costs and effort.

Extracellular Fluid Excess Is Significantly Associated With Coronary Artery Calcification in Patients With Chronic Kidney Disease.

BACKGROUND: Extracellular fluid (ECF) excess is an independent predictor of cardiovascular morbidity in patients undergoing dialysis. This study aimed to investigate the relationship between ECF status, which is affected by renal function, and coronary artery calcification (CAC), which is a marker of cardiovascular disease, in patients with chronic kidney disease (CKD). METHODS AND RESULTS: A total of 1741 patients at all stages of pre-dialysis CKD from the prospective observational cohort of CMERC-HI (Cardiovascular and Metabolic Disease Etiology Research Center-High Risk) were analyzed for the association between ECF status and CAC. ECF status was defined as extracellular water-to-total body water ratio (ECW/TBW) measured using bioelectrical impedance analysis. ECF excess was defined as ECW/TBW ≥0.390 or ≥0.400 depending on its severity. To define CAC, Agatston coronary artery calcium scores were measured. A total coronary artery calcium score of ≥400 was defined as CAC. The CKD stages were defined according to estimated glomerular filtration rate calculated using the CKD Epidemiology Collaboration equation. ECW/TBW and the proportion of ECF excess increased with progressing CKD stages. Multivariable logistic regression analyses showed that ECW/TBW was independently associated with CAC (per 0.01 increase of ECW/TBW, odds ratio 1.168, 95% confidence interval, 1.079-1.264, P<0.001). The adjusted R2 for predicting higher coronary artery calcium scores and CAC significantly improved after ECW/TBW was added to conventional factors. This association was further confirmed by net reclassification and integrated discriminant improvements, sensitivity analysis, and subgroup analysis. CONCLUSIONS: ECF status is independently associated with a high risk of CAC in patients with CKD. STUDY REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02003781.

Phosphate is a potential biomarker of disease severity and predicts adverse outcomes in acute kidney injury patients undergoing continuous renal replacement therapy.

Hyperphosphatemia is associated with mortality in patients with chronic kidney disease, and is common in critically ill patients with acute kidney injury (AKI); however, its clinical implication in these patients is unknown. We conducted an observational study in 1144 patients (mean age, 63.2 years; male, 705 [61.6%]) with AKI who received continuous renal replacement therapy (CRRT) between January 2009 and September 2016. Phosphate levels were measured before (0 h) and 24 h after CRRT initiation. We assessed disease severity using various clinical parameters. Phosphate at 0 h positively correlated with the Acute Physiology and Chronic Health Evaluation II (APACHE II; P < 0.001) and Sequential Organ Failure Assessment (SOFA; P < 0.001) scores, and inversely with mean arterial pressure (MAP; P = 0.02) and urine output (UO; P = 0.01). In a fully adjusted linear regression analysis for age, sex, Charlson comorbidity index (CCI), MAP, and estimated glomerular filtration rate (eGFR), higher 0 h phosphate level was significantly associated with high APACHE II (P < 0.001) and SOFA (P = 0.04) scores, suggesting that phosphate represents disease severity. A multivariable Cox model also showed that hyperphosphatemia was significantly associated with increased 28-day (HR 1.05, 95% CI 1.02-1.08, P = 0.001) and 90-day (HR 1.05, 95% CI 1.02-1.08, P = 0.001) mortality. Furthermore, patients with increased phosphate level during 24 h were at higher risk of death than those with stable or decreased phosphate levels. Finally, c-statistics significantly increased when phosphate was added to a model that included age, sex, CCI, body mass index, eGFR, MAP, hemoglobin, serum albumin, C-reactive protein, and APACHE II score. This study shows that phosphate is a potential biomarker that can reflect disease severity and predict mortality in critically ill patients receiving CRRT.

Vitamin D deficiency is significantly associated with depression in patients with chronic kidney disease.

BACKGROUND: Depression is reported to be the most common psychological problem in patients with chronic kidney disease (CKD). Several studies have reported that lower levels of serum vitamin D are significantly associated with depression. Both vitamin D deficiency and depression are prevalent in patients with CKD, yet the relationship between these two factors remains poorly understood. This study aimed to investigate the association between vitamin D levels and depression among CKD patients. METHODS: Totally, 21,257 individuals who participated in the Korean National Health and Nutrition Examination Survey (KNHANES V, VI) from 2010-2014 were screened for the study; 533 CKD patients were included. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D3 [25(OH)D3] ≤10 ng/mL. Patients were divided into vitamin D deficient or sufficient groups. Depression was screened for using the Korean version of the WHO Composite International Diagnostic Interview-Short Form. The association between vitamin D deficiency and depression was evaluated by multivariate logistic regression analysis. RESULTS: The mean participant age was 70.1±9.4 years; 262 patients (49.2%) were male. The median 25(OH)D3 level was 19.1±6.9 ng/mL. The prevalence of depression was higher in CKD patients than in the general population (14.3 vs. 11.1%, P = 0.03). Additionally, the prevalence of depression was significantly higher in CKD patients with (vs. without) vitamin D deficiency (32.5% vs. 50.0%, P<0.001). Multivariate logistic regression analysis showed that vitamin D deficiency was a significant independent predictor of depression after adjusting for confounding factors (adjusted odds ratio, 6.15; 95% confidence interval, 2.02-8.75; P = 0.001). CONCLUSION: Depression was highly prevalent in CKD patients, in whom vitamin D deficiency was a significant independent predictor of depression. Therefore, management of vitamin D deficiency might help prevent depression in CKD patients.

Characteristics and Clinical Outcomes of End-Stage Renal Disease Patients on Peritoneal Dialysis for Over 15 Years: A Single-Center Experience.

BACKGROUND: Maintaining peritoneal dialysis (PD) for a long time is problematic owing to a number of factors. This study aimed to clarify the characteristics and examine the clinical outcomes of patients who received PD as a long-term dialysis modality. METHODS: All end-stage renal disease (ESRD) patients who initiated PD at Yonsei University Health System between 1987 and 2000 were screened. Patients who maintained PD for over 15 years were classified as the long-term PD group and those who were treated with PD for less than 5 years were included in the short-term PD group. Demographic and biochemical data and clinical outcomes were compared between the groups. Independent factors associated with long-term PD maintenance were ascertained using multivariate logistic regression analysis. RESULTS: Among 1,116 study patients, 87 (7.8%) were included in the long-term group and 293 (26.3%) were included in the short-term group. In the long-term group, the mean patient age at PD initiation was 39.6 ± 11.5 years, 35 patients (40.2%) were male, and the mean PD duration was 205.3 ± 32.7 months. Patients were younger, body weight was lower, the proportion of patients with diabetes or cardiovascular diseases was lower, and the proportion of low to low-average transporters was higher in the long-term group than in the short-term group (p < 0.001). Multiple logistic regression analysis revealed that age, body mass index (BMI), serum creatinine, type of PD solution, and diabetes were significant independent factors associated with long-term PD maintenance. CONCLUSION: Peritoneal dialysis can be considered as a long-term renal replacement therapy option, especially in non-diabetic, not overweight, and young ESRD patients.

Prevalence of depression and suicidal ideation increases proportionally with renal function decline, beginning from early stages of chronic kidney disease.

Depression and suicidal ideation are prevalent mental health problems in patients with chronic kidney disease (CKD. However, the association between mental health problems and kidney disease has been investigated in severe cases only. Thus, this study evaluated the relationship between mental health problems and renal function in a community-based prospective cohort study comprising patients with mild to moderate kidney disease. A total of 44,938 participants who were participated in Korean National Health and Nutrition Examination Survey IV, V, and VI from 2007 to 2014 were enrolled. Estimated glomerular filtration rate (eGFR) was calculated using the CKD Epidemiology Collaboration equation. The study outcome was the prevalence of depression and suicidal ideations assessed by self-reporting surveys. Logistic regression analysis was performed to evaluate the relationship between renal function and outcomes. The mean age of the study subjects was 49.2 ±â€Š16.6 years, and the mean eGFR was 94.0 mL/min/1.73 m. The prevalence of depression and suicidal ideation increased with decreasing eGFR. Multivariate logistic regression analysis showed that the risk of depression increased in subjects with eGFR <45 mL/min/1.73 m [odds ratio (OR) 1.47; 95% confidence interval (CI) 1.09-1.98]. The risk of suicidal ideation gradually increased in groups with eGFR <90 mL/min/1.73 m (OR, 1.11; 95% CI, 1.03-1.20), even after adjustments for confounding variables. In conclusion, depression and suicidal ideation are related closely with renal dysfunction. The risk of having depression and suicidal ideation increased even in patient with mild renal dysfunction. Therefore, evaluation and management strategies regarding mental health problems should be taken into account throughout all stages of CKD.

Body mass index is inversely associated with mortality in patients with acute kidney injury undergoing continuous renal replacement therapy.

BACKGROUND: Many epidemiologic studies have reported on the controversial concept of the obesity paradox. The presence of acute kidney injury (AKI) can accelerate energy-consuming processes, particularly in patients requiring continuous renal replacement therapy (CRRT). Thus, we aimed to investigate whether obesity can provide a survival benefit in this highly catabolic condition. METHODS: We conducted an observational study in 212 patients who had undergone CRRT owing to various causes of AKI between 2010 and 2014. The study end point was defined as death that occurred within 30 days after the initiation of CRRT. RESULTS: Patients were categorized into three groups according to tertiles of body mass index (BMI). During ≥30 days after the initiation of CRRT, 39 patients (57.4%) in the highest tertile died, as compared with 58 patients (78.4%) in the lowest tertile (P = 0.02). In a multivariable analysis adjusted for cofounding factors, the highest tertile of BMI was significantly associated with a decreased risk of death (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.37-0.87; P = 0.01). This significant association remained unaltered for 60-day (HR, 0.64; 95% CI, 0.43-0.94; P = 0.03) and 90-day mortality (HR, 0.66; 95% CI, 0.44-0.97; P = 0.03). CONCLUSION: This study showed that a higher BMI confer a survival benefit over a lower BMI in AKI patients undergoing CRRT.

Fatty liver associated with metabolic derangement in patients with chronic kidney disease: A controlled attenuation parameter study.

BACKGROUND: Hepatic steatosis measured with controlled attenuation parameter (CAP) using transient elastography predicts metabolic syndrome in the general population. We investigated whether CAP predicted metabolic syndrome in chronic kidney disease patients. METHODS: CAP was measured with transient elastography in 465 predialysis chronic kidney disease patients (mean age, 57.5 years). RESULTS: The median CAP value was 239 (202-274) dB/m. In 195 (41.9%) patients with metabolic syndrome, diabetes mellitus was more prevalent (105 [53.8%] vs. 71 [26.3%], P < 0.001), with significantly increased urine albumin-to-creatinine ratio (184 [38-706] vs. 56 [16-408] mg/g Cr, P = 0.003), high sensitivity C-reactive protein levels (5.4 [1.4-28.2] vs. 1.7 [0.6-9.9] mg/L, P < 0.001), and CAP (248 [210-302] vs. 226 [196-259] dB/m, P < 0.001). In multiple linear regression analysis, CAP was independently related to body mass index (ß = 0.742, P < 0.001), triglyceride levels (ß = 2.034, P < 0.001), estimated glomerular filtration rate (ß = 0.316, P = 0.001), serum albumin (ß = 1.386, P < 0.001), alanine aminotransferase (ß = 0.064, P = 0.029), and total bilirubin (ß = -0.881, P = 0.009). In multiple logistic regression analysis, increased CAP was independently associated with increased metabolic syndrome risk (per 10 dB/m increase; odds ratio, 1.093; 95% confidence interval, 1.009-1.183; P = 0.029) even after adjusting for multiple confounding factors. CONCLUSION: Increased CAP measured with transient elastography significantly correlated with and could predict increased metabolic syndrome risk in chronic kidney disease patients.

High dietary phosphorus density is a risk factor for incident chronic kidney disease development in diabetic subjects: a community-based prospective cohort study.

Background: High serum phosphorus concentrations are associated with an increased risk of cardiovascular disease and progression of chronic kidney disease (CKD). However, the relation between dietary phosphorus intake and CKD development has not been well evaluated.Objective: In this study, we investigated the impact of dietary phosphorus density on the development of incident CKD in a cohort of subjects with normal renal function.Design: Data were retrieved from the Korean Genome and Epidemiology Study, a prospective community-based cohort study. The study cohort consisted of subjects aged 40-69 y, who were followed up biennially from 2001 to 2014. A total of 873 subjects with diabetes mellitus (DM) and 5846 subjects without DM (non-DM) were included in the final analysis. The primary endpoint was incident CKD, defined as a composite of estimated glomerular filtration rate <60 mL · min-1 · 1.73 m-2 and/or the development of proteinuria.Results: In the DM and non-DM groups, the mean ages of the participants were 55.6 ± 8.7 and 51.4 ± 8.6 y, the numbers of male subjects were 454 (52.0%) and 2784 (47.6%), and the mean estimated glomerular filtration rates were 91.6 ± 14.0 and 94.5 ± 14.0 mL · min-1 · 1.73 m-2, respectively. The mean values of dietary phosphorus density, defined as the ratio of a single-day dietary phosphorus amount to the total daily calorie intake, were 0.51 ± 0.08 mg/kcal in the DM group and 0.51 ± 0.07 mg/kcal in the non-DM group. During the follow-up, CKD newly developed in 283 (32.4%) and 792 subjects (13.5%) in the DM and non-DM groups, respectively. When the subjects were divided into quartiles according to the dietary phosphorus density in each group, the highest quartile was significantly associated with the development of incident CKD by multiple Cox proportional hazard analysis in the DM group (P = 0.02) but not in the non-DM group (P = 0.72).Conclusions: High dietary phosphorus density is associated with an increased risk of CKD development in DM patients with normal renal function. The causality in this association needs to be tested in a randomized controlled trial.

Clinical usefulness of the Oxford classification in determining immunosuppressive treatment in IgA nephropathy.

BACKGROUND: The Oxford classification has been widely used in IgA nephropathy. However, its clinical usefulness of determining immunosuppression is unknown. AIM: Whether the Oxford classification could predict the development of proteinuria ≥1 g/g Cr and worsening kidney function, as well as the clinical efficacy of corticosteroid treatment according to each histologic variable of the Oxford-MEST. METHODS: We included 377 patients with early-stage IgA nephropathy. The study endpoints were the development of a heavy proteinuria and a decline renal function. RESULTS: The results showed that among the Oxford-MEST lesions, only M1 predicted the risk of the development of proteinuria ≥1.0 g/g Cr compared to other lesions in a time-varying Cox model adjusted for multiple confounding factors. In addition, the risk of reaching a 30% decline in eGFR was significantly higher in patients with M1 than in those with M0. Furthermore, patients with M1 had a greater decline of eGFR than patients with M0. However, steroid treatment in M1 lesion was not associated with improving clinical outcomes in the unmatched and propensity score matched cohort. CONCLUSIONS: This finding may provide a rationale for using the Oxford classification as a guidance to initiate immunosuppression in the early stages of IgA nephropathy. KEY MESSAGES M1 has independently predictive role among the Oxford lesions in IgA nephropathy. Oxford classification should be defined during pathologic approach. Decision of starting immunosuppression according to the Oxford lesions.

Association Between Starting Hemodialysis for End-Stage Renal Disease and Incident Cataract Surgery: A 12-Year Nationwide Cohort Study.

PURPOSE: To evaluate incident cataract surgery in subjects who started hemodialysis for end-stage renal disease. METHODS: A nationwide propensity score-matched cohort study was performed by using a 12-year longitudinal national health insurance database of 1,025,340 subjects. The hemodialysis cohort was composed of patients who started hemodialysis between January 2003 and December 2007 (n = 291). The control cohort was composed of randomly selected patients (5 per patient in the hemodialysis cohort; n = 1467) who were matched to the hemodialysis cohort according to a propensity score based on year of hemodialysis initiation, age, sex, residential area, household income, and frequency of medical attention. Each selected patient was followed up until 2013. Cox proportional hazard regression analysis was used to calculate the overall hazard of hemodialysis initiation in regard to incident cataract surgery after adjusting for the above factors, hypertension, and diabetes mellitus. RESULTS: Starting hemodialysis was associated with increased incident cataract surgery (hazard ratio [HR] = 1.79; 95% confidence interval [CI], 1.34-2.41). Diabetes mellitus (HR = 1.68; 95% CI, 1.22-2.32) also increased the incidence of cataract surgery. With respect to age, the effect size of hemodialysis for incident cataract surgery was greater among younger adults (aged <60 years; HR = 5.32; 95% CI, 3.06-9.26) than among older adults (aged ≥60 years; HR = 1.17; 95% CI, 0.79-1.72). CONCLUSIONS: Patients who began hemodialysis for end-stage renal disease were more likely to undergo cataract surgery than control subjects, and this risk was more pronounced in younger patients.