Characterizing Glomerular Barrier Dysfunction with Patient-Derived Serum in Glomerulus-on-a-Chip Models: Unveiling New Insights into Glomerulonephritis.

Glomerulonephritis (GN) is characterized by podocyte injury or glomerular filtration dysfunction, which results in proteinuria and eventual loss of kidney function. Progress in studying the mechanism of GN, and developing an effective therapy, has been limited by the absence of suitable in vitro models that can closely recapitulate human physiological responses. We developed a microfluidic glomerulus-on-a-chip device that can recapitulate the physiological environment to construct a functional filtration barrier, with which we investigated biological changes in podocytes and dynamic alterations in the permeability of the glomerular filtration barrier (GFB) on a chip. We also evaluated the potential of GN-mimicking devices as a model for predicting responses to human GN. Glomerular endothelial cells and podocytes successfully formed intact monolayers on opposite sides of the membrane in our chip device. Permselectivity analysis confirmed that the chip was constituted by a functional GFB that could accurately perform differential clearance of albumin and dextran. Reduction in cell viability resulting from damage was observed in all serum-induced GN models. The expression of podocyte-specific marker WT1 was also decreased. Albumin permeability was increased in most models of serum-induced IgA nephropathy (IgAN) and membranous nephropathy (MN). However, sera from patients with minimal change disease (MCD) or lupus nephritis (LN) did not induce a loss of permeability. This glomerulus-on-a-chip system may provide a platform of glomerular cell culture for in vitro GFB in formation of a functional three-dimensional glomerular structure. Establishing a disease model of GN on a chip could accelerate our understanding of pathophysiological mechanisms of glomerulopathy.

Hyperchloremia is associated with poor renal outcome after coronary artery bypass grafting.

BACKGROUND: Hyperchloremia is associated with the risks of several morbidities and mortality. However, its relationship with acute kidney injury (AKI) and end-stage renal disease (ESRD) in patients undergoing coronary artery bypass grafting (CABG) remains unresolved. METHODS: A total of 2977 patients undergoing CABG between 2003 and 2015 were retrospectively reviewed from two tertiary hospitals. Patients were categorized by serum chloride levels into normochloremia (95-105 mmol/L), mild hyperchloremia (106-110 mmol/L), and severe hyperchloremia (> 110 mmol/L). The odds ratios (ORs) for AKI and hazard ratios (HRs) for ESRD were calculated after adjustment for multiple covariates. The death-adjusted risk of ESRD was additionally evaluated. RESULTS: Postoperative AKI occurred in 798 patients (26.5%). The hyperchloremia group had a higher risk of AKI than the normochloremia group, wherein the risk was incremental depending on the severity of hyperchloremia, as follows: ORs were 1.26 (1.06-1.51) and 1.95 (1.52-2.51) in the mild and severe hyperchloremia groups, respectively. During a median period of 7 years (maximum 15 years), 70 patients (2.3%) had ESRD. The severe hyperchloremia group was at an elevated risk of ESRD compared with the normochloremia group, with an HR of 2.43 (1.28-4.63). Even after adjusting for the competing risk of death, hyperchloremia was associated with the risk of ESRD. CONCLUSIONS: Preoperative hyperchloremia is associated with poor renal outcomes such as AKI and ESRD after CABG. Accordingly, serum chloride should be monitored in patients undergoing CABG.

Real-Time Clinical Decision Support Based on Recurrent Neural Networks for In-Hospital Acute Kidney Injury: External Validation and Model Interpretation.

BACKGROUND: Acute kidney injury (AKI) is commonly encountered in clinical practice and is associated with poor patient outcomes and increased health care costs. Despite it posing significant challenges for clinicians, effective measures for AKI prediction and prevention are lacking. Previously published AKI prediction models mostly have a simple design without external validation. Furthermore, little is known about the process of linking model output and clinical decisions due to the black-box nature of neural network models. OBJECTIVE: We aimed to present an externally validated recurrent neural network (RNN)-based continuous prediction model for in-hospital AKI and show applicable model interpretations in relation to clinical decision support. METHODS: Study populations were all patients aged 18 years or older who were hospitalized for more than 48 hours between 2013 and 2017 in 2 tertiary hospitals in Korea (Seoul National University Bundang Hospital and Seoul National University Hospital). All demographic data, laboratory values, vital signs, and clinical conditions of patients were obtained from electronic health records of each hospital. We developed 2-stage hierarchical prediction models (model 1 and model 2) using RNN algorithms. The outcome variable for model 1 was the occurrence of AKI within 7 days from the present. Model 2 predicted the future trajectory of creatinine values up to 72 hours. The performance of each developed model was evaluated using the internal and external validation data sets. For the explainability of our models, different model-agnostic interpretation methods were used, including Shapley Additive Explanations, partial dependence plots, individual conditional expectation, and accumulated local effects plots. RESULTS: We included 69,081 patients in the training, 7675 in the internal validation, and 72,352 in the external validation cohorts for model development after excluding cases with missing data and those with an estimated glomerular filtration rate less than 15 mL/min/1.73 m2 or end-stage kidney disease. Model 1 predicted any AKI development with an area under the receiver operating characteristic curve (AUC) of 0.88 (internal validation) and 0.84 (external validation), and stage 2 or higher AKI development with an AUC of 0.93 (internal validation) and 0.90 (external validation). Model 2 predicted the future creatinine values within 3 days with mean-squared errors of 0.04-0.09 for patients with higher risks of AKI and 0.03-0.08 for those with lower risks. Based on the developed models, we showed AKI probability according to feature values in total patients and each individual with partial dependence, accumulated local effects, and individual conditional expectation plots. We also estimated the effects of feature modifications such as nephrotoxic drug discontinuation on future creatinine levels. CONCLUSIONS: We developed and externally validated a continuous AKI prediction model using RNN algorithms. Our model could provide real-time assessment of future AKI occurrences and individualized risk factors for AKI in general inpatient cohorts; thus, we suggest approaches to support clinical decisions based on prediction models for in-hospital AKI.

Role of Human Primary Renal Fibroblast in TGF-ß1-Mediated Fibrosis-Mimicking Devices.

Renal fibrosis is a progressive chronic kidney disease that ultimately leads to end-stage renal failure. Despite several approaches to combat renal fibrosis, an experimental model to evaluate currently available drugs is not ideal. We developed fibrosis-mimicking models using three-dimensional (3D) co-culture devices designed with three separate layers of tubule interstitium, namely, epithelial, fibroblastic, and endothelial layers. We introduced human renal proximal tubular epithelial cells (HK-2), human umbilical-vein endothelial cells, and patient-derived renal fibroblasts, and evaluated the effects of transforming growth factor-ß (TGF-ß) and TGF-ß inhibitor treatment on this renal fibrosis model. The expression of the fibrosis marker alpha smooth muscle actin upon TGF-ß1 treatment was augmented in monolayer-cultured HK-2 cells in a 3D disease model. In the vascular compartment of renal fibrosis models, the density of vessels was increased and decreased in the TGF-ß-treated group and TGF-ß-inhibitor treatment group, respectively. Multiplex ELISA using supernatants in the TGF-ß-stimulating 3D models showed that pro-inflammatory cytokine and growth factor levels including interleukin-1 beta, tumor necrosis factor alpha, basic fibroblast growth factor, and TGF-ß1, TGF-ß2, and TGF-ß3 were increased, which mimicked the fibrotic microenvironments of human kidneys. This study may enable the construction of a human renal fibrosis-mimicking device model beyond traditional culture experiments.

Cancer development and mortality differences in patients with glomerulonephritis after renal biopsy: a single center retrospective cohort study.

BACKGROUND: The association between glomerulonephritis (GN) and cancer has been well known for decades. However, studies evaluating long-term de novo cancer development in patients with GN are limited. This study aimed to evaluate the incidence of cancer development among patients with renal biopsy-proven GN during post-biopsy follow-up and the differences in outcomes according to cancer occurrence. METHODS: We conducted a retrospective cohort study of adult patients who underwent renal biopsy at Seoul National Bundang Hospital between 2003 and 2017. After excluding 778 patients with age < 18 years, cancer diagnosis before or within 6 months after renal biopsy, immunosuppressant therapy before renal biopsy, or pathologic diagnoses other than GN, 822 patients were included in the analysis. Data on baseline clinical characteristics, renal biopsy results, and types and doses of immunosuppressant agents were collected from electronic medical records. The incidence of cancer was censored on the date when the first cancer was diagnosed. We evaluated rates of mortality and end-stage renal disease (ESRD) development during follow-up. RESULTS: During a mean follow-up period of 58.9 ± 44.5 months, 45 subjects (5.5%) developed de novo cancer. A comparison of clinical characteristics between subjects who did and did not develop cancer revealed that cancer patients were older and had higher comorbidities and immunosuppressant use. Overall, patients with GN had an elevated standardized incidence ratio (SIR) of 7.16 (95% confidence interval (CI): 5.22-9.61) relative to the age- and sex-matched general population. In particular, the SIR was significantly higher in GNs such as membranous nephropathy (MN), IgA nephropathy, lupus nephritis, and focal segmental glomerulosclerosis. Multivariable Cox proportional hazard model revealed that patients with MN had an increased risk of cancer development, with a hazard ratio of 2.30 [95% CI: 1.06-4.98]. Patients with MN who developed cancer had a significantly higher risk of mortality (hazard ratio: 6.59; 95% CI: 1.22-35.56, P = 0.03) than those without cancer, but there was a non-significant difference in ESRD development. CONCLUSIONS: Patients with GN without concurrent cancer, particularly those with MN, have significantly higher risks of cancer development and subsequent mortality and should remain aware of the potential development of malignancy during follow-up.

Hyperuricemia is associated with acute kidney injury and all-cause mortality in hospitalized patients.

AIM: Hyperuricemia is a risk factor for high morbidity and mortality in several diseases. However, the relationship between uric acid (UA) and the risk of acute kidney injury (AKI) and mortality remain unresolved in hospitalized patients. METHODS: Data from 18 444 hospitalized patients were retrospectively reviewed. The odds ratio (OR) for AKI and the hazard ratio (HR) for all-cause mortality were calculated based on the UA quartiles after adjustment for multiple variables. All analyses were performed after stratification by sex. RESULTS: The fourth quartile group (male, UA > 6.7 mg/dL; female, UA > 5.4 mg/dL) showed a higher risk of AKI compared with the first quartile group (male, UA < 4.5 mg/dL; female, UA < 3.6 mg/dL), with the following OR: 3.2 (2.55-4.10) in males (P < 0.001); and 3.1 (2.40-4.19) in females (P < 0.001). There were more patients who did not recover from AKI in the fourth quartile compared with the first quartile, with the following OR: 2.0 (1.32-3.04) in males (P = 0.001) and 2.4 (1.43-3.96) in females (P = 0.001). The fourth quartile group had a higher risk of all-cause mortality compared with the first quartile group, with the following HR: 1.4 (1.20-1.58) in males (P < 0.001) and 1.2 (1.03-1.46) in females (P = 0.019). The in-hospital mortality risk was also higher in the fourth quartile compared with the first quartile, which was significant only in males (OR, 2.1 (1.33-3.31) (P = 0.002)). CONCLUSION: Hyperuricemia increases the risks of AKI and all-cause mortality in hospitalized patients.

Development of a new mortality scoring system for acute kidney injury with continuous renal replacement therapy.

AIM: On the basis of the worst outcomes of patients undergoing continuous renal replacement therapy (CRRT) in intensive care unit, previously developed mortality prediction model, Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA) needs to be modified. METHODS: A total of 828 patients who underwent CRRT were recruited. Mortality prediction model was developed for the prediction of death within 7 days after starting the CRRT. Based on regression analysis, modified scores were assigned to each variable which were originally used in the APACHE II and SOFA scoring models. Additionally, a new abbreviated Mortality Scoring system for AKI with CRRT (MOSAIC) was developed after stepwise selection analysis. RESULTS: We used all the variables included in the APACHE II and SOFA scoring models. The prediction powers indicated by C-statistics were 0.686 and 0.683 for 7-day mortality by the APACHE II and SOFA systems, respectively. After modification of these models, the prediction powers increased up to 0.752 for the APACHE II and 0.724 for the SOFA systems. Using multivariate analysis, seven significant variables were selected in the MOSAIC model wherein its C-statistic value was 0.772. These models also showed good performance with 0.720, 0.734 and 0.773 of C-statistics in the modified APACHE II, modified SOFA and MOSAIC scoring models in the external validation cohort (n = 497). CONCLUSION: The modified APACHE II/SOFA and newly developed MOSAIC models could be more useful tool for predicting mortality for patients receiving CRRT.

Hyperphosphatemia and risks of acute kidney injury, end-stage renal disease, and mortality in hospitalized patients.

BACKGROUND: Hyperphosphatemia is associated with vascular calcification and bone mineral disorders and is a major concern among patients with chronic kidney disease (CKD). However, the relationship between hyperphosphatemia and renal outcome in non-CKD patients has not been studied. Furthermore, the clinical implications of hyperphosphatemia in relation to the risks of acute kidney injury (AKI), end-stage renal disease (ESRD), and mortality after hospitalization remain unresolved. METHODS: A total of 20,686 patients (aged ≥18 years) admitted to Seoul National University Bundang Hospital from January 2013 to December 2013 were retrospectively reviewed. Patients were divided into quartiles according to serum phosphorus level at the time of admission. The odds ratios (ORs) for AKI and hazard ratios (HRs) for ESRD and all-cause mortality were calculated after adjustment of multiple covariates. RESULTS: AKI developed in 2319 patients (11.2%), with higher ORs for patients in the third and fourth quartiles (1.4 [1.24-1.68] and 2.8 [2.44-3.22], respectively) compared with the first quartile group. During a median follow-up period of 4.0 years, 183 patients (0.88%) developed ESRD and 3675 patients (17.8%) died. Patients in the fourth quartile had higher risks of ESRD and mortality than patients in the first quartile (HRs, 2.3 [1.46-3.75] and 1.4 [1.22-1.49], respectively). These trends remained consistent in patients with an estimated glomerular filtration rate > 60 ml/min/1.73 m2. CONCLUSIONS: Hyperphosphatemia is related to the risks of AKI, ESRD, and mortality, and it may therefore be necessary to monitor serum phosphorus level in hospitalized patients, irrespective of kidney function.

Evaluation of a Telehealth Counseling Program for Expatriates.

Background: Health problems for expatriates are common due to their vulnerability to local infectious diseases, psychosocial problems, and chronic diseases, but many problems go largely unmet in this unique population. Introduction: Telehealth counseling was developed and tested for Korean expatriates. We explored the current status of using telehealth counseling systems and showed its feasibility and acceptability in three countries. Materials and Methods: This retrospective study was based on the "Development and demonstration of telehealth counseling program for overseas Koreans" project funded by the Korea Health Industry Development Institute. In this project, we established five Digital Healthcare Centers (DHCs): 3 in Vietnam and 1 each in Uzbekistan and Cambodia. We used data from October 2016 to September 2017; descriptive analysis and one-way ANOVA were used to present detailed information. Results: A total of 442 patients made an appointment for telehealth counseling services. Overall user satisfaction rates were 96.1%. Over two thirds of patients (302/442, 68.3%) completed one-time telehealth counseling. About 13% were referred to primary care, and 17 (3.8%) were referred to specialists or tertiary hospital. The most common diagnostic category was endocrine, nutritional, and metabolic diseases (14%), followed by diseases of the circulatory system (12.3%) for one-time visit patients. Discussion: Our telehealth counseling program for expatriates was feasible and acceptable in three countries. It also has the potential to minimize language barriers and the cost of healthcare usage. Conclusion: Further research for sustainable effective telehealth systems for expatriates will be needed.

Impact of Electronic Acute Kidney Injury (AKI) Alerts With Automated Nephrologist Consultation on Detection and Severity of AKI: A Quality Improvement Study.

BACKGROUND: Several electronic alert systems for acute kidney injury (AKI) have been introduced. However, their clinical benefits require further investigation. STUDY DESIGN: Before-and-after quality improvement study. SETTING & PARTICIPANTS: A tertiary teaching hospital in Korea, which adopted an AKI alert system on June 1, 2014. Before and after launch of the alert system, 1,884 and 1,309 patients with AKI were included in the usual-care and alert groups, respectively. QUALITY IMPROVEMENT PLAN: Implementation of an AKI alert system through which clinicians could generate automated consultations to the nephrology division for all hospitalized patients. OUTCOMES: Primary outcomes included overlooked AKI events, defined as not measuring the follow-up creatinine value, and the consultation pattern of clinicians. Secondary outcomes were severe AKI events; AKI recovery, defined based on the creatinine-based criterion; and patient mortality. MEASUREMENTS: ORs for events of overlooked AKI, early consultation, and severe AKI were calculated with logistic regression. AKI recovery rate and patient mortality were assessed using Cox regression. RESULTS: After introduction of the alert system, the odds of overlooked AKI events were significantly lower (adjusted OR, 0.40; 95% CI, 0.30-0.52), and the odds of an early consultation with a nephrologist were greater (adjusted OR, 6.13; 95% CI, 4.80-7.82). The odds of a severe AKI event was reduced after implementation of the alerts (adjusted OR, 0.75; 95% CI, 0.64-0.89). Furthermore, the likelihood of AKI recovery was improved in the alert group (adjusted HR, 1.70; 95% CI, 1.53-1.88). Mortality was not affected by the AKI alert system (adjusted HR, 1.07; 95% CI, 0.68-1.68). LIMITATIONS: Possible unreported differences between the alert and usual-care groups. CONCLUSIONS: Implementation of the AKI alert system was associated with beneficial effects in terms of an improved rate of recovery from AKI. Therefore, widespread adoption of such systems could be considered in general hospitals.

Pregnancy in women with immunoglobulin A nephropathy: are obstetrical complications associated with renal prognosis?

Background: Recent studies regarding immunoglobulin A nephropathy (IgAN) suggest no relationship between pregnancy and disease progression, although complicated pregnancies and impaired renal function are closely related. Methods: This study used a propensity-score-matched cohort analysis. Among biopsy-confirmed IgAN women in three hospitals in Korea, those who experienced pregnancy after their diagnosis were included in the study group. Renal outcome was the composite of serum creatinine doubling, estimated glomerular filtration rate (eGFR) halving and events of end-stage renal disease. Pregnancies with preterm birth, low birth weight and pre-eclampsia were defined as complicated. Results: Overall, 59 IgAN women who became pregnant after their diagnosis, and the same number of IgAN women who did not experience pregnancy were included in the control group. Although pregnancy itself did not worsen renal outcomes [adjusted hazard ratio (HR): 1.51; 95% confidence interval (CI) 0.57-4.01; P = 0.41], mothers with complicated pregnancies experienced worse renal prognosis, even after adjustment for baseline and pre-gestational characteristics (adjusted HR: 5.07; 95% CI 1.81-14.22; P = 0.002). Moreover, this relationship was only significant in mothers with decreased renal function (eGFR <60 mL/min/1.73 m2) (adjusted HR: 18.70; 95% CI 1.63-214.40; P = 0.02), baseline hypertension (adjusted HR: 4.17; 95% CI 1.13-15.33; P = 0.03) and overt proteinuria (≥1 g/day) (adjusted HR: 4.21; 95% CI 1.24-14.27; P = 0.02). In contrast, patients who experienced pregnancies without complications showed better renal outcomes than did those without post-biopsy pregnancy (P = 0.01). Conclusion: Obstetric complications in patients with high renal risk, rather than pregnancy itself, are associated with renal progression of IgAN women.

Gestational Estimated Glomerular Filtration Rate and Adverse Maternofetal Outcomes.

BACKGROUND/AIMS: The association between gestational estimated glomerular filtration rate (eGFR) and adverse pregnancy outcomes has not been fully investigated. METHODS: This observational cohort study included pregnancy cases of singleton mothers whose serum creatinine levels were measured during pregnancy at two tertiary hospitals in Korea from 2000 to 2015. Those with identified substantial renal function impairment (eGFR < 60 mL/min/1.73 m2 at baseline, during, or after pregnancy) were excluded. The Chronic Kidney Disease Epidemiology Collaboration equation was used for the eGFR calculation. We computed the time-averaged eGFR during gestation to determine representative values when there were multiple measurements. We studied the following three gestational complications: preterm birth (< 37 weeks' gestational age), low birth weight (< 2.5 kg), and preeclampsia. RESULTS: Among the 12,899 studied pregnancies, 4,360 cases experienced one or more gestational complications. The adjusted odds ratio (aOR) and 95% confidence interval of composite gestational complications for eGFR ranges other than the reference range of 120-150 mL/ min/1.73m2 were: ≥150 mL/min/1.73m2, aOR 1.64 (1.38-1.95), P< 0.001; 90-120 mL/min/1.73m2, aOR 1.41 (1.28-1.56), P< 0.001; and 60-90 mL/min/1.73m2, aOR 2.56 (1.70-3.84), P< 0.001. Incidence of preterm birth or low birth weight showed similar U-shaped association with eGFR values; otherwise, preeclampsia or small for gestational age occurred more often in mothers with a lower gestational eGFR than in those with a higher value. CONCLUSION: Considering the unique association between gestational eGFR and pregnancy outcomes, carefully interpreting these results may help predict obstetric complications.

Systolic and diastolic dysfunction affects kidney outcomes in hospitalized patients.

BACKGROUNDS: Knowledge on cross-talk between the heart and kidney has been established by basic and clinical research. Nevertheless, the effects of systolic and diastolic heart dysfunctions on the development of acute kidney injury (AKI) and end-stage renal disease (ESRD) remain unresolved in hospitalized patients. METHODS: A total of 1327 hospitalized patients who had baseline transthoracic echocardiography performed were retrospectively analyzed. Patients were categorized by the quartiles of ejection fraction (EF) and the ratio of the early transmitral blood flow velocity to early diastolic velocity of the mitral annulus (E/e'). The odds ratios (ORs) for AKI and the hazard ratios (HRs) for ESRD were calculated after adjustment of multiple covariates. RESULTS: During hospital admission, AKI occurred in 210 (15.8%) patients. The lowest quartile of EF was associated with a risk of AKI (OR, 1.60 [1.07-2.41]) and the highest quartile of E/e' was associated with a risk of AKI (OR, 1.90 [1.26-2.41]). When two echocardiographic parameters were combined, patients with a low EF (first to second quartiles) and high E/e' (fourth quartile) showed the highest OR for AKI (OR, 2.27 [1.49-3.45]) compared with the counterpart patients. When the risk of ESRD was evaluated, E/e', but not EF, was a significant parameter of high risk (fourth vs. first quartiles: HR, 4.13 [1.17-14.64]). CONCLUSIONS: Baseline systolic and diastolic dysfunction is related to subsequent risks of AKI and ESRD in hospitalized patients. Monitoring of these parameters may be a useful strategy to predict the risk of these adverse events in the kidney.

Clinical Usefulness of Unenhanced Computed Tomography in Patients with Acute Pyelonephritis.

BACKGROUND: Unenhanced computed tomography (UCT) may be useful for evaluating acute pyelonephritis; however, no study has compared UCT with enhanced computed tomography (ECT) as a diagnostic tool. We evaluated a clinical usefulness of UCT versus ECT in acute pyelonephritis (APN). METHODS: We reviewed the clinical and radiological data from 183 APN-suspected patients who underwent UCT and ECT simultaneously at emergency room (ER) over a two-year period. Demographic, clinical parameters and computed tomography (CT) parameters of 149 patients were compared. RESULTS: The average patient age was 61.2 (± 10) years: 31 patients were men. Ninety-nine (66.4%) patients showed stones (18.7%), perinephric infiltration (56%), swelling (21%), and hydronephrosis (6.7%) on UCT. Seventeen patients (11.4%) had an atypical clinical course, requiring additional tests for accurate diagnosis. In 7 patients UCT and ECT results did not differ; in 10 patients, the diagnosis changed on ECT. On ECT, 112/149 (75.2%) patients had stones (16.7%), perinephric infiltrations (57%), swelling (21%), and hydronephrosis (6.7%); 62.5% showed parenchymal involvement: 34 (22.8%) patients had no abnormal ECT findings. APN CT findings are similar on stone, perinephric infiltration, swelling and hydronephrosis on both CTs. Twelve patients (8.0%) had an abnormal ECT finding, i.e., low-grade (1 and 2) parenchymal involvement. Six (4%) patients developed contrast-induced acute kidney injury within 2 days after ECT. CONCLUSION: We demonstrate that UCT is not inferior to ECT as an initial tool for evaluating APN for screening nephrolithiasis and hydronephrosis without the risk of contrast-induced acute kidney injury (CIAKI). However, patients with an atypical clinical course may still need ECT.

Differential Signature of Obesity in the Relationship with Acute Kidney Injury and Mortality after Coronary Artery Bypass Grafting.

BACKGROUND: Obesity is related to several comorbidities and mortality, but its relationship with acute kidney injury (AKI) and long-term mortality remain undetermined in patients undergoing coronary artery bypass grafting. METHODS: Data from 3,018 patients (age ≥ 18 years) who underwent coronary artery bypass graft surgery from two tertiary referral centers were retrospectively reviewed between 2004 and 2015. Obesity was defined using the body mass index, according to the World Health Organization's recommendation. The odds and hazard ratios in post-surgical, AKI, and all-cause mortality were calculated after adjustment for multiple covariates. Patients were followed for 90 ± 40.9 months (maximum: 13 years). RESULTS: Among the cohort, 37.4%, 2.4%, 21.1%, 35.1%, and 4.0% of patients were classified as normal weight, underweight, overweight-at-risk, obese I, and obese II, respectively. Post-surgical AKI developed in 799 patients (26.5%). Patients in the obese groups (overweight-at-risk to obese II) had a higher risk of AKI than did those in the normal-weight group. During the follow-up period, 787 patients (26.1%) died. Underweight patients had a higher risk of mortality than did normal-weight patients, whereas overweight-at-risk, obese I, and obese II patients showed better survival rates. CONCLUSION: After coronary artery bypass graft surgery, obese patients encountered a high risk of AKI, and underweight patients exhibited a low chance of survival. Awareness of both obese and underweight statuses should be raised in these patients.

Higher Serum Levels of Osteoglycin Are Associated with All-Cause Mortality and Cardiovascular and Cerebrovascular Events in Patients with Advanced Chronic Kidney Disease.

Patients with chronic kidney disease (CKD) have markedly increased rates of major adverse cardiovascular and cerebrovascular events (MACCEs) and mortality. Therefore, identifying early biomarkers predicting clinical outcomes in patients with CKD is critical. We aimed to determine whether osteoglycin, a basic component of the vascular extracellular matrix, was associated with MACCEs or all-cause mortality, using data from a prospective randomized controlled study, K-STAR (Kremezin STudy Against Renal disease progression in Korea: NCT 00860431). A total of 383 patients (mean age: 56.4 years, men/women = 252/131) with CKD stage 3 to 4 from the original trial were enrolled in the present study. We measured serum osteoglycin level and examined the impact of osteoglycin on clinical outcomes. The mean value of osteoglycin levels was 13.3 ± 9.4 ng/mL (healthy control: 5.3 ± 2.1 ng/mL). In multivariable analysis, lower levels of proteinuria and hemoglobin and higher levels of C-reactive protein were significantly associated with higher osteoglycin levels. Estimated glomerular filtration rate was not related to osteoglycin level. During a mean follow-up period of 56 months, 25 deaths, 61 MACCEs, and 76 composite outcomes (all-cause mortality or MACCEs) occurred. In the non-diabetic group, each 1-ng/mL increase in serum osteoglycin was associated with all-cause mortality and composite outcome (hazard ratio [HR] = 1.058, P = 0.031; HR = 1.041, P = 0.036). However, osteoglycin levels were not associated with mortality, MACCEs, or composite outcome in the diabetic group. Our results indicate that serum osteoglycin is a potential predictor of adverse outcomes in patients with CKD.

Is Frailty a Modifiable Risk Factor of Future Adverse Outcomes in Elderly Patients with Incident End-Stage Renal Disease?

Little is known about the clinical significance of frailty and changes of frailty after dialysis initiation in elderly patients with end-stage renal disease (ESRD). We prospectively enrolled 46 elderly patients with incident ESRD at a dialysis center of a tertiary hospital between May 2013 and March 2015. Frailty was assessed by using a comprehensive geriatric assessment protocol and defined as a multidimensional frailty score of ≥ 10. The main outcome was the composite of all-cause death or cardiovascular hospitalization, as determined in June 2016. The median age of the 46 participants was 71.5 years, and 63.0% of them were men. During the median 17.7 months follow-up, the rate of composite outcome was 17.4%. In multivariate logistic regression analysis, after adjusting for age, sex, diabetes, body mass index (BMI), and time of predialytic nephrologic care, female sex, and increased BMI were associated with increased and decreased odds of frailty, respectively. In multivariate Cox proportional hazards analysis, after adjusting for age, sex, diabetes, BMI, and time of predialytic nephrologic care, frailty was significantly associated with the composite adverse outcome. In repeated frailty assessments, the multidimensional frailty score significantly improved 12 months after the initiation of dialysis, which largely relied on improved nutrition. Therefore, frailty needs to be assessed for risk stratification in elderly patients with incident ESRD.

Long-term Prognosis of Anti-Neutrophil Cytoplasmic Antibody-Negative Renal Vasculitis: Cohort Study in Korea.

Few studies have reported on the long-term prognosis of anti-neutrophil cytoplasmic antibody (ANCA)-negative renal vasculitis. Between April 2003 and December 2013, 48 patients were diagnosed with renal vasculitis. Their ANCA status was tested using indirect immunofluorescence and enzyme-linked immunosorbent assays. During a median (interquartile range) follow-up duration of 933.5 (257.5-2,079.0) days, 41.7% of patients progressed to end stage renal disease (ESRD) and 43.8% died from any cause. Of 48 patients, 6 and 42 were ANCA-negative and positive, respectively. The rate of ESRD within 3 months was higher in ANCA-negative patients than in ANCA-positive patients (P = 0.038). In Kaplan-Meier survival analysis, ANCA-negative patients showed shorter renal survival than did ANCA-positive patients (log-rank P = 0.033). In univariate Cox-proportional hazard regression analysis, ANCA-negative patients showed increased risk of ESRD, with a hazard ratio 3.190 (95% confidence interval, 1.028-9.895, P = 0.045). However, the effect of ANCA status on renal survival was not statistically significant in multivariate analysis. Finally, ANCA status did not significantly affect patient survival. In conclusion, long-term patient and renal survival of ANCA-negative renal vasculitis patients did not differ from those of ANCA-positive renal vasculitis patients. Therefore, different treatment strategy depending on ANCA status might be unnecessary.

Effects of acute kidney injury and chronic kidney disease on long-term mortality after coronary artery bypass grafting.

BACKGROUND: Both acute kidney injury (AKI) and chronic kidney disease (CKD) are important issues in patients undergoing coronary artery bypass grafting (CABG), particularly with regard to mortality. However, their synergistic or discrete effects on long-term mortality remain unresolved. METHODS: A total of 1,899 patients undergoing CABG were retrospectively analyzed. The adjusted hazard ratios for all-cause mortality were calculated after stratifying the timeframes. To evaluate the synergistic effects between AKI and CKD, the relative excess risk due to interaction was applied. RESULTS: The presence of AKI, CKD, or both increased the hazard ratios for mortality, compared with the absence of both: AKI alone, 1.84 (1.464-2.319); CKD alone, 2.46 (1.735-3.478); and AKI and CKD together, 3.21 (2.301-4.488). However, the relationships with mortality were different between AKI and CKD, according to the timeframes: AKI primarily affected early mortality, particularly within 3 years, whereas CKD had a relatively constant effect on both the early and late periods. When the parameters from the relative excess risk due to interaction were obtained, there was a synergistic additive effect on early mortality between AKI and CKD. CONCLUSIONS: The relationships with mortality after CABG were different between AKI and CKD. However, their effects were not exclusive but synergistic.

Anemia Is a Risk Factor for Acute Kidney Injury and Long-Term Mortality in Critically Ill Patients.

Acute kidney injury (AKI) is a major health concern, because AKI is related with an increase in morbidity and mortality. Anemia is related to AKI in several clinical settings. However, the relationship between anemia and AKI and the effect of anemia on long-term mortality are unresolved in critically ill patients. A total of 2,145 patients admitted to the intensive care unit were retrospectively analyzed. We calculated a threshold value of hemoglobin associated with an increased risk of AKI and used this value to define anemia. The odds ratios (ORs) and hazard ratios for AKI and all-cause mortality were calculated after adjusting for multiple covariates. The OR of AKI increased depending on the decrease in hemoglobin level and the ideal threshold point of hemoglobin linked to increasing AKI risk was 10.5 g/dL. We categorized patients into anemia (< 10.5 g/dL) and non-anemia (≥ 10.5 g/dL) groups. The risk of AKI was higher in the anemia group than the non-anemia group and this trend remained significant irrespective of the AKI development time (early vs. late) or duration (< 3 days vs. ≥ 3 days). Both anemia and AKI increased the 10-year mortality risk and this risk prediction was significantly separated by the presence of anemia and AKI. Furthermore, the risk prediction remained consistent irrespective of the AKI severity (i.e., recovery, stage, or duration of AKI). Based on these, we urge clinicians to monitor anemia and AKI in critically ill patients.