Uncertain Clinical Effect of Polymyxin B Hemoperfusion in Patients with Septic Acute Kidney Injury Requiring Continuous Renal Replacement Therapy.

ABSTRACT: Polymyxin B hemoperfusion (PMX-HP) may improve the clinical outcomes of patients with sepsis and gram-negative bacteremia by reducing endotoxin levels. However, the recent studies with the variable degree of renal support have shown that the improvement of survival rate by PMX-HP remains unclear in such patients. Therefore, we investigated whether the addition of PMX-HP to continuous renal replacement therapy (CRRT) could improve the survival rate than CRRT alone. This study included 231 patients with sepsis undergoing CRRT alone or PMX-HP with CRRT. Primary outcomes were 28-day and 90-day all-cause mortality. Urine output, ventilator support, and Sequential Organ Failure Assessment (SOFA) score were not significantly different between the two groups. Crude 28-day and 90-day mortality rates were higher in the PMX-HP with CRRT group than in the CRRT-alone group. To correct for disease severity, propensity score (PS) matching was performed with acute respiratory distress syndrome, mechanical ventilation support, extracorporeal membrane oxygenation, infection source (abdomen), age, inotropic score, SOFA score, C-reactive protein, and procalcitonin levels. Sixty-six PS-matched pairs revealed significantly higher 28-day and 90-day mortality rates in the PMX-HP with CRRT group than in the CRRT-alone group. Considering the mortality rates after PS matching, the additional use of PMX-HP does not improve the clinical outcomes of patients with sepsis and acute kidney injury requiring CRRT.

Blood temperature monitoring-guided vascular access intervention improved dialysis adequacy.

OBJECTIVES: The aim of this study was to investigate whether blood temperature monitoring-guided vascular access intervention could improve dialysis adequacy. METHODS: We retrospectively evaluated all patients who received outpatient-based prevalent hemodialysis patients (n = 84) in our artificial kidney room between January 2019 and October 2019. Through blood temperature monitoring, access blood flow was calculated every month and Kt/V was calculated every 3 months. The reference point was set at the time of vascular intervention in the patients (n = 27) who underwent intervention or at the middle of the study period in patients (n = 57) who did not undergo intervention. The mean blood temperature monitoring-estimated access flow and Kt/V before and after the reference point were calculated and compared. RESULTS: Among 84 patients, 30 (35.7%) showed access flow rates of <500 mL/min, calculated by blood temperature monitoring during the study period. Twenty-seven patients (32.1%) underwent vascular intervention, of whom 24 (28.6%) showed access flow rates of <500 mL/min, 2 (2.4%) showed weak bruit or thrill incapable of needling, and 1 (1.2%) presented acute occlusion. Six patients (7.1%) whose access flow rates were <500 mL/min refused to undergo intervention. All angiographies in the patients whose access flow rates were <500 mL/min who underwent intervention showed a significant stenosis. The mean change in blood temperature monitoring-estimated access flow and Kt/V before and after vascular intervention was 483.3 ± 490.6 and 0.19 ± 0.21, respectively, which showed significant differences (all p < 0.05). A weak positive correlation between the mean change in blood temperature monitoring-estimated access flow and Kt/V was shown in all study patients by Pearson's correlation analysis (r = 0.234, p = 0.033). CONCLUSION: Access flow estimation by blood temperature monitoring might identify candidates who require vascular intervention. Blood temperature monitoring-guided vascular intervention significantly improved access flow and dialysis adequacy.

A deep learning algorithm to detect anaemia with ECGs: a retrospective, multicentre study.

BACKGROUND: Anaemia is an important health-care burden globally, and screening for anaemia is crucial to prevent multi-organ injury, irreversible complications, and life-threatening adverse events. We aimed to establish whether a deep learning algorithm (DLA) that enables non-invasive anaemia screening from electrocardiograms (ECGs) might improve the detection of anaemia. METHODS: We did a retrospective, multicentre, diagnostic study in which a DLA was developed using ECGs and then internally and externally validated. We used data from two hospitals, Sejong General Hospital (hospital A) and Mediplex Sejong Hospital (hospital B), in South Korea. Data from hospital A was for DLA development and internal validation, and data from hospital B was for external validation. We included individuals who had at least one ECG with a haemoglobin measurement within 1 h of the index ECG and excluded individuals with missing demographic, electrocardiographic, or haemoglobin information. Three types of DLA were developed with 12-lead, 6-lead (limb lead), and single-lead (lead I) ECGs to detect haemoglobin concentrations of 10 g/dL or less. The DLA was built by a convolutional neural network and used 500-Hz raw ECG, age, and sex as input data. FINDINGS: The study period ran from Oct 1, 2016, to Sept 30, 2019, in hospital A and March 1, 2017, to Sept 30, 2019, in hospital B. 40 513 patients at hospital A and 4737 patients at hospital B were eligible for inclusion. We excluded 281 patients at hospital A and 72 patients at hospital B because of missing values for clinical information and ECG data. The development dataset comprised 57 435 ECGs from 31 898 patients, and the algorithm was internally validated with 7974 ECGs from 7974 patients. The external validation dataset included 4665 ECGs from 4665 patients. 586 (internal) and 194 (external) patients within the combined dataset were found to be anaemic. During internal and external validation, the area under the receiver operating characteristics curve (AUROC) of the DLA using a 12-lead ECG for detecting anaemia was 0·923 for internal validation and 0·901 for external validation. Using a 90% sensitivity operating point for the development data, the sensitivity, specificity, negative predictive value, and positive predictive value of internal validation were 89·8%, 81·5%, 99·4%, and 20·0%, respectively, and those of external validation were 86·1%, 76·2%, 99·2%, and 13·5%, respectively. The DLA focused on the QRS complex for deciding the presence of anaemia in a sensitivity map. The AUROCs of DLAs using 6 leads and a single lead were in the range of 0·841-0·890. INTERPRETATION: In this study, using raw ECG data, a DLA accurately detected anaemia. The application of artificial intelligence to ECGs could enable screening for anaemia. FUNDING: None.

Dialysis-specific factors and incident atrial fibrillation in hemodialysis patients.

BACKGROUND: Atrial fibrillation (AF) is common in end-stage renal disease patients. Besides the traditional risk factors, we aimed to find dialysis-specific factors for developing incident AF. METHODS: From March 2017 to August 2018, we retrospectively reviewed all outpatient-based prevalent hemodialysis patients in our artificial kidney room, and they were followed up until August 2019. Dialysate calcium concentration (3 versus 2.5 mEq/L), time length (4 versus 3.5 h), frequency (thrice weekly versus twice weekly), dialyzer size (effective surface area of 1.4 m2 versus 1.8 m2), membrane permeability (high flux versus low flux), ultrafiltration rate (mL/kg/hour), and blood flow rate (mL/min) were evaluated. RESULTS: Among a total of 84 patients, 15 (17.9%) had newly detected AF with a follow-up period of 21 (13.3-24) months. By performing multivariate Cox regression analysis, blood flow rate (mL/min) and ultrafiltration rate (mL/kg/h) were considered significant factors for developing incident AF (adjusted hazard ratio [HR], 0.977; p = 0.011 and adjusted HR, 1.176; p = 0.013, respectively), while dialysis bath, time length, and frequency, dialyzer size, and membrane type were not considered significant factors. Ultrafiltration cutoff rate of 8.6 mL/kg/h was the best predictive factor for incident AF (area under the curve-receiver operating characteristic [AUC-ROC], 0.746; p < 0.005), while blood flow rate was not considered a significant factor for incident AF in ROC analysis (AUC-ROC, 0.623; p = 0.126). Ultrafiltration rate was largely dependent on interdialytic weight gain (p < 0.005, linear-by-linear association). CONCLUSION: Higher ultrafiltration rate was associated with incident AF in hemodialysis patients.

Nutritional Adequacy and Latent Tuberculosis Infection in End-Stage Renal Disease Patients.

BACKGROUND: Latent tuberculosis infection (LTBI) is prevalent in end-stage renal disease (ESRD) patients. The risk of tuberculosis activation is also high. The appropriate LTBI screening and treatment is required in this population. Meanwhile, whether hemodialysis adequacy is associated with LTBI in the ESRD population is unclear. In this study, we aimed to investigate the association between hemodialysis adequacy and LTBI in ESRD patients. METHODS: In the present cross-sectional study, we reviewed all outpatient-based ESRD patients in our artificial kidney room. Interferon gamma release assay (IGRA) was used for the diagnosis of LTBI. Clinical variables including nutritional adequacy (i.e., normalized protein catabolic rate, nPCR) and dialysis adequacy (i.e., Kt/V) were compared between IGRA-positive and IGRA-negative patients. RESULTS: A total of 90 patients were enrolled, of which 20 (22.2%) had positive IGRA results using the QuantiFERON-TB method. Old fibrotic changes and nPCR (g/kg/day) were significantly different between IGRA-positive and IGRA-negative patients (both p < 0.005), while serum albumin and Kt/V were comparable (p = 0.429 and p = 0.590, respectively). Normalized PCR remained to be significant in a multivariate logistic regression analysis (adjusted hazard ratio, 0.911 (0.861-0.963); p = 0.001). The cutoff nPCR value less than 0.87 g/kg/day had an adjusted hazard ratio of 7.74 (1.77-33.74) for predicting LTBI. Patients with nPCR value less than 0.87 g/kg/day were older and had lower serum hemoglobin, albumin, calcium concentration, and Kt/V levels than those with nPCR value greater than 0.87 g/kg/day. CONCLUSIONS: Nutritional adequacy, especially when assessing nPCR value, was associated with LTBI, while dialysis adequacy was not associated with LTBI.

A risk scoring model to predict renal progression associated with postcontrast acute kidney injury in chronic kidney disease patients.

Postcontrast acute kidney injury (AKI) occurs more frequently in patients with lower estimated glomerular filtration rate. We hypothesized that postcontrast AKI in chronic kidney disease (CKD) patients with distinct risk factors might be associated with accelerated renal progression.We undertook this retrospective cohort study to develop and validate a risk scoring model for predicting renal progression. In a development dataset, 18,278 contrast-enhanced CT scans were performed in 9097 patients with CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m) who were not undergoing dialysis. Postcontrast AKI was observed in 5.8% (1051/18,278) of all contrast-enhanced CTs with 7.6% (689/9097) of the total CKD patients. We investigated the 1-year renal outcome in 224 eligible patients. A risk scoring model was developed with multivariate regression analysis and was assessed in external validation (independent 154 patients).Among 224 patients, 70 (31.3%) patients had progression of renal dysfunction at 1 year (defined as reduction in estimated GFR ≥25% at 1 year). A risk score of 4, 4, 6, 6, 7, or 6 was assigned to diabetes, baseline estimated GFR < 45 mL/min/1.73 m, hypertension, repeated contrast exposure, congestive heart failure, and persistent renal injury (defined as an elevation of serum creatinine ≥25% at 3 months), respectively. An increasing risk score was associated with renal progression. Of note, persistent renal injury was more prevalent in the progression group than in the non-progression group. The AUROC of the model in the development population was 0.765. In the validation dataset, however, the discriminative power decreased (AUROC = 0.653).Our suggested model provided the risk of renal progression, aiding in predicting prognosis, counseling, and improving outcomes in CKD patients complicated by postcontrast AKI.

Predictive Factors of Duration of Continuous Renal Replacement Therapy in Acute Kidney Injury Survivors.

The factors influencing continuous renal replacement therapy (CRRT) duration for critically ill patients with acute kidney injury (AKI) are unclear. Therefore, we investigated the clinical factors that could influence the duration of CRRT for AKI survivors. In this retrospective observational study, the medical records of all hospital survivors who required CRRT for AKI in intensive care units were analyzed. The CRRT duration (median, 6 days) was categorized as short-duration CRRT (≤ 6 days, n = 65) and long-duration CRRT (> 6 days, n = 59), according to the median CRRT duration. A urine output of less than 0.5 mL/kg/h (adjusted odds ratio [OR], 3.4; P = 0.010), mechanical ventilation use (adjusted OR, 7.9; P = 0.001), and extracorporeal membrane oxygenation (ECMO) use (adjusted OR, 6.5; P = 0.010) were independent predictors of long-duration CRRT, whereas serum creatinine and neutrophil gelatinase-associated lipocalin were not significant predictors. A clinical model demonstrated a good discriminatory ability to predict long-duration CRRT (area under the curve, 0.84; 95% confidence interval, 0.76-0.90). The urine output immediately before CRRT initiation and factors associated with disease severity significantly affected the duration of CRRT. Simultaneously considering the urine output, mechanical ventilation use, and ECMO use predicted CRRT duration in AKI survivors.

Change in alkaline phosphatase activity associated with intensive care unit and hospital length of stay in patients with septic acute kidney injury on continuous renal replacement therapy.

BACKGROUND: Evidence suggests that alkaline phosphatase attenuates inflammatory response in sepsis by lipopolysaccharide detoxification and adenosine triphosphate dephosphorylation. We sought to determine changes in alkaline phosphatase (AP) activity during septic acute kidney injury (AKI) and clinical parameters associated with AP activity. METHODS: In this retrospective study, we investigated baseline (when initiating CRRT) and follow-up AP activity on day 3, and associated outcomes in patients who underwent continuous renal replacement therapy (CRRT) due to septic AKI. RESULTS: We analyzed the baseline AP activity of 155 patients and day 3 AP activity in 123 patients. Baseline AP activity was not associated with renal or inflammatory biomarkers, or outcomes. It did not significantly differ between the 75 survivors and 80 non-survivors (p = 0.155). AP activity was higher on day 3 than at baseline (105 U/L [interquartile range, 79-156] vs 90 U/L [interquartile range, 59-133]). In particular, liver and bone isoforms increased significantly (p < 0.05), but intestine isoforms did not reach statistical significance (p = 0.367). In addition, day 3 AP activity showed a weak correlation with length of ICU stay (r = 0.213, p = 0.018) and length of hospital stay (r = 0.216, p = 0.017), but not with survival (r = - 0.035, p = 0.698). CONCLUSION: Endogenous AP activity significantly increased in patients with septic AKI. However, neither baseline nor follow-up AP activity was associated with survival.

Association between afebrile status and in-hospital mortality among adult chronic hemodialysis patients with bacteremia.

AIM: We aimed to compare the in-hospital mortality between febrile and afebrile chronic hemodialysis (HD) patients with bacteremia and analyze the blood culture positive rate according to the C-reactive protein (CRP) level. METHODS: We collected data from 2006 to 2014. One hundred ninety bacteremic events were assigned to the "febrile group" (n = 162) and "afebrile group" (n = 28) based on the presence of fever. Fever was defined as a tympanic temperature >37.5°C or axillary temperature >37.0°C. RESULTS: In-hospital mortality (41.4% vs. 6.1%) was higher; and the interval between admission and blood culture was longer (3 vs. 1 h) in the afebrile group than in the febrile group. The mean reason for blood culture in the afebrile group was a high CRP level. CONCLUSIONS: An afebrile status in HD patients with bacteremia is associated with higher in-hospital mortality. Blood culture and empirical antibiotic administration, irrespective of the fever status, should be considered in HD patients with a CRP ≥ 5 mg/dL.

Outcomes of living donor kidney transplantation in diabetic patients: age and sex matched comparison with non-diabetic patients.

BACKGROUND/AIMS: Kidney transplantation (KT) reportedly provides a significant survival advantage over dialysis in diabetic patients. However, KT outcome in diabetic patients compared with that in non-diabetic patients remains controversial. In addition, owing to recent improvements in the outcomes of KT and management of cardiovascular diseases, it is necessary to analyze outcomes of recently performed KT in diabetic patients. METHODS: We reviewed all diabetic patients who received living donor KT between January 2008 and December 2011. Each patient was age- and sex-matched with two non-diabetic patients who received living donor KT during the same period. The outcomes of living donor KT were compared between diabetic and non-diabetic patients. RESULTS: Among 887 patients, 89 diabetic patients were compared with 178 non-diabetic patients. The incidence of acute rejection was not different between the diabetic and non-diabetic patients. Urinary tract infection and other infections as well as cardiovascular events occurred more frequently in diabetic patients. However, diabetes, cardiovascular disease, and infection were not significant risk factors of graft failure. Late rejection (acute rejection after 1 year of transplantation) was the most important risk factor for graft failure after adjusting for diabetes mellitus (DM), human leukocyte antigen mismatch, rejection and infection (hazard ratio, 56.082; 95% confidence interval, 7.169 to 438.702; p < 0.001). Mortality was not significantly different between diabetic and non-diabetic patients (0 vs. 2, p = 0.344 by log-rank test). CONCLUSIONS: End-stage renal disease patients with DM had favorable outcomes with living donor kidney transplantation.

Early continuous renal replacement therapy in septic acute kidney injury could be defined by its initiation within 24 hours of vasopressor infusion.

PURPOSE: The optimal timing for the initiation of early continuous renal replacement therapy (CRRT) is uncertain and requires a practically feasible definition with acceptable evidence. MATERIALS AND METHODS: We investigated the clinical impacts of 3-time interval parameters on the morbidity and mortality of 177 patients with septic shock-induced acute kidney injury: (1) time from vasopressor initiation to CRRT initiation (Tvaso-CRRT), (2) time from intensive care unit (ICU) admission to CRRT initation (TICU-CRRT), and (3) time from endotracheal intubation to CRRT initiation (Tendo-CRRT). RESULTS: The proportion of the patients with Tvaso-CRRT less than 24 h (median, 14 h, interquartile range [IQR], 5-30 h) was significantly higher in the survival group than in the non-survival group (84.3% vs. 58.5%, p < 0.001). Tvaso-CRRT less than 24 h and Sequential Organ Failure Assessment score were independent factors associated with 28-day mortality and 90-day mortality. TICU-CRRT (median, 17 h, IQR, 5-72 h) and Tendo-CRRT (median, 13 h, IQR, 4-48 h) were significantly correlated with both the length of ICU stay (p < 0.001) and mechanical ventilation duration (p < 0.001), but not mortality. CONCLUSIONS: Considering the possible therapeutic measurement by physician on the basis of the results in this study, early CRRT could be defined by a Tvaso-CRRT less than 24 h.

Risk factors for new-onset diabetes mellitus after living donor kidney transplantation in Korea - a retrospective single center study.

BACKGROUND: New-onset diabetes mellitus after transplantation (NODAT) is a serious complication following renal transplantation. The aim of this study was to identify the risk factors for the development of NODAT in Korean transplant patients. METHODS: Recipients who underwent living donor kidney transplantation between January 2009 and April 2012 at Asan Medical Center were reviewed. Diagnosis of NODAT was defined according to the American Diabetes Association criteria. RESULTS: A total of 418 patients were enrolled. NODAT was diagnosed in 85 (20.4 %) patients within 1 year. By multivariate analysis, old age (odds ratio [OR], 1.05; 95 % Confidence interval [CI]: 1.01-1.08), family history of diabetes mellitus (OR, 2.48; 95 % CI: 1.04-5.94), pre-transplant high serum glucose level (OR, 1.04; 95 % CI: 1.01-1.08), and obesity (OR, 3.46; 95 % CI: 1.55-7.73) were independent risk factors for NODAT. CONCLUSION: Old age, family history of diabetes, pre-transplant high plasma glucose level, and obesity are independent factors associated with the development of diabetes after renal transplantation. In contrast, serum magnesium levels and the use of tacrolimus are not associated with the development of NODAT.

Does stage III chronic kidney disease always progress to end-stage renal disease? A ten-year follow-up study.

OBJECTIVE: Clinically, it may be appropriate to subdivide patients with stage 3 chronic kidney disease (CKD) into two subgroups, as they show different risks for kidney outcomes. This study evaluated the proportion of patients with stage 3 CKD who progressed to stage 4 or 5 CKD over 10 years and independent predictors of progression of renal dysfunction. It sought to validate whether stage 3 CKD patients should be subdivided. MATERIAL AND METHODS: This retrospective cohort study enrolled 347 stage 3 CKD patients between January 1997 and December 1999, who were followed up through June 2010. The baseline clinical characteristics and outcomes were compared in patients with stage 3A [45

Fatal rhabdomyolysis in a patient with liver cirrhosis after switching from simvastatin to fluvastatin.

HMG-CoA reductase inhibitors (statins) are widely used to treat hypercholesterolemia. Among the adverse effects associated with these drugs are statin-associated myopathies, ranging from asymptomatic elevation of serum creatine kinase to fatal rhabdomyolysis. Fluvastatin-induced fatal rhabdomyolysis has not been previously reported. We describe here a patient with liver cirrhosis who experienced fluvastatin-induced fatal rhabdomyolysis. This patient had been treated with simvastatin (20 mg/day) for coronary artery disease and was switched to fluvastatin (20 mg/day) 10 days before admission. He was also taking aspirin, betaxolol, candesartan, lactulose, and entecavir. Rhabdomyolysis was complicated and continued to progress. He was treated with massive hydration, urine alkalization, intravenous furosemide, and continuous renal replacement therapy for acute renal failure, but eventually died due to rhabdomyolysis complicated by hepatic failure. In conclusion, fluvastatin should be used with caution in patients with liver cirrhosis, especially with other medications metabolized with CYP2C9.