Short-term All-cause In-hospital Mortality Prediction by Machine Learning Using Numeric Laboratory Results.

Introduction: A critical value (or panic value) is a laboratory test result that significantly deviates from the normal value and represents a potentially life-threatening condition requiring immediate action. Although notification of critical values by critical value list (CVL) is a well-established method, their contribution to mortality prediction is unclear. Methods: A total of 335,430 clinical laboratory results from 92,673 patients from July 2018 to December 2019 were used. Data in the first 12 months were divided into two datasets at a ratio of 70:30, and a 7-day mortality prediction model by machine learning (eXtreme Gradient Boosting [XGB] decision tree) was created using stratified random undersampling data of the 70% dataset. Mortality predictions by the CVL and XGB model were validated using the remaining 30% of the data, as well as different 6-month datasets from July to December 2019. Results: The true results which were the sum of correct predictions by the XGB model and CVL using the remaining 30% data were 61,535 and 61,024 tests, and the false results which were the sum of incorrect predictions were 5,492 and 6,003, respectively. Furthermore, the true results with the different datasets were 105,956 and 102,061 tests, and the false results were 6,052 and 9,947, respectively. The XGB model was significantly better than CVL (p < 0.001) in both datasets.The receiver operating characteristic-area under the curve values for the 30% and validation data by XGB were 0.9807 and 0.9646, respectively, which were significantly higher than those by CVL (0.7549 and 0.7172, respectively). Conclusions: Mortality prediction within 7 days by machine learning using numeric laboratory results was significantly better than that by conventional CVL. The results indicate that machine learning enables timely notification to healthcare providers and may be safer than prediction by conventional CVL.

The Role of Nurse on the Treatment Decision Support for Older People with Cancer: A Systematic Review.

Background: The number of older adults with cancer is increasing worldwide. The role of nurses in supporting patients' decision-making is expanding, as this process is fraught with complexity and uncertainty due to comorbidities, frailty, cognitive decline, etc., in older adults with cancer. The aim of this review was to examine the contemporary roles of oncology nurses in the treatment decision-making process in older adults with cancer. Methods: A systematic review of PubMed, CINAHL, and PsycINFO databases was conducted in accordance with PRISMA guidelines. Results: Of the 3029 articles screened, 56 full texts were assessed for eligibility, and 13 were included in the review. We identified three themes regarding nurses' roles in the decision-making process for older adults with cancer: accurate geriatric assessments, provision of available information, and advocacy. Nurses conduct geriatric assessments to identify geriatric syndromes, provide appropriate information, elicit patient preferences, and communicate efficiently with patients and caregivers, promoting physicians. Time constraints were cited as a barrier to fulfilling nurses' roles. Conclusions: The role of nurses is to elicit patients' broader health and social care needs to facilitate patient-centered decision-making, respecting their preferences and values. Further research focusing on the role of nurses that considers diverse cancer types and healthcare systems is needed.

Impact of a continuous quality improvement program on contrast-induced nephropathy in outpatients with chronic kidney disease: an interrupted time-series study.

BACKGROUND: Contrast-induced nephropathy (CIN) caused by exposure to radioactive contrast media can cause acute kidney injury in patients with chronic kidney disease (CKD). We developed a multifaceted approach in a CIN-quality improvement (QI) program based on a shorter saline hydration protocol for the prevention of CIN in outpatients and assessed the effect of our CIN-QI program on decreasing both the incidence rate of CIN and overall use of contrast agents in patients undergoing contrast-enhanced computed tomography (CT). METHODS: We conducted a multi-center prospective interrupted time-series study from 2006 to 2018 investigating the efficacy of a CIN-QI program in preventing CIN among outpatients with CKD. An automatic medical record system alert was implemented to instruct physicians to consult a nephrologist and administer prophylactic hydration and follow-up when ordering contrast-enhanced imaging in patients with an estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2. The primary outcomes were the rates of prophylactic hydration and follow-up kidney function assessment, and the incidence of CIN for eligible patients. The usage rate of contrast-enhanced CT was also examined. RESULTS: A total of 95 594 patients who underwent contrast-enhanced CT were included in the study. The annual prophylactic hydration rate before the CIN-QI program ranged from 2.0% to 23.2% but increased to 59.2%-75.2% during the CIN-QI program (P < .001). The annual rate of follow-up kidney function testing also improved from 18.6%-25.8% to 34.1%-42.5% after implementation of the CIN-QI program (P < .001). The rate of CIN significantly declined in level by 10.0% at the start of the CIN-QI program (P = .002) and in trend by 2.9%/year (P < .001). The number of contrast-enhanced CT orders showed a positive level change in patients with advanced CKD, who were the CIN-QI program target group of patients with eGFR <45 mL/min/1.73 m2, at the start of the implementation of the CIN-QI program. After implementing the CIN-QI program, the number of contrast-enhanced CT orders showed a negative trend change across all patients, which decreased from -1.4%/year to -10.0%/year for patients with advanced CKD. CONCLUSION: The multifaceted approach in the CIN-QI program may be associated with the decreased incidence of CIN and increased rates of prophylactic hydration and follow-up kidney function testing.

RNA editing facilitates the enhanced production of neoantigens during the simultaneous administration of oxaliplatin and radiotherapy in colorectal cancer.

Most cases of colorectal cancers (CRCs) are microsatellite stable (MSS), which frequently demonstrate lower response rates to immune checkpoint inhibitors (ICIs). RNA editing produces neoantigens by altering amino acid sequences. In this study, RNA editing was induced artificially by chemoradiation therapy (CRT) to generate neoantigens in MSS CRCs. Altogether, 543 CRC specimens were systematically analyzed, and the expression pattern of ADAR1 was investigated. In vitro and in vivo experiments were also performed. The RNA editing enzyme ADAR1 was upregulated in microsatellite instability-high CRCs, leading to their high affinity for ICIs. Although ADAR1 expression was low in MSS CRC, CRT including oxaliplatin (OX) treatment upregulated RNA editing levels by inducing ADAR1. Immunohistochemistry analyses showed the upregulation of ADAR1 in patients with CRC treated with CAPOX (capecitabine + OX) radiation therapy relative to ADAR1 expression in patients with CRC treated only by surgery (p < 0.001). Compared with other regimens, CRT with OX effectively induced RNA editing in MSS CRC cell lines (HT29 and Caco2, p < 0.001) via the induction of type 1 interferon-triggered ADAR1 expression. CRT with OX promoted the RNA editing of cyclin I, a neoantigen candidate. Neoantigens can be artificially induced by RNA editing via an OX-CRT regimen. CRT can promote proteomic diversity via RNA editing.

Longitudinal relationship between long sleep duration and future kidney function decline.

Background: Evidence linking chronic kidney disease (CKD) and sleep duration is inconsistent. This study examined whether sleep duration is associated with a long-term risk of kidney function decline. Methods: This retrospective, longitudinal cohort study included 82 001 participants who visited a primary care centre in Japan. Participants were categorized into CKD risk groups and sleep duration categories according to their self-reported average nightly sleep duration. The relationship between average nightly sleep duration and the incidence of composite renal outcome comprised a ≥40% reduction in estimated glomerular filtration rate (eGFR) from baseline and a decline in eGFR to <15 mL/min/1.73 m² was evaluated. Results: The mean age and eGFR (±standard deviation) of the patient cohort were 45.8 (±12.4) years and 81.8 (±15.4) mL/min/1.73 m², respectively. A total of 41 891 participants (51.1%) were women. During the median follow-up of 5.1 years [interquartile range 2.2-9.6], 4214 (5.1%) participants achieved the composite renal outcome. Only the long and very long sleep durations (≥8 h/night) were associated with an increased incidence of the composite renal outcome compared with the reference duration (7 h/night) [adjusted odds ratio (OR) 1.22 and 1.44; 95% confidence interval (CI) 1.09-1.36 and 1.13-1.84, for long and very long sleep durations, respectively]. Furthermore, this association was significant for both long and very long sleep durations in the low CKD risk group but only for long sleep duration in the intermediate CKD risk group. The results of the sex-specific analysis showed that men had a decreased risk of achieving the composite renal outcome (OR 0.91; 95% CI 0.79-1.06), while there was an increased risk for women (OR 1.14; 95% CI 1.02-1.28). Conclusions: Average sleep durations ≥8 h/night were associated with an increased incidence of poor renal outcomes over time. However, a longitudinal cohort study is required to confirm whether sleep duration can prevent poor renal outcomes.

Implementation of a rapid response system at an isolated radiotherapy facility through simulation training.

A rapid response system is required in a radiotherapy department for patients experiencing a critical event when access to an emergency department is poor due to geographic location and the patient is immobilised with a fixation device. We, therefore, rebuilt the response system and tested it through onsite simulations. A multidisciplinary core group was created and onsite simulations were conducted using a Plan-Do-Study-Act cycle. We identified the important characteristics of our facility, including its distance from the emergency department; the presence of many staff with little direct contact with patients; the treatment room environment and patient fixation with radiotherapy equipment. We also examined processes in each phase of the emergency response: detecting an emergency, calling the medical emergency team (MET), MET transportation to the site and on-site response and patient transportation to the emergency department. The protocol was modified, and equipment was updated. On-site simulations were held with and without explanation of the protocol and training scenario in advance. The time for the MET to arrive at the site during a 2017 simulation prior to the present project was 7 min, whereas the time to arrive after the first simulation session was shortened to 5 min and was then shortened further to 4 min in the second session, despite no prior explanation of the situation. A multidisciplinary project for emergency response with on-site simulations was conducted at an isolated radiation facility. A carefully planned emergency response is important not only in heavy ion therapy facilities but also in other departments and facilities that do not have easy access to hospital emergency departments.

Frequency of tooth brushing as a predictive factor for future kidney function decline.

BACKGROUND: Tooth brushing is important for maintaining oral health and preventing periodontal diseases (PDs), which commonly arise in patients with chronic kidney disease (CKD). However, the association between tooth brushing frequency and kidney function decline remains unclear. METHODS: We conducted a retrospective longitudinal study at St Luke's International Hospital, Japan, and participants who underwent health examinations at the Centre for Preventive Medicine from 2005 to 2011 were included. Participants' tooth brushing frequencies were assessed; multivariate analyses were conducted using a generalized estimating equation to evaluate the association between tooth brushing frequency and a composite renal outcome-composed of a 25% estimated glomerular filtration rate (eGFR) reduction, an eGFR of < 15 mL/min/1.73 m2, and a requirement for regular dialysis-after adjusting for potential covariates. We also stratified participants by baseline CKD risk category to perform sub-analyses. RESULTS: Overall, 76,472 participants were included (mean age of 45.9 years) and 38,233 (50%) were male. During follow-up, 8219 participants (10.8%) experienced composite renal outcomes. Brushing teeth at least once to twice a day was associated with significantly lower incidences of composite renal outcomes than brushing teeth less frequently (adjusted odds ratio [OR] 0.26; 95% confidence interval [CI] 0.24-0.28 for once to twice a day; adjusted OR 0.65; 95% CI 0.62-0.69 for after every meal). In our sub-analyses, brushing at least once to twice a day related to a decreased likelihood of composite renal outcomes; however, this effect was only observed within the low and moderate baseline risk groups. CONCLUSION: Frequent tooth brushing benefits oral health and may be associated with slower kidney function decline, which could have implications for other systemic diseases. However, a longitudinal cohort study is required to confirm whether tooth brushing and overall oral health can haver a role in improving  renal outcomes.

A phase 3, open-label, single-arm study of vadadustat for anemia in chronic kidney disease for Japanese patients on hemodialysis not receiving erythropoiesis-stimulating agents.

Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor approved in Japan for the treatment of anemia in patients with chronic kidney disease (CKD). This phase 3, open-label, single-arm study evaluated the efficacy and safety of vadadustat in 24 Japanese patients with CKD-associated anemia on hemodialysis who were not receiving erythropoiesis-stimulating agents (ESAs). Patients received vadadustat for 24 weeks; the starting dose was 300 mg/day and doses were adjusted to achieve the target hemoglobin (Hb) range of 10.0-12.0 g/dL. The least squares mean of average Hb at Weeks 20 and 24 (95% confidence interval) was 10.75 g/dL (10.35, 11.14). The most common adverse event was shunt stenosis (25.0%). Adverse drug reactions (diarrhea and vomiting) occurred in two patients (8.3%) and the severity was mild. Vadadustat increased and maintained Hb levels within the target range and was generally well-tolerated in Japanese patients with anemia on hemodialysis not receiving ESAs.

Assessing urine ammonium concentration by urine osmolal gap in chronic kidney disease.

Acidemia is one of the risk factors for end-stage kidney disease and increases the mortality rate of patients with chronic kidney disease (CKD). Although urinary ammonium (U-NH4 + ) is the crucial component of renal acid excretion, U-NH4 + concentration is not routinely measured. To estimate U-NH4 + , urine osmolal gap (UOG = urine osmolality - [2(Na+ + K+ ) + urea + glucose]) is calculated and the formula (U-NH4 +  = UOG/2) has traditionally been used. However, the usefulness of this formula is controversial in CKD patients. We assessed the relationship between U-NH4 + and UOG in patients with CKD. Blood and spot urine samples were collected in 36 patients who had non-dialysis-dependent CKD. The mean ± SD age of patients was 72.0 ± 14.8 years, and the mean ± SD serum creatinine and U-NH4 + were 2.7 ± 2.3 mg/dl and 9.3 ± 9.2 mmol/L, respectively. A significant relationship was found between UOG/2 and U-NH4 + (r = .925, p < .0001). U-NH4 + estimated using the UOG was on average higher by 4.7 mmol/L than the measured one. Our results suggested that UOG could be a useful tool in clinical settings, especially in patients with moderate to severe CKD.

Immuno-hyperthermia effected by antibody-conjugated nanoparticles selectively targets and eradicates individual cancer cells.

Hyperthermia has been used for cancer therapy for a long period of time, but has shown limited clinical efficacy. Induction-heating hyperthermia using the combination of magnetic nanoparticles (MNPs) and an alternating magnetic field (AMF), termed magnetic hyperthermia (MHT), has previously shown efficacy in an orthotopic mouse model of disseminated gastric cancer. In the present study, superparamagnetic iron oxide nanoparticles (SPIONs), a type of MNP, were conjugated with an anti-HER2 antibody, trastuzumab and termed anti-HER2-antibody-linked SPION nanoparticles (anti-HER2 SPIONs). Anti-HER2 SPIONs selectively targeted HER2-expressing cancer cells co-cultured along with normal fibroblasts and HER2-negative cancer cells and caused apoptosis only in the HER2-expressing individual cancer cells. The results of the present study show proof-of-concept of a novel hyperthermia technology, immuno-MHT for selective cancer therapy, that targets individual cancer cells.Abbreviations: AMF: alternating magnetic field; DDW: double distilled water; DMEM: Dulbecco's Modified Eagle's; Medium; f: frequency; FBS: fetal bovine serum; FITC: Fluorescein isothiocyanate; GFP: green fluorescent protein; H: amplitude; Hsp: heat shock protein; MHT: magnetic hyperthermia; MNPs: magnetic nanoparticles; PI: propidium iodide; RFP: red fluorescent protein; SPION: superparamagnetic iron oxide (Fe3O4) nanoparticle.

Phase 3 Randomized Study Comparing Vadadustat with Darbepoetin Alfa for Anemia in Japanese Patients with Nondialysis-Dependent CKD.

BACKGROUND: Standard care for treating anemia in patients with CKD includes use of erythropoiesis-stimulating agents, which sometimes involves increased risks of cardiovascular morbidity and mortality. Previous studies in patients with anemia and nondialysis-dependent CKD (NDD-CKD) found significantly elevated hemoglobin levels with use of vadadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, compared with placebo. METHODS: In this phase 3, open-label, active-controlled noninferiority trial, we randomized 304 Japanese adults with anemia in NDD-CKD (including erythropoiesis-stimulating agent users and nonusers) to oral vadadustat or subcutaneous darbepoetin alfa for 52 weeks. The primary efficacy end point was average hemoglobin at weeks 20 and 24. Safety data included adverse events (AEs) and serious AEs. RESULTS: A total of 151 participants received vadadustat and 153 received darbepoetin alfa. Least squares mean of the average hemoglobin at weeks 20 and 24 was 11.66 (95% confidence interval [95% CI], 11.49 to 11.84) g/dl for vadadustat and 11.93 (95% CI, 11.76 to 12.10) g/dl for darbepoetin alfa. The 95% CIs for both treatments were within the target hemoglobin range (11.0-13.0 g/dl), and the lower 95% confidence limit for the difference between groups (-0.50 g/dl) was above the predefined noninferiority margin (-0.75 g/dl), demonstrating noninferiority of vadadustat to darbepoetin alfa. Similar proportions of patients in each group reported AEs and serious AEs. The most frequent AEs with vadadustat were nasopharyngitis, diarrhea, and constipation. CONCLUSIONS: In Japanese patients with NDD-CKD, vadadustat was noninferior to darbepoetin alfa, was effective up to week 52 in terms of average hemoglobin, and was generally well tolerated. These results suggest that vadadustat may be a potential treatment for anemia in this patient population.

Efficacy and safety of vadadustat compared with darbepoetin alfa in Japanese anemic patients on hemodialysis: a Phase 3, multicenter, randomized, double-blind study.

BACKGROUND: Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis. METHODS: The efficacy and safety of vadadustat, compared with darbepoetin alfa, was determined in a Phase 3 double-blind study in Japanese anemic patients on hemodialysis. Patients receiving erythropoiesis-stimulating agents (ESAs) were randomized and switched to either vadadustat or darbepoetin alfa for 52 weeks. Doses were adjusted to maintain a hemoglobin (Hb) level of 10.0-12.0 g/dL. The primary endpoint was average Hb level at Weeks 20 and 24. RESULTS: Of the 323 randomized patients, 120 and 135 completed the 52-week treatment period in the vadadustat and darbepoetin alfa groups, respectively. The average Hb levels at Weeks 20 and 24 [least square mean (LSM) and 95% confidence interval (CI)] were 10.61 (10.45-10.76) and 10.65 (10.50-10.80) g/dL in the vadadustat and darbepoetin alfa groups, respectively, demonstrating vadadustat's noninferiority to darbepoetin alfa (difference: -0.05 g/dL; 95% CI -0.26 to 0.17). In both groups, the mean Hb levels were maintained within the target range for 52 weeks. Furthermore, irrespective of patient backgrounds, the LSMs of Hb at Week 52 were within the target range. The most common adverse events were nasopharyngitis, diarrhea and shunt stenosis, which occurred at similar frequencies in both groups. No new safety concerns were identified. CONCLUSIONS: Vadadustat was as well-tolerated and effective as darbepoetin alfa in maintaining Hb levels within the target range. The findings suggest that vadadustat can be an alternative to ESA in the management of anemia in Japanese hemodialysis patients receiving ESA (ClinicalTrials.gov, NCT03439137).

Vadadustat for anemia in chronic kidney disease patients on peritoneal dialysis: A phase 3 open-label study in Japan.

Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor for the treatment of anemia in patients with chronic kidney disease (CKD). This phase 3, open-label, 24-week single-arm study evaluated the efficacy and safety of vadadustat in 42 Japanese CKD patients with anemia undergoing peritoneal dialysis. Patients received oral vadadustat for 24 weeks, initiated at 300 mg/day and doses were adjusted to achieve the target hemoglobin (Hb) range of 11.0-13.0 g/dL. Least squares mean of average Hb at weeks 20 and 24 was 11.35 g/dL, which was within the target range. The most frequent adverse events were catheter site infections (23.8%), which were not related to vadadustat treatment. Vadadustat was generally well tolerated and effective in controlling Hb levels within the target range, indicating the usefulness of vadadustat for treating anemia in Japanese CKD patients undergoing peritoneal dialysis.

The role and attitude of senior leaders in promoting group-based community physical activity: a qualitative study.

BACKGROUND: In the context of worldwide public health, it is very important to promote physical activity among the older people. This study explored the roles and attitudes of senior leaders in promoting group-based exercise in their local communities, specifically to determine the level and extent to which to elderly participation was encouraged. METHODS: This study conducted semi-structured face-to-face in-depth interviews and employed a subsequent thematic analysis. Participants included 10 club leaders and five sub-leaders who were working at senior clubs in Fujisawa-city, Kanagawa, Japan, from July to September 2018. RESULTS: Four themes emerged from the interview responses, including "unwavering attitude/conviction in relation to the vision," "leaders must set an example," "a search for balance in delegating responsibilities to members," and "creating and fostering culture and environment of mutual help." Further, each participant outlined several aims, including "achieving healthy longevity for the entire local community," "having older people promote healthy activities among the older people," and "creating a pro-health town." CONCLUSIONS: Findings indicate that policymakers, public health workers, and healthcare providers should recognize the pivotal roles that senior group leaders play in promoting healthy activities for the older people. These efforts should be strongly considered when developing policies and strategies designed to promote overall healthy longevity from a general community perspective.

Association between chronic kidney disease and mortality in stage IV cancer.

BACKGROUND: Chronic kidney disease (CKD) is known to be associated with cancer mortality. However, no study has considered the well-known cancer prognostic factors, ECOG Performance Status (PS) and cancer treatment, as confounding factors. We assessed the independent relationship between CKD and cancer death in stage IV cancer patients. METHODS: In this retrospective observational study, we included stage IV cancer patients diagnosed from 2009 to 2014 in a single center. We collected baseline clinical and laboratory variables, and cancer-specific variables, and assessed the presence of CKD. Our primary outcome was all-cause mortality. The secondary outcome was cancer-specific mortality and site-specific cancer mortality. RESULTS: Among 961 eligible stage IV cancer patients (median age 69 years, 51.8% male), 150 patients had CKD. During follow-up (median 9.8 months), 638 patients died, of whom 526 patients died from cancer. After adjusting for prognostic variables, including ECOG PS and cancer treatment, all-cause mortality and cancer-specific mortality were significantly higher in CKD patients than in non-CKD patients (HR 1.41, 95% CI 1.13-1.77 and HR 1.43, 95% CI 1.12-1.83, respectively). In patients with breast and kidney and urinary tract cancers, CKD was associated with a significantly increased risk of death (HR 7.01, 95% CI 1.47-33.4 and HR 3.33, 95% CI 1.42-7.78, respectively). CONCLUSIONS: CKD at the time of stage IV cancer diagnosis was associated with all-cause mortality and cancer-specific mortality. Moreover, the association between CKD and cancer-specific death was site specific for breast cancer and kidney and urinary tract cancer.

Possible solution for the problem of unread image interpretation reports: the "Gunma University Star Search".

PURPOSE: To propose a new strategy to prevent communication errors caused by unread radiology reports. MATERIALS AND METHODS: Medical emergencies were prefixed with triple stars on radiology reports, and the attending physician was contacted by telephone. Semi-emergencies (medical issues needing addressing within 2 weeks) were prefixed with double stars. Two weeks later, the duty radiologist would search the double-starred reports, and reviewed relevant patient charts to confirm that the information had been appropriately understood and acted upon. If not, the duty radiologist contacted the referral physician by telephone. One year after implementing this strategy, we retrospectively evaluated 1-year worth of data for all the reports of CT, MRI, nuclear medicine and ultrasonography (April 2018 to March 2019). RESULTS: Three hundred and twenty-one reports were double starred (0.52% of 62,143 reports, 1.32 reports/day), and transmission of relevant information was incomplete in 23 cases (7.17%). Causes of incomplete transmission were (1) reports not being opened (n = 17), (2) relevant information on reports being overlooked (n = 5), and (3) the wrong report being opened (n = 1). Sixty-five reports contained triple stars (0.10%, 0.27 reports/day). CONCLUSION: The proposed strategy may be effective in preventing communication errors in radiology reports with important findings requiring semi-emergency clinical action.

Serial measurement of electrolyte and citrate concentrations in blood-primed continuous hemodialysis circuits during closed-circuit dialysis.

BACKGROUND: For continuous renal replacement therapy in small infants, due to the large extracorporeal volume involved, blood priming can be necessary to prevent hypotension and hemodilution. Because packed red blood cells (RBCs) have high levels of potassium and citrate, closed-circuit dialysis is often performed. We assessed the metrics of closed-circuit dialysis and serial citrate concentration changes. METHODS: We performed dialysis of closed circuits primed with expired human packed RBC solution and 5% albumin. Blood and dialysate flow rates were 70 and 33.3 mL/min, respectively. The extracorporeal volume was 70 mL. We measured pH, electrolytes, and citrate in the closed circuit every 3 min for 15 min. We also assessed the adequacy of closed-circuit dialysis using the formula: [dialysate flow rate (mL/min) × time of dialysis (min)]/extracorporeal volume (mL) and we assessed the correlation between citrate and ionized calcium concentrations. RESULTS: To reach normal concentrations of sodium, potassium, and chloride, 2.4 times as much dialysate fluid as extracorporeal volume was needed. In contrast, for ionized calcium, bicarbonate, and citrate, 3.8 times as much dialysate fluid as extracorporeal volume was required. By simple linear regression analysis, the concentration of citrate was significantly correlated with that of ionized calcium. CONCLUSIONS: For closed-circuit dialysis using an RBC solution, the formula [dialysate flow rate (mL/min) × time of dialysis (min)]/extracorporeal volume (mL) would be a better parameter to estimate efficacy, compared with other metrics. Additionally, the citrate concentration can be readily estimated from the ionized calcium concentration during closed-circuit dialysis.