A Low-cost Creatinine Biosensor by Differential Optical Signal Readout for the Whole Blood Analysis.

This study developed a low-cost paper-based biosensor for point-of-care (POC) detection of blood creatinine by using differential optical signal readout. Dual-channel photochemical paper-based test strips were fabricated with stackable multilayer films containing pre-immobilized enzymes and reagents for the identification and conversion of creatinine and creatine. Enzyme-linked reactions generated hydrogen peroxide (H2O2), which formed a blue oxidized condensate with aniline derivatives. The color depth was quantified via the differential optical signal of the two channels and positively correlated with the concentration of the analyte. This method was first proposed to address the issue of endogenous interferences in the enzymatic assay of creatinine, greatly improving the detection accuracy. The proposed biosensor was calibrated with spiked blood samples, and achieved a wide detection range of 31-1483 µmol/L, showing superior detection performance to general enzymatic methods, especially in the low concentration range. Creatine interference testing demonstrated that the biosensor could resist the interference of ≤ 300 µmol/L endogenous creatine. It is believed that the proposed optical differential biosensor for blood creatinine could enable to pave the way for a daily monitoring system for renal diseases.Clinical Relevance- This stackable multilayer paper-based biosensor provides an enzymatic colorimetric assay of creatinine in whole blood, which can be read out by the differential optical signal to exclude interference from endogenous creatine.

Risk assessment and environmental determinants of urinary phthalate metabolites in pregnant women in Southwest China.

Pregnant women are widely exposed to phthalic acid esters (PAEs) that are commonly used in most aspects of modern life. However, few studies have examined the cumulative exposure of pregnant women to a variety of PAEs derived from the living environmental conditions in China. Therefore, this study aimed to determine the urinary concentrations of nine PAE metabolites in pregnant women, examine the relationship between urinary concentrations and residential characteristics, and conduct a risk assessment analysis. We included 1,888 women who were in their third trimester of pregnancy, and we determined their urinary concentrations of nine PAE metabolites using high-performance gas chromatography-mass spectrometry. The risk assessment of exposure to PAEs was calculated based on the estimated daily intake. A linear regression model was used to analyze the relationship between creatinine-adjusted PAE metabolite concentrations and residential characteristics. The detection rate of five PAE metabolites in the study population was > 90%. Among the PAE metabolites adjusted by creatinine, the urinary metabolite concentration of monobutyl phthalate was found to be the highest. Residential factors, such as housing type, proximity to streets, recent decorations, lack of ventilation in the kitchen, less than equal to three rooms, and the use of coal/kerosene/wood/wheat straw fuels, were all significantly associated with high PAE metabolite concentrations. Due to PAE exposure, ~ 42% (n = 793) of the participants faced potential health risks, particularly attributed to dibutyl phthalate, diisobutyl phthalate, and di(2-ethyl)hexyl phthalate exposure. Living in buildings and using coal/kerosene/wood/wheat straw as domestic fuel can further increase the risks.

Assessment of Measurement of Salivary Urea by ATR-FTIR Spectroscopy to Screen for CKD.

Stages of CKD are currently defined by eGFR and require measurement of serum creatinine concentrations. Previous studies have shown a good correlation between salivary and serum urea levels and the stage of CKD. However, quantitative salivary urea assays in current clinical use require costly and labor-intensive commercial kits, which restricts the advantage of using saliva and limits wider applicability as a quick and easy means of assessing renal function. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy has been shown to provide a potentially straightforward, reagent-free method for the identification of a range of disease-related biomarkers and is in current clinical use for analyses of the chemical composition of kidney stones. We assessed the feasibility of ATR-FTIR spectroscopy as an alternative method to measure salivary urea in patients with different stages of CKD. The ATR-FTIR spectra of dried saliva samples from six healthy controls and 20 patients with CKD (stages 1-5) were analyzed to provide their urea concentrations. The lower limit of detection of salivary urea by the ATR-FTIR spectroscopy method was 1-2 mM, at the lower end of the clinically relevant range. Statistically significant differences in salivary urea concentrations were demonstrated between healthy subjects (4.1±0.5 mM) and patients with CKD stages 3-5 (CKD stage 3, 6.8±0.7 mM; CKD stage 4, 9.1±1 mM; CKD stage 5, 14.8±1.6 mM). These salivary urea concentrations correlated well with serum urea levels in the same patients measured by an automated analyzer (Spearman rank correlation coefficient of 0.71; P<0.001). The ability of the method to detect and stage CKD was assessed from the sensitivity and specificity parameters of a receiver operating characteristics (ROC) curve analysis. This proof-of-concept study demonstrates that quantitation of salivary urea by ATR-FTIR spectroscopy could provide a viable tool for rapid and cost-effective diagnosis of stages 3-5 CKD.

Biomonitoring of bisphenol A, 4-nonylphenol, and 4-t-octylphenol in Turkish population: exposure and risk assessment.

Biomonitoring studies are important tools to understand the effects of endocrine-disrupting compounds on human health. Up to now, there have been no biomonitoring and risk assessment studies conducted in Turkish population in which urinary bisphenol A (BPA), 4-nonylphenol (4-NP), and 4-t-octylphenol (4-t-OP) levels were measured simultaneously. The aim of this study is to measure urinary BPA, 4-NP, and 4-t-OP on Turkish population and conduct a risk assessment using urinary levels of chemicals of interest. During the study, liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used to measure urinary levels of above-mentioned chemicals, and human biomonitoring was used as a risk assessment tool in 103 volunteers, living in Mersin Region, Turkey. Urinary BPA, 4-NP, and 4-t-OP were founded as 0.0079 µg/g creatinine, 0.0177 µg/g creatinine, and 0.0114 µg/g creatinine, respectively. The obtained estimated daily intakes (EDIs) were calculated as 0.095 µg/kg bw/day, 0.041 µg/kg bw/day, and 0.091 µg/kg bw/day, for BPA, 4-NP, and 4-t-OP, respectively. In conclusion, although no potential health risk due to BPA and 4-NP exposure was observed, there might be health risks associated with 4-t-OP exposure in the Turkish population.

Multivariate Longitudinal Assessment of Kidney Function Outcomes on Graft Survival after Kidney Transplantation Using Multivariate Joint Modeling Approach: A Retrospective Cohort Study.

Background: The performance of a transplanted kidney is evaluated by monitoring variations in the value of the most important markers. These markers are measured longitudinally, and their variation is influenced by other factors. The simultaneous use of these markers increases the predictive power of the analytical model. This study aimed to determine the simultaneous longitudinal effect of serum creatinine and blood urea nitrogen (BUN) markers, and other risk factors on allograft survival after kidney transplantation. Methods: In a retrospective cohort study, the medical records of 731 renal transplant patients, dated July 2000 to December 2013, from various transplant centers in Mashhad (Iran) were examined. Univariate and multivariate joint models of longitudinal and survival data were used, and the results from both models were compared. The R package joineRML was used to implement joint models. P values <0.05 were considered statistically significant. Results: Results of the multivariate model showed that allograft rejection occurred more frequently in patients with elevated BUN levels (HR=1.68, 95% CI: 1.24-2.27). In contrast, despite a positive correlation between serum creatinine and allograft rejection (HR=1.49, 95% CI: 0.99-2.22), this relationship was not statistically significant. Conclusion: Results of the multivariate model showed that longitudinal measurements of BUN marker play a more important role in the investigation of the allograft rejection.

Point-of-care creatinine tests to assess kidney function for outpatients requiring contrast-enhanced CT imaging: systematic reviews and economic evaluation.

BACKGROUND: Patients with low estimated glomerular filtration rates may be at higher risk of post-contrast acute kidney injury following contrast-enhanced computed tomography imaging. Point-of-care devices allow rapid measurement of estimated glomerular filtration rates for patients referred without a recent estimated glomerular filtration rate result. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of point-of-care creatinine tests for outpatients without a recent estimated glomerular filtration rate measurement who need contrast-enhanced computed tomography imaging. METHODS: Three systematic reviews of test accuracy, implementation and clinical outcomes, and economic analyses were carried out. Bibliographic databases were searched from inception to November 2018. Studies comparing the accuracy of point-of-care creatinine tests with laboratory reference tests to assess kidney function in adults in a non-emergency setting and studies reporting implementation and clinical outcomes were included. Risk of bias of diagnostic accuracy studies was assessed using a modified version of the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Probabilities of individuals having their estimated glomerular filtration rates correctly classified were estimated within a Bayesian framework and pooled using a fixed-effects model. A de novo probabilistic decision tree cohort model was developed to characterise the decision problem from an NHS and a Personal Social Services perspective. A range of alternative point-of-care testing approaches were considered. Scenario analyses were conducted. RESULTS: Fifty-four studies were included in the clinical reviews. Twelve studies reported diagnostic accuracy for estimated glomerular filtration rates; half were rated as being at low risk of bias, but there were applicability concerns for most. i-STAT (Abbott Point of Care, Inc., Princeton, NJ, USA) and ABL (Radiometer Ltd, Crawley, UK) devices had higher probabilities of correctly classifying individuals in the same estimated glomerular filtration rate categories as the reference laboratory test than StatSensor® devices (Nova Biomedical, Runcorn, UK). There was limited evidence for epoc® (Siemens Healthineers AG, Erlangen, Germany) and Piccolo Xpress® (Abaxis, Inc., Union City, CA, USA) devices and no studies of DRI-CHEM NX 500 (Fujifilm Corporation, Tokyo, Japan). The review of implementation and clinical outcomes included six studies showing practice variation in the management decisions when a point-of-care device indicated an abnormal estimated glomerular filtration rate. The review of cost-effectiveness evidence identified no relevant studies. The de novo decision model that was developed included a total of 14 strategies. Owing to limited data, the model included only i-STAT, ABL800 FLEX and StatSensor. In the base-case analysis, the cost-effective strategy appeared to be a three-step testing sequence involving initially screening all individuals for risk factors, point-of-care testing for those individuals with at least one risk factor, and including a final confirmatory laboratory test for individuals with a point-of-care-positive test result. Within this testing approach, the specific point-of-care device with the highest net benefit was i-STAT, although differences in net benefit with StatSensor were very small. LIMITATIONS: There was insufficient evidence for patients with estimated glomerular filtration rates < 30 ml/minute/1.73 m2, and on the full potential health impact of delayed or rescheduled computed tomography scans or the use of alternative imaging modalities. CONCLUSIONS: A three-step testing sequence combining a risk factor questionnaire with a point-of-care test and confirmatory laboratory testing appears to be a cost-effective use of NHS resources compared with current practice. The risk of contrast causing acute kidney injury to patients with an estimated glomerular filtration rate of < 30 ml/minute/1.73 m2 is uncertain. Cost-effectiveness of point-of-care testing appears largely driven by the potential of point-of-care tests to minimise delays within the current computed tomography pathway. FUTURE WORK: Studies evaluating the impact of risk-stratifying questionnaires on workflow outcomes in computed tomography patients without recent estimated glomerular filtration rate results are needed. STUDY REGISTRATION: This study is registered as PROSPERO CRD42018115818. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 39. See the NIHR Journals Library website for further project information.

Before computed tomography scans are done, a contrast agent is usually needed to improve the visibility of internal body structures. After receiving a contrast agent (through a vein), some patients' kidneys may be affected, especially if their kidneys already do not work well. A blood test can identify these patients before a computed tomography scan, to reduce the risk of kidney harm. The blood test measures creatinine, which is a marker of how well the kidneys work. Before a contrast-enhanced computed tomography scan, some patients have a recent creatinine result from an earlier blood test. Blood tests are normally done in a central laboratory, and usually take at least 1 hour. Other patients do not have a recent creatinine result, so their computed tomography scan may be delayed or rearranged. Sometimes, to avoid risking kidney harm, patients may have scans without contrast. 'Point-of-care' (handheld, tabletop or portable) devices can quickly measure creatinine (usually in patients with risk factors), often from a finger-prick blood sample. Many point-of-care devices are available but they may not be as exact as laboratory tests, so their benefit is unclear. This study reviewed all available evidence on the benefits and harms of point-of-care creatinine tests before computed tomography scans and assessed whether or not they are a cost-effective use of NHS resources. The study found that some devices [i.e. i-STAT (Abbott Point of Care, Inc., Princeton, NJ, USA) and ABL (Radiometer Ltd, Crawley, UK)] were more accurate than others [i.e. StatSensor^® (Nova Biomedical, Runcorn, UK)]. There was insufficient evidence for other devices. The study found that, for outpatients, doing a point-of-care test in patients who are at a higher risk of kidney harm (according to a questionnaire) and then confirming this with a laboratory test appeared to be a cost-effective use of NHS resources. The study found that the risk of kidney harm as a result of contrast agents appears very low. The main benefit of point-of-care testing may be to reduce needless delays or rearranged computed tomography scan appointments.

Uric acid and uric acid to creatinine ratio in the assessment of chronic obstructive pulmonary disease: Potential biomarkers in multicomponent models comprising IL-1beta.

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease, with oxidative stress and inflammation implicated in its development. Uric acid (UA) could exert anti-oxidative, pro-oxidative or pro-inflammatory effects, depending on the specific context. It was recently shown that soluble UA, and not just its crystals, could activate the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, leading to interleukin (IL)-1ß secretion. We aimed to assess the differences in blood levels of UA and its ratio with creatinine (UCR) between COPD patients and healthy subjects, as well as their association with disease severity, smoking status, common COPD comorbidities and therapy regimes. The diagnostic characteristics of UA and UCR were also explored. This study included 109 stable COPD patients and 95 controls and measured white blood cells (WBC), C-reactive protein (CRP), fibrinogen (Fbg), IL-1ß, creatinine (CREAT) and UA. All of the parameters were increased in COPD patients, except for CREAT. UA and UCR were positively associated with WBC, CRP and IL-1ß. COPD smokers had lower UA and UCR values. Common COPD therapy did not affect UA or UCR, while patients with cardiovascular diseases (CVD) had higher UA, but not UCR, levels. Patients with higher UCR values showed worse disease-related outcomes (lung function, symptoms, quality of life, history of exacerbations, BODCAT and BODEx). Also, UCR differentiated patients with different severity of airflow limitation as well as symptoms and exacerbations. The great individual predictive potential of UCR and IL-1ß was observed with their odds ratios (OR) being 2.09 and 5.53, respectively. Multiparameter models of UA and UCR that included IL-1ß were able to correctly classify 86% and 90% of cases, respectively. We suggest that UA might be a useful biomarker when combined with IL-1ß, while UCR might be even more informative and useful in overall COPD assessments.

Prevalence and awareness of chronic kidney disease among adult diabetic outpatients in Northeast Ethiopia.

BACKGROUND: Chronic kidney disease (CKD) is a serious complication of diabetes associated with adverse outcomes of renal failure, cardiovascular disease and mortality. Despite this, data regarding the burden and awareness of CKD among adults with diabetes in Sub-Saharan Africa countries are lacking. The aim of this study was, therefore to determine the prevalence and awareness of CKD among diabetic outpatients attending a hospital in Northeast Ethiopia. METHODS: We conducted a cross-sectional study on 323 diabetic adults at the diabetes clinic of a hospital in Northeast Ethiopia, from February 1 to July 30, 2016. Each patient provided a blood sample for serum creatinine and urine for albuminuria. Glomerular filtration rate (eGFR) was estimated using the Modification of Diet in Renal Disease (MDRD) equation. CKD was defined as eGFR < 60 ml/min/1.73 m2 and/or albuminuria. Awareness was defined as a positive response to "Has a doctor or other health care professional ever told you that you had kidney disease?" RESULTS: Of the 323 patients, 85 (26.3%) had Stage 1-5 CKD, 42 (13.0%) had eGFR < 60 ml/min/1.73m2 and 58 (18.0%) had albuminuria. In patients with eGFR < 60 ml/min/1.73m2 (stage 3-5 CKD), serum creatinine was abnormal (> 1.5 mg/dl) in 23.5% and albuminuria was absent in 31.8%. Of the patients with CKD, only 10.6% of them were aware of their CKD. The proportion of patients who were aware of their disease increased with worsening of CKD stages, from 3.4% of with stage 1 to 75.0% with stage 4. Awareness for all individuals with advanced stages of CKD was only 11.9%. Having albuminuria, high serum creatinine, a family history of kidney disease and being obese were significantly associated with CKD awareness. CONCLUSION: A high prevalence but low awareness of CKD was found in diabetic outpatients attending our clinic in Northeast Ethiopia. Our results highlight the need for more diagnostic strategies for CKD screening among diabetic adults and primary care education on the impact of detecting CKD in the early stage to prevent adverse outcomes and improve diabetes care.

2013 Banff Criteria for Acute Antibody-Mediated Rejection Are Superior to 2007 Banff Criteria in the Diagnosis and Assessment of Renal Allograft Outcomes.

BACKGROUND: The 2013 Banff meeting updated the requirements for the diagnosis of acute/active antibody-mediated rejection (AAMR) in kidney allografts. There has been speculation that the changes lower the threshold for diagnosing AAMR, and may lead to possible unnecessary and expensive treatment. METHODS: We compared the 2013 Banff classification for AAMR to the previous 2007 Banff to determine if there was an increase in the number of patients receiving a diagnosis of AAMR and if the diagnosis affected allograft survival and post-biopsy 3-month and 6-month creatinine and eGFR values. RESULTS: A total of 212 renal allograft biopsies were compared to both 2007 and 2013 Banff classification requirements for AAMR. Ten patients (11 biopsies) met the 2007 criteria. An additional 15 patients (20 biopsies) met the 2013 criteria. These 2 groups showed no statistically significant demographic differences. By applying the 2013 Banff classification, we observed a 2.5-fold increase in the number of AAMR cases. One-year post-transplant allograft survival was higher in the 2013 group (.85 vs .55) and the 3-month and 6-month post-biopsy creatinine values were significantly lower for the 2013 group (1.6 ± .6 vs 3.3 ± 2.2, P value .01, and 1.7 ± .6 vs 3.4 ± 2.8, P value .03). The 3-month and 6-month eGFR values were higher in the 2013 group, although not statistically significant. CONCLUSIONS: These results suggest that use of Banff 2013 criteria in place of Banff 2007 may result in diagnosing milder and earlier cases of AAMR with the possibility of initiating earlier treatment and improving graft outcomes.

Urinary bisphenol A (BPA) concentrations and exposure predictors among pregnant women in the Laizhou Wan Birth Cohort (LWBC), China.

Although BPA use is widespread and often detectable in humans, little is known about its exposure levels and potential exposure predictors in pregnant women in China. We investigated the BPA exposure levels in pregnant women and its health implications and potential exposure predictors. Urinary BPA levels were measured for 506 pregnant women in northern China. Hazard quotients (HQs) based on estimated daily intakes (EDIs) were conducted. Sociodemographic characteristics and food consumption during pregnancy were collected and seasons of sample collection were recorded. The detection rate of urinary BPA was 86.6% and the median concentrations were 0.48 µg/L (1.05 µg/g creatinine). The EDI (median = 0.008 µg/kg bw/day) was much lower than the recommended tolerable daily doses and the HQ (median = 0.002) much lower than 1. The urine collected in summer had significantly higher BPA levels than that collected in other seasons (ß = 0.225; 95% CI - 0.008, 0.458; p = 0.03). Women "always consuming shellfish" had significantly higher BPA levels than those "seldom consuming shellfish" (ß = 0.341; 95% CI 0.022, 0.66; p = 0.04). The study found a wide exposure to BPA among pregnant women in this region, which might be associated with seasonal variation and shellfish consumption. Although the HQs suggested no obvious risk, further attention to the comprehensive exposure and potential determinants should be paid in view of its endocrine-disrupting potential.

Value of assessment of multivoxel proton chemical shift imaging to predict long term outcome in patients after out-of-hospital cardiac arrest: A preliminary prospective observational study.

BACKGROUND: Existing methods to predict recovery after out-of-hospital cardiac arrest (OHCA) lack of accuracy. The aim of this study was to determine whether quantitative proton chemical shift imaging (1H-CSI) during the subacute stage of OHCA can predict neurological outcome of such patients. METHODS: This monocentric prospective observational study was conducted in a Intensive Care Unit of a teaching hospital. Forty consecutive patients with OHCA were enrolled between January 1st 2011-December 31st 2013. Multivoxel 1H-CSI values were compared to structural magnetic resonance imaging (MRI) sequences (fluid-attenuated inversion recovery and diffusion-weighted imaging). Ratios of N-acetyl-aspartate (NAA) to creatine (Cr) and choline compounds were analyzed using region of interest in bilateral lenticular cores and thalami. The outcome evaluated was the Cerebral Performance Category (CPC) at 6 months, dichotomized as favorable (CPC 1-2) and unfavorable outcome (CPC 3-5). The performance was compared by area under the receiver operating characteristic (ROCAUC) curves analysis. RESULTS: Twenty nine OHCA had an interpretable MRI. Eight patients (28%) had favorable outcome at 6 months. The worst NAA/Cr in lenticular cores was the best 1H-CSI marker, with 80% sensitivity (95% confidence interval (CI), 57-94) and a 100% specificity (95% CI, 63-100) with a positive predictive value of 100%. Prognostic accuracy, as quantified by the ROCAUC, was higher with the worst NAA/Cr in lenticular cores (ROCAUC 0.88; 95% CI, 0.70-0.97) than with the structural MRI sequences. CONCLUSION: In this preliminary study we found that multivoxel 1H-CSI in lenticular cores was highly predictive of unfavorable outcome at 6 months.

Evaluation of Renal Function Estimation Formulas Specific to Dynamic Renal Function for Drug Dosing in Critically Ill Patients.

OBJECTIVES: The study compared estimated creatinine clearance (eCrCl) between the Cockcroft-Gault (CG) equation and the Jelliffe, Chiou, and Brater equations designed for estimation in dynamic renal function and resulting antimicrobial dosing concordance of five antimicrobials (cefepime, meropenem, piperacillin/tazobactam, vancomycin, and fluconazole) commonly used in the intensive care unit (ICU). METHODS: Electronic medical records were used to identify the target patient population. Analysis of variance tests with repeated measures were performed to compare eCrCl. Bowker's tests of symmetry were applied to compare the dosing regimen discordance between CG and candidate equations. RESULTS: From January 1, 2008 through December 31, 2012, we identified 387 patients with acute kidney injury (AKI), among whom 62% (n = 240) were older adults (65 years and older) and 46% (n = 178) were obese (body mass index ≥30). In the declining phase of renal function, eCrCl means were different between the CG and Brater equations (32.0 vs 26.1 mL/min, P < 0.001). The dosing regimen discordance rates (CG vs candidate equations) in declining renal function varied from 19.3% to 25% and were statistically significant for cefepime and meropenem (P < 0.001) based on Food and Drug Administration recommendations for dose adjustment. In the improving phase, eCrCl means were different (P < 0.001) between CG (43.0 mL/min) and candidate formulas (Brater 47.9, Chiou 31.7, and Jelliffe 55.3 mL/min). The dosing regimen discordance rates (CG vs candidate equations) in the improving phase varied from 8.3% to 39% and were statistically significant for all 5 antimicrobials (P < 0.001). CONCLUSIONS: Differences in eCrCl between CG and candidate formulas were observed in surgical ICU patients with acute kidney injury. Discordant dosing recommendations may affect antimicrobial regimens in ICU patients with dynamic renal function.

Evaluation of the dialyser inner diameter in online haemodiafiltration. / Valoración del diámetro interno del dializador en hemodiafiltración on-line.

INTRODUCTION: Online haemodiafiltration (OL-HDF) has been associated with increased survival. To date, the influence of the inner diameter of the hollow fibres of the dialyser on convective volume has not been well established. The objective of the study was to evaluate the effect of increasing the inner diameter of the dialyser on the convective volume and removal capacity. MATERIAL AND METHODS: We included 16 patients in posdilutional OL-HDF with autosubstitution. Each patient was analysed in 4 sessions in which the inner diameter varied; 185µm (FX60 Cordiax and FX80 Cordiax) versus 210µm (FX600 Cordiax and FX800 Cordiax). Different solutes were measured at the beginning and end of each dialysis session. RESULTS: No differences in the convective volume were found with an increased inner diameter: 32.3±3.1 vs. 31.8±3.6 l/session (FX60 vs. FX600) and 33.7±4.3 vs. 33.5±3.8 l/session (FX80 vs. FX800). The reduction percentages also did not differ: urea 83.7±4.5 vs. 84.1±3.4 for FX60 and FX600, and 82.7±4.1 vs. 83.6±3.8 for FX80 vs. FX800; creatinine similar 78.2±5.6 vs. 77.8±4.6 y 77.1±5.4 vs. 78.1±4.9; ß2-microglobulin 82.2±4.3 vs. 82.9±4.2, and 82.9±4.7 vs. 84.0±3.8; myoglobin 71.0±10 vs. 70.2±9 and 72.8±11 vs. 75.0±10; prolactin 70.4±9 vs. 68.1±9, and 72.2±10 vs. 73.4±8.2; and α1-microglobulin 22.9±10 vs. 21.6±10, and 26.5±12 vs. 28.8±11, respectively. CONCLUSION: The increase in the inner diameter of the hollow fibres did not result in improved convective volume and removal capacity.

The effect of establishing pre-angiography thresholds on contrast utilization.

INTRODUCTION: Contrast induced nephropathy is linked to contrast utilization and strategies for minimizing renal injury are incorporated into many laboratories that perform coronary angiography. Contrast limits have been described, below which there is minimal incremental increase in the risk of renal injury. Whether a priori acknowledgement of these limits as part of a contrast "Time-Out" reduces contrast utilization has not been established. In this study, we investigate the effect of verbalizing pre-angiography and ½ time contrast thresholds on contrast utilization and associated clinical outcomes. METHODS: We retrospectively reviewed 5265 cases of coronary angiography (984 with contrast thresholds defined pre-procedure compared to 4281 without pre-defined contrast thresholds). There were two primary endpoints: (1) proportion of procedures that utilized an amount of contrast ≤ threshold, and (2) median difference between amount of contrast utilized and the contrast threshold. Secondary outcomes incorporated indices of renal function, and included changes in serum creatinine levels, eGFR, and CKD stage. RESULTS: Compared to pre-"Time-Out" group, the post-"Time-Out" group had a higher proportion of procedures with contrast ≤ stated contrast threshold (88% vs 84%, P < 0.002), and a lower amount of total contrast volume (88 mL [IQR 60-136] versus 78 mL [IQR 53-119]). The post-"Time-Out" group also had a lower incidence of any increase in post-procedure serum creatinine (45% vs 36%; P = 0.04), and a larger median decrease of pre- to post-procedure eGFR (P = 0.04). CONCLUSION: Acknowledgement of contrast threshold as part of a contrast "Time-Out" is associated with reduced overall contrast utilization, and likely minimizes risks of contrast-induced nephropathy.

Malignant Hyperthermia Susceptibility and Fitness for Duty.

INTRODUCTION: Malignant hyperthermia (MH) is an inherited hypermetabolic condition characterized by uncontrolled calcium release from the sarcoplasmic reticulum of skeletal muscle, usually from exposure to inhaled general anesthetics and/or the depolarizing neuromuscular blocking agent succinylcholine. Multiple case reports now reveal that crises may be precipitated by environmental factors such as exercise or high ambient temperatures. Common signs of an MH crisis include life-threatening hyperthermia, metabolic acidosis, muscle rigidity, and tachycardia. Treatment consists of stopping triggering agents, administering dantrolene, and actively cooling the patient. MH is a medically disqualifying condition for service in the U.S. Armed Forces. However, patients with MH-causative mutations may never have experienced an MH episode. If they previously have had an event concerning for MH, details are often sparse and a formal evaluation is absent. MATERIALS AND METHODS: We present 2 case reports with military service implications, one as a formal applicant to the service academies and the other as the father of an active duty Navy chief. Both patients experienced prior MH-like reactions to anesthesia but had not undergone testing with a caffeine-halothane contracture test (CHCT) or genetic analysis. Both patients underwent skeletal muscle biopsies of the left vastus lateralis with nontriggering anesthetics at Children's National Medical Center in Washington, DC, and MH diagnostic CHCT at the Uniformed Services University of the Health Sciences (USUHS) in Bethesda, Maryland. The CHCT was performed according to the North American MH Registry Protocol. With USUHS Institutional Review Board approval, ryanodine receptor type 1 gene (RYR1) and L-type calcium channel α-1 subunit gene (CACNA1S) sequencing was performed on the remaining muscle at USUHS. RESULTS: Each subject was CHCT positive, confirming a diagnosis of MH. One was found to have a known MH-causative gene mutation. The applicant to the service academy was therefore determined unfit for military service. The active duty son of the MH-positive patient underwent muscle biopsy and CHCT in order to continue his military career. CONCLUSION: A personal or familial history concerning for MH raises important questions on fitness for duty in the U.S. Armed Forces. Department of Defense regulation uniformly defines MH as a disqualifying condition; however, screening for a history of anesthetic complications during accession into the military is inconsistent. Medical standards across the services are also variable in the context of a familial history of MH. These case reports highlight the need for clinicians to seek expert consultation about how to proceed with MH-related issues. They also stress the importance of applying current understanding of heritable conditions to our fitness for duty determinations. Further investigation is also recommended to establish an MH-susceptible individual's propensity for exercise or heat-related injury outside the operating room. Department of Defense policy may thereafter be updated to reflect a quantitative assessment of MH's relative risk during inherently strenuous military operations.

Outcome disparities between African Americans and Caucasians in contemporary kidney transplant recipients.

BACKGROUND: Racial disparities in African-American (AA) kidney transplant have persisted for nearly 40 years, with limited data available on the scope of this issue in the contemporary era of transplantation. METHODS: Descriptive retrospective cohort study of US registry data including adult solitary kidney transplants between Jan 1, 2005 to Dec 31, 2009. RESULTS: 60,695 recipients were included; 41,426 Caucasians (68%) and 19,269 AAs (32%). At baseline, AAs were younger, had lower college graduation rates, were more likely to be receiving public health insurance and have diabetes. At one-year post-transplant, AAs had 62% higher risk of graft loss (RR 1.62, 95% CI 1.50-1.75) which increased to 93% at five years (RR 1.93, 95% CI 1.85-2.01). Adjusted risk of graft loss, accounting for baseline characteristics, was 60% higher in AAs (HR 1.61 [1.52-1.69]). AAs had significantly higher risk of acute rejection and delayed graft function. CONCLUSION: AAs continue to experience disproportionately high rates of graft loss within the contemporary era of transplant, which are related to a convergence of an array of socioeconomic and biologic risk factors.

Assessment of Perioperative Variables That Predict the Need for Surgical Drains Following Robotic Partial Nephrectomy Utilizing Quantitative Drain Creatinine Analysis.

OBJECTIVE: To utilize body fluid creatinine analysis to determine which patients will require a surgical drain following robotic-assisted partial nephrectomy (RAPN). MATERIALS AND METHODS: One hundred fifty consecutive RAPN performed by a single surgeon were reviewed. Postoperative day (POD) 1 drain creatinine was compared to serum creatinine to calculate the drain to serum creatinine ratio (D/S ratio). Elevated D/S ratio was defined as any value >1.2. RESULTS: From February 2008 to April 2015, 140 patients underwent RAPN and had a drain placed (124 had D/S ratio available on POD 1). In the 103 patients with a D/S ratio of <1.2 and the 21 with D/S ratio of >1.2, the mean tumor size was 3.0 and 3.9 cm (P = .001) and mean RENAL score was 7.6 and 8.1 (P = .270), respectively. Collecting system entry occurred in 68.2% of patients with a D/S ratio of <1.2 and 71.4% of patients with a D/S ratio of >1.2. Mean drain time was 2.4 and 4.2 days (P = .001), hospital stay was 2.7 and 3.3 days (P = .036) for the D/S ratio <1.2 and D/S ratio >1.2 groups, respectively. Those with renal mass size of 4-7 cm had increased likelihood of D/S ratio >1.2 (OR 2.78; P = .041). CONCLUSIONS: Most RAPN do not require a surgical drain. A POD 1 elevated D/S ratio is more likely to occur with larger masses (those approaching or greater than 4 cm) and can be associated with prolonged drain time and hospital stay.

Metformin and contrast-induced acute kidney injury in diabetic patients treated with primary percutaneous coronary intervention for ST segment elevation myocardial infarction: Amulticenter study.

AIM: To analyze the association between chronic metformin treatment and the development of contrast-induced acute kidney injury (CI-AKI) after primary percutaneous coronary intervention (PCI) for ST segment elevation myocardial infarction (STEMI). METHODS: Patients with type 2 diabetes mellitus (T2DM) treated with PCI <24h in 2 coronary care units were included. Serum creatinine (Cr) was measured before and <48h after PCI. CI-AKI was defined as an increase in Cr>27µmol/l (0.3mg/dl) or >50% over baseline after PCI. Since PCI was urgent, metformin could not be withheld prior to PCI but was usually stopped after PCI. RESULTS: Among the 372 patients included, 147 (40%) were using metformin, which had older diabetes, but had risk factors similar to patients without metformin. Baseline eGFR was better in patients under metformin therapy. After PCI, we observed an increase of ≈10% in Cr, for both groups. There was a trend toward a lower rate of CI-AKI in patients under metformin (16% vs 25%, p=0.051). In patients with chronic kidney disease, 31 (26%) were under metformin therapy, and the rate of CI-AKI was similar in both groups (41% vs 40%, p=0.915). By multivariate analysis, metformin showed a trend toward a reduced rate of CI-AKI, even when adjusted for confounding (OR (95% CI): 0.548 (0.276-1.087)). No case of lactic acidosis was reported during the hospital stay. Moreover, there was no increased rate of cardiogenic shock or death with metformin treatment. CONCLUSION: In this multicenter observational study, chronic metformin treatment prior to primary PCI had no significant impact on CI-AKI.

In-hospital mortality risk assessment in elective and non-elective cardiac surgery: a comparison between EuroSCORE II and age, creatinine, ejection fraction score.

OBJECTIVES: Age, creatinine, ejection fraction (ACEF) score is a simplified algorithm for prediction of mortality after elective cardiac surgery. Although mainly conceived for elective cardiac surgery, no information is available on its performance in non-elective surgery and on comparison with the new EuroSCORE II. This study was undertaken to compare the performance of ACEF score and EuroSCORE II within classes of urgency. METHODS: Complete data on 13 871 consecutive patients who underwent major cardiac surgery in a 6-year period were retrieved from three prospective institutional databases. Discriminatory power was assessed using the c-index and h with Delong, bootstrap and Venkatraman methods. Calibration was evaluated with calibration curves and associated statistics. RESULTS: The in-hospital mortality rate was 2.5%. The discriminatory power of ACEF score within elective and non-elective surgery was similar (area under the curve (AUC) 0.71, 95% confidence interval (CI) 0.67-0.74 and AUC 0.68, 95% CI 0.62-0.73, respectively) but significantly lower than that of EuroSCORE II (AUC 0.80, 95% CI 0.77-0.83 for elective surgery; AUC 0.82, 95% CI 0.78-0.85 for non-elective surgery). The calibration patterns were different in the two subgroups, but the summary statistics underscored a miscalibration in both of them (U-statistic and Spiegelhalter Z-test P-values <0.05). Even the calibration of EuroSCORE II was insufficient, although it was demonstrated to be well calibrated in the first tertile of predicted risk. CONCLUSIONS: This study demonstrated that the performance of ACEF score in predicting in-hospital mortality in elective and non-elective cardiac surgery is comparable. Nonetheless, it is not as satisfactory as the new EuroSCORE II, as its discrimination is significantly lower and it is also miscalibrated.

Assessment of changes in brain metabolites in Indian patients with type-2 diabetes mellitus using proton magnetic resonance spectroscopy.

BACKGROUND: The brain is a target for diabetic end-organ damage, though the pathophysiology of diabetic encephalopathy is still not well understood. The aim of the present study was to investigate the effect of diabetes on the metabolic profile of brain of patients having diabetes in comparison to healthy controls, using in-vivo magnetic resonance spectroscopy to get an insight into the pathophysiology of cerebral damages caused due to diabetes. METHODS: Single voxel proton magnetic resonance spectroscopy (1H-MRS) was performed at 1.5 T on right frontal, right parieto-temporal and right parieto-occipital white matter regions of the brain of 10 patients having type-2 diabetes along with 7 healthy controls. Absolute concentration of N-acetylaspartate (NAA), choline (cho), myo-inositol (mI), glutamate (Glu) and glutamine (Gln), creatine (Cr) and glucose were determined using the LC-Model and compared between the two groups. RESULTS: The concentration of N-acetylaspartate was significantly lower in the right frontal [4.35 ±0.69 vs. 5.23 ±0.74; p = 0.03] and right parieto-occipital region [5.44 ±0.52 vs.6.08 ±0.25; p = 0.02] of the brain of diabetics as compared to the control group. The concentrations of glutamate and glutamine were found to be significantly higher in the right frontal region of the brain [7.98 ±2.57 vs. 5.32 ±1.43; P = 0.01] in diabetics. Glucose levels were found significantly elevated in all the three regions of the brain in diabetics as compared to the control group. However, no significant changes in levels of choline, myo-inositol and creatine were observed in the three regions of the brain examined among the two groups. CONCLUSIONS: 1H-MRS analysis indicates that type-2 diabetes mellitus may cause subtle changes in the metabolic profile of the brain. Decreased concentrations of NAA might be indicative of decreased neuronal viability in diabetics while elevated concentrations of Gln and Glu might be related to the fluid imbalance resulting from disruption of glucose homeostasis.