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Background Urine tissue inhibitor of metalloproteinases-2/insulin-like growth factor-binding protein 7 (TIMP-2/IGFBP7) (NephroCheck, Ortho Clinical Diagnostics, Raritan, NJ, USA) is a US Food and Drug Administration-approved biomarker for risk assessment of acute kidney injury (AKI) in critically ill adult patients in intensive care units; however, its clinical impact in the emergency department (ED) remains unproven. We evaluated the utility of NephroCheck for predicting AKI development and short-term mortality in the ED. Methods This was a prospective, observational, five-center international study. We consecutively enrolled ED patients admitted with ≥30% risk of AKI development (assessed by ED physician: ED score) or acute diseases. Serum creatinine was tested on ED arrival (T0), day 1, and day 2 (T48); urine for NephroCheck was collected at T0 and T48. We performed ROC curve and reclassification analyses. Results Among the 529 patients enrolled (213 females; median age, 65 years), AKI developed in 59 (11.2%) patients. The T0 NephroCheck value was higher in the AKI group than in the non-AKI group (median 0.77 vs. 0.29 (ng/m)2/1,000, P=0.001), and better predicted AKI development than the ED score (area under the curve [AUC], 0.64 vs. 0.53; P=0.04). In reclassification analyses, adding NephroCheck to the ED score improved the prediction of AKI development (P Conclusions NephroCheck can predict both AKI development and short-term mortality in at-risk ED patients. NephroCheck would be a useful biomarker for early ruling-in or ruling-out of AKI in the ED.

In this report, we describe 8 patients with critical illness and diabetes mellitus who developed euglycemic ketosis during continuous kidney replacement therapy (CKRT) with a glucose-free CKRT solution. Two patients had chronic kidney disease stage 5, while the rest had acute kidney injury. The patients had improvement in all metabolic parameters following CKRT commencement, except for a worsening high anion gap metabolic acidosis, in spite of improvement in serum lactate. This led to detection of elevated serum β-hydroxybutyrate in the setting of normoglycemia. Following diagnosis of ketosis, the patients' caloric intake was increased from a median of 15 (IQR, 10-20) to 25 (IQR, 20-29) kcal/kg/d by adding a dextrose infusion. This allowed for a corresponding increase in the insulin administered, from a median of 0.2 (IQR, 0-0.2) to 3.0 (IQR, 2.3-3.9) U/h. These contributed to a complete resolution of ketosis. This report of 8 cases demonstrates that critically ill patients are at risk of developing euglycemic ketosis during CKRT, which can be mitigated by providing adequate caloric intake and using glucose-containing CKRT solutions with appropriate insulin therapy. We recommend vigilance in evaluating for euglycemic ketosis in patients who have a persistent metabolic acidosis despite improvements in solute control during CKRT.

Polyethyleneimine-layered membrane with grafted heparin (oXiris) may improve filter life during continuous renal replacement therapy (CRRT) in addition to its immunoadsorptive capability, compared with that of conventional membrane. In this single center, prospective, open-label pilot study, we randomized critically ill patients with bleeding risk who underwent anticoagulation-free CRRT, to commence with oXiris or M150 filter with sequential crossover. We examined the filter life with each circuit and its effect on systemic coagulation parameters. We randomized 11 and nine patients to commence CRRT with oXiris and M150 respectively, with 19 oXiris and 20 M150 filter-circuits in all. Patient profiles in both arms were comparable for illness severity and comorbidities. Median filter lives for oXiris versus M150 circuits were 13 h versus 18 h (p = 0.10). Among 11 patients with paired crossover filters, filter lives for 14 oXiris-M150 circuit pairs were 13 h versus 16 h (p = 0.27), and corresponding transmembrane pressures increased to 111 mmHg versus 75 mmHg by 12 h (p = 0.02). Patients' coagulation parameters were comparable following both filter-circuits. CRRT with oXiris (vs. M150) was independently associated with shorter filter life, adjusted for prescribed dose, vascular access, and coagulopathy. Use of oXiris did not prolong filter life over conventional membrane with no evidence of systemic heparin exposure; significant membrane clogging is observed by 12 h with oXiris.

To determine if contrast-enhanced CT imaging performed in patients during their episode of AKI contributes to major adverse kidney events (MAKE). A propensity score–matched analysis of 1127 patients with AKI defined by KDIGO criteria was done. Their mean age was 63 ± 16 years with 56% males. A total of 419 cases exposed to CT contrast peri-AKI were matched with 798 non-exposed controls for 14 covariates including comorbidities, acute illnesses, and initial AKI severity; outcomes including MAKE and renal recovery in hospital were compared using bivariate analysis and logistic regression. MAKE was a composite of mortality, renal replacement therapy, and doubling of serum creatinine on discharge over baseline; renal recovery was classified as early versus late based on a 7-day timeline from AKI onset to nadir creatinine or cessation of renal replacement therapy in survivors. Sixty-two patients received cumulatively > 100 mL of CT contrast, 143 patients had > 50–100 mL, and 214 patients had 50 mL or less; MAKE occurred in 34%, 17%, and 21%, respectively, as compared with 20% in non-exposed controls (p = 0.008 for patients with > 100 mL contrast versus none). More contrast-exposed patients experienced late renal recovery (27% versus 20%) and longer hospital days (median 10 versus 8) than non-exposed patients (all p 100 mL was independently associated with MAKE (odds ratio 2.39 versus non-contrast, adjusted for all confounders, p = 0.005); cumulative CT contrast under 100 mL was not associated with MAKE. High cumulative volume of CT contrast administered to patients with AKI is associated with worse short-term renal outcomes and delayed renal recovery. • Cumulative intravenous iodinated contrast for CT imaging of more than 100 mL, during an episode of acute kidney injury, was independently associated with worse renal outcomes and less renal recovery. • These adverse outcomes including renal replacement therapy were not more frequent in similar patients who received cumulatively 100 mL or less of CT contrast, compared with non-exposed patients. • More patients with CT contrast exposure during acute kidney injury experienced delayed renal recovery.

Aims: Cardiorenal syndrome (CRS) is a common problem of great morbidity and mortality. Hydralazine–isosorbide dinitrate (H-ISDN) may be used in renal failure and may improve exercise capacity in heart failure (HF). Our proof-of-concept study aimed to evaluate early evidence of efficacy, safety, and feasibility of H-ISDN compared with standard of care in CRS. Methods and results: This multi-centre, single-blind, randomized trial in Singapore enrolled CRS patients, defined as chronic HF with concomitant renal failure [estimated glomerular filtration rate (eGFR)

Aims The COVID‐19 pandemic poses unprecedented operational challenges to nephrology divisions in every country as they cope with COVID‐19‐related kidney disease in addition to regular patient care. Although general approaches have been proposed, there is a lack of practical guidance for nephrology division response in a hospital facing a surge of cases. Here, we describe the specific measures that our division has taken in the hope that our experience in Singapore may be helpful to others Methods Descriptive narrative Results A compilation of operational responses to the COVID‐19 pandemic taken by a nephrology division at a Singapore university hospital Conclusion Nephrology operational readiness for COVID‐19 requires a clinical mindset shift from usual standard of care to a crisis exigency model that targets best outcomes for available resources. Rapid multi‐disciplinary efforts that evolve flexibly with the local dynamics of the outbreak are required. This article is protected by copyright. All rights reserved.

Introduction We aimed to describe the extrapulmonary manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, including their frequency, onset with respect to respiratory symptoms, pathogenesis and association with disease severity. Methods We searched the MEDLINE and Embase databases for SARS-CoV-2-related studies. Meta-analysis, observational studies, case series and case reports published in English or Chinese between 1 January and 1 May 2020 were included. Reports with only paediatric or obstetric cases were excluded. Results 169 articles were included. Early manifestations (preceding respiratory symptoms until Day 6 of onset) included olfactory and gustatory disturbance (self-reported in up to 68% and 85% of cases, respectively), gastrointestinal symptoms (up to 65.9%) and rash (up to 20.4%). From Day 7 onwards, hypercytokinaemia, paralleled multi-organ complications including acute cardiac injury (pooled incidence of 17.7% in 1,412 patients, mostly with severe disease and 17.4% mortality), kidney and liver injury (up to 17% and 33%, respectively) and thrombocytopenia (up to 30%). Hypercoagulability resulted in venous thromboembolic events in up to 31% of all patients. Uncommon disease presentation and complications comprised Guillain-Barre syndrome, rhabdomyolysis, otitis media, meningoencephalitis and spontaneous pneumomediastinum. Conclusion Although the systemic manifestations of SARS-CoV-2 infection are variegated, they are deeply interwoven by shared mechanisms. Two phases of extrapulmonary disease were identified: (a) an early phase with possible gastrointestinal, ocular and cutaneous involvement and (b) a late phase characterised by multiorgan dysfunction and clinical deterioration. A clear, multidisciplinary consensus to define and approach thromboinflammation and cytokine release syndrome in SARS-CoV-2 is needed.

BackgroundSerum electrolyte imbalances are highly prevalent in COVID-19 patients. However, their associations with COVID-19 outcomes are inconsistent, and of unknown prognostic value.ObjectivesTo systematically clarify the associations and prognostic accuracy of electrolyte imbalances (sodium, calcium, potassium, magnesium, chloride and phosphate) in predicting poor COVID-19 clinical outcome.MethodsPubMed, Embase and Cochrane Library were searched. Odds of poor clinical outcome (a composite of mortality, intensive-care unit (ICU) admission, need for respiratory support and acute respiratory distress syndrome) were pooled using mixed-effects models. The associated prognostic sensitivity, positive and negative likelihood ratios (LR+, LR-) and predictive values (PPV, NPV; assuming 25% pre-test probability), and area under the curve (AUC) were computed.ResultsWe included 28 observational studies from 953 records with low to moderate risk-of-bias. Hyponatremia (OR=2.08, 95%CI=1.48-2.94, I2=93%, N=8), hypernatremia (OR=4.32, 95%CI=3.17-5.88, I2=45%, N=7) and hypocalcemia (OR=3.31, 95%CI=2.24-4.88, I2=25%, N=6) were associated with poor COVID-19 outcome. These associations remained significant on adjustment for covariates such as demographics and comorbidities. Hypernatremia was 97% specific in predicting poor outcome (LR+ 4.0, PPV=55%, AUC=0.80) despite no differences in CRP and IL-6 levels between hypernatremic and normonatremic patients. Hypocalcemia was 76% sensitive in predicting poor outcome (LR- 0.44, NPV=87%, AUC=0.71). Overall quality of evidence ranged from very low to moderate.ConclusionHyponatremia, hypernatremia and hypocalcemia are associated with poor COVID-19 clinical outcome. Hypernatremia is 97% specific for a poor outcome and the association is independent of inflammatory marker levels. Further studies should evaluate if correcting these imbalances help improve clinical outcome.

Background: :Drug-induced Acute Kidney Injury (AKI) develops in 10-15% of patients who receive nephrotoxic medications. Urinary biomarkers of renal tubular dysfunction may detect nephrotoxicity early and predict AKI.Methods::We prospectively studied patients who received aminoglycosides, vancomycin, amphotericin, or calcineurin inhibitors, and collected their serial urine while on therapy. Patients who developed drug-induced AKI (fulfilling KDIGO criteria) were matched with non-AKI controls in a 1:2 ratio. Their urine samples were batch-analyzed at time-intervals leading up to AKI onset; the latter benchmarked against the final day of nephrotoxic therapy in non- AKI controls. Biomarkers examined include clusterin, beta-2-microglobulin, KIM1, MCP1, cystatin-C, trefoil-factor- 3, NGAL, interleukin-18, GST-Pi, calbindin, and osteopontin; biomarkers were normalized with corresponding urine creatinine.Results::Nine of 84 (11%) patients developed drug-induced AKI. Biomarkers from 7 AKI cases with pre-AKI samples were compared with those from 14 non-AKI controls. Corresponding mean ages were 55(±17) and 52(±16) years; baseline eGFR were 99(±21) and 101(±24) mL/min/1.73m2 (all p=NS). Most biomarker levels peaked before the onset of AKI. Median levels of 5 biomarkers were significantly higher in AKI cases than controls at 1-3 days before AKI onset (all µg/mmol): clusterin [58(8-411) versus 7(3-17)], beta-2-microglobulin [1632(913-3823) versus 253(61-791)], KIM1 [0.16(0.13-0.76) versus 0.07(0.05-0.15)], MCP1 [0.40(0.16-1.90) versus 0.07(0.04-0.17)], and cystatin-C [33(27-2990) versus 11(7-19)], all p0.80 (confidence intervals >0.50), with average accuracy highest for clusterin (86%), followed by beta-2-microglobulin, cystatin-C, MCP1, and KIM1 (57%) after cross-validation.Conclusion: :Serial surveillance of these biomarkers could improve the lead time for nephrotoxicity detection by days.

Patients with acute kidney injury needing prolonged renal replacement therapy (AKI-RRT) may benefit from a structured care process in form of an AKI transitional care program (ATCP), to facilitate RRT weaning and recovery. We examined outcomes following ATCP implementation in adults with AKI-RRT from a tertiary institution (versus pre-ATCP controls), including mortality, cumulative hospital days, and renal function over one year; RRT and haemodialysis catheter days in initial 90 days. We studied 89 patients with age 62 ( ± 15) years. 47% had septic AKI, 20% cardiorenal syndrome, and 29% had baseline eGFR

Background : Chronic kidney disease (CKD) is associated with fluid retention, which increases total body water (TBW) and leads to changes in intracellular water (ICW) and extracellular water (ECW). This complicates accurate assessments of body composition. Analysis of bioelectrical impedance may improve the accuracy of evaluation in CKD patients and multiple machines and technologies are available. We compared body composition by bioimpedance spectroscopy (BIS) against multi-frequency bioimpedance analysis (BIA) in a multi-ethnic Asian population of stable, non-dialysis CKD patients. Methods : We recruited 98 stable CKD patients comprising 54.1% men and 70.4% Chinese, 9.2% Malay, 13.3% Indian, and 8.2% other ethnicities. Stability was defined as no variation in serum creatinine > 20% over three months. Patients underwent BIS analyses using a Fresenius body composition monitor, while BIA analyses employed a Bodystat Quadscan 4000. Results : Mean TBW values by BIS and BIA were 33.6 ± 7.2 L and 38.3 ± 7.4 L; mean ECW values were 15.8 ± 3.2 L and 16.9 ± 2.7 L; and mean ICW values were 17.9 ± 4.3 L and 21.0 ± 4.9 L, respectively. Mean differences for TBW were 4.6 ± 1.9 L (P < 0.001), for ECW they were 1.2 ± 0.5 L (P < 0.001), and for ICW they were 3.2 ±1.8 L (P < 0.001). BIA and BIS measurements were highly correlated: TBW r = 0.970, ECW r = 0.994, and ICW r = 0.926. Compared with BIA, BIS assessments of fluid overload appeared to be more associated with biochemical and clinical indicators. Conclusion : Although both BIA and BIS can be used for body water assessment, clinicians should be aware of biases that exist between bioimpedance techniques. The values of body water assessments in our study were higher in BIA than in BIS. Ethnicity, sex, body mass index, and estimated glomerular filtration rate were associated with these biases.

Background: Urinary tissue inhibitor of metalloproteinase-2 (TIMP2) and insulin-like growth factor binding protein-7 (IGFBP7) predict severe acute kidney injury (AKI) in critical illness. Earlier but subtle elevation of either biomarker from nephrotoxicity may predict drug-induced AKI. Methods: A prospective study involving serial urine collection in patients treated with vancomycin, aminoglycosides, amphotericin, foscarnet, or calcineurin inhibitors was performed. Urinary TIMP2 and IGFBP7, both absolute levels and those normalized with urine creatinine, were examined in days leading to AKI onset by KDIGO criteria in cases or at final day of nephrotoxic therapy in non-AKI controls, who were matched for age, baseline kidney function, and nephrotoxic exposure. Results: Urinary biomarker analyses were performed in 21 AKI patients and 28 non-AKI matched-controls; both groups had comparable baseline kidney function and duration of nephrotoxic drug therapy. Significantly higher absolute, normalized, and composite levels of TIMP2 and IGFBP7 were observed in AKI cases versus controls as early as 2-3 days before AKI onset (all P70% of patients with corresponding levels above 75th percentile developed AKI. Normalized TIMP2 at 2-3 days pre-AKI predicted AKI with the highest average AUROC of 0.81, followed by that of composite [TIMP2]x[IGFBP7] (0.78) after cross-validation. [TIMP2]x[IGFBP7] >0.01 (ng/mL)2/1000 predicted AKI with a sensitivity of 79% and specificity of 60%. Conclusion: Elevated urinary TIMP2 or IGFBP7 predicts drug-induced AKI with a lead-time of 2-3 days; an opportune time for interventions to reduce nephrotoxicity.

BACKGROUND Acute kidney injury (AKI) develops in 4% of hospitalized patients and is a marker of clinical deterioration and nephrotoxicity. AKI onset is highly variable in hospitals, which makes it difficult to time biomarker assessment in all patients for preemptive care. OBJECTIVE The study sought to apply machine learning techniques to electronic health records and predict hospital-acquired AKI by a 48-hour lead time, with the aim to create an AKI surveillance algorithm that is deployable in real time. METHODS The data were sourced from 20,732 case admissions in 16,288 patients over 1 year in our institution. We enhanced the bidirectional recurrent neural network model with a novel time-invariant and time-variant aggregated module to capture important clinical features temporal to AKI in every patient. Time-series features included laboratory parameters that preceded a 48-hour prediction window before AKI onset; the latter’s corresponding reference was the final in-hospital serum creatinine performed in case admissions without AKI episodes. RESULTS The cohort was of mean age 53 (SD 25) years, of whom 29%, 12%, 12%, and 53% had diabetes, ischemic heart disease, cancers, and baseline eGFR 2, respectively. There were 911 AKI episodes in 869 patients. We derived and validated an algorithm in the testing dataset with an AUROC of 0.81 (0.78-0.85) for predicting AKI. At a 15% prediction threshold, our model generated 699 AKI alerts with 2 false positives for every true AKI and predicted 26% of AKIs. A lowered 5% prediction threshold improved the recall to 60% but generated 3746 AKI alerts with 6 false positives for every true AKI. Representative interpretation results produced by our model alluded to the top-ranked features that predicted AKI that could be categorized in association with sepsis, acute coronary syndrome, nephrotoxicity, or multiorgan injury, specific to every case at risk. CONCLUSIONS We generated an accurate algorithm from electronic health records through machine learning that predicted AKI by a lead time of at least 48 hours. The prediction threshold could be adjusted during deployment to optimize recall and minimize alert fatigue, while its precision could potentially be augmented by targeted AKI biomarker assessment in the high-risk cohort identified.

Introduction. Derangement in calcium homeostasis is common in nephrotic syndrome (NS). It is postulated that low serum total calcium and vitamin D levels are due to loss of protein-bound calcium and vitamin D. It is unclear if free calcium and free vitamin D levels are truly low. The guideline is lacking with regards to calcium and vitamin D supplementation in NS. This study aims to examine calcium and vitamin D homeostasis and bone turnover in NS to guide practice in calcium and vitamin D levels supplementation. Methodology. This is a prospective pilot study of ten patients diagnosed with NS, and eight healthy controls. Calcium, vitamin D, and bone turnover-related analytes were assessed at baseline, partial and complete remission in NS patients and in healthy controls. Results. NS patients had low free and total serum calcium, low total 25(OH)D, normal total 1,25(OH)D levels and lack of parathyroid hormone response. With remission of disease, serum calcium and vitamin D metabolites improved. However, nephrotic patients who do not attain complete disease remission continue to have low 25(OH)D level. Conclusion. In this study, the vitamin D and calcium derangement observed at nephrotic syndrome presentation trended towards normalisation in remission. This suggested calcium and vitamin D replacement may not be indicated in early-phase nephrotic syndrome but may be considered in prolonged nephrotic syndrome.

In high stakes applications such as healthcare and finance analytics, the interpretability of predictive models is required and necessary for domain practitioners to trust the predictions. Traditional machine learning models, e.g., logistic regression (LR), are easy to interpret in nature. However, many of these models aggregate time-series data without considering the temporal correlations and variations. Therefore, their performance cannot match up to recurrent neural network (RNN) based models, which are nonetheless difficult to interpret. In this paper, we propose a general framework TRACER to facilitate accurate and interpretable predictions, with a novel model TITV devised for healthcare analytics and other high stakes applications such as financial investment and risk management. Different from LR and other existing RNN-based models, TITV is designed to capture both the time-invariant and the time-variant feature importance using a feature-wise transformation subnetwork and a self-attention subnetwork, for the feature influence shared over the entire time series and the time-related importance respectively. Healthcare analytics is adopted as a driving use case, and we note that the proposed TRACER is also applicable to other domains, e.g., fintech. We evaluate the accuracy of TRACER extensively in two real-world hospital datasets, and our doctors/clinicians further validate the interpretability of TRACER in both the patient level and the feature level. Besides, TRACER is also validated in a high stakes financial application and a critical temperature forecasting application. The experimental results confirm that TRACER facilitates both accurate and interpretable analytics for high stakes applications., A version of this preprint will appear in ACM SIGMOD 2020

We examined the incidence of myocardial ischemia (MI) in kidney transplant recipients (KTR) using myocardial perfusion imaging (MPI), and its association with long-term outcomes after transplantation. A retrospective observational study was conducted of asymptomatic KTRs who underwent post-transplant MPI screening for MI, as defined by moderate to severe myocardial perfusion defects, post-stress myocardial stunning or balanced ischemia. A composite outcome of all-cause mortality, graft loss, and major adverse cardiovascular events (MACE) was examined over minimum 5 years. We studied 135 KTRs who underwent 226 MPIs, with follow-up duration of 10 (7–13) years. 110 (81%) patients had normal MPIs, 11 (8%) had mild perfusion defects, and 14 (10%) had MI. Correspondingly, composite outcome developed in 6%, 27%, and 43% (p = 0.04), and MACE occurred in 7%, 0%, and 21% (p = 0.11), of the respective subgroups. Twenty-six patients developed the composite outcome after 5 (3–7) years post-transplantation, including 11 patients with MACE. On multivariate analysis, MI, higher low-density lipoprotein levels, and proteinuria > 0.3 g/day independently predicted the composite outcome; only MI predicted MACE (all p

Purpose: We aim to determine whether hyperlactatemia, which suggests multi-organ dysfunction and impaired organic substrate metabolism, may predict intolerance to regional citrate anticoagulation (RCA) during continuous venovenous hemofiltration (CVVH). Methods: We performed a single-center, retrospective observational study in critically ill patients with acute kidney injury or end-stage renal disease and evaluated the association of peak serum lactate levels with citrate intolerance (CI) during the initial 72 hours of RCA-CVVH, defined by serum total-to-ionized calcium >2.5 plus systemic hypocalcemia. Results: Eighty-eight patients were studied (aged 59 ± 14 years, 66% males, Acute Physiology and Chronic Health Evaluation II: 31 ± 8). Citrate was dosed at median 2.1 mmol/L of blood flow, with citrate load of 30 mmol/h, and CVVH effluent of 43 mL/kg/h. Twenty patients developed CI. Comparing patients with CI versus none, peak lactate levels were 8 (5-11) versus 3 (2-6) mmol/L, calcium replacement was 13 (10-17) versus 11 (8-12) mmol/h, and standard base excess was −4 (−12 to 1) versus 2(−4 to 7) mmol/L, respectively ( P < .05). Citrate intolerance developed in 38%, 44%, and 55%, in patients with peak lactate >4, >6, >7 mmol/L, respectively, versus 7% in those with peak lactate ≤4 mmol/L ( P ≤ .001), despite comparable citrate load and effluent rates across all categories. On multivariate analysis, hyperlactatemia and hyperbilirubinemia predicted CI ( P ≤ .01), which was associated with increasing calcium infusion requirement. Higher peak lactate from >4 to >7 mmol/L predicted CI with graded increase in odds ratio and specificity from 59% to 87%, but the corresponding negative predictive value from 93% to 87%. Area under nonparametric receiver operating characteristic curve for peak lactate and CI was 0.78. Conclusion: Hyperlactatemia predicts CI during RCA-CVVH with reasonable discriminatory performance in critically ill patients. Serum lactate surveillance may help preempt issues with citrate toxicity.

Plasma galectin-3 (pG3) regulates inflammation. B-type natriuretic peptide (BNP), high-sensitivity Troponin I (hsTnI), and pG3 concentrations are elevated in chronic kidney disease (CKD) patients. The associations of pG3 with hsTnI/BNP are unclear. We explored the relationship of hsTnI and BNP with pG3 in Asian CKD patients and healthy controls. We retrieved prospectively collected frozen plasma samples from 163 stable CKD patients and 105 healthy controls. BNP, hsTnI and pG3 were assayed. pG3 was assessed for associations with age, gender, ethnicity, blood pressures; height, weight, body mass index (BMI), previously diagnosed CKD, diabetes, hypertension, coronary artery disease, estimated glomerular filtration rate (eGFR); C-reactive protein, beta-trace protein, 24 h urine protein, serum albumin, uric acid and cystatin C. We created two models predicting pG3 using multiple linear regression. Akaike Information Criterion (AIC) was used for comparison. Significance was taken at P

The utility of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) utility in predicting immune-related adverse events (irAEs) and survival have not been well studied in the context of treatment with immune checkpoint inhibitors (ICIs). We performed a case-control study of cancer patients who received at least one dose of ICI in a tertiary hospital. We examined NLR and PLR in irAE cases and controls. Logistic and Cox regression models were used to identify independent risk factors for irAEs, progression-free survival (PFS), and overall survival (OS). The study included 91 patients with irAEs and 56 controls. Multiple logistic regression showed that NLR &lt, 3 at baseline was associated with higher occurrence of irAEs. Multivariate Cox regression showed that development of irAEs and reduction in NLR from baseline to week 6 were associated with longer PFS. Higher NLR values at baseline and/or week 6 were independently associated with shorter OS. A reduction in NLR from baseline to week 6 was associated with longer OS. In this study of cancer patients treated with ICIs, NLR has a bidirectional relationship with adverse outcomes. Lower NLR was associated with increased occurrence of irAEs while higher NLR values were associated with worse clinical outcomes.

Introduction: End stage renal failure patients on hemodialysis have significant vascular calcification This is postulated to be related to sub-clinical vitamin K deficiency, which is prevalent in hemodialysis patients. Vitamin K deficiency result in the failure of the matrix GLA protein (MGP) to undergo carboxylation. MGP is a natural local inhibitor of vascular calcification and the lack of functional carboxylated MGP may contribute to increase vascular calcification. Vitamin K supplement should therefore correct this anomaly and decrease the rate or severity of vascular calcification in this population of patients on long-term maintenance hemodialysis. Our study seeks to evaluate the prevalence and the progression of vascular calcification in a cohort of maintenance hemodialysis patients. It will also evaluate the efficacy of vitamin K supplementation in reducing the progression of vascular calcification in this group of patients. Methods: This will be a single-center randomized, prospective and open-label interventional clinical trial of end stage renal failure patients on hemodialysis. We aim to recruit 200 patients. Eligible patients will be randomized to either the standard care arm or active treatment arm. Active treatment arm patients will receive standard care plus supplementation with oral vitamin K2 isoform 360 mcg 3 times weekly for a total duration of 18 months. Primary outcome measured will be absolute difference in coronary artery calcification score at 18-month between control and intervention arms. Secondary outcomes will be to compare absolute difference in aortic valve calcification, percentage of patients with regression of coronary artery calcification of at least 10%, absolute difference in aortic and systemic arterial stiffness, mortality from any cause and major adverse cardiovascular over the same period. Discussion: Evidence of successful regression or retardation of vascular calcification will support the conduct of larger and longer-term trials aimed at reducing cardiovascular disease mortality and major adverse cardiovascular events in this high-risk population using a safe and inexpensive strategy Trial registration: ClinicalTrials.gov NCT02870829. Registered on 17 August 2016 – Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02870829 National University Hospital's Institutional Review Board (2015/01000)

Intravenous maintenance fluid (IMF) tonicity and composition influence plasma electrolyte balance.To determine if hypotonic IMF therapy contributes to post-surgical hyponatremia.Single-center tertiary institution.Adults who underwent major surgery and received peri-surgical IMF, with exclusive administration of hypotonic pre-mixed 0.33% saline, 5% dextrose and potassium chloride (DK0.33%S), or isotonic 0.9% saline with or without 5% dextrose (NS/DNS).We examined post-surgical hyponatremia, hypokalemia and acute kidney injury (AKI), associated with use of either IMF.We studied 659 patients, of whom 161 patients (24%) developed post-surgical hyponatremia. DK0.33%S (versus NS/DNS) IMF was administered in 52% of patients who developed hyponatremia, compared to 38% of patients with stable natremia (p = 0.001). More patients with hyponatremia underwent gastrointestinal-hepatobiliary or abdominal (GI/HBS/Abd) surgery versus other surgical-sites (p = 0.001). Hypokalemia developed in 1% versus 10% of patients who received DK0.33%S and NS/DNS IMF respectively (p 0.001), with corresponding AKI rates of 3% versus 7% (p = 0.02). On multivariate analysis, adjusted for timing of biochemistry post-surgery, IMF infusion rate and volume; independent factors associated with post-surgical hyponatremia included DK0.33%S administration, GI/HBS/Abd surgery (versus other sites), and post-surgical AKI (p 0.05). Subgroup analysis by surgical sites showed that association of DK0.33%S administration with hyponatremia was most evident in GI/HBS/Abd surgery.Administration of DK0.33%S IMF, compared with NS/DNS, is associated with post-surgical hyponatremia in adults after major surgery, but with less hypokalemia. The higher rate of AKI observed with NS/DNS IMF requires further evaluation.

Figure S1. Figure on secondary outcomes. AKI stages based on modified KDIGO criteria at time of EHR-AKI detection, and peak AKI severity in stages. Proportion of patients admitted to Intensive Care Unit (ICU) on detection of AKI, and those who subsequently received ICU care, are shown. All figures are in percentages. (PPTX 45â kb)

Critical illness induces an inflammatory milieu in patients that is exacerbated by acute kidney injury (AKI) and results in derangements in protein metabolism. Proteins are polymers of amino acids (AAs), with nitrogen as a fundamental component. Metabolic equilibrium between intake/synthesis and degradation/loss exists physiologically. Protein synthesis and muscle hypertrophy are promoted by activity-driven insulin-like growth factor-1 action and downstream induction of autocrine and paracrine activities. These are counterbalanced by protein breakdown via the ubiquitin-proteasome pathway. The oxidative stress and catabolic hormonal surge during critical illness and AKI tip the balance into net protein catabolism, with increased hepatic gluconeogenesis, ureagenesis, and disordered plasma AA profile. These are worsened by metabolic acidosis and restricted intake with acute illness and oligoanuric state. Protein catabolism translates to early and severe muscle wasting in critically ill patients, especially with multiorgan failure. Renal replacement therapy (RRT) facilitates nutritional support by volume and azotemic control during AKI but leads to undesired losses, including AAs because of their small molecular weight and membrane adsorption of proteins. AAs are lost selectively at 5% to 20% of daily intake but account for less than 10% of total nitrogen loss, the majority being urea nitrogen. Corresponding protein loss during RRT can exceed 2 g/kg/day. However, purported benefits of early, enhanced nutritional support and increased protein delivery during initial acute illness on patient outcomes are not proven by recent large-scale randomized controlled trials (RCTs). Individualized nutritional management during recovery phase of AKI, with objective assessments of nitrogen balance during RRT, muscle mass indices, and early patient mobilization, are desirable for future research.

Because of a technical error, the code corresponding to the outcome for the Basir et al. cohort was mis-implemented in the original version of our article. Characteristics of the cohort are in fact the followings.

Purpose: To evaluate 1-year mortality in patients with septic acute kidney injury (AKI) and to determine association between initial AKI recovery patterns ( reversal within 5 days, beyond 5 days but recovery, or nonrecovery) and chronic kidney disease (CKD) progression. Methods: Prospective observational study, with retrospective evaluation of initial nonconsenters, of critically ill patients with septic AKI. Results: We studied 207 patients (age, mean [SD]: 64 [16] years, 39% males), of which 56 (27%), 18 (9%), and 9 (4%) died in intensive care unit (ICU), post-ICU in hospital, and posthospitalization, respectively. Infections (including pneumonia) and major adverse cardiac events accounted for 64% and 12% of deaths, respectively. Factors independently associated with 1-year mortality include older age, ischemic heart disease, higher Simplified Acute Physiology Score II, central nervous system or musculoskeletal primary infections, higher daily fluid balance (FB), and frusemide administration during ICU stay (all P < .05). Among 63 patients receiving renal replacement therapy (RRT), hospital mortality was higher with cumulative median FB >8 L versus ≤8 L at RRT initiation (57% vs 24%; P = .009); there was trend for less ICU- and RRT-free days at day 28 in patients with higher FB pre-RRT ( P = NS). Chronic kidney disease progression over 1 year developed in 21%, 30%, and 79% of 105 initial survivors with AKI reversal, recovery, and nonrecovery, respectively ( P < .001). Acute kidney injury nonrecovery during hospitalization independently predicted CKD progression ( P = .001). Conclusions: Patients with septic AKI had 40% 1-year mortality, mainly associated with infections. High FB and frusemide administration were modifiable risk factors. Risk of CKD progression is high especially with initial AKI nonrecovery.

Supplemental Material, R1_Septic_AKI_supplementary_tables_and_figure_HR_2-2-18 for Extended Mortality and Chronic Kidney Disease After Septic Acute Kidney Injury by Horng-Ruey Chua, Weng-Kin Wong, Venetia Huiling Ong, Dipika Agrawal, Anantharaman Vathsala, Hui-Ming Tay, and Amartya Mukhopadhyay in Journal of Intensive Care Medicine

Correction Volume: 44 Issue: 11 Pages: 2022-2023 DOI: 10.1007/s00134-018-5372-9 Catecholamines have been the mainstay of pharmacological treatment of cardiogenic shock (CS). Recently, use of epinephrine has been associated with detrimental outcomes. In the present study we aimed to evaluate the association between epinephrine use and short-term mortality in all-cause CS patients. We performed a meta-analysis of individual data with prespecified inclusion criteria: (1) patients in non-surgical CS treated with inotropes and/or vasopressors and (2) at least 15% of patients treated with epinephrine administrated alone or in association with other inotropes/vasopressors. The primary outcome was short-term mortality. Fourteen published cohorts and two unpublished data sets were included. We studied 2583 patients. Across all cohorts of patients, the incidence of epinephrine use was 37% (17-76%) and short-term mortality rate was 49% (21-69%). A positive correlation was found between percentages of epinephrine use and short-term mortality in the CS cohort. The risk of death was higher in epinephrine-treated CS patients (OR [CI] = 3.3 [2.8-3.9]) compared to patients treated with other drug regimens. Adjusted mortality risk remained striking in epinephrine-treated patients (n = 1227) (adjusted OR = 4.7 [3.4-6.4]). After propensity score matching, two sets of 338 matched patients were identified and epinephrine use remained associated with a strong detrimental impact on short-term mortality (OR = 4.2 [3.0-6.0]). In this very large cohort, epinephrine use for hemodynamic management of CS patients is associated with a threefold increase of risk of death.

The risk of catheter-related infection or bacteremia, with initial and extended use of femoral versus nonfemoral sites for double-lumen vascular catheters (DLVCs) during continuous renal replacement therapy (CRRT), is unclear.Retrospective observational cohort study.Critically ill patients on CRRT in a combined intensive care unit of a tertiary institution.Femoral versus nonfemoral venous DLVC placement.Catheter-related colonization (CRCOL) and bloodstream infection (CRBSI).CRCOL/CRBSI rates expressed per 1,000 catheter-days.We studied 458 patients (median age, 65 years; 60% males) and 647 DLVCs. Of 405 single-site only DLVC users, 82% versus 18% received exclusively 419 femoral versus 82 jugular or subclavian DLVCs, respectively. The corresponding DLVC indwelling duration was 6±4 versus 7±5 days (P=0.03). Corresponding CRCOL and CRBSI rates (per 1,000 catheter-days) were 9.7 versus 8.8 events (P=0.8) and 1.2 versus 3.5 events (P=0.3), respectively. Overall, 96 patients with extended CRRT received femoral-site insertion first with subsequent site change, including 53 femoral guidewire exchanges, 53 new femoral venipunctures, and 47 new jugular/subclavian sites. CRCOL and CRBSI rates were similar for all such approaches (P=0.7 and P=0.9, respectively). On multivariate analysis, CRCOL risk was higher in patients older than 65 years and weighing90kg (ORs of 2.1 and 2.2, respectively; P0.05). This association between higher weight and greater CRCOL risk was significant for femoral DLVCs, but not for nonfemoral sites. Other covariates, including initial or specific DLVC site, guidewire exchange versus new venipuncture, and primary versus secondary DLVC placement, did not significantly affect CRCOL rates.Nonrandomized retrospective design and single-center evaluation.CRCOL and CRBSI rates in patients on CRRT are low and not influenced significantly by initial or serial femoral catheterizations with guidewire exchange or new venipuncture. CRCOL risk is higher in older and heavier patients, the latter especially so with femoral sites.

Purpose The safety of femoral vein (FV) catheterization for continuous renal replacement therapy is uncertain. We sought to determine the incidence of clinically manifest venous thromboembolism (VTE) in such patients. Methods We retrospectively studied patients with femoral high flow catheters (≥ 13F) (December 2005 to February 2011). Discharge diagnostic codes were independently screened for VTE. The incidence of VTE was also independently similarly assessed in a control cohort of patients ventilated for more than 2 days (January 2011 to December 2011) in the same intensive care unit (ICU). Results We studied 380 patients. Their mean age was 61 years, and 59% were male. The mean Acute Physiology and Chronic Health Evaluation III score was 84; average duration of continuous renal replacement therapy was 74 hours, and 232 patients (61%) survived to hospital discharge with an average length of hospital stay of 22 days. Only 5 patients (1.3%) had clinically manifest VTE after FV catheterization. In the control cohort of 514 ICU patients, the incidence of VTE was 4.4% (P Conclusion The incidence of clinically manifest VTE after FV catheterization with high flow catheters is low and lower to that seen in general ICU patients.