Delaying renal replacement therapy (RRT) for some time in critically ill patients with severe acute kidney injury and no severe complication is safe and allows optimisation of the use of medical ...devices. Major uncertainty remains concerning the duration for which RRT can be postponed without risk. Our aim was to test the hypothesis that a more-delayed initiation strategy would result in more RRT-free days, compared with a delayed strategy.
This was an unmasked, multicentre, prospective, open-label, randomised, controlled trial done in 39 intensive care units in France. We monitored critically ill patients with severe acute kidney injury (defined as Kidney Disease: Improving Global Outcomes stage 3) until they had oliguria for more than 72 h or a blood urea nitrogen concentration higher than 112 mg/dL. Patients were then randomly assigned (1:1) to either a strategy (delayed strategy) in which RRT was started just after randomisation or to a more-delayed strategy. With the more-delayed strategy, RRT initiation was postponed until mandatory indication (noticeable hyperkalaemia or metabolic acidosis or pulmonary oedema) or until blood urea nitrogen concentration reached 140 mg/dL. The primary outcome was the number of days alive and free of RRT between randomisation and day 28 and was done in the intention-to-treat population. The study is registered with ClinicalTrial.gov, NCT03396757 and is completed.
Between May 7, 2018, and Oct 11, 2019, of 5336 patients assessed, 278 patients underwent randomisation; 137 were assigned to the delayed strategy and 141 to the more-delayed strategy. The number of complications potentially related to acute kidney injury or to RRT were similar between groups. The median number of RRT-free days was 12 days (IQR 0–25) in the delayed strategy and 10 days (IQR 0–24) in the more-delayed strategy (p=0·93). In a multivariable analysis, the hazard ratio for death at 60 days was 1·65 (95% CI 1·09–2·50, p=0·018) with the more-delayed versus the delayed strategy. The number of complications potentially related to acute kidney injury or renal replacement therapy did not differ between groups.
In severe acute kidney injury patients with oliguria for more than 72 h or blood urea nitrogen concentration higher than 112 mg/dL and no severe complication that would mandate immediate RRT, longer postponing of RRT initiation did not confer additional benefit and was associated with potential harm.
Programme Hospitalier de Recherche Clinique.
In the early phase of the pandemic, we were among the first to postulate that neutrophil extracellular traps (NETs) play a key role in COVID‐19 pathogenesis. This exploratory prospective study based ...on 279 individuals showed that plasma levels of neutrophil elastase, myeloperoxidase and circulating DNA of nuclear and mitochondrial origins in nonsevere (NS), severe (S) and postacute phase (PAP) COVID‐19 patients were statistically different as compared to the levels in healthy individuals, and revealed the high diagnostic power of these NETs markers in respect to the disease severity. The diagnostic power of NE, MPO, and cir‐nDNA as determined by the Area Under Receiver Operating Curves (AUROC) was 0.95, 097, and 0.64; 0.99, 1.0, and 0.82; and 0.94, 1.0, and 0.93, in NS, S, and PAP patient subgroups, respectively. In addition, a significant fraction of NS, S as well as of PAP patients exhibited aCL IgM/IgG and anti‐B2GP IgM/IgG positivity. We first demonstrate persistence of these NETs markers in PAP patients and consequently of sustained innate immune response imbalance, and a prolonged low‐level pro‐thrombotic potential activity highlighting the need to monitor these markers in all COVID‐19 PAP individuals, to investigate postacute COVID‐19 pathogenesis following intensive care, and to better identify which medical resources will ensure complete patient recovery.
Osteoprotegerin (OPG), sclerostin and DKK1 constitute opposite bone turnover inhibitors, OPG inhibiting osteoclastogenesis while sclerostin and DKK1 exerting their inhibitory effects on ...osteoblastogenesis. Both proteins have been recognized as strong risk factors of vascular calcifications in non-dialysis chronic kidney disease (ND-CKD) patients. The aim of this study was to investigate the relationships between these inhibitors and coronary artery calcifications (CAC) in this population.
A total of 241 ND-CKD patients 143 males; 69.0 (25.0-95.0) years; median estimated glomerular filtration rate using CKD-EPI 35.1 (6.7-120.1) mL/min/1.73 m(2) were enrolled in this cross-sectional study. All underwent chest multidetector computed tomography for CAC scoring. OPG, sclerostin, DKK1 and mineral metabolism markers including PTH and bone alkaline phosphatase were measured. Logistic regression analyses were used to study the relationships between CAC and these markers.
Decline in renal function was associated with a significant increase in OPG and sclerostin while a slight but significant decrease in DKK1 was observed. The main crude associations with presence of CAC were a high level of OPG OR = 2.55 95% confidence interval (95% CI) (1.35-4.82) for a level ranging from 6.26 to 9.15 pmol/L and OR = 5.74 95% CI (2.87-11.5) for a level ≥9.15 pmol/L; P < 0.0001 and a high level of sclerostin OR = 2.64 95% CI (1.39-5.00) for a level ranging from 0.748 to 1.139 ng/mL and OR = 3.78 95% CI (1.96-7.31) for a level ≥1.139 ng/mL; P = 0.0002. A logistic regression model clearly showed that the risk to present CAC was significantly increased when both OPG (≥6.26 pmol/L) and sclerostin (≥0.748 ng/mL) levels were high crude model: OR = 11.47 95% CI (4.54-29.0); P < 0.0001; model adjusted for age, gender, diabetes, body mass index and smoking habits: OR = 5.69 95% CI (1.76-18.4); P = 0.02. No association between DKK1 and presence of CAC was observed.
Our results strongly suggest that bone turnover inhibitors, OPG and sclerostin, are independently associated with CAC with potential additive effects in ND-CKD patients.
While several studies from China have reported COVID‐19‐related liver injury, there are currently no data on liver dysfunction in hospitalized COVID‐19 patients in Europe. The aim of this study was ...to describe the prevalence and predictive value of abnormal liver function in patients hospitalized with COVID‐19. This was a retrospective cohort study of confirmed COVID‐19 patients hospitalized in two referral hospitals in France. Clinical, biological and radiological data were collected and analysed. In all, 234 patients confirmed to have COVID‐19 by RT‐PCR were included. Liver function was abnormal in 66.6% of patients on admission. In multivariate logistic regression, abnormal liver test on admission were associated with in‐hospital aggravation (OR = 4.1, 95% CI 1.5‐10.8; P = .004) and mortality (OR 3.3; 95% CI = 1.04‐10.5; P = .04). This study of liver tests in a European COVID‐19 population confirms a high prevalence of abnormal liver tests on admission that are predictive of severe disease course and higher in‐hospital mortality.
Muscle weakness following critical illness is the consequence of loss of muscle mass and alteration of muscle quality. It is associated with long-term disability. Ultrasonography is a reliable tool ...to quantify muscle mass, but studies that evaluate muscle quality at the critically ill bedside are lacking. Shear wave ultrasound elastography (SWE) provides spatial representation of soft tissue stiffness and measures of muscle quality. The reliability and reproducibility of SWE in critically ill patients has never been evaluated.
Two operators tested in healthy controls and in critically ill patients the intra- and inter-operator reliability of the SWE using transversal and longitudinal views of the diaphragm and limb muscles. Reliability was calculated using the intra-class correlation coefficient and a bootstrap sampling method assessed their consistency.
We collected 560 images. Longitudinal views of the diaphragm (ICC 0.83 0.50-0.94), the biceps brachii (ICC 0.88 0.67-0.96) and the rectus femoris (ICC 0.76 0.34-0.91) were the most reliable views in a training set of healthy controls. Intra-class correlation coefficient for inter-operator reproducibility and intra-operator reliability was above 0.9 for all muscles in a validation set of healthy controls. In critically ill patients, inter-operator reproducibility and intra-operator 1 and 2 reliability ICCs were respectively 0.92 0.71-0.98, 0.93 0.82-0.98 and 0.92 0.81-0.98 for the diaphragm; 0.96 0.86-0.99, 0.98 0.94-0.99 and 0.99 0.96-1 for the biceps brachii and 0.91 0.51-0.98, 0.97 0.93-0.99 and 0.99 0.97-1 for the rectus femoris. The probability to reach intra-class correlation coefficient greater than 0.8 in a 10,000 bootstrap sampling for inter-operator reproducibility was respectively 81%, 84% and 78% for the diaphragm, the biceps brachii and the rectus femoris respectively.
SWE is a reliable technique to evaluate limb muscles and the diaphragm in both healthy controls and in critically ill patients.
The study was registered (ClinicalTrial NCT03550222).
Objective
Previous studies have unveiled a relationship between the severity of coronavirus disease 2019 (COVID‐19) pneumonia and obesity. The aims of this multicenter retrospective cohort study were ...to disentangle the association of BMI and associated metabolic risk factors (diabetes, hypertension, hyperlipidemia, and current smoking status) in critically ill patients with COVID‐19.
Methods
Patients admitted to intensive care units for COVID‐19 in 21 centers (in Europe, Israel, and the United States) were enrolled in this study between February 19, 2020, and May 19, 2020. Primary and secondary outcomes were the need for invasive mechanical ventilation (IMV) and 28‐day mortality, respectively.
Results
A total of 1,461 patients were enrolled; the median (interquartile range) age was 64 years (40.9‐72.0); 73.2% of patients were male; the median BMI was 28.1 kg/m2 (25.4‐32.3); a total of 1,080 patients (73.9%) required IMV; and the 28‐day mortality estimate was 36.1% (95% CI: 33.0‐39.5). An adjusted mixed logistic regression model showed a significant linear relationship between BMI and IMV: odds ratio = 1.27 (95% CI: 1.12‐1.45) per 5 kg/m2. An adjusted Cox proportional hazards regression model showed a significant association between BMI and mortality, which was increased only in obesity class III (≥40; hazard ratio = 1.68 95% CI: 1.06‐2.64).
Conclusions
In critically ill COVID‐19 patients, a linear association between BMI and the need for IMV, independent of other metabolic risk factors, and a nonlinear association between BMI and mortality risk were observed.
Around 10% of critically ill patients suffer acute kidney injury (AKI) requiring kidney replacement therapy (KRT), with a mortality rate approaching 50%. Although most survivors achieve sufficient ...renal recovery to be weaned from KRT, there are no recognized guidelines on the optimal period for weaning from KRT. A systematic review was conducted using a peer-reviewed strategy, combining themes of KRT (intermittent hemodialysis, CKRT: continuous veno-venous hemo/dialysis/filtration/diafiltration, sustained low-efficiency dialysis/filtration), factors predictive of successful weaning (defined as a prolonged period without new KRT) and patient outcomes. Our research resulted in studies, all observational, describing clinical and biological parameters predictive of successful weaning from KRT. Urine output prior to KRT cessation is the most studied variable and the most widely used in practice. Other predictive factors, such as urinary urea and creatinine and new urinary and serum renal biomarkers, including cystatin C and neutrophil gelatinase-associated lipocalin (NGAL), were also analyzed in the light of recent studies. This review presents the rationale for early weaning from KRT, the parameters that can guide it, and its practical modalities. Once the patient's clinical condition has stabilized and volume status optimized, a diuresis greater than 500 mL/day should prompt the intensivist to consider weaning. Urinary parameters could be useful in predicting weaning success but have yet to be validated.
Background. To examine whether the new urinary biomarkers TIMP2 and IGFBP7 can predict progression within 24 hours and 72 hours from mild and moderate (KDIGO 1 or 2) to severe (KDIGO 3) AKI in ...patients with septic shock. Methods. A prospective, multicenter observational study performed in three French ICUs. The urinary biomarkers TIMP2∗IGFBP7 were analyzed at the early phase (<6 hours) of patients admitted for septic shock with mild and moderate AKI. Results. Among the 112 patients included, 45 (40%) progressed to the KDIGO 3 level 24 hours after inclusion (KDIGO 3 H24) and 47 (42%) 72 hours after inclusion (KDIGO 3 H72). The median urinary TIMP2∗IGFBP7 at inclusion (baseline) were higher in the KDIGO 3 group than in the KDIGO<3 group at H24 and H72. All covariates with a p value < 0.1 in the univariate analysis were included in stepwise multiple logistic regression models to identify factors independently associated with the risk of KDIGO 3 at H24 and H72. TIMP2∗IGFBP7 remained independently associated with KDIGO 3 at H24 and H72. Baseline posology of norepinephrine, baseline urine output, and baseline serum creatinine remained also significantly associated with progression to KDIGO 3 at H24. Baseline TIMP2∗IGFBP7 and baseline urinary output had the best AUC ROC. A baseline TIMP2∗IGFBP7>2.0 (ng/ml)2/1,000 identified the population at high risk of KDIGO 3 H24 (relative risk 4.19 (1.7-10.4)) with a sensitivity of 76% (60-87) and a specificity of 81% (69-89). But the diagnostic performance at H72 of baseline TIMP2∗IGFBP7 was poor (AUC: 0.69 (0.59-0.77)). Conclusion. The urinary TIMP2∗IGFBP7 concentration and the urine output at the early phase of septic shock are independent factors to identify the population at high risk of progression from mild and moderate to severe AKI over the next 24 but not 72 hours. A TIMP2∗IGFBP7 concentration>2.0 (ng/ml)2/1,000 quadruples the risk of KDIGO 3 AKI within 24 hours. This trial is registered with (NCT03547414).
The timing of initiation of renal replacement therapy (RRT) in the critically ill with acute kidney injury (AKI) has been widely studied and discussed in detail recently 1–3. However, there is ...limited information and few recommendations for when to discontinue RRT in patients who appear to be improving.
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