Characterization of acute kidney injury in critically ill patients with severe coronavirus disease 2019

Abstract Background Coronavirus disease 2019 (COVID-19)-associated acute kidney injury (AKI) frequency, severity and characterization in critically ill patients has not been reported. Methods Single-centre cohort performed from 3 March 2020 to 14 April 2020 in four intensive care units in Bordeaux University Hospital, France. All patients with COVID-19 and pulmonary severity criteria were included. AKI was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria. A systematic urinary analysis was performed. The incidence, severity, clinical presentation, biological characterization (transient versus persistent AKI; proteinuria, haematuria and glycosuria) and short-term outcomes were evaluated. Results Seventy-one patients were included, with basal serum creatinine (SCr) of 69 ± 21 µmol/L. At admission, AKI was present in 8/71 (11%) patients. Median [interquartile range (IQR)] follow-up was 17 (12–23) days. AKI developed in a total of 57/71 (80%) patients, with 35% Stage 1, 35% Stage 2 and 30% Stage 3 AKI; 10/57 (18%) required renal replacement therapy (RRT). Transient AKI was present in only 4/55 (7%) patients and persistent AKI was observed in 51/55 (93%). Patients with persistent AKI developed a median (IQR) urine protein/creatinine of 82 (54–140) (mg/mmol) with an albuminuria/proteinuria ratio of 0.23 ± 20, indicating predominant tubulointerstitial injury. Only two (4%) patients had glycosuria. At Day 7 after onset of AKI, six (11%) patients remained dependent on RRT, nine (16%) had SCr >200 µmol/L and four (7%) had died. Day 7 and Day 14 renal recovery occurred in 28% and 52%, respectively. Conclusion Severe COVID-19-associated AKI is frequent, persistent, severe and characterized by an almost exclusive tubulointerstitial injury without glycosuria

Les mutations contemporaines du droit de l’animal

Le droit de l’animal a connu des mutations d’ampleur au cours des vingt dernières années. Il s’est structuré en champ disciplinaire autonome, a pris une importance croissante dans le débat public et a fait l’objet de réformes remarquées. Le présent ouvrage rend compte de ces évolutions en publiant les actes d’une université d’automne qui s’est tenue à la faculté de droit d’Aix-en-Provence en octobre 2021. Il rassemble les contributions des auteurs – juristes, politistes et historiens – autour de sept thématiques : le droit de l’animal comme champ disciplinaire ; les mots du droit de l’animal ; la fabrique du droit de l’animal ; droit de l’animal et participation démocratique ; droit de l’animal, droits fondamentaux et droit constitutionnel ; la représentation des animaux devant les juridictions et l’action au nom et pour le compte d’un animal ; juridictions pénales et animaux. Le lecteur pourra apprécier, en les parcourant, l’intérêt et la richesse d’une matière en plein essor, particulièrement en phase avec les préoccupations de son temps

Augmented Renal Clearance, Muscle Catabolism and Urinary Nitrogen Loss: Implications for Nutritional Support in Critically Ill Trauma Patients

The main objective of this pilot study was to determine the association between augmented renal clearance (ARC), urinary nitrogen loss and muscle wasting in critically ill trauma patients. We conducted a retrospective analysis of a local database in 162 critically ill trauma patients without chronic renal dysfunction. Nutritional-related parameters and 24 h urinary biochemical analyses were prospectively collected and averaged over the first ten days after admission. Augmented renal clearance was defined by a mean creatinine clearance (CLCR) > 130 mL/min/1.73 m2. The main outcome was the cumulated nitrogen balance at day 10. The secondary outcome was the variation of muscle psoas cross-sectional area (ΔCSA) calculated in the subgroup of patients who underwent at least two abdominal CT scans during the ICU length of stay. Overall, there was a significant correlation between mean CLCR and mean urinary nitrogen loss (normalized coefficient: 0.47 ± 0.07, p < 0.0001). ARC was associated with a significantly higher urinary nitrogen loss (17 ± 5 vs. 14 ± 4 g/day, p < 0.0001) and a lower nitrogen balance (−6 ± 5 vs. −4 ± 5 g/day, p = 0.0002), without difference regarding the mean protein intake (0.7 ± 0.2 vs. 0.7 ± 0.3 g/kg/day, p = 0.260). In the subgroup of patients who underwent a second abdominal CT scan (N = 47), both ΔCSA and %ΔCSA were higher in ARC patients (−33 [−41; −25] vs. −15 [−29; −5] mm2/day, p = 0.010 and −3 [−3; −2] vs. −1 [−3; −1] %/day, p = 0.008). Critically ill trauma patients with ARC are thus characterized by a lower nitrogen balance and increased muscle loss over the 10 first days after ICU admission. The interest of an increased protein intake (>1.5 g/kg/day) in such patients remains a matter of controversy and must be confirmed by further randomized trials

Are Standard Dosing Regimens of Ceftriaxone Adapted for Critically Ill Patients with Augmented Creatinine Clearance?

ABSTRACT The objective of the present study was to determine whether augmented renal clearance (ARC) impacts negatively on ceftriaxone pharmacokinetic (PK)/pharmacodynamic (PD) target attainment in critically ill patients. Over a 9-month period, all critically ill patients treated with ceftriaxone were eligible. During the first 3 days of antimicrobial therapy, every patient underwent 24-h creatinine clearance (CL CR ) measurements and therapeutic drug monitoring of unbound ceftriaxone. ARC was defined by a CL CR of ≥150 ml/min. Empirical underdosing was defined by a trough unbound ceftriaxone concentration under 2 mg/liter (percentage of the time that the concentration of the free fraction of drug remained greater than the MIC [ fT \textgreaterMIC ], 100%). Monte Carlo simulation (MCS) was performed to determine the probability of target attainment (PTA) of different dosing regimens for various MICs and three groups of CL CR (\textless150, 150 to 200, and \textgreater200 ml/min). Twenty-one patients were included. The rate of empirical ceftriaxone underdosing was 62% (39/63). A CL CR of ≥150 ml/min was associated with empirical target underdosing with an odds ratio (OR) of 8.8 (95% confidence interval [CI] = 2.5 to 30.7; P \textless 0.01). Ceftriaxone PK concentrations were best described by a two-compartment model. CL CR was associated with unbound ceftriaxone clearance ( P = 0.02). In the MCS, the proportion of patients who would have failed to achieve a 100% fT \textgreaterMIC was significantly higher in ARC patients for each dosage regimen (OR = 2.96; 95% CI = 2.74 to 3.19; P \textless 0.01). A dose of 2 g twice a day was best suited to achieve a 100% fT \textgreaterMIC . When targeting a 100% fT \textgreaterMIC for the less susceptible pathogens, patients with a CL CR of ≥150 ml/min remained at risk of empirical ceftriaxone underdosing. These data emphasize the need for therapeutic drug monitoring in ARC patients

Higher than standard dosing regimen are needed to achieve optimal antibiotic exposure in critically ill patients with augmented renal clearance receiving piperacillin-tazobactam administered by continuous infusion

Purpose To determine whether augmented renal clearance (ARC) impacts negatively on piperacillin-tazobactam unbound concentrations in critically ill patients receiving 16 g/2 g/day administered continuously. Material and methods Fifty nine critically ill patients without renal impairment underwent 24-h creatinine clearance (Cr CL ) measurement and therapeutic drug monitoring during the first three days of antimicrobial therapy by piperacillin-tazobactam. The main outcome was the rate of piperacillin underexposure, defined by at least one of three samples under 16 mg/L. Monte Carlo simulation was performed to predict the distribution of piperacillin concentrations for various Cr CL and minimal inhibitory concentration (MIC) values. Results The rate of piperacillin underexposure was 19%, significantly higher in ARC patients (0 vs. 31%, p = .003). A threshold of Cr CL ≥ 170 mL/min had a sensitivity and specificity of 1 (95%CI: 0.79–1) and 0.69 (95%CI: 0.61–0.76) to predict piperacillin underexposure. In ARC patients, a 20 g/2.5 g/24 h PTZ dosing regimen was associated with the highest probability to reach the 16 mg/L empirical target, without risk of excessive dosing. Conclusions When targeting a theoretical MIC at the upper limit of the susceptibility range, the desirable target (100%fT >16 ) may not be achieved in patients with Cr CL ≥ 170 mL/min receiving PTZ 16 g/2 g/day administered continuously