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Continuous kidney replacement therapy (CKRT) is well entrenched as one of the dominant KRT modalities in modern critical care practice. Since its introduction four decades ago, there have been considerable innovations in CKRT machines that have improved precision, safety, and simplicity. CKRT is the preferred KRT modality for critically ill patients with hemodynamic instability. Early physical therapy and rehabilitation can be feasibly and safely provided to patients connected to CKRT, thus obviating concerns about immobility. Although randomized clinical trials have not shown a mortality difference when comparing CKRT and intermittent hemodialysis, CKRT allows precision delivery of solute and fluid removal that can be readily adjusted in the face of dynamic circumstances. Accumulated evidence from observational studies, although susceptible to bias, has shown that CKRT, when compared with intermittent hemodialysis, is associated with better short- and long-term kidney recovery and KRT independence. Critical care medicine encompasses a wide range of sick patients, and no single KRT modality is likely to ideally suit every patient in every context and for every condition. The provision of KRT represents a spectrum of modalities to which patients can flexibly transition in response to their evolving condition. As a vital tool for organ support in the intensive care unit, CKRT enables the personalization of KRT to meet the clinical demands of patients during the most severe phases of their illness., (Copyright © 2023 by the American Society of Nephrology.)

Cefepime, ceftazidime, and piperacillin/tazobactam are commonly used beta-lactam antibiotics in the critical care setting. For critically ill patients receiving prolonged intermittent renal replacement therapy (PIRRT), limited pharmacokinetic data are available to inform clinicians on the dosing of these agents. Monte Carlo simulations (MCS) can be used to guide drug dosing when pharmacokinetic trials are not feasible. For each antibiotic, MCS using previously published pharmacokinetic data derived from critically ill patients was used to evaluate multiple dosing regimens in 4 different prolonged intermittent renal replacement therapy effluent rates and prolonged intermittent renal replacement therapy duration combinations (4 L/h × 10 hours or 5 L/h × 8 hours in hemodialysis and hemofiltration modes). Antibiotic regimens were also modeled depending on whether drugs were administered during or well before prolonged intermittent renal replacement therapy therapy commenced. The probability of target attainment (PTA) was calculated using each antibiotic's pharmacodynamic target during the first 48 hours of therapy. Optimal doses were defined as the smallest daily dose achieving ≥90% probability of target attainment in all prolonged intermittent renal replacement therapy effluent and duration combinations. Cefepime 1 g every 6 hours following a 2 g loading dose, ceftazidime 2 g every 12 hours, and piperacillin/tazobactam 4.5 g every 6 hours attained the desired pharmacodynamic target in ≥90% of modeled prolonged intermittent renal replacement therapy patients. Alternatively, if an every 6-hours cefepime regimen is not desired, the cefepime 2 g pre-prolonged intermittent renal replacement therapy and 3 g post-prolonged intermittent renal replacement therapy regimen also met targets. For ceftazidime, 1 g every 6 hours or 3 g continuous infusion following a 2 g loading dose also met targets. These recommended doses provide simple regimens that are likely to achieve the pharmacodynamics target while yielding the least overall drug exposure, which should result in lower toxicity rates. These findings should be validated in the clinical setting., (© 2018, The American College of Clinical Pharmacology.)

Background and Objectives: AKI is frequent and is associated with poor outcomes. There is limited information on the epidemiology of AKI worldwide. This study compared patients with AKI in emerging and developed countries to determine the association of clinical factors and processes of care with outcomes., Design, Setting, Participants, & Measurements: This prospective observational study was conducted among intensive care unit patients from nine centers in developed countries and five centers in emerging countries. AKI was defined as an increase in creatinine of ≥0.3 mg/dl within 48 hours., Results: Between 2008 and 2012, 6647 patients were screened, of whom 1275 (19.2%) developed AKI. A total of 745 (58% of those with AKI) agreed to participate and had complete data. Patients in developed countries had more sepsis (52.1% versus 38.0%) and higher Acute Physiology and Chronic Health Evaluation (APACHE) scores (mean±SD, 61.1±27.5 versus 51.1±25.2); those from emerging countries had more CKD (54.3% versus 38.3%), GN (6.3% versus 0.9%), and interstitial nephritis (7.0% versus 0.6%) (all P<0.05). Patients from developed countries were less often treated with dialysis (15.5% versus 30.2%; P<0.001) and started dialysis later after AKI diagnosis (2.0 [interquartile range, 0.75-5.0] days versus 0 [interquartile range, 0-5.0] days; P=0.02). Hospital mortality was 22.0%, and 13.3% of survivors were dialysis dependent at discharge. Independent risk factors associated with hospital mortality included older age, residence in an emerging country, use of vasopressors (emerging countries only), dialysis and mechanical ventilation, and higher APACHE score and cumulative fluid balance (developed countries only). A lower probability of renal recovery was associated with residence in an emerging country, higher APACHE score (emerging countries only) and dialysis, while mechanical ventilation was associated with renal recovery (developed countries only)., Conclusions: This study contrasts the clinical features and management of AKI and demonstrates worse outcomes in emerging than in developed countries. Differences in variations in care may explain these findings and should be considered in future trials., (Copyright © 2015 by the American Society of Nephrology.)

Objective: Acute kidney injury (AKI) is a highly morbid condition in critically ill patients that is associated with high mortality. Previous clinical studies have demonstrated the safety and efficacy of the Selective Cytopheretic Device (SCD) in the treatment of AKI requiring continuous renal replacement therapy in the intensive care unit (ICU)., Design, Setting, Patients: A randomized, controlled trial of 134 ICU patients with AKI, 69 received continuous renal replacement therapy (CRRT) alone and 65 received SCD therapy., Results: No significant difference in 60-day mortality was observed between the treated (27/69; 39%) and control patients (21/59; 36%, with six patients lost to follow up) in the intention to treat (ITT) analysis. Of the 19 SCD subjects (CRRT+SCD) and 31 control subjects (CRRT alone) who maintained a post-filter ionized calcium (iCa) level in the protocol's recommended range (≤ 0.4 mmol/L) for greater or equal to 90% of the therapy time, 60-day mortality was 16% (3/19) in the SCD group compared to 41% (11/27) in the CRRT alone group (p = 0.11). Dialysis dependency showed a borderline statistically significant difference between the SCD treated versus control CRRT alone patients maintained for ≥ 90% of the treatment in the protocol's recommended (r) iCa target range of ≤ 0.4 mmol/L with values of, 0% (0/16) and 25% (4/16), respectively (P = 0.10). When the riCa treated and control subgroups were compared for a composite index of 60 day mortality and dialysis dependency, the percentage of SCD treated subjects was 16% versus 58% in the control subjects (p<0.01). The incidence of serious adverse events did not differ between the treated (45/69; 65%) and control groups (40/65; 63%; p = 0·86)., Conclusion: SCD therapy may improve mortality and reduce dialysis dependency in a tightly controlled regional hypocalcaemic environment in the perfusion circuit., Trial Registration: ClinicalTrials.gov NCT01400893 http://clinicaltrials.gov/ct2/show/NCT01400893.

Background and Objectives: Current recommendations for piperacillin-tazobactam dosing in patients receiving continuous renal replacement therapy originate from studies with relatively few patients and lower continuous renal replacement therapy doses than commonly used today. This study measured the pharmacokinetic and pharmacodynamic characteristics of piperacillin-tazobactam in patients treated with continuous renal replacement therapy using contemporary equipment and prescriptions., Design, Setting, Participants, & Measurements: A multicenter prospective observational study in the intensive care units of two academic medical centers was performed, enrolling patients with AKI or ESRD receiving piperacillin-tazobactam while being treated with continuous renal replacement therapy. Pregnant women, children, and patients with end stage liver disease were excluded from enrollment. Plasma and continuous renal replacement therapy effluent samples were analyzed for piperacillin and tazobactam levels using HPLC. Pharmacokinetic and pharmacodynamic parameters were calculated using standard equations. Multivariate analyses were used to examine the association of patient and continuous renal replacement therapy characteristics with piperacillin pharmacokinetic parameters., Results: Forty-two of fifty-five subjects enrolled had complete sampling. Volume of distribution (median=0.38 L/kg, intraquartile range=0.20 L/kg) and elimination rate constants (median=0.104 h(-1), intraquartile range=0.052 h(-1)) were highly variable, and clinical parameters could explain only a small fraction of the large variability in pharmacokinetic parameters. Probability of target attainment for piperacillin was 83% for total drug but only 77% when the unbound fraction was considered., Conclusions: There is significant patient to patient variability in pharmacokinetic/pharmacodynamic parameters in patients receiving continuous renal replacement therapy. Many patients did not achieve pharmacodynamic targets, suggesting that therapeutic drug monitoring might optimize therapy.

Sustained low-efficiency dialysis (SLED) is an increasingly popular form of renal replacement therapy for patients with renal failure in the intensive care unit. Advantages of SLED are efficient clearance of small solutes, good hemodynamic tolerability, flexible treatment schedules, and reduced costs. Studies comparing outcomes of SLED with those of other dialysis modalities are being performed.