Rhabdomyolysis and acute kidney injury potentiated by a drug-drug interaction between cyclosporine, leflunomide, and rosuvastatin in a kidney transplant recipient: A missed opportunity for pharmacist involvement.

BACKGROUND: This study aimed to describe a case of rhabdomyolysis and acute kidney injury potentiated by a drug-drug interaction (DDI) between cyclosporine, leflunomide, and rosuvastatin in a kidney transplant recipient. CASE SUMMARY: A 74-year-old male with end-stage kidney disease secondary to type 2 diabetes mellitus and hypertension received a deceased by cardiac death kidney transplant. The patient's medical history included coronary artery disease and hyperlipidemia for which he was receiving rosuvastatin 40 mg daily. Five months after transplant, the patient developed BK viremia, which required multiple changes in immunosuppression and resulted in the initiation of leflunomide and cyclosporine modified. The patient used multiple pharmacies and coupon cards that delayed the identification of the DDIs between leflunomide, cyclosporine, and rosuvastatin. Approximately, 13 months after transplant, the biopsy report of the patient's allograft kidney showed acute cellular rejection Banff IB, hypertensive changes, and transplant glomerulopathy. This prompted the patient to receive a 3-day course of methylprednisolone 250 mg intravenous at the outpatient infusion center. Two weeks later, the patient presented to the transplant clinic with lightheadedness, dizziness, weakness, fatigue, bilateral eye drainage, and a decrease in appetite and was admitted to the hospital for further workup. On admission, creatine kinase was 2080 IU/L with myoglobin of 7601 ng/mL. The patient's diagnosis was statin myopathy with possible rhabdomyolysis acute kidney injury. Likely contributing factors included cyclosporine, leflunomide, and rosuvastatin DDI and administration of high-dose methylprednisolone. PRACTICE IMPLICATIONS: This case demonstrates the importance of pharmacist involvement throughout all phases of care in a kidney transplant recipient.

Evaluation of Gabapentin and Pregabalin Use in Hospitalized Patients With Decreased Kidney Function.

Background: Gabapentin and pregabalin are well-tolerated medications primarily cleared by the kidney. Patients receiving higher gabapentinoid doses with decreased kidney function may be at an increased risk of adverse effects (AEs), but limited evidence exists evaluating gabapentinoid dosing and AEs in this population. Objective: To determine whether patients with decreased creatinine clearance (CrCl) experienced increased frequency of AEs related to gabapentinoid dose at hospital admission. Methods: Single-center retrospective cohort study in adults with a gabapentinoid prescription and serum creatinine measurement documented on hospital admission. The primary outcome was the appropriateness of gabapentinoid prescription based on CrCl (stratified by CrCl ≥60 mL/min, <60 mL/min, 15-29 mL/min, and <15 mL/min) at admission. Secondary outcomes included the incidence of AEs related to gabapentinoids and concomitant opioid and psychiatric prescriptions. Results: A total of 286 patients were included in this study (gabapentin n = 234, pregabalin n = 52). Patients with a CrCl <60 mL/min and doses above the manufacturer's recommendation were prescribed gabapentin (34%) and pregabalin (22.7%). For patients with a CrCl of 15 to 29 mL/min and <15 mL/min groups, inappropriately high doses were prescribed for gabapentin (48.8%) and pregabalin (45%). A significant increase in recorded falls (P = 0.029) was identified in patients with a CrCl <60 mL/min. Concomitant opioid and psychiatric medications contributed to a higher prevalence of AEs regardless of CrCl. Conclusions: Patients with a CrCl <60 mL/min were frequently prescribed inappropriately high doses of gabapentinoids. The relationship between gabapentinoid dosing, kidney function, and the incidence of gabapentinoid-related AEs at hospital admission requires larger, multicentre studies.

The Physical Compatibility of Clinically Used Concentrations of Diltiazem Hydrochloride With Heparin Sodium.

Background: Acute treatment of atrial fibrillation often requires concomitant intravenous (IV) continuous infusions of unfractionated heparin and diltiazem. Concomitantly infusing these medications through the same IV line minimizes multiple IV sites. Diltiazem and heparin visual compatibility have been previously investigated but with limited drug dwell times and differing drug concentrations leading to inconsistent published results. Objective: To investigate the physical compatibility of diltiazem hydrochloride at concentrations of 5 and 1 mg/mL combined with an equal volume of heparin sodium 100 units/mL. Methods: Using a 0.22-µm filter, 15 mL of heparin sodium were placed into a polyvinyl chloride infusion bag followed by 15 mL of either diltiazem hydrochloride 5 or 1 mg/mL. Admixtures were prepared in triplicate. Each admixture was investigated for visual precipitation, spectrophotometric absorbance, and pH change at baseline and 1, 5, 8, and 24 hours after mixing. Physical incompatibility was determined by visual observation, increased spectrophotometric absorbance, and demonstrative pH changes. Results: Each diltiazem 5 mg/mL admixture exhibited a slight haze and enhanced absorbance readings indicating turbidity while none revealed a demonstrative pH change. None of the diltiazem 1 mg/mL assessments revealed visual precipitation or suggested turbidity. Only one pH reading at 5 hours revealed a demonstrative change from baseline. Conclusions: Our findings indicate that infusing diltiazem hydrochloride 5 mg/mL with heparin sodium 100 units/mL in the same IV line cannot be advocated. In contrast, our findings suggest that heparin sodium 100 units/mL infused with diltiazem hydrochloride 1 mg/mL is physically compatible but chemical stability was not assessed.

Compatibility, Stability, and Efficacy of Vancomycin Combined With Gentamicin or Ethanol in Sodium Citrate as a Catheter Lock Solution.

Background: Indwelling catheters deliver lifesaving medical treatments for many chronically ill patients but are frequently a source of infection. Treatment may include an antimicrobial agent(s) and anticoagulant solution dwelling within the catheter. In vitro determinations of solution compatibility and stability are necessary prior to use in patients. Objective: The aim of this study was to determine the physical compatibility, chemical stability, and antimicrobial activity of vancomycin (5 or 10 mg/mL) with gentamicin (1 mg/mL) or 40% ethanol in 4% sodium citrate lock solution over 72 hours. Methods: All solutions were prepared per manufacturer's instructions. Samples were studied under 4 conditions: (1) 25°C with light, (2) 25°C without light, (3) 37°C with light, and (4) 37°C without light. Physical compatibility and chemical stability were assessed at 0, 24, 48, and 72 hours. Antimicrobial susceptibility testing was conducted at 0 and 72 hours. All studies were carried out in triplicate. Results: All solution combinations under each condition remained patent from baseline to 48 hours. One solution combination of vancomycin (5 mg/mL) and ethanol (40% v/v) in 4% sodium citrate revealed a slight turbidity at 72 hours. Clarity and pH remained stable in all other solutions during the entire study period. Chemical compatibility and antibiotic activity ranged from 95% to 105% and 95% to 106% of initial baseline values, respectively, for all solutions under 4 storage conditions. Conclusions: All antibiotic-anticoagulant lock solutions were found to be physically, chemically, and microbiologically stable during the 72-hour study period except vancomycin (5 mg/mL) and ethanol (40% v/v) in 4% sodium citrate solution which showed slight turbidity at 72 hours.

Examining Competency-Based Education Through the Lens of Implementation Science: A Scoping Review.

OBJECTIVES: This study aimed to identify evidence for the implementation and assessment of competency-based education (CBE) in health professions curricula using an implementation science framework. FINDINGS: Using the PRISMA framework, a systematic review of the literature applying a prespecified and piloted search strategy from 2017 to the present in PubMed and CINAHL was performed. References identified from the search strategy were imported into Covidence for title and abstract screening and full-text review by 2 researchers. A third researcher resolved discrepancies. Data were extracted and synthesized to identify key elements from the article related to implementation science, with a quality appraisal. A total of 25 studies out of 304 initially identified records were included. The studies covered a broad range of health professions and countries. Key findings were limited use of implementation science elements, including variability in CBE implementation, limited fidelity assessment, and partial examination of the process continuum. Programs with a more robust implementation approach have a team-based strategy to lead, implement, and support CBE. Motivation and training of faculty are also key components of successful CBE implementation. SUMMARY: Competency-based education is implemented differently across institutions, with variation among programs in their choice of elements of implementation science used. Further research is needed to examine CBE from an implementation science perspective and address remaining questions.

Physical compatibility of ceftriaxone and cefepime in 0.45% sodium chloride, Ringer's lactate solution, and Plasma-Lyte A.

OBJECTIVES: The compatibility of intravenous fluids with medications is of paramount concern to pharmacists and is an imperative component of ensuring patient safety. Data regarding the physical compatibility of medications with intravenous fluids has not been examined, or published with conflicting results or the concentrations studied were not consistent with current practice. Our objective was to determine the physical compatibility of ceftriaxone and cefepime in 0.45% sodium chloride, Ringer's lactate solution, and Plasma-Lyte A. METHODS: An in vitro analysis of the physical compatibility of ceftriaxone and cefepime at 10 mg/mL, 20 mg/mL, and 40 mg/mL concentrations was conducted in 0.45% sodium chloride, Ringer's lactate solution, and Plasma-Lyte A. Admixtures were evaluated in triplicate at hours 0, 1, 5, 8, and 24. Physical compatibility was assessed by visual inspection, spectrophotometry, and pH analysis. RESULTS: Ceftriaxone 40 mg/mL was found to be physically incompatible in 0.45% sodium chloride and Ringer's lactate solution beyond 5 hours and in Plasma-Lyte A beyond 8 hours. Cefepime was found to be physically incompatible with all fluids and in all concentrations beyond 1 hour. CONCLUSIONS: This work contributes to the body of literature dedicated to the evaluation of intravenous drug and fluid physical compatibility by identifying demonstrable changes in admixtures containing 0.45% sodium chloride, Plasma-Lyte A, and Ringer's lactate solution. Ceftriaxone should not be administered with 0.45% sodium chloride, Ringer's lactated solution, or Plasma-Lyte A at selected concentrations and time points and cefepime is not considered to be physically compatible at 10 mg/mL, 20 mg/mL, or 40 mg/mL in any of the studied fluids beyond 1 hour.

The Need for Competency-Based Education.

OBJECTIVES: While pharmacy education updates learning as new information arises, changes to learning experiences can trail behind current practices and technology. There have been multiple calls for radical changes in how health professions education is delivered to ensure patients are receiving high-quality care. Competency-based education has been one way discussed in the literature for how to handle this need to develop students who have a willingness to learn and can problem-solve. The goal of this review is to examine whether competency-based education is needed to drive the profession of pharmacy forward. FINDINGS: To address, we collaboratively identified stakeholder perspectives to evaluate the need. The following stakeholders achieved consensus among the committee members: patients/society, learners, workplace/profession, and academic institutions. SUMMARY: Based on those perspectives, needs, and gaps to address those needs were identified and are presented in this review.

Evaluating the Need for Competency-Based Pharmacy Education (CBPE): The Report of the 2023-2024 Academic Affairs Standing Committee.

The 2023-2024 Academic Affairs Committee was charged to create a sense of urgency around the concept of Competency-Based Pharmacy Education and develop a "readiness for change" instrument that is based on the 5 essential elements that make up the definition of Competency-Based Pharmacy Education. This report describes the process undertaken by the committee to determine the societal needs of pharmacists and current state of pharmacy practice and pharmacy education. The practice gaps in pharmacy education and the key drivers needed to close these gaps are evaluated. To complete the charges, the committee conducted evidence-based literature reviews and completed a series of focus groups with stakeholders and thought leaders with experience in competency-based education.

Stability and compatibility of intraperitoneal antimicrobials in peritoneal dialysate solutions.

To optimise antimicrobial administration in patients with peritoneal dialysis (PD)-related peritonitis, healthcare providers need literature-based information to develop patient-centred pharmacotherapeutic plans. Traditional PD solutions promote osmosis using dextrose or icodextrin with a lactate buffer. Newer PD solutions have modified the osmotic vehicle and buffer. Knowledge of antimicrobial compatibility and stability with newer PD solutions will assist with determining the route of antimicrobial administration as compatible and stable solutions could be delivered directly to the peritoneum using intraperitoneal administration. This review updates the compatibility and stability of antimicrobial additives in newer PD solutions for PD-related peritonitis.

Recommendations and Next Steps For Competency-Based Pharmacy Education.

In July 2021, the chairs of the American Association of Colleges of Pharmacy Council of Deans, Council of Faculties, and Council of Sections developed a task force to discuss potential ways to improve pharmacy education. The Competency-Based Education (CBE) Joint Task Force was created to explore the pros and cons of advancing a competency-based approach to pharmacy education (CBPE) and to determine ways to create more flexibility within pharmacy curricula to enable CBE. To achieve these goals, the Task Force systematically reviewed available resources and outlined the pros and cons of CBPE, best practices for implementation, strategies to minimize barriers, and recommendations on whether CBE should be implemented in pharmacy education. This commentary summarizes the Task Force's findings regarding whether CBPE is a suitable approach for pharmacy education and the next steps if implemented.

Intravenous Physical Compatibility of Heparin Sodium and Furosemide.

Continuous infusions of heparin and furosemide are often required for hospitalized patients to treat cardiac-related disease states. Concomitant infusion of heparin and furosemide through the same intravenous line minimizes the need for multiple intravenous sites. For concomitant infusions to be administered, knowledge of the physical compatibility for intravenous medications is imperative for patient safety and administering medications to maximize their effectiveness. Currently, heparin and furosemide are listed as Y-site compatible, but precipitation was reported at a large academic medical center, which questions this compatibility. This study investigated the in vitro physical compatibility of heparin sodium premix 25,000 units/250 mL in dextrose 5% water from two different manufacturers with furosemide 40 mg/4 mL at concentrations of 4:1 for heparin sodium and furosemide. The admixtures were prepared in triplicate using aseptic technique, stored at 19°C to 24°C and examined for visual precipitation, turbidity, and pH change at baseline, 1, 5, 8, 24, and 48 hours. Heparin sodium, B. Braun Medical Inc. or Hospira, Inc. solutions, and furosemide admixtures revealed changes over 48 hours. Changes in visual appearance, absorbance, and pH were observed at hour 5 compared to baseline for the B. Braun Medical Inc. admixture. The Hospira, Inc. admixture revealed visual changes by hour 48, but demonstrative changes in absorbance and pH did not occur. Our observations found demonstrative changes in physical compatibility in the admixtures of heparin sodium and furosemide at a ratio of 4:1. The findings suggest that a combination of the solutions in this study be avoided until further research is completed.

Longitudinal hemodiafilter performance in modeled continuous renal replacement therapy.

BACKGROUND/AIMS: With advanced anticoagulation, many institutions operate continuous renal replacement therapy (CRRT) circuits longer than manufacturers' recommendations. This extended use may change hemodiafilter performance and clearance properties. However, hemodiafilter performance over time has not been assessed. We investigated solute clearance over time in modeled CRRT. METHODS: In vitro continuous hemofiltration (CH) and continuous hemodialysis (CD) were operated for 48 h using AN69 polyacrylonitrile, cellulose triacetate, F70 polysulfone, and Optiflux F160NR polysulfone hemodiafilters with citrated bovine blood. Urea, creatinine, gentamicin, vancomycin, and albumin clearances were assessed in CH (ultrafiltration rates = 1 and 3 l/h). Clearances of urea, creatinine, gentamicin, and albumin, were assessed in CD with dialysate flow rate of 2 l/h. RESULTS: Solute CH clearances were significantly higher at 3 l/h. Only creatinine and gentamicin clearances were affected by time. Creatinine CD clearance significantly declined at 48 h for all hemodiafilters, especially polysulfone hemodiafilters. CONCLUSIONS: CRRT duration affects solute transmembrane clearance. Clinicians should consider hemodiafilter age when assessing hemodialysis dose or drug clearance.

Physical Compatibility, Antimicrobial Activity, and Stability of Cefazolin Combined with Gentamicin or Ethanol in Sodium Citrate as a Catheter Lock Solution.

BACKGROUND: Catheters provide vascular access for patients requiring intravenous treatments, but frequently are a source of infection and/or thrombosis. Instilling a solution of an antimicrobial agent with an anticoagulant into the catheter lumen may salvage-infected catheters. OBJECTIVE: The aim is to evaluate the physical compatibility, antibacterial activity, and stability of varying combinations of cefazolin (10 mg/mL), 40% ethanol, 4% sodium citrate with or without gentamicin (1 mg/mL) as a catheter lock solution over 48 h. METHODS: Admixtures were prepared using aseptic technique and stored under four conditions with or without light at 25°C or 37°C. Prepared admixtures were assessed for physical compatibility, antimicrobial susceptibility, and chemical stability in triplicate at 0, 24 and 48 h. Admixture physical compatibility was determined by visual clarity, pH, and ultraviolet (UV) spectroscopy. Antibacterial activity was determined using the Kirby-Bauer disk diffusion method. The chemical stability of cefazolin and gentamicin were assessed using high performance liquid chromatography and UV spectroscopy, respectively. RESULTS: All admixtures maintained clarity for 48 h. All admixtures stored at 25°C and the admixture containing 10 mg/mL cefazolin-4% sodium citrate stored at 37°C sustained antimicrobial activity and were chemically stable. A significant change in pH, antimicrobial activity, cefazolin concentration (<95% of baseline), were observed in admixtures containing ethanol stored at 37°C after 24 h. Gentamicin concentrations remained stable throughout the study. CONCLUSION: The admixture of 10 mg/mL cefazolin-4% sodium citrate sustained antimicrobial activity over 48 h and was chemically stable. However, admixtures containing ethanol stored at 37°C showed incompatibility with decreased antibacterial activity and cefazolin degradation after 24 h.

Single-dose daptomycin pharmacokinetics in chronic haemodialysis patients.

BACKGROUND: Daptomycin has concentration-dependent antibacterial activity against Gram-positive bacteria. Its use is increasing in haemodialysis units. The manufacturer recommends a 4-6-mg/kg dose administered every 48 hrs for patients receiving haemodialysis. However, there are no published data about daptomycin pharmacokinetics and clearance during haemodialysis. The recommended dosing regimen would conflict with asymmetric thrice-weekly haemodialysis, which yields two ~44-hr and one ~68-hr interdialytic periods. This is the first study to evaluate daptomycin pharmacokinetics in haemodialysis patients, assess the extent of daptomycin dialytic removal and model serum concentrations at 44 and 68 hrs. METHODS: Six otherwise healthy subjects on chronic haemodialysis (55.3 +/- 16.1 years old, three females, 66.2 +/- 14.2 kg) received a single 6-mg/kg dose of daptomycin post-haemodialysis infused over 30 minutes. Serial blood samples were collected for ~44 hrs (pre-next haemodialysis) and throughout the subsequent haemodialysis session with a high permeability haemodialyser. Individual pharmacokinetic parameters determined by compartmental analysis were used to model trough serum concentrations at 44 and 68 hrs with 6-, 8- and 10-mg/kg post-haemodialysis doses. RESULTS: The haemodialysis session in this trial yielded mean urea and daptomycin reduction ratios of 79.6 +/- 5.8% and 57.6 +/- 9.2%, respectively. Daptomycin half-life was 19.4 +/- 6.5 and 3.8 +/- 1.1 hrs 'off' and 'on haemodialysis', respectively, with minimal rebound 1 hr post-haemodialysis. All modelled trough concentrations at 44 and 68 hrs at all doses exceed typical minimum inhibitory concentration (MIC(90)) values for Staphylococcus aureus and Enterococcus faecalis. CONCLUSIONS: Daptomycin serum concentrations declined by ~50% after a 4-hr haemodialysis session with a high permeability haemodialyser. A 6-mg/kg i.v. post-haemodialysis thrice-weekly dose should result in sufficient pre-haemodialysis daptomycin serum concentrations even after a 68-hr interdialytic period.

Modeled dalbavancin transmembrane clearance during intermittent and continuous renal replacement therapies.

BACKGROUND/AIMS: Knowledge of dalbavancin renal replacement therapy (RRT) disposition is vital to ensure appropriate dosing. In vitro models of continuous RRT and intermittent hemodialysis (IHD) were used to determine dalbavancin transmembrane clearance (CLtm). METHODS: Dalbavancin saturation and sieving coefficients (SCs) were determined for hemodialysis and hemofiltration therapies, respectively, using various hemodiafilter and effluent rate combinations. Dalbavancin CLtm estimates were calculated from observed saturation and SCs. RESULTS: Saturation and SCs for both modalities of continuous dialysis and hemofiltration and IHD with high permeability hemodiafilters were small. Nonetheless, during continuous RRT with high dialysate and ultrafiltration rates, dalbavancin CLtm (0.20-1.26 ml/min) matched and often exceeded literature-derived dalbavancin renal clearances. Dalbavancin CLtm was undetectable during IHD with low-permeability hemodialyzers, but with high-permeability hemodialyzers, substantial CLtm (1.90-2.43 ml/min) was noted. CONCLUSION: Dalbavancin CLtm is dependent on RRT modality, hemodiafilter, and effluent flow. Dalbavancin doses may need to be adjusted depending on RRT parameters.

Novel therapeutic agents for the treatment of diabetic kidney disease.

INTRODUCTION: Diabetic kidney disease (DKD) involves multifaceted pathophysiology which increases the risk of cardiorenal events and mortality. Conventional therapy is limited to renin-angiotensin aldosterone system inhibition and management of hyperglycemia and hypertension. Recent clinical trials have demonstrated promising nephroprotective effects of antihyperglycemic agents thus modifying guideline treatment recommendations for type 2 diabetic patients with chronic kidney disease. AREAS OF COVERED: Relevant studies and clinical trials were searched via PubMed and clinicaltrials.gov through August 2020. Authors offer an update on clinical evidence regarding nephroprotective effects and side effects of sodium-glucose-cotransporter-2 (SGLT2) inhibitors, glucagon-like-peptide-1 (GLP1) agonists and dipeptidylpeptidase-4 (DPP4) inhibitors. They discuss the potential benefits of novel therapy targeting DKD pathogenic processes including inflammation, oxidative stress, fibrosis, and vasoconstriction shown in early phases of clinical trials and offer an opinion on key challenges and directions for future progress. EXPERT OPINION: SGLT2 inhibitors are the most promising agents for DKD and improving cardiorenal outcomes. Mineralocorticoid-receptor antagonists and janus kinase inhibitors are also promising investigational therapies that target oxidative stress, nitric oxide synthesis, and inflammation. Novel therapeutic targets and the identification of clinically useful biomarkers may provide future therapies that detect early stages of DKD enabling a slower kidney function decline.

Enhanced clearance of highly protein-bound drugs by albumin-supplemented dialysate during modeled continuous hemodialysis.

BACKGROUND: In 2006, there were 16 796 toxic exposures attributed to valproic acid (VPA), carbamazepine (CBZ) and phenytoin (PHT) reported to the US Toxic Exposure Surveillance System. Of these, 30% (5046) were treated in a health care facility with 12 cases resulting in death. These drugs are highly protein bound and poorly dialyzable; however, it has been suggested that albumin-supplemented dialysate may enhance dialytic clearance. We investigated whether the addition of albumin to dialysate affects dialytic clearance of VPA, CBZ and PHT. METHODS: VPA, CBZ and PHT were added to a bovine blood-based in vitro continuous hemodialysis circuit, which included a polysulfone or an AN69 hemodialyzer. VPA, CBZ and PHT clearances were calculated from spent dialysate and pre-dialyzer plasma concentrations. VPA, CBZ and PHT clearances with control (albumin-free) dialysate were compared to clearances achieved with 2.5% or 5% human albumin-containing dialysate. The influences of blood flow (180 and 270 mL/min) and dialysate flow (1, 2 and 4 L/h) on dialysis clearance were also assessed. RESULTS: The addition of 2.5% albumin to dialysate significantly enhanced dialytic clearance of VPA and CBZ, but not PHT. Use of 5% albumin dialysate further increased VPA and CBZ clearance. Overall, drug clearance was related directly to dialysate flow but independent of blood flow. CONCLUSION: Continuous hemodialysis with albumin-supplemented dialysate significantly enhanced VPA and CBZ, but not PHT, clearance compared to control dialysate. Continuous hemodialysis with albumin-supplemented dialysate may be a promising therapy to enhance dialytic clearance of selected highly protein-bound drugs.

Drug dosing during continuous renal replacement therapy.

Continuous renal replacement therapy (CRRT) has given clinicians an important option in the care of critically ill patients. The slow and continuous dialysate and ultrafiltrate flow rates that are employed with CRRT can yield drug clearances similar to an analogous glomerular filtration rate of the native kidneys. Advantages such as superior volume control, excellent metabolic control, and hemodynamic tolerance by critically ill patients are well documented, but an understanding of drug dosing for CRRT is still a bit of a mystery. Although some pharmaceutical companies have dedicated postmarket research in this direction, many pharmaceutical companies have chosen not to pursue this information as it is not mandated and represents a relatively small part of their market. This lack of valuable information has created many challenges in the care of the critically ill patient as intermittent hemodialysis drug dosing recommendations cannot be extrapolated to CRRT. This drug dosing review will highlight factors that clinicians should consider when determining a pharmacotherapy regimen for a patient receiving CRRT.

Clinical review: Drug metabolism and nonrenal clearance in acute kidney injury.

Decreased renal drug clearance is an obvious consequence of acute kidney injury (AKI). However, there is growing evidence to suggest that nonrenal drug clearance is also affected. Data derived from human and animal studies suggest that hepatic drug metabolism and transporter function are components of nonrenal clearance affected by AKI. Acute kidney injury may also impair the clearance of formed metabolites. The fact that AKI does not solely influence kidney function may have important implications for drug dosing, not only of renally eliminated drugs but also of those that are hepatically cleared. A review of the literature addressing the topic of drug metabolism and clearance alterations in AKI reveals that changes in nonrenal clearance are highly complicated and poorly studied, but they may be quite common. At present, our understanding of how AKI affects drug metabolism and nonrenal clearance is limited. However, based on the available evidence, clinicians should be cognizant that even hepatically eliminated drugs and formed drug metabolites may accumulate during AKI, and renal replacement therapy may affect nonrenal clearance as well as drug metabolite clearance.