Practical considerations to drug dosing in children with acute kidney injury

2016 ◽  
Vol 56 (4) ◽  
pp. 399-407 ◽  
Author(s):  
Farahnak Assadi ◽  
Fatemeh Ghane Sharbaf
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Drug Dosing

scholarly journals 1335. A Translational Nephrotoxicity Model to Probe Acute Kidney Injury with Vancomycin and Piperacillin–Tazobactam

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S483-S483
Author(s):  
Gwendolyn M Pais ◽  
Jiajun Liu ◽  
Sean N Avedissian ◽  
Danielle Hiner ◽  
Theodoros Xanthos ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Repeated Measures ◽  
Hospital Setting ◽  
Kidney Injury ◽  
Urinary Biomarkers ◽  
Urinary Output ◽  
Plasma Creatinine ◽  
Sprague Dawley ◽  
Research Support ◽  
Drug Dosing

Abstract Background Vancomycin and piperacillin–tazobactam (VAN+TZP) are two of the most commonly utilized antibiotics in the hospital setting and are reported in clinical studies to increase acute kidney injury (AKI). However, no clinical study has demonstrated that synergistic AKI occurs, only that serum creatinine increases with VAN+TZP. Previous preclinical work demonstrated that novel urinary biomarkers and histopathologic scores were not increased in the VAN+TZP group compared with VAN alone. The purpose of this study was to assess changes in urinary output and plasma creatinine between VAN, TZP, and VAN+TZP treatments. Methods Male Sprague–Dawley rats (n = 32) received either saline, VAN 150 mg/kg/day intravenously, TZP 1,400 mg/kg/day intraperitoneally, or VAN+TZP for 3 days. Animals were placed in metabolic cages pre-study and on drug dosing days 1–3. Urinary output, plasma creatinine, urinary biomarkers were compared daily and kidney histopathology was compared at the end of therapy between the groups. Mixed-effects, repeated-measures models were employed to assess differences between the groups. Results In the VAN-treated rats, urinary output was increased on days 1, 2 and 3 compared with baseline and saline (P < 0.01 for all), whereas it increased later for VAN+TZP (i.e., day 2 and 3 compared with saline, P < 0.001). No changes in urinary output were observed with saline and TZP alone. Plasma creatinine rose for VAN on days 1, 2, and 3 from baseline and VAN+TZP on day 3 (P < 0.02 for all), but no treatment group was different from saline. In the VAN-treated rats, urinary KIM-1 and clusterin were increased on days 1, 2, and 3 compared with controls (P < 0.001). Elevations were seen only after 3 days of treatment with VAN+TZP (P < 0.001 KIM-1, P < 0.05 clusterin). No changes in urinary biomarkers output were observed with saline and TZP alone. Histopathology was only elevated in the VAN group compared with saline (P < 0.002). No histopathology changes were noted with VAN+TZP. Conclusion All groups with VAN demonstrated kidney injury; however, VAN+TZP did not cause more kidney injury than VAN alone in a rat model of VIKI when using plasma creatinine, urinary output, or urinary biomarkers as outcomes. Histopathology data suggest that adding TZP did not worsen VAN-induced AKI and may even be protective. Disclosures Kevin J. Downes, MD, Merck: Grant/Research Support, Research Grant; Pfizer: Grant/Research Support.

scholarly journals Principles of Drug Dosing in Sustained Low Efficiency Dialysis (SLED) and Review of Antimicrobial Dosing Literature

Pharmacy ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 33
Author(s):  
Paula Brown ◽  
Marisa Battistella
Keyword(s):  
Acute Kidney Injury ◽  
Renal Replacement Therapy ◽  
Critically Ill Patients ◽  
Dose Adjustment ◽  
Kidney Injury ◽  
Hemodynamic Instability ◽  
Drug Dosing ◽  
Low Efficiency ◽  
Preliminary Recommendation ◽  
Selection Of

The use of sustained low-efficiency dialysis (SLED) as a renal replacement modality has increased in critically ill patients with both acute kidney injury (AKI) and hemodynamic instability. Unfortunately, there is a paucity of data regarding the appropriate dosing of medications for patients undergoing SLED. Dose adjustment in SLED often requires interpretation of pharmacodynamics and pharmacokinetic factors and extrapolation based on dosing recommendations from other modes of renal replacement therapy (RRT). This review summarizes published trials of antimicrobial dose adjustment in SLED and discusses pharmacokinetic considerations specific to medication dosing in SLED. Preliminary recommendation is provided on selection of appropriate dosing for medications where published literature is unavailable.

scholarly journals Use of Estimating Equations for Dosing Antimicrobials in Patients with Acute Kidney Injury Not Receiving Renal Replacement Therapy

2018 ◽  
Vol 7 (8) ◽  
pp. 211 ◽  
Author(s):  
Linda Awdishu ◽  
Ana Connor ◽  
Josée Bouchard ◽  
Etienne Macedo ◽  
Glenn Chertow ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Glomerular Filtration Rate ◽  
Kidney Function ◽  
Filtration Rate ◽  
Kidney Injury ◽  
Estimating Equations ◽  
Retrospective Evaluation ◽  
Antimicrobial Drugs ◽  
Drug Dosing ◽  
Discordance Rate

Acute kidney injury (AKI) can potentially lead to the accumulation of antimicrobial drugs with significant renal clearance. Drug dosing adjustments are commonly made using the Cockcroft-Gault estimate of creatinine clearance (CLcr). The Modified Jelliffe equation is significantly better at estimating kidney function than the Cockcroft-Gault equation in the setting of AKI. The objective of this study is to assess the degree of antimicrobial dosing discordance using different glomerular filtration rate (GFR) estimating equations. This is a retrospective evaluation of antimicrobial dosing using different estimating equations for kidney function in AKI and comparison to Cockcroft-Gault estimation as a reference. Considering the Cockcroft-Gault estimate as the criterion standard, antimicrobials were appropriately adjusted at most 80.7% of the time. On average, kidney function changed by 30 mL/min over the course of an AKI episode. The median clearance at the peak serum creatinine was 27.4 (9.3–66.3) mL/min for Cockcroft Gault, 19.8 (9.8–47.0) mL/min/1.73 m2 for MDRD and 20.5 (4.9–49.6) mL/min for the Modified Jelliffe equations. The discordance rate for antimicrobial dosing ranged from a minimum of 8.6% to a maximum of 16.4%. In the event of discordance, the dose administered was supra-therapeutic 100% of the time using the Modified Jelliffe equation. Use of estimating equations other than the Cockcroft Gault equation may significantly alter dosing of antimicrobials in AKI.

Drug Dosing in Acute Kidney Injury

2017 ◽  
Author(s):  
Steven Gabardi ◽  
Marjan Sadegh ◽  
Jamil Azzi ◽  
Craig A Stevens
Keyword(s):  
Acute Kidney Injury ◽  
Renal Dysfunction ◽  
Kidney Injury ◽  
Drug Clearance ◽  
Tubular Secretion ◽  
Drug Dosing ◽  
Drug Concentrations ◽  
Individualized Dosing ◽  
Altered Pharmacokinetic ◽  
Pharmacologic Agents

The prevalence of acute kidney injury (AKI) among hospitalized patients has increased sharply over the past 10 to 20 years. One complicating factor in this population is that many pharmacologic agents that are administered to these patients are handled, to some degree, by the kidneys. These medications may experience altered pharmacokinetic and pharmacodynamic profiles in patients with renal dysfunction, increasing the chances of drug misadventures. Historically, drug dosing in patients with AKI has been approached in the same manner as in patients with chronic renal insufficiency (CRI). The majority of dosing recommendations for AKI have been extrapolated from studies performed in patients with stable CRI. Renal drug clearance, composed of glomerular filtration, tubular secretion, and renal drug metabolism, is affected by renal dysfunction. It is clear that there is a reduction in renal clearance of drugs and toxins in both AKI and CRI. However, the type of renal dysfunction may affect other parameters of drug handling. Thus, dosing stratagems extrapolated from patients with CRI may result in subtherapeutic drug concentrations and ineffective treatment. Achieving a balance between under- and overdosing requires rigorous monitoring and individualized dosing.  Key words: acute kidney injury, drug dosing, pharmacokinetics

Drug Dosing in Acute Kidney Injury

2017 ◽  
Author(s):  
Steven Gabardi ◽  
Marjan Sadegh ◽  
Jamil Azzi ◽  
Craig A Stevens
Keyword(s):  
Acute Kidney Injury ◽  
Renal Dysfunction ◽  
Kidney Injury ◽  
Drug Clearance ◽  
Tubular Secretion ◽  
Drug Dosing ◽  
Drug Concentrations ◽  
Individualized Dosing ◽  
Altered Pharmacokinetic ◽  
Pharmacologic Agents

The prevalence of acute kidney injury (AKI) among hospitalized patients has increased sharply over the past 10 to 20 years. One complicating factor in this population is that many pharmacologic agents that are administered to these patients are handled, to some degree, by the kidneys. These medications may experience altered pharmacokinetic and pharmacodynamic profiles in patients with renal dysfunction, increasing the chances of drug misadventures. Historically, drug dosing in patients with AKI has been approached in the same manner as in patients with chronic renal insufficiency (CRI). The majority of dosing recommendations for AKI have been extrapolated from studies performed in patients with stable CRI. Renal drug clearance, composed of glomerular filtration, tubular secretion, and renal drug metabolism, is affected by renal dysfunction. It is clear that there is a reduction in renal clearance of drugs and toxins in both AKI and CRI. However, the type of renal dysfunction may affect other parameters of drug handling. Thus, dosing stratagems extrapolated from patients with CRI may result in subtherapeutic drug concentrations and ineffective treatment. Achieving a balance between under- and overdosing requires rigorous monitoring and individualized dosing.  Key words: acute kidney injury, drug dosing, pharmacokinetics

Non-dialytic management of the patient with acute kidney injury

2015 ◽  
Author(s):  
Achim Jörres ◽  
Dietrich Hasper ◽  
Michael Oppert
Keyword(s):  
Acute Kidney Injury ◽  
Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Drug Disposition ◽  
Caloric Intake ◽  
Kidney Injury ◽  
Target Range ◽  
Drug Dosing ◽  
Enhanced Production ◽  
Inadequate Nutrition

The main focus in the non-dialytic management of patients with acute kidney injury (AKI) is the prevention and treatment of complications.Nutritional support is an important aspect as many patients tend to be hypercatabolic, thus requiring adequate caloric intake, yet without administration of excessive fluid volumes. Inadequate nutrition in AKI may lead to enhanced production of urea nitrogen and azotaemia. However, hyperglycaemia is a frequent complication in these patients, often requiring continuous insulin therapy to achieve the recommended blood glucose target range of 110–150 mg/dL (6.11–8.33 mmol/L).Patients with AKI are prone to infections which are a common cause of death in this population. Careful search for and intensive treatment of infections is therefore of utmost importance, and antimicrobial chemotherapy must be initiated as early as possible, especially in patients with sepsis and AKI.Drug dosing in patients with AKI is complex and difficult. Residual kidney function can be highly variable and drug disposition may be altered due to changes in distribution volume, protein binding, and metabolism. Moreover, many drugs can be removed by renal replacement therapy (RRT). Therefore, adequate dosing must take into account the patient’s individual clinical characteristics, the specific pharmacokinetic/pharmacodynamic properties of the drug, and the mode and intensity of renal replacement therapy.

Drug dosing in acute kidney injury

2015 ◽  
Author(s):  
Thomas A. Golper ◽  
Andrew A. Udy ◽  
Jeffrey Lipman
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Function ◽  
Metabolic Pathways ◽  
Kidney Injury ◽  
Medication Administration ◽  
Therapeutic Interventions ◽  
Drug Dosing ◽  
Kidney Replacement Therapy ◽  
Pass Through ◽  
Drug Pharmacokinetics

Drug dosing in acute kidney injury (AKI) is one of the broadest topics in human medicine. It requires an understanding of markedly altered and constantly changing physiology under many disease situations, the use of the drugs to treat those variety of diseases, and the concept of drug removal during blood cleansing therapies. Early in AKI kidney function may be supraphysiologic, while later in the course there may be no kidney function. As function deteriorates other metabolic pathways are altered in unpredictable ways. Furthermore, the underlying disorders that lead to AKI alter metabolic pathways. Heart failure is accompanied by vasoconstriction in the muscle, skin and splanchnic beds, while brain and cardiac blood flow proportionally increase. Third spacing occurs and lungs can become congested. As either kidney or liver function deteriorates, there may be increased or decreased drug sensitivity at the receptor level. Acidosis accompanies several failing organs. Protein synthesis is qualitatively and quantitatively altered. Sepsis affects tissue permeability. All these abnormalities influence drug pharmacokinetics and dynamics. AKI is accompanied by therapeutic interventions that alter intrinsic metabolism which is in turn complicated by kidney replacement therapy (KRT). So metabolism and removal are both altered and constantly changing. Drug management in AKI is exceedingly complex and is only beginning to be understood. Thus, we approach this discussion in a physiological manner. Critically ill patients pass through phases of illness, sometimes rapidly, other times slowly. The recognition of the phases and the need to adjust medication administration strategies is crucial to improving outcomes. An early phase involving supraphysiologic kidney function may be contributory to therapeutic failures that result in the complication of later AKI and kidney function failure.

Drug Dosing in Acute Kidney Injury

2018 ◽  
pp. 343-361
Author(s):  
Jeremy R. DeGrado ◽  
James F. Gilmore ◽  
Benjamin Hohlfelder ◽  
Craig A. Stevens ◽  
Steven Gabardi
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Drug Dosing
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