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

scholarly journals Acute Kidney Injury Pharmacokinetic Changes and Its Impact on Drug Prescription

Healthcare ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 10 ◽  
Author(s):  
Victoria Blanco ◽  
Carolina Hernandorena ◽  
Paula Scibona ◽  
Waldo Belloso ◽  
Carlos Musso
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Function ◽  
Drug Prescription ◽  
Kidney Injury ◽  
Drug Dosage ◽  
Tubular Secretion ◽  
Metabolizing Enzymes ◽  
Drug Concentrations ◽  
The Impact

Acute kidney injury (AKI) is a common problem in hospitalized patients that is associated with significant morbid-mortality. The impact of kidney disease on the excretion of drugs eliminated by glomerular filtration and tubular secretion is well established, as well as the requirement for drug dosage adjustment in impaired kidney function patients. However, since impaired kidney function is associated with decreased activity of several hepatic and gastrointestinal drug-metabolizing enzymes and transporters, drugs doses adjustment only based on kidney alteration could be insufficient in AKI. In addition, there are significant pharmacokinetics changes in protein binding, serum amino acid levels, liver, kidney, and intestinal metabolism in AKI, thus the determination of plasma drug concentrations is a very useful tool for monitoring and dose adjustment in AKI patients. In conclusion, there are many pharmacokinetics changes that should be taken into account in order to perform appropriate drug prescriptions in AKI patients.

scholarly journals Impact of Cardiac Function Improvement on Cardiac Surgery Associated Acute Kidney Injury for Patients with Preoperative Renal Dysfunction

2020 ◽  
Author(s):  
Jiarui Xu ◽  
Xin Chen ◽  
Jing Lin ◽  
Yang Li ◽  
Bo Shen ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Cardiac Surgery ◽  
Cardiac Function ◽  
Renal Dysfunction ◽  
Significant Risk ◽  
Kidney Injury ◽  
Normal Function ◽  
Function Group ◽  
Postoperative Aki

Abstract Background: We aim to investigate whether the postoperative cardiac function improve or not would affect the risk of cardiac surgery associated acute kidney injury (AKI) for patients with preoperative renal dysfunction. Method: Data from patients underwent cardiac surgery from April 2012 to February 2016 were collected. Renal dysfunction was defined as preoperative SCr >1.2 mg/dL (females) or >1.5 mg/dL (males). Patients were grouped as normal renal function group, renal dysfunction with chronic kidney disease (CKD group), and non CKD group. △LVEF=postoperative LVEF - preoperative LVEF. Cardiac function improved was defined as △LVEF ≥10. Patients were further divided into non CKD & cardiac function improved (non CKD+), non CKD & cardiac function not improved (non CKD-), CKD & cardiac function improved (CKD+) and CKD & cardiac function not improved (CKD-) subgroups.Results: A total of 8,661 patients were allocated as normal renal function (n=7,903), non CKD(n = 662) and CKD (n = 136) groups. Both non CKD and CKD groups had higher AKI incidence than normal function group (39.5% vs 30.0%, P < 0.001; 61.8% vs 30.0%, P<0.001), and non CKD+ group had the similar AKI incidence with normal function group (30.9% vs 30.0%, P=0.729). Multivariate logistic regression analysis revealed that non CKD-, CKD+ and CKD- were significant risk factors, whereas non CKD+ was not a significant risk factor for postoperative AKI. The SCr at discharge in non CKD+ subgroup was significantly lower than its preoperative SCr (1.4 ± 0.8 vs 1.7 ± 0.9 mg/dL, P = 0.020).Conclusions: For renal dysfunction patients with no CKD, the risk of postoperative AKI did not exist if the cardiac function improved after surgery. For CKD patients, the risk of postoperative AKI increase regardless whether the cardiac function improved or not.

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 Concentration of meropenem in patients with sepsis and acute kidney injury before and after initiation of continuous renal replacement therapy: a prospective observational trial

2020 ◽  
Vol 72 (1) ◽  
pp. 147-155 ◽  
Author(s):  
Ilona Nowak-Kózka ◽  
Kamil J. Polok ◽  
Jacek Górka ◽  
Jakub Fronczek ◽  
Anna Gielicz ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Kidney Injury ◽  
Regional Citrate Anticoagulation ◽  
High Dose ◽  
Prolonged Infusion ◽  
Time Points ◽  
Drug Concentrations ◽  
Before And After

Abstract Background The effect of renal replacement therapy on drug concentrations in patients with sepsis has not been fully elucidated because the pharmacokinetic properties of many antimicrobials are influenced by both pathophysiological and treatment-related factors. The aim of this study was to determine meropenem concentrations in patients with sepsis before and after the initiation of continuous venovenous hemodialysis with regional citrate anticoagulation (RCA-CVVHD). Methods The study included 15 critically ill patients undergoing RCA-CVVHD due to sepsis-induced acute kidney injury. All participants received 2 g of meropenem every 8 h in a prolonged infusion lasting 3 h. Meropenem concentrations were measured in blood plasma using high-performance liquid chromatography coupled with tandem mass spectrometry. Blood samples were obtained at six-time points prior to and at six-time points after introducing RCA-CVVHD. Results The median APACHE IV and SOFA scores on admission were 118 points (interquartile range [IQR] 97–134 points) and 19.5 points (IQR 18–21 points), respectively. There were no significant differences in the plasma concentrations of meropenem measured directly before RCA-CVVHD and during the first 450 min of the procedure. The drug concentration reached its peak 2 h after initiating the infusion and then steadily declined. Conclusions The concentration of high-dose meropenem (2 g every 8 h) administered in a prolonged infusion was similar before and after the introduction of RCA-CVVHD in patients with sepsis who developed acute kidney injury.

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 Long-Term Outcomes and Risk Factors of Renal Failure Requiring Dialysis after Heart Transplantation: A Nationwide Cohort Study

2020 ◽  
Vol 9 (8) ◽  
pp. 2455 ◽  
Author(s):  
Tsai-Jung Wang ◽  
Ching-Heng Lin ◽  
Hao-Ji Wei ◽  
Ming-Ju Wu
Keyword(s):  
Risk Factors ◽  
Acute Kidney Injury ◽  
Renal Failure ◽  
Heart Transplantation ◽  
Renal Dysfunction ◽  
Heart Transplant ◽  
Kidney Injury ◽  
Dialysis Patients ◽  
Term Survival

Acute kidney injury and renal failure are common after heart transplantation. We retrospectively reviewed a national cohort and identified 1129 heart transplant patients. Patients receiving renal replacement therapy after heart transplantation were grouped into the dialysis cohort. The long-term survival and risk factors of dialysis were investigated. Patients who had undergone dialysis were stratified to early or late dialysis for subgroup analysis. The mean follow-up was five years, the incidence of dialysis was 28.4% (21% early dialysis and 7.4% late dialysis). The dialysis cohort had higher overall mortality compared with the non-dialysis cohort. The hazard ratios of mortality in patients with dialysis were 3.44 (95% confidence interval (CI), 2.73–4.33) for all dialysis patients, 3.58 (95% CI, 2.74–4.67) for early dialysis patients, and 3.27 (95% CI, 2.44–4.36; all p < 0.001) for late dialysis patients. Patients with diabetes mellitus, chronic kidney disease, acute kidney injury, and coronary artery disease were at higher risk of renal failure requiring dialysis. Cardiomyopathy, hepatitis B virus infection, and hyperlipidemia treated with statins were associated with a lower risk of renal dysfunction requiring early dialysis. The use of Sirolimus and Mycophenolate mofetil was associated with a lower incidence of late dialysis. Renal dysfunction requiring dialysis after heart transplantation is common in Taiwan. Early and late dialysis were both associated with an increased risk of mortality in heart transplant recipients.

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