Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Pharmacokinetic assessment in patients receiving continuous RRT: perspectives from the Kidney Health Initiative.

ABSTRACT: The effect of AKI and modern continuous RRT (CRRT) methods on drug disposition (pharmacokinetics) and response has been poorly studied. Pharmaceutical manufacturers have little incentive to perform pharmacokinetic studies in patients undergoing CRRT because such studies are neither recommended in existing US Food and Drug Administration (FDA) guidance documents nor required for new drug approval. Action is urgently needed to address the knowledge deficit. The Kidney Health Initiative has assembled a work group composed of clinicians and scientists representing academia, the FDA, and the pharmaceutical and dialysis industries with expertise related to pharmacokinetics, AKI, and/or CRRT. The work group critically evaluated key considerations in the assessment of pharmacokinetics and drug dosing in CRRT, practical constraints related to conducting pharmacokinetic studies in critically ill patients, and the generalizability of observations made in the context of specific CRRT prescriptions and specific patient populations in order to identify efficient study designs capable of addressing the knowledge deficit without impeding drug development. Considerations for the standardized assessment of pharmacokinetics and development of corresponding drug dosing recommendations in critically ill patients with AKI receiving CRRT are proposed.

SUBMITTER: Nolin TD

PROVIDER: S-EPMC4284416 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Pragmatic Trials in Maintenance Dialysis: Perspectives from the Kidney Health Initiative.

Project description:Pragmatic clinical trials are conducted under the real-world conditions of clinical care delivery. As a result, these trials yield findings that are highly generalizable to the nonresearch setting, identify interventions that are readily translatable into clinical practice, and cost less than trials that require extensive research infrastructures. Maintenance dialysis is a setting especially well suited for pragmatic trials because of inherently frequent and predictable patient encounters, highly granular and uniform data collection, use of electronic data systems, and delivery of care by a small number of provider organizations to approximately 90% of patients nationally. Recognizing the potential for pragmatic trials to generate much needed evidence to guide the care of patients receiving maintenance dialysis, the Kidney Health Initiative assembled a group of individuals with relevant expertise from academia, industry, and government to provide the nephrology community with information about the design and conduct of such trials, with a specific focus on the dialysis setting. Here, we review this information, and where applicable, use experience from the ongoing Time to Reduce Mortality in End Stage Renal Disease Trial, a large cluster-randomized, pragmatic trial evaluating hemodialysis session duration, to illustrate challenges and solutions to operational, ethical, and regulatory issues.

| S-EPMC5042681 | biostudies-literature

Pharmacokinetic profile of acyclovir in a child receiving continuous kidney replacement therapy for acute liver failure.

Project description:BackgroundContinuous venovenous hemodiafiltration (CVVHDF) is one of the treatments of critically ill children presenting severe acute liver failure. This affliction might be induced by HSV infection requiring a treatment by acyclovir. Continuous kidney replacement therapy (CKRT) can alter its pharmacokinetics, according to its physicochemical properties and CVVHDF settings.Case-diagnosis/treatmentThe patient was a 21-month-old female presenting liver failure with hyperammonemia treated by acyclovir with presumed HSV infection. CKRT was initiated on day 1 with substantial replacement and dialysate flow rates (respectively 75 and 220 mL/kg/h). Acyclovir was intravenously administered every 8 h with a 1-h infusion of 500 mg/m2. Plasma and effluent concentrations were measured by liquid chromatography-tandem mass spectrometry assay to estimate the area under a curve (AUC) and CKRT clearance by 2 methods (one based on pre- and post-filter concentrations and the other one on dialysate flow rates). Clearance was estimated between 19.2 and 26.3 mL/min with the first method and between 27.6 and 44.3 mL/min with the second one. Concentrations were highly above the therapeutic index (peak concentration was measured at 28 mg/L), but AUC was appropriate.ConclusionsThis case describes acyclovir pharmacokinetics during CKRT in a pediatric patient treated by acyclovir. The patient was treated with adapted exposure with the usual dosing, but lower dosing should be investigated with complementary studies.Trial registrationClinicalTrials.gov NCT02539407.

| S-EPMC9880359 | biostudies-literature

Biomarker Enhanced Risk Prediction for Adverse Outcomes in Critically Ill Patients Receiving RRT.

Project description:Background and objectivesHigher plasma concentrations of inflammatory and apoptosis markers in critically ill patients receiving RRT are associated with RRT dependence and death. This study objective was to examine whether plasma inflammatory (IL-6, -8, -10, and -18; macrophage migration inhibitory factor) and apoptosis (death receptor-5, tumor necrosis factor receptor I and II) biomarkers augment risk prediction of renal recovery and mortality compared with clinical models.Design, setting, participants, & measurementsThe Biologic Markers of Recovery for the Kidney study (n=817) was a prospective, nested, observational cohort study conducted as an ancillary to the Veterans Affairs/National Institutes of Health Acute renal failure Trial Network study, a randomized trial of intensive versus less intensive RRT in critically ill patients with AKI conducted between November 2003 and July 2007 at 27 Veterans Affairs- and university-affiliated centers. Primary outcomes of interest were renal recovery and mortality at day 60.ResultsA parsimonious clinical model consisting of only four variables (age, mean arterial pressure, mechanical ventilation, and bilirubin) predicted renal recovery (area under the receiver-operating characteristic curve [AUROC], 0.73; 95% confidence interval [95% CI], 0.68 to 0.78) and mortality (AUROC, 0.74; 95% CI, 0.69 to 0.78). By contrast, individual biomarkers were only modestly predictive of renal recovery (AUROC range, 0.55-0.63) and mortality (AUROC range, 0.54-0.68). Adding plasma IL-8 to a parsimonious model augmented prediction of recovery (AUROC, 0.76; 95% CI, 0.71 to 0.81; P=0.04) and mortality (AUROC, 0.78; 95% CI, 0.73 to 0.82; P<0.01) compared with the clinical model alone.ConclusionsThis study suggests that a simple four-variable clinical model with plasma IL-8 had predictive value for renal recovery and mortality. These findings require external validation but could easily be used by clinicians.

| S-EPMC4527029 | biostudies-literature

Consensus guidelines for management of hyperammonaemia in paediatric patients receiving continuous kidney replacement therapy.

Project description:Hyperammonaemia in children can lead to grave consequences in the form of cerebral oedema, severe neurological impairment and even death. In infants and children, common causes of hyperammonaemia include urea cycle disorders or organic acidaemias. Few studies have assessed the role of extracorporeal therapies in the management of hyperammonaemia in neonates and children. Moreover, consensus guidelines are lacking for the use of non-kidney replacement therapy (NKRT) and kidney replacement therapies (KRTs, including peritoneal dialysis, continuous KRT, haemodialysis and hybrid therapy) to manage hyperammonaemia in neonates and children. Prompt treatment with KRT and/or NKRT, the choice of which depends on the ammonia concentrations and presenting symptoms of the patient, is crucial. This expert Consensus Statement presents recommendations for the management of hyperammonaemia requiring KRT in paediatric populations. Additional studies are required to strengthen these recommendations.

| S-EPMC7366888 | biostudies-literature

Health numeracy: perspectives about using numbers in health management from African American patients receiving dialysis.

Project description:Health numeracy is linked to important clinical outcomes. Kidney disease management relies heavily on patient numeracy skills across the continuum of kidney disease care. Little data are available eliciting stakeholder perspectives from patients receiving dialysis about the construct of health numeracy. Using focus groups, we asked patients receiving hemodialysis open-ended questions to identify facilitators and barriers to their understanding, interpretation, and application of numeric information in kidney care. Transcripts were analyzed using content analysis. Twelve patients participated with a mean (standard deviation) age of 56 (12) years. All were African American, 50% were women, and 83% had an annual income <$20,000/year. Although patients felt numbers were critical to every aspect in life, they noted several barriers to understanding, interpreting and applying quantitative information specifically to manage their health. Low patient self-efficacy related to health numeracy and limited patient-provider communication about quantitatively based feedback, were emphasized as key barriers. Through focus groups of key patient stakeholders we identified important modifiable barriers to effective kidney care. Additional research is needed to develop tools that support numeracy-sensitive education and communication interventions in dialysis.

| S-EPMC4489845 | biostudies-literature

Steady-State Serum IgG Trough Levels Are Adequate for Pharmacokinetic Assessment in Patients with Immunodeficiencies Receiving Subcutaneous Immune Globulin.

Project description:Patients with primary immunodeficiency diseases often require lifelong immunoglobulin (IG) therapy. Most clinical trials investigating IG therapies characterize serum immunoglobulin G (IgG) pharmacokinetic (PK) profiles by serially assessing serum IgG levels. This retrospective analysis evaluated whether steady-state serum IgG trough level measurement alone is adequate for PK assessment. Based on individual patient serum IgG trough levels from two pivotal trials (phase 2/3 European [NCT01412385] and North American [NCT01218438]) of weekly 20% subcutaneous IG (SCIG; Cuvitru, Ig20Gly), trough level-predicted IgG AUC (AUCτ,tp) were calculated and compared with the reported AUC calculated from serum IgG concentration-time profiles (AUCτ). In both studies, mean AUCτ,tp values for Ig20Gly were essentially equivalent to AUCτ with point estimates of geometric mean ratio (GMR) of AUCτ,tp/AUCτ near 1.0 and 90% CIs within 0.80-1.25. In contrast, for IVIG, 10%, mean AUCτ,tp values were lower than AUCτ by >20%, (GMR [90% CI]: 0.74 [0.70-0.78] and 0.77 [0.73-0.81] for the two studies, respectively). Mean AUCτ,tp values calculated for 4 other SCIG products (based on mean IgG trough levels reported in the literature/labels) were also essentially equivalent to the reported AUCτ (differences <10% for all except HyQvia, a facilitated SCIG product), while differences for IVIG products were >20%. In conclusion, steady-state serum IgG levels following weekly SCIG remain stable, allowing for reliable prediction of AUC over the dosing interval using trough IgG levels. These findings indicate that measuring steady-state serum IgG trough levels alone may be adequate for PK assessment of weekly SCIG.

| S-EPMC8310849 | biostudies-literature

The Association of an Early Net Ultrafiltration Rate and 28-Day Mortality in Patients Receiving Continuous Kidney Replacement Therapy.

Project description:Background: An early net ultrafiltration (NUF) rate may be associated with prognosis in patients receiving continuous kidney replacement therapy (CKRT). In this study, we tested whether high or low early NUF rates in patients treated with CKRT were associated with increased mortality. Methods: We conducted a retrospective, observational study among all patients in the Medical Information Mart for Intensive Care IV database who received CKRT for more than 24 h within 14 days after intensive care unit admission. We defined the early (initial 48 h) NUF rate as the amount of fluid removal per hour adjusted by the patients' weight and took it as a classified variable (low rate: <1.6, moderate rate: 1.6-3.1 and high rate: > 3.1 ml/kg/h). The association between 28-day mortality and the NUF rate was analyzed by logistic regression and mediation analyses. Results: A total of 911 patients were included in our study. The median NUF rate was 2.71 (interquartile range 1.90-3.86) ml/kg/h and the 28-day mortality was 40.1%. Compared with the moderate NUF rate, the low NUF rate (adjusted odds ratio 1.56, 95% CI 1.04-2.35, p = 0.032) and high NUF rate (adjusted odds ratio 1.43, 95% CI 1.02-2.01, p = 0.040) were associated with higher 28-day mortality. The putative effect of high or low NUF rates on 28 day mortality was not direct [adjusted average direct effects (ADE) for a low NUF rate = 0.92, p = 0.064; adjusted ADE for a high NUF rate = 1.03, p = 0.096], but mediated by effects of the NUF rate on fluid balance during the same period [adjusted average causal mediation effects (ACME) 0.96, p = 0.010 for a low NUF rate; adjusted ACME 0.99, p = 0.042 for a high NUF rate]. Moreover, we found an increase trend in the NUF rate corresponding to the lowest mortality when fluid input increased. Conclusion: Compared with NUF rates between 1.6-3.1 ml/kg/h in the first 48 h of CKRT, NUF rates > 3.1 and <1.6 ml/kg/h were associated with higher mortality.

| S-EPMC8674682 | biostudies-literature

Net ultrafiltration rate and its impact on mortality in patients with acute kidney injury receiving continuous renal replacement therapy.

Project description:BackgroundFluid overload, a critical consequence of acute kidney injury (AKI), is associated with worse outcomes. The optimal fluid removal rate per day during continuous renal replacement therapy (CRRT) is unknown. The purpose of this study is to evaluate the impact of the ultrafiltration rate on mortality in critically ill patients with AKI receiving CRRT.MethodsThis was a retrospective cohort study where we reviewed 1398 patients with AKI who received CRRT between December 2006 and November 2015 at the Mayo Clinic, Rochester, MN, USA. The net ultrafiltration rate (UFNET) was categorized into low- and high-intensity groups (<35 and ≥35 mL/kg/day, respectively). The impact of different UFNET intensities on 30-day mortality was assessed using logistic regression after adjusting for age, sex, body mass index, fluid balance from intensive care unit (ICU) admission to CRRT initiation, Acute Physiologic Assessment and Chronic Health Evaluation III and sequential organ failure assessment scores, baseline serum creatinine, ICU day at CRRT initiation, Charlson comorbidity index, CRRT duration and need of mechanical ventilation.ResultsThe mean ± SD age was 62 ± 15 years, and 827 (59%) were male. There were 696 patients (49.7%) in the low- and 702 (50.2%) in the high-intensity group. Thirty-day mortality was 755 (54%). There were 420 (60%) deaths in the low-, and 335 (48%) in the high-intensity group (P < 0.001). UFNET ≥35 mL/kg/day remained independently associated with lower 30-day mortality (adjusted odds ratio = 0.47, 95% confidence interval 0.37-0.59; P < 0.001) compared with <35 mL/kg/day.ConclusionsMore intensive fluid removal, UFNET ≥35 mL/kg/day, among AKI patients receiving CRRT is associated with lower mortality. Future prospective studies are required to confirm this finding.

| S-EPMC7886538 | biostudies-literature

Implementing the Kidney Health Initiative Surrogate Efficacy Endpoint in Patients With IgA Nephropathy (the PROTECT Trial).

Project description: Not available

| S-EPMC6933476 | biostudies-literature

Predicting the dose of vancomycin in ICU patients receiving different types of RRT therapy: a model-based meta-analytic approach.

Project description:AimPrevious pharmacokinetic (PK) studies have proposed various dosing regimens for vancomycin in intensive care unit (ICU) patients undergoing renal replacement therapy (RRT), but all are restricted to specific RRT modalities. To be useful in practice, a population PK model would need to predict vancomycin clearance during any RRT modality. Development of such a model is feasible using meta-analysis of published summarized estimates of vancomycin PK parameters. Our aims were: (i) to develop and validate a population PK model for vancomycin that takes into account any RRT modalities, and (ii) to predict vancomycin dosing for RRT patients in ICU.MethodsVancomycin pharmacokinetics were assumed to be two-compartmental, total body clearance being the sum of non-RRT clearance and RRT-induced clearance. Drug disposition and non-RRT clearance parameters were estimated by systematic review and meta-analysis of previously published parameter estimates. The relationship between RRT-induced clearance and RRT flowrate settings was assessed using a model-based meta-analysis. Prediction performances of the PK model were assessed using external data.ResultsThe meta-analyses of disposition parameters, non-RRT clearance and RRT-induced clearance included 11, 6 and 38 studies (84 RRT clearance measurements) respectively. The model performed well in predicting external individual PK data. Individual vancomycin concentrations during RRT were accurately predicted using Bayesian estimation based solely on pre-RRT measurements.ConclusionsThe PK model allowed accurate prediction of the vancomycin pharmacokinetics during RRT in ICU patients. Based on the model of RRT-induced clearance, an appropriate adjustment of the vancomycin dosing regimen could be proposed for any kind of flowrate settings.

| S-EPMC6533443 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data