scholarly journals Impact of different renal function equations on direct oral anticoagulant concentrations

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shin-Yi Lin ◽  
Ching-Hua Kuo ◽  
Tao-Min Huang ◽  
Yu-Fong Peng ◽  
Chih-Fen Huang ◽  
...  
Keyword(s):  
Renal Function ◽  
Oral Anticoagulant ◽  
Multivariate Regression ◽  
High Performance ◽  
Vitamin K Antagonist ◽  
Disease Epidemiology ◽  
Drug Concentrations ◽  
Gault Formula ◽  
Trough Concentrations ◽  
Disease Study

AbstractThe purpose of this study is to investigate the correlation between glomerular filtration rate (GFR) estimated by different renal function equations and non-vitamin K antagonist oral anticoagulant concentration. Atrial fibrillation patients who aged ≥ 20 years and used dabigatran, rivaroxaban, or apixaban for thromboembolism prevention were enrolled to collect blood samples and measure drug concentrations using ultra-high-performance liquid chromatography with tandem mass spectrometry. The GFR was estimated using the Cockroft–Gault formula (abbreviated as creatinine clearance, CrCL), Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI) featuring both creatinine and cystatin C, and the Modification of Diet in Renal Disease Study equation (MDRD). Multivariate regression was used to investigate the associations of different renal function estimates with drug concentrations. A total of 511 participants were enrolled, including 146 dabigatran users, 164 rivaroxaban users and 201 apixaban users. Compared to clinical trials, 35.4% of dabigatran, 4.9% of rivaroxaban, and 5.5% of apixaban concentrations were higher than the expected range (p < 0.001). CKD-EPI and MDRD estimates classified fewer patients as having GFR < 50 mL/min than CrCL in all 3 groups. Both CrCL and CKD-EPI were associated with higher-than-expected ranges of dabigatran or rivaroxaban concentrations. Nevertheless, none of the renal function equations was associated with higher-than-expected apixaban concentrations. For participants aged ≥ 75 years, CKD-EPI may be associated with higher-than-expected trough concentration of dabigatran. In conclusion, CrCL and CKD-EPI both can be used to identify patients with high trough concentrations of dabigatran or rivaroxaban. Among elderly patients who used dabigatran, CKD-EPI may be associated with increased drug concentration.

scholarly journals Should We Continue Assessing Glomerular Filtration Rate with the Cockroft–Gault Formula in NOAC-Treated Patients? The Magnitude of the Problem

2020 ◽  
Vol 9 (6) ◽  
pp. 1893
Author(s):  
Roberto Cemin ◽  
Luisa Foco ◽  
Carmine Zoccali ◽  
Raffaele De Caterina
Keyword(s):  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Oral Anticoagulants ◽  
Function Class ◽  
Normal Function ◽  
City Hospital ◽  
Disease Epidemiology ◽  
Gault Formula

Despite the proven superiority of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) over the Cockcroft–Gault (CG) formula, current guidelines recommend the latter to assess renal function in patients treated with non-vitamin K antagonist oral anticoagulants (NOACs). To assess the relationship between the CG and the recommended CKD-EPI formulas, in a cohort of atrial fibrillation (AF) patients treated with NOACs, and the misclassifications introduced by the CG formula for renal function levels, we estimated renal function with three equations: CG, CKD-EPI with body surface adjustment (1.73 mL/m2, CKD-EPI) and without such adjustment (CKD-EPI_noBSA), in all consecutive AF patients discharged from NOACs from the Cardiology Division of a main city hospital between February 1st and May 31st 2018. We compared the different estimates of glomerular filtration rate and potential renal function class misclassifications. We reclassified 37/115 patients (32.1%) when switching from the CG to the CKD-EPI; and 24/115 (20.8%) switching from the CG to the CKD-EPI_noBSA formulas. Class reallocation was distributed across all levels of renal function, but mostly affected the “hyper-normal” function. In estimating consequences of such reallocation, a change in NOAC dosages would have occurred in 10/115 patients (8.7%) when switching from the CG to the CKD-EPI formula and in 10/115 patients when switching from the CG to the CKD-EPI_noBSA formula. Although the CG method has been traditionally used to calculate renal function in all NOAC studies, a renal dysfunction class reallocation occurs in a substantial fraction of hospital-admitted AF patients with the use of better estimates of renal function.

scholarly journals Cystatin C-Based Renal Function Changes After Antiretroviral Initiation: A Substudy of a Randomized Trial

2014 ◽  
Vol 1 (1) ◽  
Author(s):  
Samir K. Gupta ◽  
Douglas Kitch ◽  
Camlin Tierney ◽  
Eric S. Daar ◽  
Paul E. Sax ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Cystatin C ◽  
Estimating Equation ◽  
The Other ◽  
Lamivudine Treatment ◽  
Open Label ◽  
Disease Epidemiology ◽  
Gault Formula ◽  
Treatment Naïve

Abstract Background.  The effects of antiretrovirals on cystatin C-based renal function estimates are unknown. Methods.  We analyzed changes in renal function using creatinine and cystatin C-based estimating equations in 269 patients in A5224s, a substudy of study A5202, in which treatment-naive patients were randomized to abacavir/lamivudine or tenofovir/emtricitabine with open-label atazanavir/ritonavir or efavirenz. Results.  Changes in renal function significantly improved (or declined less) with abacavir/lamivudine treatment compared with tenofovir/emtricitabine using the Cockcroft-Gault formula (P = .016) and 2009 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI; P = .030) and 2012 CKD-EPI cystatin C-creatinine (P = .025). Renal function changes significantly improved (or declined less) with efavirenz compared with atazanavir/ritonavir (P &lt; .001 for all equations). Mean (95% confidence interval) renal function changes specifically for tenofovir/emtricitabine combined with atazanavir/ritonavir were −8.3 (−14.0, −2.6) mL/min with Cockcroft-Gault; −14.9 (−19.7, −10.1) mL/min per 1.732 with Modification of Diet in Renal Disease; −12.8 (−16.5, −9.0) mL/min per 1.732 with 2009 CKD-EPI; +8.9 (4.2, 13.7) mL/min per 1.732 with 2012 CKD-EPI cystatin C; and −1.2 (−5.1, 2.6) mL/min per 1.732 with 2012 CKD-EPI cystatin C-creatinine. Renal function changes for the other treatment arms were more favorable but similarly varied by estimating equation. Conclusions.  Antiretroviral-associated changes in renal function vary in magnitude and direction based on the estimating equation used.

scholarly journals Adverse outcomes after worsening renal function in patients with atrial fibrillation: the Fushimi AF Registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Ogawa ◽  
Y An ◽  
S Ikeda ◽  
Y Aono ◽  
K Doi ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Renal Function ◽  
Oral Anticoagulants ◽  
Adverse Outcomes ◽  
Funding Source ◽  
Worsening Renal Function ◽  
Gault Formula ◽  
Bayer Healthcare ◽  
Artery Disease

Abstract Background Patients with atrial fibrillation (AF) commonly coexist with chronic kidney disease (CKD). Non-vitamin K antagonist oral anticoagulants (NOAC) are recommended for stroke prevention in patients with non-valvular atrial fibrillation (AF), and worsening renal function (WRF) as well as CKD is an important issue in using NOAC. However, little is known about the clinical outcomes of patients after WRF. Purpose We aimed to investigate outcomes after WRF in AF patients. Methods The Fushimi AF Registry is a community-based prospective survey of the AF patients in our city. Follow-up data including prescription status were available for 4,441 patients. Of them, 1,890 patients who have baseline and at least 1 follow-up creatinine clearance (CrCl) measurements, estimated by the Cockcroft-Gault formula, were analyzed in the present study. WRF was defined as a decrease of ≥20% from baseline CrCl measurement at any time point during follow-up. We evaluated demographics and outcomes after WRF in AF patients. Results During the median follow-up period of 2,194 days, mean CrCl decrease of 2.2 ml/min/year was observed and WRF occurred in 981 patients (51.9%). Patients with WRF were significantly more often female (with vs. without WRF; 40.3% vs. 35.4%; p=0.03), older (73.4 vs. 71.1 years of age; p&lt;0.01), more often paroxysmal type (49.9% vs. 47.1%; p&lt;0.01), and more likely to have prior stroke (17.9% vs. 12.7%; p&lt;0.01), heart failure (30.8% vs. 24.8%; p&lt;0.01), diabetes (31.7% vs. 27.1%; p=0.03), and coronary artery disease (19.9% vs. 12.1%; p&lt;0.01) than those without WRF. Co-existing of CKD and mean CrCl at baseline were comparable (37.4% vs. 36.9%; p=0.82, 65.3 vs. 63.5 ml/min; p=0.66, respectively). Mean CHA2DS2-VASc score was significantly higher in WRF patients (3.55 vs. 3.03; p&lt;0.01). On landmark analysis, all-cause mortality occurred in 135 patients (8.6 /100 person-years) after WRF and 82 patients (1.7 /100 person-years) without WRF, with an adjusted hazard ratio (HR) of 6.33 (95% confidence interval [CI], 4.33–9.50; p&lt;0.01), adjusted by sex, age, body weight, serum creatinine, type of AF, oral anticoagulant prescription and comorbidities. Stroke or systemic embolism occurred in 45 patients after WRF (3.0 /100 person-years) and 78 (1.7 /100 person-years) patients without WRF (adjusted HR 1.60 [95% CI, 1.04–2.49; p=0.03]) (Figure). Conclusions AF patients after WRF had higher incidence of various adverse events. Incidence of Adverse Outcomes Funding Acknowledgement Type of funding source: Other. Main funding source(s): The Practical Research Project for Life-Style related Diseases including Cardiovascular Diseases and Diabetes Mellitus from Japan Agency for Medical Research and Development. Boehringer Ingelheim, Bayer Healthcare, Pfizer, Bristol-Myers Squibb, Astellas Pharma, AstraZeneca, Daiichi-Sankyo, Novartis Pharma, MSD, Sanofi-Aventis, and Takeda Pharmaceutical.

scholarly journals Comparison of Plasma, Epithelial Lining Fluid, and Alveolar Macrophage Concentrations of Solithromycin (CEM-101) in Healthy Adult Subjects

2012 ◽  
Vol 56 (10) ◽  
pp. 5076-5081 ◽  
Author(s):  
Keith A. Rodvold ◽  
Mark H. Gotfried ◽  
J. Gordon Still ◽  
Kay Clark ◽  
Prabhavathi Fernandes
Keyword(s):  
Steady State ◽  
High Performance ◽  
Healthy Adult ◽  
Plasma Concentrations ◽  
Epithelial Lining ◽  
Time Curve ◽  
Epithelial Lining Fluid ◽  
Once Daily ◽  
Drug Concentrations ◽  
The Mean

ABSTRACTThe steady-state concentrations of solithromycin in plasma were compared with concomitant concentrations in epithelial lining fluid (ELF) and alveolar macrophages (AM) obtained from intrapulmonary samples during bronchoscopy and bronchoalveolar lavage (BAL) in 30 healthy adult subjects. Subjects received oral solithromycin at 400 mg once daily for five consecutive days. Bronchoscopy and BAL were carried out once in each subject at either 3, 6, 9, 12, or 24 h after the last administered dose of solithromycin. Drug concentrations in plasma, ELF, and AM were assayed by a high-performance liquid chromatography-tandem mass spectrometry method. Solithromycin was concentrated extensively in ELF (range of mean [± standard deviation] concentrations, 1.02 ± 0.83 to 7.58 ± 6.69 mg/liter) and AM (25.9 ± 20.3 to 101.7 ± 52.6 mg/liter) in comparison with simultaneous plasma concentrations (0.086 ± 0.070 to 0.730 ± 0.692 mg/liter). The values for the area under the concentration-time curve from 0 to 24 h (AUC0–24values) based on mean and median ELF concentrations were 80.3 and 63.2 mg · h/liter, respectively. The ratio of ELF to plasma concentrations based on the mean and median AUC0–24values were 10.3 and 10.0, respectively. The AUC0–24values based on mean and median concentrations in AM were 1,498 and 1,282 mg · h/L, respectively. The ratio of AM to plasma concentrations based on the mean and median AUC0–24values were 193 and 202, respectively. Once-daily oral dosing of solithromycin at 400 mg produced steady-state concentrations that were significantly (P< 0.05) higher in ELF (2.4 to 28.6 times) and AM (44 to 515 times) than simultaneous plasma concentrations throughout the 24-h period after 5 days of solithromycin administration.

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