Remdesivir for Covid-19 pneumonia in patients with severe chronic kidney disease: Case series and review of the literature

Remdesivir was the first antiviral agent to receive FDA authorization for severe COVID-19 management, which restricts its use with severe renal impairment due to concerns that active metabolites might accumulate, causing renal toxicities. With limited treatment options, available evidence on such patient groups is important to assess for future safety.

Pharmacokinetics and Pharmacodynamics of Sacubitril/Valsartan in Maintenance Hemodialysis Patients with Heart Failure

<b><i>Background:</i></b> Heart failure (HF) is one of the main comorbidities in patients receiving maintenance hemodialysis (HD). Sacubitril/valsartan (SAC/VAL) is widely used in HF patients with reduced ejection fraction (HFrEF) or HF mid-range ejection fraction (HFmrEF). However, the pharmacokinetic (PK) and pharmacodynamic properties of SAC/VAL in HD patients with HF remain uncertain. <b><i>Objectives:</i></b> This study aimed to analyze the efficacy and PK properties of SAC/VAL in HD patients with HFrEF or HFmrEF. <b><i>Methods:</i></b> HD patients with HFrEF or HFmrEF were treated with SAC/VAL 50 or 100 mg twice a day (BID) and the concentrations of valsartan and LBQ657 (active metabolite of SAC) were determined by high-performance liquid chromatography-tandem mass spectrometry during HD and on the days between HD sessions (interval days). N-terminal-pro B-type natriuretic peptide and high-sensitivity troponin T were measured, and left ventricular ejection fraction (LVEF) was evaluated by echocardiography. <b><i>Results:</i></b> The mean maximum plasma concentrations (<i>C</i>_max) of LBQ657 and VAL on the interval days were 15.46 ± 6.01 and 2.57 ± 1.23 mg/L, respectively. Compared with previous values in patients with severe renal impairment and healthy volunteers, these levels both remained within the safe concentration ranges during treatment with SAC/VAL 100 mg BID. Moreover, SAC/VAL significantly improved LVEF in HD patients with HFrEF or HFmrEF (<i>p</i> &#x3c; 0.05). <b><i>Conclusions:</i></b> HD did not remove the SAC metabolite LBQ657 or VAL in patients with HF. However, SAC/VAL 100 mg BID was safe and effective in patients undergoing HD.

1102. Evaluation of Vancomycin Accumulation in Patients with Obesity

Background Current vancomycin guidelines recommend using actual body weight for dosing. However, in patients with obesity, this may result in lower initial vancomycin concentrations that can accumulate with continued doses due to differences in volume of distribution. The objective of this study is to evaluate the incidence of vancomycin accumulation in patients with obesity and identify potential factors associated with accumulation. Methods This is a single-center, retrospective, observational study at a tertiary academic medical center. Adult patients with a BMI ≥ 30 kg/m2 and with ≥ 2 vancomycin serum trough concentrations within the same encounter in 2019 were screened. Patients were excluded if they were pregnant, had unstable renal function or severe renal impairment, received &lt; 3 doses before a concentration was drawn, or had inconsistent dosing prior to a concentration draw. Linear kinetics were used to correct for differences in timing of concentration or dose changes. The major endpoint was the incidence of vancomycin accumulation, defined as a 20% increase in trough concentration between the first and any subsequent trough concentrations within the first 10 days of therapy. Minor endpoints included the percentage of supratherapeutic concentrations and the incidence of acute kidney injury (AKI). Descriptive statistics were used to evaluate endpoints and multivariable logistic regression was used to evaluate factors associated with accumulation. Results We screened 543 patients, and 162 were included in our analysis. The median age was 56.5 years (interquartile range [IQR] 43 - 65.3), and 62.3% were male. The median weight was 112.7 kg (IQR 99.8 - 122.6) and the median BMI was 36.8 kg/m2 (IQR 33.1 - 41). The median total daily vancomycin dose at initiation was 28.7 mg/kg/day (IQR 25.4 - 31.2). Vancomycin accumulation occurred in 99 patients (61.1%) within the first 10 days of therapy and AKI occurred in 21 patients (14.9%). No factors studied, including age, gender, obesity class, initial dose, SCr, or frequency were associated with accumulation. Conclusion Most patients with obesity experienced vancomycin accumulation within the first 10 days of therapy. Providers should be cautious when assessing a vancomycin concentration early in the treatment course. Disclosures All Authors: No reported disclosures

Rivaroxaban dosing in patients with atrial fibrillation: results from the RIVER registry – is dosing according to renal function appropriate?

Introduction Rivaroxaban is recommended as an option for anticoagulation in patients with nonvalvular atrial fibrillation (AF) with one or more risk factors for stroke. The approved/recommended rivaroxaban dose for stroke prevention in patients with atrial fibrillation (AF) is solely based on renal function: 20 mg once daily (od) for patients with a creatinine clearance [CrCl] ≥50 ml/min and 15 mg od in patients with CrCl 15–49 mL/min). Purpose To assess the patterns of rivaroxaban prescription as per the creatinine clearances levels and to assess the impact of the rivaroxaban dosing on the rate of events at 2-year follow-up in patients with AF. Methods RIVaroxaban Evaluation in Real Life setting (RIVER) is a prospective international registry of patients with newly diagnosed non-valvular AF treated with rivaroxaban for the prevention of thromboembolic stroke and at least one investigator-determined risk factor for stroke. Adjusted hazard ratios (HRs) were obtained through Cox proportional-hazard model. Results Among 3402 patients with normal renal function (CrCl ≥50 mL/min), 82.1% were prescribed the recommended rivaroxaban dose of 20 mg (od) at baseline. Among 524 patients with moderate or severe renal impairment (CrCl 15–50 mL/min), 55.3% patients received rivaroxaban 15 mg (od), 39.9% received 20 mg (od) and 4.2% 10 mg (od). Non-recommended dosing was rare in patients younger than 70 (13.5%) but more frequent in older patients (28.8%). Non-recommended low dosing was more frequent in Asians (38.9%), compared to non-Asian patients (13.8%). Regarding clinical outcomes, adjusted hazards ratios (HR, presented with 95% confidence intervals) showed that the non-recommended low dosing (&lt;20 mg od) was associated with higher risk of non-cardiovascular mortality (HR 2.09 (1.16–3.77)) in patients with normal renal function. The non-recommended high dosing (&gt;15 mg od) was associated with lower risk of all-cause mortality (HR 0.63 (0.42–0.93)) and cardiovascular mortality (HR 0.32 (0.13–0.77)) and higher risk of major bleeding (HR 2.86 (1.49–5.50)) in patients with moderate to severe renal impairment (figure 1 and 2). Conclusion In patients with normal renal function, non-recommended low dose rivaroxaban was associated with increased cardiovascular mortality without reducing the risk of major bleeding compared to recommended dosing. In patients with CrCl &lt;50 ml/min, non-recommended high dose rivaroxaban was associated with reduced cardiovascular mortality but at the cost of increased major bleeding. These observational data largely support the reduction of rivaroxaban dosing according to renal function but educational strategies are needed to ensure that rivaroxaban is used appropriately. FUNDunding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): This work was supported by an unrestricted research grant from Bayer AG, Berlin, Germany, to TRI, London, UK, which sponsors the RIVER registry. This work is supported by KANTOR CHARITABLE FOUNDATION for the Kantor-Kakkar Global Centre for Thrombosis Science.

Applicability of Creatinine-based equations for estimating glomerular filtration rate in elderly Chinese patients

Background The accuracy of the estimated glomerular filter rate (eGFR) in elderly patients is debatable. In 2020, a new creatinine-based equation by European Kidney Function Consortium (EKFC) was applied to all age groups. The objective of this study was to assess the appropriateness of the new EKFC equation with Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Lund-Malmö Revised (LMR), Berlin Initiative Study 1 (BIS1), and full age spectrum (FAS) equations based on serum creatinine (SCR) for elderly Chinese patients. Methods A total of 612 elderly patients with a measured glomerular filtration rate (mGFR) by the dual plasma sample clearance method with Technetium-99 m-diethylenetriamine-pentaacetic acid (Tc-99 m-DTPA) were divided into four subgroups based on age, sex, mGFR, and whether combined with diabetes. The performance of GFR was assessed while considering bias, precision, accuracy, and root-mean-square error (RMSE). Bland-Altman plots, concordance correlation coefficients (CCCs), and correlation coefficients were applied to evaluate the validity of eGFR. Results The median age of the 612 participants was 73 years, and 386 (63.1%) were male. Referring to mGFR (42.1 ml/min/1.73 m2), the CKD-EPI, LMR, BIS1, FAS, and EKFC equations estimated GFR at 44.4, 41.1, 43.6, 41.8 and 41.9 ml/min/1.73 m2, respectively. Overall, the smallest bias was found for the BIS1 equation (− 0.050 vs. range − 3.015 to 0.795, P<0.05, vs. the CKD-EPI equation). Regarding P30, interquartile range (IQR), RMSE, and GFR category misclassification, the BIS1 equation generally performed more accurately than the other eqs. (73.9%, 12.7, 12.9, and 35.3%, respectively). Nevertheless, no equation achieved optimal performance for the mGFR≥60 ml/min/1.73 m2 subgroup. Bland-Altman analysis showed the smallest mean difference (− 0.3 ml/min/1.73 m2) for the BIS1 equation when compared to the other equations. Conclusions This study suggested that the BIS1 equation was the most applicable for estimating GFR in Chinese elderly patients with moderate to severe renal impairment.

High Dependency Renal Unit (HDRU) for the management of COVID-19 in patients with severe acute or chronic kidney disease

Background: COVID-19 in patients on dialysis for acute or chronic kidney disease is associated with high mortality. We evaluated the effect of high dependency renal unit (HDRU) with nephrologists as primary care physicians for management of these patients. Methods: This was an observational, cohort study conducted at a tertiary care teaching hospital in western India. Patients needing dialysis for COVID-19 associated Acute Kidney Injury (AKI-D) and patients with End-Stage-Renal-Disease (ESRD) hospitalized for COVID-19 were included in the study. After 2 months into the pandemic (28 March to 28 May 2020), HDRU was commissioned for management of these patients. With nephrologists as primary care physicians, the components of care included completion of care bundle focusing on key nephrology and COVID-19 related issues, checklist-based clinical monitoring, integration of multispecialty care, and training of nurses and doctors. Primary outcome of the study was in hospital mortality compared between pre-HDRU and HDRU cohorts. Secondary outcomes were- dialysis dependence in AKI-D, and predictors of death. Results: 238 of 4254 (5.59%) patients with COVID-19 admitted from 28th March to 30th September had severe renal impairment (116 AKI-D and 122 ESRD). 145 (62%) had severe COVID-19. HDRU care was delivered from 28th May to 30th August. Kaplan-Meier survival analysis showed significant improvement in survival after implementation of HDRU [19 of 52 (36.5%) in pre-HDRU versus 35 of 160 (21.9%) in HDRU died, p=<0.01]. 44 (67.7%) AKI-D survivors were dialysis dependent at discharge. Breathlessness and altered mental status at presentation, development of shock during hospital stay and leukocytosis predicted mortality. Conclusions: HDRU managed by nephrologists is a feasible and potentially effective approach to improve the outcomes of patients with COVID-19 and severe renal impairment.