Augmented Renal Clearance in the Hematology and Oncology Populations: A Scoping Review for Pharmacists.

INTRODUCTION: Until recently, interest in renal function has focused on impairment to limit drug toxicity and increase medication safety. Augmented renal clearance (ARC) has been increasingly studied in multiple patient populations, including oncology, and could lead to decreased drug efficacy from faster elimination resulting in subtherapeutic concentrations. This scoping review sought to summarize ARC literature in cancer and identify areas of research to better inform pharmacy practitioners. DATA SOURCES: Electronic databases were searched for English articles related to augmented/enhanced renal function/clearance following a framework for scoping reviews. DATA SYNTHESIS: Fourteen articles were analyzed, divided according to article objective: descriptive studies or ARC's impact on pharmacokinetics/pharmacodynamics. ARC was most defined as creatinine clearance >130 mL/min/1.73 m2, reported in 10%-100% of patients. Febrile neutropenia in adult and pediatric patients, and age <50-65 years, hematologic malignancy, and lower serum creatinine in adult patients were notable risk factors for ARC. The impact of ARC has only been evaluated with antimicrobial agents consistently resulting in lower than anticipated trough levels. Identified gaps include: elucidation of ARC's mechanism and associated biomarkers, an inclusive ARC definition for relative renal enhancement, and study of additional drug classes to ascertain the breadth of ARC impact on drug therapy. CONCLUSIONS: ARC is proving to be a frequent phenomenon in patients with cancer which pharmacists could play a vital role. Further research is needed to better understand the impact of ARC in patient care and a potential need to stage ARC based on degree of renal enhancement to establish specific drug dosing recommendations.

CVD and COVID-19: Emerging Roles of Cardiac Fibroblasts and Myofibroblasts.

Cardiovascular disease (CVD) is the leading cause of death worldwide. Current data suggest that patients with cardiovascular diseases experience more serious complications with coronavirus disease-19 (COVID-19) than those without CVD. In addition, severe COVID-19 appears to cause acute cardiac injury, as well as long-term adverse remodeling of heart tissue. Cardiac fibroblasts and myofibroblasts, being crucial in response to injury, may play a pivotal role in both contributing to and healing COVID-19-induced cardiac injury. The role of cardiac myofibroblasts in cardiac fibrosis has been well-established in the literature for decades. However, with the emergence of the novel coronavirus SARS-CoV-2, new cardiac complications are arising. Bursts of inflammatory cytokines and upregulation of TGF-ß1 and angiotensin (AngII) are common in severe COVID-19 patients. Cytokines, TGF-ß1, and Ang II can induce cardiac fibroblast differentiation, potentially leading to fibrosis. This review details the key information concerning the role of cardiac myofibroblasts in CVD and COVID-19 complications. Additionally, new factors including controlling ACE2 expression and microRNA regulation are explored as promising treatments for both COVID-19 and CVD. Further understanding of this topic may provide insight into the long-term cardiac manifestations of the COVID-19 pandemic and ways to mitigate its negative effects.