Augmented renal clearance in critically ill patients: incidence, associated factors and effects on vancomycin treatment

Abstract

ObjectiveAn augmented renal clearance has been described in some groups of critically ill patients, and it might induce sub-optimal concentrations of drugs eliminated by glomerular filtration, mainly antibiotics. Studies on its occurrence and determinants are lacking. Our goals were to determine the incidence and associated factors of augmented renal clearance and the effects on vancomycin concentrations and dosing in a series of intensive care unit patients.MethodsWe prospectively studied 363 patients admitted during 1 year to a clinical-surgical intensive care unit. Patients with serum creatinine >1.3mg/dL were excluded. Creatinine clearance was calculated from a 24-hour urine collection. Patients were grouped according to the presence of augmented renal clearance (creatinine clearance >120mL/min/1.73m2), and possible risk factors were analyzed with bivariate and logistic regression analysis. In patients treated with vancomycin, dosage and plasma concentrations were registered.ResultsAugmented renal clearance was present in 103 patients (28%); they were younger (48±15 versus 65±17 years, p<0.0001), had more frequent obstetric (16 versus 7%, p=0.0006) and trauma admissions (10 versus 3%, p=0.016) and fewer comorbidities. The only independent determinants for the development of augmented renal clearance were age (OR 0.95; p<0.0001; 95%CI 0.93-0.96) and absence of diabetes (OR 0.34; p=0.03; 95%CI 0.12-0.92). Twelve of the 46 patients who received vancomycin had augmented renal clearance and despite higher doses, had lower concentrations.ConclusionsIn this cohort of critically ill patients, augmented renal clearance was a common finding. Age and absence of diabetes were the only independent determinants. Therefore, younger and previously healthy patients might require larger vancomycin dosing.

Using Population Pharmacokinetic Modeling and Monte Carlo Simulations To Determine whether Standard Doses of Piperacillin in Piperacillin-Tazobactam Regimens Are Adequate for the Management of Febrile Neutropenia

“…In a previous trial of febrile neutropenic patients, we observed that 31% of the study cohort exhibited ARC. This is comparable to other reports for intensive care unit (ICU) patients: 33% by Ruiz et al (26), 38.7% by Kawano et al (27), and 28% by Campassi et al (28). A higher incidence in ICU patients was also reported by other authors, e.g., 55.8% (29) and 65.1% (30).…”

Augmented renal clearance in critically ill patients: etiology, definition and implications for beta-lactam dose optimization

“…Minkut et al [16] showed that the risk of sub-optimal vancomycin exposure could be doubled in patients with ARC. Other recent studies have also shown that patients with ARC exhibit low vancomycin concentrations and require increased dosing for optimal exposure [11,30].…”

“…As quantifying drug clearance is typically not routine, most literature considers ARC in terms of surrogate measures of GFR. In particular, a measured urinary creatinine clearance (CL CR ) > 130 mL/min/173 m 2 has often been employed as a threshold [2,5 ,9,10]; although lower [6,11] or higher [12] GFR cut-off points have also been used. Although this definition logically reflects the potential increase in clearance for those drugs that are primarily eliminated through glomerular filtration, it may not explain any contribution from altered tubular secretion or re-absorption, which is generally more difficult to assess.…”

Implications of Augmented Renal Clearance on Drug Dosing in Critically Ill Patients: A Focus on Antibiotics

“…Physiologic changes in the critically ill, such as increased cardiac output and enhanced blood flow to major organs, increase kidney perfusion, which can lead to ARC and higher clearance of renally eliminated medications. One group hypothesized that ARC is the natural response to critical illness in patients with a greater physiologic reserve, which is activated during states of stress. Severe trauma, infection, inflammation, burns, surgery, and pancreatitis can all potentiate a systemic inflammatory response syndrome, which results in increased cardiac output and capillary permeability, both of which lead to amplified renal blood flow and increased clearance of hydrophilic medications .…”