Augmented renal clearance
In pharmacology, augmented renal clearance (ARC) is a phenomenon where certain critically ill patients may display increased
.Augmented renal clearance can be caused by increased fluid administration, certain medications, and critical illnesses. It can lead to failure of treatment in people due to a decrease in drug concentrations, increase in clearance, or shorter half life. Many medications require adjustment to account for the changed clearance in people with ARC, notably some antibiotics.
History
Normal kidney function measured by creatinine clearance varies in different populations based on age, gender, race, fluid balance, and other factors, but also can be affected by diseases themselves.
Diagnosis
The primary sign of augmented renal clearance is an increase in the creatinine clearance well above that which would be considered normal. Commonly, ARC is defined as a creatinine clearance of greater than 130 mL/min, but the effects of increased clearance on therapy are not directly correlated to a specific number. For this reason, lower cutoffs such as 120 mL/min are used by some, as well as higher cutoffs in young people who typically have higher kidney function to begin with. Another cutoff used is 10% above the upper limit of normal for a certain population.[1]
In patients who do not have their creatinine clearance or eGFR measured or calculated frequently, augmented renal clearance may be first seen by the failure of certain medications to produce the expected effect in a patient. As an example, an antibiotic that is being administered at recommended doses in accordance with
Causes
Shannon et al. observed in 1932 that dogs had an increased renal function after high protein meals – which they termed "renal function reserve".[5] Activation of this "reserve" or extra-renal function has been suggested as a potential mechanism for ARC in severe illness.[3]
The administration of medications which increase blood flow to the kidneys has also been considered a potential cause of ARC, including administration of fluids.
Risk factors and screening
Patients with critical illnesses can be screened for risk of ARC affecting therapy in a number of ways. Scoring methods may use factors such as the following to predict ARC in critically ill patients:
Management
Augmented renal clearance may result in failure of treatment due to the increased elimination of drugs. This can be prevented by increasing the dosage of the medication, or by increasing the frequency the medication is administered to account for increased elimination. ARC influences the recommended dosages for antibiotics including
The occurrence of ARC can also impact medications that are unrelated to an acute illness, such as levetiracetam for seizures. People taking a stable dose of levetiracetam at home may require an increased dose when critically ill in a hospital to maintain efficacy.[9]
Epidemiology
Disease state | ARC (CrCl >130 mL/min) |
---|---|
Severe burn | 65% |
Sepsis | 39.5–56% |
Subarachnoid hemorrhage | 100% |
Trauma | 85.7% |
Traumatic brain injury | 85% |
Augmented renal clearance can occur in many critical care instances, but is common when patients are administered large quantities of fluid replacement, as is common in an intensive care unit. It is considered a normal part of the body's response to a severe infection or other traumatic event. Changes in renal function due to trauma or infection may be in part due to changes in hormone release as part of the body's immune and healing responses.[4]