It is estimated that more than one in five patients admitted to the hospital develops acute kidney injury (AKI), and approximately one in two patients admitted to the intensive care unit — approximately 50% — will experience AKI while admitted, requiring a more comprehensive appraisal of their medication regimens.
Pharmacists have long been familiar with the issues posed by kidney function impairment, as drugs that are primarily renally eliminated will need adjustments from their usual doses. The complex process of figuring out these adjustments is explored by Rachel Eyler, PharmD, Nephrology Senior Content Specialist for Clinical Effectiveness at Wolters Kluwer, Health, and Stacey McCoy, PharmD, Pharmacy Clinical Program Manager for Clinical Surveillance & Compliance at Wolters Kluwer, Health, in the white paper “The Right Dose: Leveraging Technology and Tools to Optimize Precision Renal Dosing.”
Since, it is impractical to measure kidney function in routine practice, multiple equations have been developed to estimate kidney function. Although these equations are used to help personalize dosing and pursue a form of precision medicine, they are notably not precise. Eyler and McCoy note that kidney function equations suffer from significant limitations and are not necessarily interchangeable, making the process of properly dose adjusting drugs for renal impairment complicated even for seasoned pharmacists.
A history of guidance for industry
Officially, the U.S. Food and Drug Administration (FDA) offered no guidance on adjusting drug dosing for renal impairment prior to 1998.
However, kidney function estimate equations date back to 1976, with the development of the Cockcroft-Gault equation. Likely familiar to many pharmacists, this equation predicts a patient’s creatinine clearance and became the FDA’s recommended tool for dose adjustments in the late 1990s.
Despite being the equation with which many clinicians have the most experience and comfort, the Cockcroft-Gault does have limitations, Eyler and McCoy explain. It is focused on creatinine clearance, not estimated glomerular filtration rate (eGFR), which it tends to overestimate. Additionally, the Cockcroft-Gault was also developed using a relatively small sample size of mostly male patients and used a serum creatinine assay for which the details are no longer available.
In more recent years, other equations have developed:
- Modification of Diet in Renal Disease (MDRD) equation was introduced in 1999 and recommended by FDA in 2010 as another possible way to estimate GFR. The equation uses age, serum creatinine, and sex like Cockcroft-Gault, but also incorporates race as a variable.
- CKD-EPI equation was developed in 2009 and is considered by many to be an improvement on MDRD in determining eGFR. Like the MDRD, when used for drug dosing in patients at the extremes of body weight (large and small), it will need to be denormalized so that units are expressed in mL/minute (as opposed to mL/minute/1.73m2).
Currently, experts are reevaluating equations that include race as a variable. Eyler and McCoy explain that racial constructs are rarely based on genetics and using them in kidney function assessment is more likely to create inequity in treatment than produce any greater accuracy or precision in dosing.
Solutions help pharmacists take the lead
Pharmacists are the experts in the field of pharmacotherapy, often leading with teams of clinicians in personalizing the care and regimens for renally impaired patients, say Eyler and McCoy. The use of evidence-based clinical decision support and surveillance technology will only enhance their efforts, thereby improving safety and efficiency.
This can include:
- Medication safety screening through the EHR
- Processes to check medication/doses at various key stages of the patient’s care journey
- Safety protocols for vulnerable populations (i.e., geriatric, obese)
- Plans for de-escalation of harmful medications
- Real-time monitoring of patients on therapies that put them at risk (i.e., anti-coagulants)
An increasing number of medications being approved by the FDA are requiring eGFR-based renal dose adjustments, Eyler and McCoy report. Their recommendation is that hospital pharmacies evaluate therapeutic interchange programs to determine if updates to renal dosing protocols are required.
To learn more about renal dosing adjustments and solutions for your care team, download the white paper “The Right Dose: Leveraging Technology and Tools to Optimize Precision Renal Dosing,” or listen to Eyler and McCoy’s on-demand webinar “The Right Dose: Best Practices for Renal Dosing Optimization and Standardization.”