What is the preferred method for dose adjustment when Estimated Glomerular Filtration Rate (eGFR) and Creatinine Clearance (CrCl) from different sources recommend different dose adjustments for patients with Impaired Renal Function?

From the Guidelines

When deciding between eGFR and CrCl for medication dosing adjustments, use the method specified in the FDA-approved drug labeling or package insert, prioritizing CrCl calculated by the Cockcroft-Gault equation for medications where it is specified, as seen in the context of NOACs 1. In clinical practice, the choice between eGFR and CrCl for dose adjustments of medications, especially those with narrow therapeutic indices, is crucial for minimizing toxicity while maintaining efficacy.

• For patients with chronic kidney disease (CKD), the assessment of renal function is vital, and both eGFR and CrCl have their roles, with CrCl being preferred in certain clinical contexts, such as the dosing of non-vitamin K antagonist oral anticoagulants (NOACs) 1.
• The Cockcroft-Gault equation is recommended for calculating CrCl in the context of NOAC treatment because it was the method used in most NOAC trials, providing a basis for dosing guidelines 1.
• For medications where the labeling specifically mentions eGFR, it is appropriate to use eGFR for dose adjustments, highlighting the importance of consulting FDA-approved labeling for specific guidance on renal adjustment 1.
• In situations where different sources recommend different adjustments, prioritizing the FDA-approved labeling, followed by hospital formulary guidelines, and then clinical decision support systems, can help in making informed decisions 1.
• The difference between eGFR and CrCl calculations can lead to significant dosing differences, especially in patients with atypical body composition, emphasizing the need for careful consideration of the method used for renal function assessment in dose adjustments 1.
• Consulting with a clinical pharmacist can be beneficial, especially for critical medications with narrow therapeutic windows, to determine the most appropriate method for dose adjustment based on renal function assessment 1.

From the FDA Drug Label

DOSAGE TABLE FOR VANCOMYCIN IN PATIENTS WITH IMPAIRED RENAL FUNCTION (Adapted from Moellering et al. 1) Creatinine ClearancemL/minVancomycin Dosemg/24 h 1001,545 901,390 801,235 701,080 60925 50770 40620 30465 20310 10155 The initial dose should be no less than 15 mg/kg, even in patients with mild to moderate renal insufficiency. When only serum creatinine is known, the following formula (based on sex, weight and age of the patient) may be used to calculate creatinine clearance. Men:[Weight (kg) × (140 – age in years)] 72 × serum creatinine concentration (mg/dL) Women:0. 85 × above value

The vancomycin dose should be adjusted based on creatinine clearance (CrCl). If different sources recommend different dose adjustments, the CrCl should be used to determine the dose. The provided dosage table can be used to calculate the dose based on CrCl. If CrCl cannot be measured, it can be estimated using the provided formula. eGFR is not mentioned in the label as a method for dose adjustment. 2

From the Research

EGFR vs CRCL in Vancomycin Dosing

• The choice between estimated glomerular filtration rate (EGFR) and creatinine clearance (CRCL) for vancomycin dose adjustments is crucial in clinical practice 3, 4, 5.
• A study published in 2014 found that the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation provided a closer relationship between clearances of vancomycin and estimated glomerular filtration rate (GFR) compared to measured creatinine clearance (CLCR) 3.
• Another study from 2017 demonstrated that a vancomycin dosing algorithm based on estimated GFR from creatinine and cystatin C levels (eGFRcr-cys) improved target trough concentration achievement compared to an algorithm based on estimated creatinine clearance (eCLcr) in critically ill patients 4.
• Research from 2014 also showed that serum cystatin C predicts vancomycin trough levels better than serum creatinine in hospitalized patients, suggesting that cystatin C-inclusive models may improve vancomycin dosing 5.
• Factors associated with vancomycin-induced nephrotoxicity include increasing age, body weight, vancomycin dose and trough levels, frequency and duration of treatment, and critically ill patients 6.

Comparison of Dosing Methods

• The CKD-EPI equation appears to be a better predictor of vancomycin clearances compared to the Cockcroft-Gault formula and Modification of Diet in Renal Disease equation 3.
• AUC/MIC-guided vancomycin dosing has been shown to be associated with a lower risk of acute kidney injury and supratherapeutic trough levels compared to trough-only dosing 7.
• Cystatin C-guided vancomycin dosing may improve target trough achievement and reduce the risk of nephrotoxicity 4, 5.

Clinical Implications

• The choice of dosing method and equation used to estimate renal function can significantly impact vancomycin trough levels and the risk of nephrotoxicity 3, 7, 4, 5, 6.
• Clinicians should consider using the CKD-EPI equation and cystatin C-guided dosing to optimize vancomycin therapy and minimize the risk of adverse effects 3, 4, 5.