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 eGFR and CrCl values differ and lead to conflicting dosing recommendations, prioritize using CrCl for medication dosing adjustments, particularly for drugs primarily eliminated by the kidneys, as recommended by the 2018 European Heart Rhythm Association practical guide 1. This approach is based on the fact that the Cockcroft-Gault equation used to calculate CrCl was the method used in most NOAC trials, including those for dabigatran, edoxaban, rivaroxaban, and apixaban 1.

Key Considerations

• The CKD-EPI equation estimating the glomerular filtration rate is reliable for staging chronic kidney disease, but CrCl is preferred for drug dosing adjustments, especially for medications like NOACs 1.
• In patients with severe CKD or on renal replacement therapy, there are limited data on the use of NOACs, and VKA have also never been prospectively assessed in a RCT in this patient population 1.
• Rivaroxaban, apixaban, and edoxaban are approved in Europe for use in patients with severe CKD (Stage 4, i.e., a CrCl of 15-29 mL/min), with a reduced dose regimen 1.

Clinical Implications

• Renal function should be monitored diligently, at least yearly, to detect changes in renal function and adapt the dose accordingly 1.
• If renal function is impaired (i.e., CrCl < 60 mL/min), a more frequent evaluation is recommended, and patients with additional risk factors may require even more frequent monitoring 1.
• In situations with acute renal failure, any NOAC therapy needs to be discontinued, and parenteral anticoagulation initiated after careful risk-benefit analysis 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

When different sources recommend different dose adjustments for vancomycin, it is essential to consider the estimated glomerular filtration rate (EGFR) and creatinine clearance (CRCL) to guide dosing decisions.

• The study by 3 found that the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was the best predictor of vancomycin clearances, suggesting that EGFR may be a more reliable estimate than CRCL for vancomycin dosing.
• In contrast, the study by 4 noted that the estimated glomerular filtration rate can be misleading in some patient subsets and that alternative methods, such as the Cockcroft-Gault formula, may be required.
• The study by 5 compared vancomycin dosing algorithms based on estimated glomerular filtration rate from creatinine and cystatin C levels (eGFRcr-cys) and estimated creatinine clearance (eCLcr) and found that the eGFRcr-cys algorithm improved target trough concentration achievement.

Considerations for Vancomycin Dosing

When adjusting vancomycin doses, several factors should be considered, including:

• Renal function: Patients with moderate and severe renal dysfunction may require adjusted vancomycin doses, as noted in the study by 6.
• Age and body size: Elderly patients and those with short stature may be at risk for lower vancomycin trough concentrations, as found in the study by 7.
• Inflammation: Higher C-reactive protein (CRP) levels may be associated with lower vancomycin trough concentrations, as suggested by the study by 7.
• Dose adjustments: Insufficient total vancomycin doses may contribute to lower trough concentrations, highlighting the need for careful dose adjustments, as noted in the study by 7.

Comparison of EGFR and CRCL

The studies suggest that both EGFR and CRCL can be used to estimate renal function, but EGFR may be a more reliable estimate for vancomycin dosing, as found in the study by 3.

• The CKD-EPI equation was found to be the best predictor of vancomycin clearances, suggesting that EGFR may be a more accurate estimate than CRCL.
• However, the study by 4 noted that the estimated glomerular filtration rate can be misleading in some patient subsets, highlighting the need for careful consideration of individual patient factors when selecting a dosing method.