Using EGFR for Drug Dosing

The estimated GFR is calculated from serum creatinine, cystatin C or both, and is indexed to a body surface area of 1.73 m2. It is reported automatically, and suits most dosing decisions in a patient of average size with stable disease.

Equations. The CKD-EPI creatinine equation (2021, without a race term) is widely used. The combined creatinine and cystatin C equation is the most accurate. MDRD is older and less accurate at higher values.

Indexed and absolute values. Absolute GFR (mL/min) = eGFR × body surface area divided by 1.73. Body surface area (Mosteller) is the square root of (height in cm × weight in kg divided by 3600).

Worked examples. A man of 190 cm and 100 kg has a body surface area of 2.30 m2. An eGFR of 45 becomes about 60 mL/min. A woman of 150 cm and 45 kg has an area of 1.37 m2, so an eGFR of 60 becomes about 48 mL/min.

When the indexed value is enough. Body surface area near average (about 1.6 to 1.9 m2), a drug with a wide therapeutic index, and stable kidney function.

When to use the absolute value or Cockcroft-Gault clearance. Body size well outside that range, narrow index drugs, anticoagulants, aminoglycosides, vancomycin and cytotoxic drugs.

Ancestry. Current equations no longer use a race coefficient. None was developed mainly in East African populations, so error is possible, and cystatin C improves accuracy when a decision is close.

Special groups.

• Older adults and frail patients: creatinine based eGFR overestimates function, so add cystatin C.

• Children: use a paediatric formula.

• Pregnancy and acute kidney injury: not valid.

• Dialysis: not valid.

Medicine labels that now use eGFR include:

• Metformin: maximum 1 g daily at 30 to 44, stop under 30.

• Dapagliflozin 10 mg once daily: start when eGFR is 25 or over, and continue until dialysis.

• Empagliflozin 10 mg once daily: for heart failure or chronic kidney disease, start at eGFR 20 or over.

• Alendronate: not advised under 35. Zoledronic acid 5 mg yearly for osteoporosis is contraindicated under a clearance of 35 mL/min.

• Nitrofurantoin: avoid when eGFR is under 30 (some practice uses under 45).

Monitoring. Interpret a falling eGFR against the previous trend. A fall of more than 25 percent after a new drug needs review. Check that the report states whether the value is indexed.

Stop rules. Stop or reduce the medicine when eGFR crosses its labelled limit, and again during any acute illness that changes filtration.

Referral and escalation. If indexed and absolute values fall on opposite sides of a dosing cut-off, or the patient is at extremes of size, use cystatin C or measured GFR before a high-risk dose, and involve nephrology for narrow index drugs.

Common errors. Using the indexed value in a very large or very small patient, using it in acute kidney injury, applying a cut-off from one equation to another, and ignoring muscle mass.