Estimating Kidney Function for Medicine Dosing

No single estimate of kidney function suits every patient. The method should be chosen to fit the situation, the risk of the drug and the accuracy needed, and the report should state which one was used.

Methods available. Creatinine based eGFR, Cockcroft-Gault clearance, cystatin C based eGFR, combined creatinine and cystatin C eGFR, timed urine collection, and measured GFR by iohexol, inulin or radioisotope clearance.

Cystatin C. It is less dependent on muscle mass. It is raised by high-dose corticosteroids, thyroid disease, obesity, smoking and inflammation.

Timed urine collection. Clearance = (urine creatinine × urine volume) divided by plasma creatinine. It overestimates by 10 to 20 percent because tubular secretion adds creatinine, and incomplete collection gives falsely low values.

Choice by situation.

• Stable adult of average size: eGFR.

• Extremes of size, narrow index drug or older adult: Cockcroft-Gault clearance with the right weight, or absolute eGFR; add cystatin C when a cut-off is close.

• Cirrhosis, sarcopenia, cachexia, amputation, vegetarian diet or high muscle mass: cystatin C or the combined equation.

• Acute kidney injury: no equation is valid. Use the trend, urine output and clinical context, and assume function is low.

• Children: bedside Schwartz, eGFR = 0.413 × height in cm divided by creatinine in mg/dL, or 36.5 × height in cm divided by creatinine in micromol/L. It is unreliable in neonates.

• Pregnancy: equations are not validated. Creatinine normally falls, so a value in the usual non-pregnant range may already signal impairment.

• Chemotherapy and transplant: measured GFR.

Substances that raise creatinine without lowering GFR. Trimethoprim, cimetidine, dolutegravir and, to a lesser degree, fenofibrate block tubular secretion. Creatine supplements and cooked meat also raise it. Some assays are affected by cefoxitin, flucytosine, ketones and bilirubin.

Special groups. In East Africa, dolutegravir and tenofovir are frequent in HIV treatment, so creatinine changes need to be interpreted against the drugs in use, and cystatin C may be unavailable.

Carboplatin. Dose in mg = target AUC × (GFR + 25), with GFR capped at 125 mL/min. A target AUC of 5 to 6 is typical for single-agent use. Use measured GFR, or creatinine clearance by a validated method, and not an indexed eGFR.

Aminoglycosides, vancomycin and anticoagulants. Use Cockcroft-Gault clearance or absolute eGFR with levels, and recalculate with each creatinine result.

Monitoring. Repeat the estimate whenever creatinine changes by more than about 20 to 25 percent, or the patient's weight or clinical state changes. Repeat annually in stable chronic kidney disease, and more often if the eGFR is under 45.

Stop rules. Do not use creatinine-derived estimates for dosing during acute kidney injury, on dialysis, or in the first weeks after a transplant.

Referral and escalation. Request measured GFR when estimates disagree across a dosing cut-off, before high-risk cytotoxic dosing, in kidney donors and recipients, and when creatinine is unreliable.

Common errors. Mixing creatinine units, using the wrong weight, trusting a creatinine that is rising, and forgetting that dolutegravir or trimethoprim can raise it without a true fall in GFR.