Estimating Renal Function for Drug Dosing: Rewriting the Gospel? part 2
Although not always stated, renal drug dosing recommendations are based on comparisons of relative (not actual) renal function. In other words, they should be based on the degree of renal function of the patient in question in comparison with a “normal” patient (i.e., a 70- kg man). Clinicians should be aware that when using the original CG equation, which includes a weight variable, the resulting estimate (in mL/min) reflects the patient’s actual renal function. However, for dosing adjustments, clinicians should instead use an estimate of the patient’s relative renal function (in mL min-1 70 kg-1 or mL min-1 1.73 m-2). A modified version of the CG equation (Equation 2 in Appendix 1) calculates creatinine clearance standardized to a 70-kg man.
Drug dosing based on actual or relative creatinine clearance has not been compared for efficacy or toxicity outcomes, but basic pharmacokinetic principles explain why it makes sense to leave out the weight variable when assessing renal function for the purposes of drug dosing. Whereas the total daily dose of a medication is based on the overall systemic clearance of the drug, changes to the dosing interval should be made on the basis of relative half-life differences. The half-life is in turn based on the ratio of volume of distribution and systemic clearance (Equation 3 in Appendix 1). Smaller patients will obviously have lower clearance rates (mL/min) than larger patients (because they have smaller kidneys), but they will also have smaller volumes of distribution. Thus, the half-life for a smaller individual (with a lower clearance, measured in mL/min) should be similar to that for a larger individual. Including body weight in creatinine clearance formulas will result in lower values for smaller individuals; it will thus inappropriately underestimate their renal function and could potentially lead to unnecessary extensions of the dosage interval. eriacta 100 mg
THE “NEW TESTAMENT”
In 1999 the Modification of Diet in Renal Disease (MDRD) study equation (Equation 4 in Appendix 1) was developed by applying multiple regression to patient- specific data from 1070 patients with renal disease and measurements of iothalamate labelled with iodine-125. The equation was subsequently validated in another 533 patients from the same population. Notice that the resultant GFR is reported as milliliters per minute per 1.73 m2 body surface (mL min-1 1.73 m-2) not millilitres per minute (mL/min) (see the section entitled “Blasphemy”, above).
The equation that many laboratories now use to report estimated GFR is the abbreviated MDRD equation (Equation 5 in Appendix 1), which requires only serum creatinine and demographic variables. Similar to the CG equation, the new MDRD formulas still require that patients’ renal function be at steady state to get the most accurate assessment of renal function. As well, the MDRD equations were designed to be used as diagnostic tools— screening the population for renal dysfunction— and not for drug dosing.