Pharmacokinetics/Pharmacodynamics

The recommendations include using the estimated GFR (eGFR) or CrCl to assess renal function

for drug dosing. The update provides several equations that can be used to estimate kidney

function, including the Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), and

Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations with a stronger

emphasis on CKD-EPI over MDRD by the National Kidney Foundation. Recent evidence

has suggested the removal of race adjustment in CKD-EPI, and MDRD has improved bias,

Nov 18:zxae317.). The CKD-EPI equation can be calculated as follows:

GFR∞ = 142 × min(SCr / κ, 1)α × max(SCr/ κ 1)-1.2 × 0.9938Age × 1.012 (if female)

where SCr is serum creatinine (mg/dL), κ is 0.7 for females and 0.9 for males, α is −0.241 for

females and −0.302 for males, min indicates the minimum of SCr/κ or 1, and max indicates

vi.

The Cockcroft-Gault equation is used to estimate the CrCl as follows:

(140 – age)weight

SCr × 72

CrCl = × 0.85 (if female)

where CrCl is in milliliters per minute, weight is in kilograms, and SCr is in milligrams per

deciliter.

vii.

The MDRD equation is described as follows:

GFR = 175.6 × SCr/88.4-1.154 × age-0.203 × 0.742 (if female)

where GFR is in milliliters per minute/1.73 m2, SCr is measured in the laboratory using isotope

dilution mass spectroscopy (IDMS), and age is in years.

viii.

The update also notes that the most important factor when determining kidney function is

having at least one GFR estimate for all patients.

Secretion and reabsorption can play important roles in drug concentration and clearance. However,

it is difficult to study changes in drug secretion and reabsorption in patients. Therefore, data are not

available to describe the clinically important changes in these two variables in critically ill patients.

Kidney replacement therapies (KRTs): See the Acute Kidney Injury chapter for more information

regarding KRT and drug dosing.

Patients receiving KRT with a diagnosis of AKI may require hemodialysis and/or hemofiltration. The

choice of dialytic technique depends on the institution, clinician expertise, patient hemodynamic

stability, profile, and access to various types of renal replacement machines. Drug removal by

dialysis depends on dialytic method.

Acute intermittent hemodialysis: Intermittent hemodialysis can significantly contribute to the

elimination of drugs, whereas other drugs are not appreciably removed by hemodialysis. Removal

of drugs during hemodialysis depends on the size of the molecule, Vd, protein binding, and type of

dialysis filter (specifically the membrane size).

Continuous KRTs (CKRTs): CKRT refers to several different methods of renal replacement thera-

py. Many studies have investigated the effect of CKRT on drug removal. Considerable variability

exists in the type of CKRT used. The 2010 clinical update to the KDIGO guidelines suggests the

following equation as one option to determine the appropriate drug dose in CKRT: