Personalized_Medicine_A_New_Medical_and_Social_Challenge

(MDRD) equation (four variables) has demonstrated excellent precision and accu-
racy in the prediction of GFR. Since it provides less precise estimate of GFR in
patients with stages 1 and 2 of CKD, it is recommended to be reserved for patients
with GFR<60 ml/min/1.73 m^2. The CKD-EPI equation was recently developed
specifically to overcome this limitation. It is more accurate than the MDRD Study
equation, particularly at higher levels of GFR (see footnote 13).
Currently, the CKD-EPI method is the most accurate method for estimation of
GFR, and it appears to be emerging as the method of choice for the staging of CKD.
Clinicians should use the method that provides the most accurate assessment of
GFR. In particular, this is of utmost importance for those drugs with a narrow
therapeutic index for which dosing individualization is required. In those clinical
situations where any creatinine-based estimation equation is not likely to provide a
good estimate of GFR, measured creatinine clearance or measured GFR using
exogenous markers should be considered.
The liver plays a central role in the pharmacokinetics of most drugs and many
active or inactive metabolites because hepatic and biliary excretion processes
determine the rate of their elimination from the body, while bioavailability is
affected by first-pass mechanisms.^15 In patients affected with chronic liver disease

Table 1 Chronic kidney disease staging

Stage Description GFR (ml/min/1.73 m^2 )

1 Kidney damage with normal or increased GFR  90

2 Kidney damage with a mild decrease in GFR 60–89

3 Moderate decrease in GFR 30–59

4 Severe decrease in GFR 15–29

5 Kidney failure <15 (or dialysis)

Table 2 Equations to estimate GFR for drug dosage adjustment

Equations Units

Cockroft and Gault

Clcr¼(140-age (years)weight (kg)0.85 [female]/Scr(mg/dl)72)

ml/min

MDRD (four variable) Study equation

GFR¼186.3Scr1.154x Age0.2031.212[black]0.742[female]

ml/min per

1.73 m^2

MDRD (four variable) Study equation for IDMS serum creatinine

GFR¼175.6Scr1.154x Age0.2031.212[black]0.742[female]

ml/min per

1.73 m^2

CKD-EPIa

GFRα¼ 141 min(Scr/k, 1 )αx max(Scr/k,1)1.2090.993Age1.159

[black]1.018[female]

ml/min per

1.73 m^2

Abbreviations:CKD-EPIchronic kidney disease-epidemiology collaboration,Clcrcreatinine
clearance,GFRglomerular filtration rate,IDMSisotope dilution mass spectroscopy,MDRD
modification of diet in renal disease
akis 0.7 for females and 0.9 for males,αis0.329 for females and0.411 for males, min is the

minimum ofScr/kor 1 and max is the maximum ofScr/kor 1, and age is measured in years

(^15) Verbeeck ( 2008 ).
270 D. Vitezic ́et al.