Dosing adjustment

in

Renal Failure

“Practical approach”

Kareem El-Fass PharmD,Bpharm

Head of Nephrology Clinical Pharmacy Department

Kidney and Urology Centre (KUC)

Estimation &/or Measurement of GFR

Exogenous Filtration Markers

Inulin, iothalamate,

DTPA, iohexol

Endogenous Filtration Markers

Creatinine Cystatin

How is Cr eliminated ?

GlomerularFiltration

Tubular Secretion

10-20 %

in Normal

40-50 %

in diseased

states

How is S.Cr performing for Kidney

function assessment ??

Is a patient with s.cr =1.2 mg/dl is

essentially free of renal insult ???

How is Cr performing for Kidney

function ??

1. Nephrotic syndrome

2. Sickle cell anemia Tubular secretion of

Cr

Decrease Cr secretion

Lupus Nephritis

3. Lupus Nephritis

How is Cr performing ??

How is Cr performing ??

How is Cr performing for Kidney

function ??

Is a patient with s.cr =1.2 mg/dl is

essentially free of renal insult ???

S.Cr =1.1 mg/dlGFR =120

ml/min

S.Cr = 1.2 mg/dl GFR =60

ml/min

How is Cr performing for Kidney

function ??

How is Cr measured ?

1. Jaffe Method (Alkaline Picrate)

2. Isotope Dilution Mass Spectroscopy (IDMS)

(SCr [IDMS] = 0.95 x SCr [Jaffe]).

Crcl Vs GFR e

e-GFR for CKD Classification

eGFR GFR estimated by equations incorporating tubular secretion

such as

1.MDRD

eGFR GFR estimated by equations incorporating tubular secretion

such as 2. CKD-

EPIKDIG

O 2012

eGFR

1. When measured GFRs >60 where they

underestimate

2. When measured GFR <60 as they overestimate.

Now ……

what equation shall we use

for dosing ???

Cockcroft-Gault

ml/min

Actual

BW Jaffe

only

FDA

Stable

only

NKF Recommendations

1. Use of either CG or MDRD for dose adjustments

yields little difference .

2. When MDRD is used it should be normalized

ASHP 2010 Recommendations

1. Calculate CrCl using Cockcroft-Gault equation

2. Identify suggested dosage adjustment

3. Determine if the dosage adjustment is logical and

appropriate for your patient

What to do for ??

1. Unstable creatinine (AKI)

What to do for ??

2. Different weights

Pharmacotherapy 2012

What to do for ??

2. Different weights

Weight category Equation to use

Underweight BMI of 18.5 kg/m2 Actual Body weight

Normal weight BMI of 18.5–24.9

kg/m2

IBW

Obese and Overweight BMI of 25 -

40 kg/m2

Adjusted Body weight 0.4

Morbidly obese MBI 40 kg/m2 or

higher

Lean body weight

What to do for ??

2. Different weights

What to do for ??

2. Different weights

http://www.pharmacologyweekly.com/app/medical-calculators/body-mass-index-bmi-weight-bsa-calculator

Where to go for CrCl and e-GFR Calculation ?

• http://www.globalrph.com/multiple_crcl_2012.cgi

How to get recommendations for dosing

• Check Many references

Allopurinol

How to get recommendations for dosing

• Check Many references

Allopurinol

How to get recommendations for dosing

• Check Many references

Allopurinol

Take-Home Messages

1. Keep Cr limitations in your sight

2. Take care of equation you use and its limitation

3. Use appropriate body weight and s.cr

4. Check different resources

5. Clinical consequences follow-up