This document discusses approaches to dosing adjustment in renal failure. It outlines methods for estimating glomerular filtration rate (GFR) and limitations of using serum creatinine to assess kidney function. Specifically, it addresses how creatinine is eliminated and factors like tubular secretion that can influence creatinine levels. The document also compares creatinine clearance and estimated GFR, discussing equations like Cockcroft-Gault and MDRD. It provides recommendations on which equation to use based on a patient's weight and stability of creatinine levels. Resources for calculating creatinine clearance and estimated GFR are also presented.

1. Dosing adjustment
in
Renal Failure
“Practical approach”
Kareem El-Fass PharmD,Bpharm
Head of Nephrology Clinical Pharmacy Department
Kidney and Urology Centre (KUC)

2. Estimation &/or Measurement of GFR
Exogenous
Filtration Markers
Inulin, iothalamate,
DTPA, iohexol
Endogenous
Filtration Markers
Creatinine Cystatin

3. How is Cr eliminated ?
Glomerular
Filtration
Tubular
Secretion
10-20 %
in Normal
40-50 %
in diseased
states

4. 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 ???

5. 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

6. How is Cr performing ??

7. How is Cr performing ??

8. 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/dl
GFR =120
ml/min
GFR =60 S.Cr = 1.2 mg/dl
ml/min

9. How is Cr performing for Kidney
function ??

10. How is Cr measured ?
1. Jaffe Method (Alkaline Picrate)
2. Isotope Dilution Mass Spectroscopy (IDMS)
(SCr [IDMS] = 0.95 x SCr [Jaffe]).

11. Crcl Vs eGFR

12. e-GFR for CKD Classification

13. eGFR
 GFR estimated by equations incorporating tubular secretion
such as
1.MDRD

14. eGFR
 GFR estimated by equations incorporating tubular secretion
such as 2. CKD-EPI
KDIG
O 2012

15. eGFR
1. When measured GFRs >60 where they
underestimate
2. When measured GFR <60 as they overestimate.

16. Now ……
what equation shall we use
for dosing ???

17. Cockcroft-Gault
ml/min
FDA
Actual
Stable
only
Jaffe BW
only

18. NKF Recommendations
1. Use of either CG or MDRD for dose adjustments
yields little difference .
2. When MDRD is used it should be normalized

19. 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

20. What to do for ??
1. Unstable creatinine (AKI)

21. What to do for ??
2. Different weights
Pharmacotherapy 2012

22. 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

23. What to do for ??
2. Different weights

24. What to do for ??
2. Different weights
http://www.pharmacologyweekly.com/app/medical-calculators/body-mass-index-bmi-weight-
bsa-calculator

25. Where to go for CrCl and e-GFR Calculation ?
• http://www.globalrph.com/multiple_crcl_2012.cgi

26. How to get recommendations for dosing
• Check Many references
Allopurinol

27. How to get recommendations for dosing
• Check Many references
Allopurinol

28. How to get recommendations for dosing
• Check Many references
Allopurinol

29. 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