21. • Step 1: Obtain the following information
• Age
• Height
• Current weight
• Most recent SCr
• Step 2: Calculate Ideal Body Weight (IBW)
• Male: 50 + (2.3 X inches over 60 inches in
height)
• Female: 45.5 + (2.3 X inches over 60 inches in
height)
Creatine Clearance
22. • Step 3: Determine dosing weight
• Use total body weight to calculate CrCl if TBW<
IBW
• Use adjusted body weight for obese patients
• TBW > 1.3 times IBW
• AdjBW: IBW + 0.4 (TBW – IBW)
• Step 4: Calculate estimated Creatine
Clearance
• Male: [(140-age) X IBW] / (72 X SCr)
• Female: [(140-age) X IBW] / (72 X SCr) X 0.85
Creatine Clearance
23. • A 57 year old African American female with a
PMH of CKD, HTN, and DM is admitted to
ICU for IV antibiotics to treat an infected ulcer
on her right foot. Dr. Johnson has ordered
Ceftazidime 1 g every 12 hours and
vancomycin 1 g every 12 hours.
• SCr: 2.51 mg/dL
• Height: 65 inches
• Weight: 68 kg
Creatine Clearance Example
24. • Step 1: Obtain the following information
• Age: 57
• Height: 65 inches
• Actual current weight: 68 kg
• Most recent SCr: 2.51 mg/dL
• Step 2: Calculate Ideal Body Weight (IBW)
• Male: 50 + (2.3 X inches over 60 inches in
height)
• Female: 45.5 + (2.3 X inches over 60 inches in
height)
• IBW = 45.5 + (2.3 X 5) = 57 kg
Creatine Clearance Example
25. • Step 3: Determine dosing weight
• Use total body weight to calculate CrCl if TBW< IBW
• 68 kg /57 kg = 1.19
• Use adjusted body weight for obese patients
• TBW > 1.3 times IBW
• AdjBW: IBW +0.4 (TBW – IBW)
• Step 4: Calculate estimated Creatine Clearance
• Male: [(140-age) X IBW] / (72 X SCr)
• Female: [(140-age) X IBW] / (72 X SCr) X 0.85
• CrCl = [140-57) X 57 kg]/(72 X 2.51 mg/dL) X 0.85 =
26.55 mL/min
Creatine Clearance Example
26. • Ceftazidime renal dosing
• CrCl 31-50 mL/min: 1-2 g every 12 hours
• CrCl 10-30 mL/min: 1-2 g every 24 hours
• CrCl < 10 mL/min: 1-2 g every 48 hours
• Based on the above information and her CrCl
of 26.55 mL/min, did the doctor prescribe the
correct dose of ceftazidime (1 g every 12
hours)?
Creatine Clearance Example
27. • Most drug dosing recommendations are
based on CrCl
• There are many equations to calculate CrCl
• Cockcroft-Gault (adults)
• Schwartz Equation (children)
Using CrCl
28. • Limitations:
• CrCl is just an estimate (“eCrCl”)
• Creatinine levels dependent on many factors
• Age
• Sex
• Muscle mass
• Diet
• Renal creatinine secretion (overestimation of kidney function)
• Fluctuating renal function (e.g. ICU)
• Multiple equations
• Lack of standardization among manufacturers (FDA
labeling and institution-specific implementation)
Using CrCl
29. • Step 1: Obtain the following information
• Age
• Sex
• Ethnicity
• Most recent SCr
• Step 2: Calculate eGFR
• GFR (mL/min/1.73 m2) = 175 × (Scr)-1.154 ×
(Age)-0.203 × (0.742 if female) × (1.212 if African
American)
Estimated Glomerular
Filtration Rate (eGFR)
30. • A 57 year old African American female with a
PMH of CKD, HTN, and DM is admitted to
ICU for IV antibiotics to treat an infected ulcer
on her right foot. Dr. Johnson has ordered
Ceftazidime 1 g every 12 hours and
vancomycin 1 g every 12 hours.
• SCr: 2.51 mg/dL
• Weight: 68 kg
• Height: 65 inches
eGFR example
31. • Step 1: Obtain the following information
• Age: 57
• Sex: Female
• Ethnicity: African American
• Most recent SCr: 2.51 mg/dL
• Step 2: Calculate eGFR
• GFR (mL/min/1.73 m2) = 175 × (Scr)-1.154 × (Age)-0.203
× (0.742 if female) × (1.212 if African American)
• = 175 × (2.51)-1.154 × (57)-0.203 × (0.742 if female) ×
(1.212 if African American)= 25 mL/min/1.73m2
eGFR Example
32. • Some drug dosing recommendations are based
on eGFR
• Basis for chronic kidney disease staging
• Multiple equations:
• Modification of Diet in Renal Disease (MDRD)
• Chronic Kidney Disease Epidemiology Collaboration
(CKD-EPI)
• Limitations:
• Less accurate in very large/small patients
• Multiply eGFR by BSA
Using eGFR
34. What is Chronic Kidney
Disease?
• Presence of kidney damage or a reduction in
glomerular filtration rate for three months or
longer
• As CKD progresses, wastes can build to high
levels in your blood.
• Complications: high blood pressure, anemia,
weak bones, poor nutritional health and nerve
damage
35. CKD staging
GFR category GFR (mL/min/1.73m2) Terms
G1 ≥90 Normal to high
G2 60-89 Mild decreased
G3a 45-59 Mild to moderate
decrease
G3b 30-44 Moderate to severe
decrease
G4 15-29 Severe decrease
G5 <15 Kidney failure
37. What is AKI?
• Abrupt loss of kidney function
• Accumulation of urea and nitrogenous waste
• Inability to effectively regulate fluid and electrolytes
• ICU patients considered high-risk for AKI
• Occurs in up to ⅔ ICU patients
• Consequences:
• Prolonged hospital stay
• Hospital-related adverse events
• Development of CKD
• Acute/chronic renal replacement therapy
42. Tubular epithelial cell damage
Acute tubular necrosis **Most common in inpatient setting**
- Aminoglycoside antibiotics
- Radiographic contrast media
- Cisplatin, carboplatin
- Amphotericin B
- Cyclosporine, tacrolimus
- Adefovir, cidofovir, tenofovir
- Pentamidine
- Foscarnet
- Zoledronate
Osmotic nephrosis
- Mannitol
- Dextran
- Radiocontrast media
- IV immunoglobulin
- Drug vehicles (e.g. sucrose, polyethylene glycol)
Drug-Induced Nephrotoxicity
43. Aminiglycoside nephrotoxicity
• Gentamycin, tobramycin, streptomycin, amikacin
• 10-25% of patients treated with aminoglycoside
• Critically ill: up to 58%
• Accumulation of drug in proximal tubular epithelial
cells reactive oxygen species cell apoptosis
and proximal tubular necrosis
Drug-Induced Nephrotoxicity
44. Dose adjustment example:
• Gentamycin:
• Traditional dosing – increase dosing interval:
• Initial dose given every [SCr x 8] hours
• Traditional dosing – decrease dose:
• Give usual initial dose, then reduce dose: [initial dose/SCr]
and give every 8 hours
• Once-daily dosing:
• Give usual mg/kg dose and adjust initial interval based on
CrCl (i.e. CrCl > 60 mL/min: every 24 h; CrCl 40-60
mL/min: every 36 h; CrCl 20-40 mL/min: every 48 h)
Drug-Induced Nephrotoxicity
46. References
• Santiago C, et. al. Renal Dopamine Receptors, Oxidative Stress, and Hypertension. International Journal of Molecular
Science. 2013 Sep: 14(9): 17553-17572
• Schmitz JM, et. al. Renal alpha-1 and alpha-2 adrenergic receptors: biochemical and pharmacological correlations. J
Pharmacol Exp Ther. 1981 Nov;219(2):400-6.
• Chunling Li, et. al. Molecular Mechanisms of Antidiuretic Effect on Oxytocin. Journal of the American Society Nephrology.
2008 Feb; 19(2):225-232
• Micromedex. Truven Health Analytics Inc. (online) Available at
<http://www.micromedexsolutions.com.acphs.idm.oclc.org/micromedex2/librarian/ND_T/evidencexpert/ND_PR/evidencexpert/
CS/613E30/ND_AppProduct/evidencexpert/DUPLICATIONSHIELDSYNC/2F559D/ND_PG/evidencexpert/ND_B/evidencexpe
rt/ND_P/evidencexpert/PFActionId/pf.HomePage?navitem=Logo#> (accessed 16 Sep 2015)
• CKD and Drug Dosing: Information for Providers. National Kidney Disease Education Program. Revised Apr 2015. Available
online at: www.nkdep.nih.gov
• Perazella MA. Drug use and nephrotoxicity in the intensive care unit. Kidney International (2012) 81, 1172-1178; doi:
10.1038/ki.2010.475
• DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM: Pharmacotherapy: A Pathophysiologic Approach, Ninth
Edition: www.accesspharmacy.com
• KDIGO clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int Suppl. 2012
Dec;2(5):337-414.
47.
48.
49.
50.
51.
52.
53. Radiographic contrast media-induced nephrotoxicity
(CIN)
• 3rd leading cause of hospital-acquired AKI
• <2% in patients with normal renal function
• Up to 50% in patients with CKD or diabetes
• Systemic hypotension (i.e. renal hypoperfusion) +
acute vasoconstriction increased contrast
media remaining in tubules cytotoxicity
Drug-Induced Nephrotoxicity
54. Prevention of radiographic CIN:
• Minimize contrast dose
• Use non-iodinated and low-/iso-osmolar contrast
media
• Hydration! – before, during and after
• Avoid other nephrotoxic drugs
Drug-Induced Nephrotoxicity
Santiago C, et. al. Renal Dopamine Receptors, Oxidative Stress, and Hypertension. International Journal of Molecular Science. 2013 Sep: 14(9): 17553-17572
Schmitz JM, et. al. Renal alpha-1 and alpha-2 adrenergic receptors: biochemical and pharmacological correlations. J Pharmacol Exp Ther. 1981 Nov;219(2):400-6.
Dopamine antagonists – ex: metoclopromide, atypical antipsychotics
Alpha-1 agonists – block NE-mediated vasoconstriction
NTG - increases guanosine 3'5' monophosphate (cyclic GMP) in smooth muscle and other tissues by stimulating guanylate cyclase through formation of free radical nitric oxide. This activity results in dephosphorylation of the light chain of myosin, which improves the contractile state in smooth muscle , and subsequent vasodilation (veins and arteries)
Sodium nitroprusside – dilates peripheral arteries and veins (more so veins)
Isosorbide - arteries and veins
Micromedex: Carbonic anhydrase is an enzyme responsible for forming hydrogen and bicarbonate ions from carbon dioxide and water. By inhibiting this enzyme, methazolimide reduces the availability of these ions for active transport. Hydrogen ion concentrations in the renal tubule lumen are reduced by methazolamide, leading to alkaline urine and an increased excretion of bicarbonate, sodium, potassium, and water. A reduction in the plasma bicarbonate results in metabolic acidosis, which rapidly reverses the diuretic effect…”
Chunling Li, et. al. Molecular Mechanisms of Antidiuretic Effect on Oxytocin. Journal of the American Society Nephrology. 2008 Feb; 19(2):225-232
CKD and Drug Dosing: Information for Providers. National Kidney Disease Education Program. Revised Apr 2015. Available online at: www.nkdep.nih.gov
CKD and Drug Dosing: Information for Providers. National Kidney Disease Education Program. Revised Apr 2015. Available online at: www.nkdep.nih.gov
CKD and Drug Dosing: Information for Providers. National Kidney Disease Education Program. Revised Apr 2015. Available online at: www.nkdep.nih.gov
“Kidney function is proportional to kidney size, which is proportional to BSA” – 1.73 m^2 is the traditional average BSA…. Not so anymore (more like 1.84??)
Can use exogenous filtration markers to measure actual GFR and CrCl for narrow therapeutic indicies, or very large/small patients
