Beyond Calculations: Medication Management in Renal Insufficiency

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Beyond Calculations Medication Management in
Renal Insufficiency

• Richard A Marasco, Pharm, FASCP, CGP, HRM

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Learning Objectives

• Describe the Kidney Disease Outcomes Quality
  Initiative (KDOQI) guidelines
• Explain how the KDOQI guidelines impact upon
  geriatric patient care
• List and explain the appropriate utilization of
  formulas used to assess renal function
• Describe medication selection and dosing for
  patients with renal insufficiency
• Discuss therapeutic dilemmas impacting patients
  with renal insufficiency

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Kidney Disease OutcomesQuality Initiative (KDOQI)

• Provides evidence based clinical practice
  guidelines for all stages of chronic kidney
  disease and related complications
• KDOQI expands the Dialysis Outcomes Quality
  Initiative or DOQI, a project begun by the
  National Kidney Foundation in 1997
• There are 11 current sets of KDOQI guidelines

http//www.kidney.org/
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KDOQI Guidelines

• Hemodialysis Adequacy
• Peritoneal Dialysis
• Vascular Access
• Anemia Management
• Nutrition
• Chronic Kidney Disease Evaluation,
  Classification, and Stratification
• Dyslipidemia
• Bone Metabolism and Disease in Chronic Kidney
  Disease
• Bone Metabolism and Disease in Chronic Kidney
  Disease in Children
• Hypertension and Antihypertensive Agents in
  Chronic Kidney Disease
• Cardiovascular Disease in Dialysis Patients

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Kidney Functions

• Removes waste products toxins
• Maintains fluid and electrolyte balance
• Total body water and fluid distribution
• Sodium, Potassium, and Chloride
• Maintains normal mineral balance
• Calcium, Phosphorus, and Magnesium
• Regulates acid/base balance
• Maintains blood pH in the normal range of
  7.36-7.44
• Regulates blood pressure
• Response to the Renin-Angiotensin Aldosterone
  system (RAAS)
• Adjusts final concentration of urine
• Stimulates the production of red blood cells
• Erythropoetin production
• Activates Vitamin D (Calcitriol, 1,25(OH)2D3)
• Final step in activation process
• Response to parathyroid hormone

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Risk Factors for theProgression of Renal Disease
Huether SE, Pathophysiology,4th Edition, 2002,
Chapter 35, 1191-1216
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Effects of Aging on the Kidney

• ? kidney size
• ? renal blood flow
• ? number of functioning nephrons
• ? renal tubular secretion

Result Lower glomerular filtration rate (GFR)
Geriatrics Review Syllabus, 5th ed. Geriatrics At
Your Fingertips, 2003 ed.
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Chronic Kidney Disease (CKD)
NKF-K/DOQI. Clinical practice guidelines for
chronic kidney disease evaluation,
classification, and stratification. Am J Kidney
Dis. 200239 (suppl 1)S1-S266.
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Considerations by CKD Stage
CVD/CKD risk factor assessment early
intervention
Assessment intervention of CKD complications
Renal Failure
Renal Insufficiency
Stage 5
Stage 4
Stage 3
Stage 2
Stage 1
gt 90
90-60
60-30
30-15
?15 ESRD
GFR (mL/min/1.73 m2)
Modified from Macdougall LC. Nephrol Dial
Transplant. 200015(Suppl 3)3-7. Coresh et al.
Am J Kidney Dis 2003 Jan41(1)1-12
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Presence of CKD

• Should be established based on
• Presence of kidney damage for ?3 months
• pathological abnormalities
• markers of kidney damage (eg, proteinuria)
• Level of kidney function (glomerular filtration
  rate - GFR)
• Estimate GFR
• Serum creatinine is not sufficiently accurate on
  which to base decisions
• Use equations to estimate
• Cockcroft-Gault MDRD or others

CKD chronic kidney disease GFR glomerular
filtration rate.
NKF-K/DOQI. Clinical practice guidelines for
chronic kidney disease evaluation,
classification, and stratification. Am J Kidney
Dis. 200239 (suppl 1)S1-S266.
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Specific Interventions for Complications of CKD
A1C glycosylated hemoglobin HPT
hyperparathyroidism PTH parathyroid hormone
LDL-C low-density lipoprotein cholesterol TG
triglycerides HDL-C high-density lipoprotein
cholesterol Hgb hemoglobin.
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Treatment of Co-Morbid Conditions

• Diabetic medications oral hypoglycemics/insulin
• Antihypertensives
• Anemia Medications
• Epoetin alfa (Procrit), Darbepoetin (Aranesp)
• Oral or IV iron
• Phosphate Binders
• (PhosLo), Sevelamer (Renagel), Others
• SHPT therapy IV or oral
• IV Paricalcitol (Zemplar), Doxercalciferol
  (Hectorol)
• Oral Paricalcitol (Zemplar), Calcitriol
  (Rocaltrol), Doxercalciferol (Hectorol),
  Cinacalcet (Sensipar)
• Lipid-lowering medications
• GI medications / stool softeners
• Renal vitamins
• Disease specific medications

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Average Creatinine Clearanceof Nursing Home
Residents
Creatinine Clearance (cc/min)
N 190
Kazarian, Marasco The Association of Medication
Utilization with Anemia in LTC, Poster
presentation at the FMDA/FL-ASCP 2004 Annual
Meeting
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Calculating Creatinine Clearance
Cockcroft-Gault Equation CrCl men (140 - Age)
x LBW Scr x 72 CrCl women CrCl men x 0.85
Modification of Diet in Renal Disease Equation
(MDRD) CrCl men (Scr) -1.154 x (age)
-0.203 CrCl women CrCl men x 0.742 CrCl
African American CrCl men x 1.210
Other Formulas Include (but are not limited
to) Jelliffe Method Schwartz Formula
(children) Wright Formula Counahan-Barratt
Equation (children)
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Calculating Creatinine Clearance
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Web Creatinine Clearance Calculators

• Cockcroft-Gault Formulas
• http//www.intmed.mcw.edu/clincalc/creatinine.html
  
• http//www.globalrph.com/crcl.htm
• MDRD Formulas
• http//nephron.com/cgi-bin/MDRD_GFR.cgi
• http//www.sydpath.stvincents.com.au/other/CalcsMD
  RDeGFR.htm

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Example Creatinine Clearance
For a white female, serum creatinine 1.2 gm/dl,
weight 125 lbs
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Kidney Function is Criticalfor Drug Elimination

• Aging and some common geriatric disorders may
  impair kidney function
• Many drugs are eliminated via the kidney
• This may be after metabolism in the liver to
  inactive compounds, as the active compound, etc.
• There is a linear reduction in renal function
  with aging in most patients
• This leads to drug accumulation and toxicity if
  not monitored and acted on, especially in drugs
  that are excreted in active form (ie digoxin,
  lithium, aminoglycosides, vancomycin etc.)

Geriatrics Review Syllabus, 5th ed. Geriatrics At
Your Fingertips, 2003 ed.
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Cockcroft-Gault vs MDRD

• Drug dosing in renal disease (i.e. package insert
  guidelines) are based on estimated creatinine
  clearance using the Cockcroft-Gault equation
• MDRD equation gives an estimate of GFRand is
  intended for staging CKD patients and is NOT to
  be used for drug dosing until further studies are
  conducted

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Drug Dosing in Renal Insufficiency
A Drugs Amantadine Amikacin Cefazolin Cephalexin
B Drugs Amoxicillin Cefamandole Moxalactam Ticarci
llin
C Drugs Cephapirin
D Drugs Azlocillin Cefotaxime Piperacillin
E Drugs SMZ/TMP Dicloxacillin
F Drugs Cloxacillin Sulfoxazole
G Drugs Cefoperazone Minocycline
H Drugs Doxycycline Ketoconazole
Adapted fromClinical Nephrology 781, 1977
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Drug Dosing in Renal Insufficiency

• Antibiotics
• Aminoglycosides
• Quinolones
• Tetracyclines
• Penicillins
• Cephalosporins
• Others
• ACE Inhibitors
• Initiate with lower doses for some
• Narcotics
• Channel Calcium Blockers
• No dose reduction but use with caution with some
• Anti-Cholesterol Medications
• Use lower initial doses
• H-2 Antagonists

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Questions?