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810 > Dosing in Kidney Disease > Flashcards

Dosing in Kidney Disease Flashcards

1
Q

Why quantify renal function?

A
  • Drug dosing adjustments
  • Preventing toxicity
  • Possible diagnosing of kidney disease
  • Monitors progression of kidney disease
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2
Q

Renal Clearance

A
  • Based on collective excretory processes: glomerular filtration (F), tubular secretion (TS), tubular reabsorption (TR)
  • Renally excreted drugs may go through all of these processes
  • CLr = F + TS - TR
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3
Q

Assessment of Renal Function

A
  • Standard quantitative measure is glomerular filtration rate (GFR)
  • Volume of plasma filtered per unit time
  • Ideal substance to use for GFR stimulation: filtered ONLY, not metabolized/synthesizes by the kidney
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4
Q

Inulin

A
  • “Gold Standard” as a marker

- Plant derived polysaccharide (5200 daltons)

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5
Q

Characteristics of Inulin

A
  1. Distributed ONLY in extracellular fluid
  2. Not bound to plasma proteins
  3. Freely filtered at glomerulus
  4. Not secreted, reabsorbed, or metabolized by the kidney
  5. No nonrenal elimination
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6
Q

Inulin Advantage

A

VERY accurate estimation of GFR

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7
Q

Inulin Disadvantages

A
  1. Requires IV administration
  2. Need to collect several blood/urine samples
  3. Requires reliable assays to measure inulin
  4. Injection is not readily available
  5. Expensive
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8
Q

Creatinine

A
  • Serum creatinine is accepted as an estimate of renal function
  • Widely used in clinical practices
  • End-product of creatine metabolism in muscles
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9
Q

Rate of Creatinine Production

A

-Based on age, sex, and muscle mass:
Male: 20 mg/kg/day
Female: 15 mg/kg/day

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10
Q

Serum Creatinine Concentration Ranges

A

Male: 0.62-1.66 mg/dL
Female: 0.5-1.5 mg/dL

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11
Q

Do creatinine levels increase or decrease as GFR decreases?

A

Increases

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12
Q

Creatinine Properties

A
  1. Small, endogenous molecule (113 Daltons)
  2. Distributed in total body water
  3. Not bound to plasma proteins
  4. Freely filtered at glomerulus
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13
Q

Creatinine Disadvantages

A
  1. ~10-15% undergoes tubular secretion, therefore CrCl overestimates GFR
  2. CrCl is considered an estimate of GFR
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14
Q

Creatinine Clearance Levels in Adults

A

Male: 97 - 140 mL/min (mean = 120)
Female: 85-125 mL/min (mean = 100)

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15
Q

CrCl Equations

A
  1. Crockcroft & Gault
  2. MDRD
  3. 24 Hour Urine Collection
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16
Q

Equations to Estimate Renal Function

A
  • Many different ones
  • Adult and pediatric equations are available (only adult in this lecture)
  • Based on single measurement of creatinine concentration
  • Considers various patient clinical factors
  • Assumes renal function is stable
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17
Q

Cockcroft & Gault

A
  • Commonly used in clinical practice
  • Have to evaluate BW and determine which is approproiate measurement

ClCr = [(140 - age) * BW / (72 * SCr)]
-Multiply by 0.85 if the patient is a female

18
Q

Cockcroft & Gault Weight Considerations

A
  • Use ideal BW if patient isn’t underweight or obese
  • Use TBW if patient is underweight (TBW < IBW)
  • Use ABW if patient is obese (TBW > 1.3 * IBW)
19
Q

IBW Equations

A

Males: [2.3 * every inch over 5’] + 50 kg
Females: [2.3 * every inch over 5’] + 45.5 kg

20
Q

ABW Equation

A

(TBW - IBW) * 0.4 + IBW

21
Q

MDRD Equation Information

A
  • Based on multiple regression analysis of patients enrolled in Mod. of Diet in Renal Disease Study
  • Used to diagnose chronic kidney disease and monitor its progression
  • Can be used to dose adjust medications
  • 4-variable
  • Standardized assay used to measure SCr
  • Places patients in one of 5 stages of CKD
22
Q

MDRD Equation

A

eGFR = 175 * [SCr]^-1.154 * [Age]^-0.203

  • Multiply by 0.742 if female
  • Multiple by 1.212 if African American
23
Q

CKD Stage 1

A
  • Kidney damage with normal or increased GFR

- eGFR = >90 mL/min/1.73 m^2

24
Q

CKD Stage 2

A
  • Kidney damage with mild decrease in GFR

- eGFR = 60-89 mL/min/1.73 m^2

25
Q

CKD Stage 3

A
  • Moderate decrease in GFR

- 30-59 mL/min/1.73 m^2

26
Q

CKD Stage 4

A
  • Severe decrease in GFR

- 15-29 mL/min/1.73 m^2

27
Q

CKD Stage 5

A

-Kidney Failure

<15 mL/min/1.73 m^2

28
Q

24-Hour Urine Collection

A
  • Collected over 24 hours
  • SCr = ideally measured at midpoint in collection
ClCr = U * V / P * T
U = urinary creatinine concentration (mg/dL)
V = volume of urine collected over 24 hours period
P = SCr (mg/dL)
T = time in minutes
29
Q

Is it appropriate to use SCr from different appointment?

A

No, preferably take it at midpoint of collection. If that’s not possible then take it as close to collection time as possible.

30
Q

When is 24-hour ClCr used??

A
  • In the elderly and in those with extreme sizes

- Any time where the standard equation will not work properly

31
Q

Assessment of Renal Function in Practice

A
  • Different tools available to calculate ClCr
  • Patients disease and drug factors should be considered when interprettying ClCr using SCr
  • Validity of ClCr in special popoulations needs to be part of clinical decision making process
32
Q

Clearance

A
  • Measures drug elimination from body with mechanism specified
  • Volume drug cleared/unit time
  • CLt = CLr + CLnr
  • CL = VK
33
Q

fe = 1

A
  • Problem in those with kidney problems
  • Graph should pass through origin
  • Dettli plots: relationship between renal function as determined by CrCl and drug clearance
34
Q

fe = 0

A
  • CrCl not affected by drug since it is completely metabolized by the liver
  • Don’t need to adjust doses in those with renal disease
35
Q

0 < fe < 1

A
  • The y-intercept is knr (nonrenal elimination rate constant)
  • If fe is 0.3 or more, need to consider adjusting doses in those with renal failure
36
Q

Css,avg

A

F * Dose / (V * kel * Tau)

-Used to adjust renal doses

37
Q

Can drug accumulation occur in those with decreased renal function?

A

Yes

38
Q

Approaches to Adjust Maintenance Dose

A
  1. Lower dose, keep same dosing interval
  2. Keep dose, increase dosing interval
  3. Lower dose and increase dosing interval

**Approach used depends on goal of therapy

39
Q

Dose Reduction Advantages and Disadvantages

A

Advantage: Less fluctuations
Disadvantage: Reduced, ideal dose may not be a commercially available strength, low peak concentrations and high troughs

40
Q

Extended Dose Interval Advantages and Disadvantages

A

Advantage: Any SE or pharmacologics related to peaks and troughs (antibiotics), don’t have to give dose as often
Disadvantages: huge fluctuations, inconvenient dosing intervals

810 (22 decks)

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