Dosing in Kidney Disease Flashcards
Why quantify renal function?
- Drug dosing adjustments
- Preventing toxicity
- Possible diagnosing of kidney disease
- Monitors progression of kidney disease
Renal Clearance
- 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
Assessment of Renal Function
- 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
Inulin
- “Gold Standard” as a marker
- Plant derived polysaccharide (5200 daltons)
Characteristics of Inulin
- Distributed ONLY in extracellular fluid
- Not bound to plasma proteins
- Freely filtered at glomerulus
- Not secreted, reabsorbed, or metabolized by the kidney
- No nonrenal elimination
Inulin Advantage
VERY accurate estimation of GFR
Inulin Disadvantages
- Requires IV administration
- Need to collect several blood/urine samples
- Requires reliable assays to measure inulin
- Injection is not readily available
- Expensive
Creatinine
- Serum creatinine is accepted as an estimate of renal function
- Widely used in clinical practices
- End-product of creatine metabolism in muscles
Rate of Creatinine Production
-Based on age, sex, and muscle mass:
Male: 20 mg/kg/day
Female: 15 mg/kg/day
Serum Creatinine Concentration Ranges
Male: 0.62-1.66 mg/dL
Female: 0.5-1.5 mg/dL
Do creatinine levels increase or decrease as GFR decreases?
Increases
Creatinine Properties
- Small, endogenous molecule (113 Daltons)
- Distributed in total body water
- Not bound to plasma proteins
- Freely filtered at glomerulus
Creatinine Disadvantages
- ~10-15% undergoes tubular secretion, therefore CrCl overestimates GFR
- CrCl is considered an estimate of GFR
Creatinine Clearance Levels in Adults
Male: 97 - 140 mL/min (mean = 120)
Female: 85-125 mL/min (mean = 100)
CrCl Equations
- Crockcroft & Gault
- MDRD
- 24 Hour Urine Collection
Equations to Estimate Renal Function
- 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
Cockcroft & Gault
- 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
Cockcroft & Gault Weight Considerations
- 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)
IBW Equations
Males: [2.3 * every inch over 5’] + 50 kg
Females: [2.3 * every inch over 5’] + 45.5 kg
ABW Equation
(TBW - IBW) * 0.4 + IBW
MDRD Equation Information
- 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
MDRD Equation
eGFR = 175 * [SCr]^-1.154 * [Age]^-0.203
- Multiply by 0.742 if female
- Multiple by 1.212 if African American
CKD Stage 1
- Kidney damage with normal or increased GFR
- eGFR = >90 mL/min/1.73 m^2
CKD Stage 2
- Kidney damage with mild decrease in GFR
- eGFR = 60-89 mL/min/1.73 m^2
CKD Stage 3
- Moderate decrease in GFR
- 30-59 mL/min/1.73 m^2
CKD Stage 4
- Severe decrease in GFR
- 15-29 mL/min/1.73 m^2
CKD Stage 5
-Kidney Failure
<15 mL/min/1.73 m^2
24-Hour Urine Collection
- 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
Is it appropriate to use SCr from different appointment?
No, preferably take it at midpoint of collection. If that’s not possible then take it as close to collection time as possible.
When is 24-hour ClCr used??
- In the elderly and in those with extreme sizes
- Any time where the standard equation will not work properly
Assessment of Renal Function in Practice
- 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
Clearance
- Measures drug elimination from body with mechanism specified
- Volume drug cleared/unit time
- CLt = CLr + CLnr
- CL = VK
fe = 1
- Problem in those with kidney problems
- Graph should pass through origin
- Dettli plots: relationship between renal function as determined by CrCl and drug clearance
fe = 0
- CrCl not affected by drug since it is completely metabolized by the liver
- Don’t need to adjust doses in those with renal disease
0 < fe < 1
- 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
Css,avg
F * Dose / (V * kel * Tau)
-Used to adjust renal doses
Can drug accumulation occur in those with decreased renal function?
Yes
Approaches to Adjust Maintenance Dose
- Lower dose, keep same dosing interval
- Keep dose, increase dosing interval
- Lower dose and increase dosing interval
**Approach used depends on goal of therapy
Dose Reduction Advantages and Disadvantages
Advantage: Less fluctuations
Disadvantage: Reduced, ideal dose may not be a commercially available strength, low peak concentrations and high troughs
Extended Dose Interval Advantages and Disadvantages
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
