Renal Clearance Flashcards
What are the components of renal clearance/ the kidney
- Filtration
- Secretion and active reabsorption
- Passive reabsorption
ƒe; fraction eliminated unchanged
Discuss renal blood flow and GFR
GFR: Glomerular Filtration Rate
- GFR: Glomerular Filtration Rate
- 20-25% of cardiac output (1100 mL/min)
- 10% is filtered at the glomerulus
- Hence, normal GFR ≈ 110-120 mL/min
> GFR ≈ 60-90 mL/min (from CLCr)
> Moderate renal impt GFR ≈ 30-60 mL/min
> Severe renal impt GFR < 30 mL/min
Discuss renal filtration
- Molecules with MW < 2,000 are filtered
- Lower filtration if MW > 20,000
- Negligible filtration of albumin, haemoglobin and α1 acid glycoprotein (orosomucoid)
- Drug bound to plasma proteins is not filtered
- CLFiltration = fu × GFR
- By definition, CLFiltration ≤ 120 mL/min
- If CL renal > 120 mL / min, secretion must occur
Discuss tubular secretion
- Anionic transporters: Penicillins, cephalosporins, quinolones, NSAIDs and thiazides
- Cationic transporters: Digoxin, quinine, vancomycin, cimetidine and ranitidine
- Probenecid inhibits secretion of penicillins
Discuss reabsorption
- Polarity and degree of ionisation of drug are important factors
- Weak acids (pKa < 7.0) - moderate reabsorption at urinary pH of 5.0-6.0, due to a high proportion of unionised molecules.
- Alkalinization ↑ excretion of weak acids
- Acidification ↑ excretion of weak bases
Discuss formulas for renal clearance
CL total = Cl renal + CL non-renal
What is creatinine clearance?
CLCr provides an estimate of GFR
Creatinine
- Produced endogenously (muscle metabolism)
- Affected by age, muscle mass, level of physical activity and acute muscle damage
- Mostly filtered, minimal secretion (» 10-15%)
Serum creatinine (Scr)
- relatively convenient and inexpesnive
What is the Cockcroft and gault equation?
- Reliable estimate of CLCr and ∴ GFR
- SCr must be at steady-state
- Good estimate of GFR at 15-98 mL/min
- Altered tubular secretion at low GFR ∴ greater variability expected at low estimates of CLCr
How to measure creatinine clearance for obese patients?
- Use ideal body weight
- Defined from the body mass index
- Normal (acceptable) BMI is 20-25 kg/m^2
BMI = Wt/Ht^2
What are some GFR estimations
MDRD equation (eGFR)
- ‘Modified Diet in Renal Disease’ study
- Uses age, gender and SCr of patient
- ∴ Not adjusted for size
- eGFR is mL/min/1.73m2
> eGFR not recommended in children or pregnancy
CKD-EPI equation to calculate eGFR
What are some recommendations when it comes to creatine clearance?
APF 24 recommendation
- “CLCr (C-G equation) is considered to approximate GFR in stable renal function; C-G equation is used for dose adjustment of renally excreted drugs”
- Renal function equations are not interchangeable
Australasian creatinine consensus guidelines
- eGFR (CKD-EPI) and CLCr (C-G equation) provide an estimate of renal drug clearance … if using eGFR, adjust for body size (BSA)
At Curtin: Cockcroft & Gault equation will be used for estimation of CLCr and renal (drug dose) calculations
What are some limitations of Scr as GFR marker
Serum creatinine
- Non-renal influences
> Gender, Ethnicity, Recent dietary intake, Drugs (blocking tubular secretion), Muscle mass (amputees), Extrarenal clearance
- Clinical utility
> poor sensitivity for CKD, Not useful in acute kidney injury
- Analytical problems
> Non-specificity (endogenous compounds)
What are some clinical situations in which an estimated renal function might be unreliable or misleading?
- Acute changes in kidney function
- Dietary intake (vegetarian, high-protein)
- Extremes of body size
- Disease of skeletal muscle
- Amputees
- Severe liver disease
- Pregnancy
- Frail older people
- Children <18 years
