4 Clinical Evaluation of Renal Function Flashcards
1
Q
Kidney
- Roles of the kidney
- Most important parameter in assessing kidney function & kidney disease progression
A
- Roles of the kidney
- Maintain homeostasis & a constant extracellular environment
- Excrete metabolic waste
- Reabsorb & secrete in tubules
- Concentrate, dilute, & acidify urine
- Secrete hormones
- Maintain homeostasis & a constant extracellular environment
- Most important parameter in assessing kidney function & kidney disease progression
- Glomerular filtration rate (GFR): renal ecretory capacity
2
Q
GFR
- General
- Most common methods to estimate GFR
- Other markers of kidney function
A
- General
- Most important parameter in clinically evalutating kidney funciton
- Overall index of kidney function
- = sum of filtration rates in all functioning nephrons
- Measure of excretory function
- Used w/ H&P, urinalysis, imaging, & biopsy to evaluate disease etiology
- Most common methods to estimate GFR
- Serum creatinine & estimation equations
- Most common
- Rely upon creatinine
- Creatinine clearance
- Serum creatinine & estimation equations
- Other markers of kidney function
- Blood urea nitrogen (BUN)
- Serum cystatin C (only in reserach)
3
Q
Normal GFR
- How much plasma glomeruli filter
- GFR depends on…
- Normal GFR value
- GFR vs. age
- GFR is corrected for…
- Significance of decreased GFR
A
- Glomeruli filter ~125 ml/min of plasma
- GFR depends on age, sex, & body size
- Normal GFR = 130 ml/min in men & 120 ml/min in women
- GFR declines ~1% per year above 40yo
- GFR is corrected for body surface area (important in children)
- Significance of decreased GFR
- Acute or chronic kidney disease
- Level of GFR assesses disease severity
- Not an exact correlation b/c kidney adapts to nephron loss by compensatory hyperfiltration in remaining normal nephrons
4
Q
Assessing GFR
- Measured directly vs. estimated
- Clearance
- Amt of plasma filtered by glomeruli
- Substance chosen for clearance measurement in clinical practice
- Inulin characteristics
- Measurement of GFR using inulin clearance
A
- Measured directly vs. estimated
- GFR can’t be measured directly but can be estimated from clearance of an ideal filtration marker
- Clearance
- Volume of plasma cleared entirely of a substane / time
- Clearance = (U * V) / P
- Amt of plasma filtered by glomeruli
- Estimated by the clearance of ideal markers like inulin
- Substance chosen for clearance measurement in clinical practice
- Endogenous creatinine
- Inulin characteristics
- Neither absorbed nor secreted by renal tubules
- Freely filterable across glomerular membranes
- Not metabolized or produced by kidneys
- Measurement of GFR using inulin clearance
- GFR is measured by determining plasma conc & excretion of inulin
- Amt of inulin excreted = amt filtered
- Inulin clearance determines amt of plasma filtered by glomreuli (GFR)
5
Q
Assessing GFR w/ inulin clearance
- Filterability of inulin
- Equation derivation
- Equation
- How Cin is measured
- Criteria for the clerance of a substance to equal GFR
A
- Inulin is freely filterable
- Amt excreted = amt filtered
- Conc in filtrate = conc in plasma
- Equation derivation
- Filtered amt of inulin = GFR * plasma inulin conc
- Excreted amt of inulin = urine inulin conc * urine volume
- Volume units: L / min
- Filtered amt of inulin = excreted amt of inulin
- GFR * plasma inulin conc = urine inulin conc * urine volume
- Equation
- GFR = [urine inulin conc (Uin) * urine volume (V)] / plasma inulin conc (Pin)
- GFR = inulin clearance (Cin)
- How Cin is measured
- Infuse inulin IV to achieve steady state blood level
- Measure plasma inulin, urine inulin, & urine volume simultaneously
- Criteria for the clerance of a substance to equal GFR
- Substance must be freely filterable at the glomerulus
- Substance can/t be secreted or reabsorbed in tubules
- Substance must be in steady state concs in the blood w/ no extrarenal route of excretion
6
Q
Measurement of GFR in clinical practice
- Inulin vs. creatinine
- Creatinine characteristics
- Methods to assess GFR using creatinine
A
- Inulin vs. creatinine: in clinical practice…
- Not practical to use inulin infusion to calc Cin to assess GFR
- Assess GFR w/ endogenous creatinine
- Creatinine characteristics
- Endogenously produced from the metabolism of creatine & phosphocreatine in skeletal muscle
- Excreted by kidneys
- Freely filtered across the glomerulus
- Neither reabsorbed nor metabolized by the kidney
- Amt filtered = amt excreted when renal function is stable (steady state)
- Methods to assess GFR using creatinine
- Calc GFR w/ creatinine clearance
- Measure serum creatinine
- Estimate equations using serum creatinine to estimate GFR
7
Q
Steady state
- Achieved when…
- Creatinine in steady state
A
- Achieved when…
- Ingested amt + produced amt = excreted amt + consumed amt
- Creatinine in steady state
- Filtered creatinine = GFR * serum creatinine conc (Pcr)
- Excreted creatinine = urine creatinine conc (Ucr) * urine flow rate (V)
- Constant in absence of acute kidney failure b/c muscle mass remains relatively constant
- V units: L / min
- Filtered creatinine = excreted creatinine
- Take-home about steady state
- Methods that evaluate GFR (Cr clearance, estimatoin equations) can only be used when Pcr is stable (in steady state), as in pts w/ CKD or stable normal Cr
8
Q
Measurement of creatinine clearance
- Equation derivation
- Equation
- Technique
A
- Equation derivation
- Amt excreted = amt filtered
- Creatinine is freely filterable so filtrate conc = plasma conc in steady state
- Filtered Cr = GFR * plasma Cr conc (Pcr)
- Excreted Cr = urine Cr (Ucr) * urine volume (V)
- Filtered Cr = excreted Cr
- CrCl * Pcr = Ucr * V
- Equation
- CrCl = GFR = (Ucr * V) / Pcr
- Units: ml / min
- Technique
- 24 hr urine collection
- Measure Ucr & Pcr
- Normalized to BSA of 1.73 m2 (esp for children)
9
Q
Example
- 60 kg women
- Pcr = 1.2 mg/dL
- Ucr = 100 mg/dL
- V = 1.2 L/day
- Calculate CrCl
A
- V
- = 1.2 L/day
- = 1.2 L/day * 1000 ml/L * 1/1440 day/min
- = 0.83 ml/min
- CrCl
- = (Ucr * V) / Pcr
- = (100 mg/dL * 0.83 ml/min) / 1.2 mg/dL
- = 70 ml/min
- CrCl = 70 ml/min
10
Q
Limitations of creatinine clearance
- (1)
- How (1) is checked
- Muscle mass in dif pt populations
- (2)
A
- (1) Incomplete urine collection
- Difficult to obtain a complete 24 hr urine, esp in children
- Pts forget, collect too much, etc.
- Impossible to obtain in pts w/ incontinence or diarrhea
- Difficult to obtain a complete 24 hr urine, esp in children
- Adequacy of a 24 hr urine collection is checked by comparing the measured amt of Cr excretion to the expected amt based on weight, gender, & age
- Women: 15-25 mg/kg/d
- Men: 20-30 mg/kg/day
- Elderly (muscle wasting): 10 mg/kg/d
- Children: 14.7 + (0.45 * age) mg/kg/d
- Muscle mass in dif pt populations
- Muscle mass & Cr production/excretion decreases w/ age > 40yo
- Muslce mass decreases in pts who are bed-ridden, physically inactive, amputed, or on chronic corticosteroids
- (2) Increasing Cr secretion
- Decrease GFR –> increase Pcr + enhance tubular secretion
- Advanced CKD: Cr excreted > Cr filtered –> overestimate GFR
11
Q
Measurement of serum creatinine
- Cr characteristics
- GFR vs. Pcr
- Pcr vs. kidney function
- Normal Pcr
- Pcr is affected by…
A
- Cr characteristics
- Endogenously produced from the metabolism of Cr in skeletal muscle
- Excreted by kidneys
- Freely filtered across the glomerulus
- Neither reabsorbed nor metabolized by the kidney
- GFR vs. Pcr
- GFR = CrCl = (Ucr * V) / Pcr
- Decrease GFR –> increase Pcr curvilinearly
- Pcr vs. kidney function
- Higher Pcr –> worse kidney function
- Normal Pcr
- Adult: 0.6 - 1.2 mg/dl
- Children: lower
- Pcr is affected by both Cr production & clearance
- Muscle mass
- Diet
- Creatine supplements
- Malnutrition
- Amputations
12
Q
Limitations of serum Cr measurement
A
- Cr production differs b/n pts depending on muscle mass
- More muscle mass –> higher Cr
- Less muscle mass –> lower Cr
- Amputation, muscle wasting, malnutrition –> low muscle mass –> Pcr appear normal but could represent low GFR
- Glomerular injury may not initially change GFR or Pcr
- If this is suspected, look for other signs of kidney disease (ex. protein or blood in urine, abnormal renal imaging)
13
Q
Estimation equations based on Pcr
- Why used
- Cockroft-Gault formula
- MDRD formula
- Ex. 23yo white man, 80kg, Cr 1.2 mg/dl
A
- Why used
- Limitations of Pcr due to variatoins in muscle mass
- Alternatives to 24 hr urine collection
- Equations take into account variables like age, sex, race, & body size (predictors of muscle mass)
- Cockroft-Gault formula
- GFR = [(140 - age) * (weight in kg)] / (72 * PCr)
- For older drug dosing guidelines
- Based on demographics, serum Cr, & lean body weight
- Multiply by 0.85 for women b/c they have less muscle mass than men
- Obese pts: weight can over-estimate Cr cleraance, so use lean body weight
- MDRD (modificaiton of diet in renal disease) formula
- Most commonly used in clinical practice
- Effect of dietery protein restriction & BP control on renal disease progression –> equation that predicts GFR from Pcr
- Ex. 23yo white man, 80kg, Cr 1.2 mg/dl
- GFR = 80 ml/min
14
Q
Limitations of estimation equations
- MDRD
- Cockcroft-Gault
- Validation in clinical populations
- Newer methods proposed but not widely used
A
- MDRD
- Tends to underestimate GFR when r is normal or near-normal
- Why labs report GFR > 60 ml/min when it’s expected to be close to nromal (80 ml/min)
- Cockcroft-Gault
- Tends to overestimate GFR due to tubular secretion
- Validation in clinical populations: formulas haven’t been validated in…
- Children
- Pregnant women
Certain ethnic groups - Pts w/ unusual muscle mass, body habitus, & weight
- Newer methods proposed but not widely used
- CKD-EPI
- Blood test Cystatin C
15
Q
Example
- 23yo female, 55 kg, 24 hr urine collection
- V = 2000 ml / 24 hr
- Ucr = 50 mg/dl
- Pcr = 0.6 mg/dl
- CrCl?
- Is kidney function normal?
A
- CrCl = (50 mg/dl * 2000 ml / 1440 min) / 0.6 mg/dl = 115 ml/min
- Normal renal function
- Normal = 110 ml/min