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Summary
damage
Monitor functional
damage
Help determine
etiology
rate (GFR)
plasma creatinine
plasma urea
urine volume
urine urea
minerals in urine
urine protein
urine glucose
hematuria
osmolality
rate=GFR
plasma creatinine= Pcr
plasma urea-Purea
urine volume= V
urine urea- Uurea
cystatin C in plasma?
urine protein
urine glucose
hematuria
osmolality
GFR
Normally 100-130 ml/min
Determined by:
Net filtration pressure across glomerular
basement membrane
Permeability and surface area of glomerular
basement membrane
GFR
Patients remain asymptomatic until there has
GFR
Ideal Marker
Creatinine
+ An endogenous product of muscle
metabolism; near-constant production
Filtered, but a bit secreted
Urea
+ An endogenous product of protein intake
Filtered and absorbed; synthesis varies with diet0
Urea
Used historically as marker of GFR
Freely filtered but both re-absorbed and
Urea
Product of protein catabolism
Filtered
Reabsorbed in proximal tubule
If sodium is avidly reabsorbed, so is urea
Serum urea concentration measured as Blood
Urea
Increase
Volume depletion
Decrease
Volume Expansion
Dietary protein
Corticosteroids
Liver disease
Severe malnutrition
Tetracyclines
Blood in G-I tract
BUN: Uses
Imperfect marker of GFR
Marker for adequacy of protein intake
Marker for presence of uremic toxins in
10:1 = normal
>20:1 if ECV contracted. Why???
Creatinine
Product of muscle metabolism
Some creatinine is of dietary origin
Freely filtered, but also actively secreted into
urine
Secretion is affected by several drugs
Serum Creatinine
Increase
Male
Meat in diet
Muscular body type
Cimetidine & some
other medications
Decrease
Age
Female
Malnutrition
Muscle wasting
Amputation
muscle mass
Inversely proportional to GFR
Good way to follow changes in GFR
BUT also elevated by muscle mass,
tubular secretion
Creatinine Clearance
Measure serum and urine creatinine levels
Creatinine Clearance
creatinine excreted / unit time [Cr ]urine V
CrCl
[Cr ]serum
[Cr ]serum
Therefore, it represents the volume of serum completely
Creatinine Clearance
EXAMPLE:
UCr = 72 mg/dl
SCr = 2.0 mg/dl
V = 2 liters
time = 24 hours
CrCl
Limitations of Creatinine
Clearance
Only valid at steady state[Cr]serum must be stable
Trimethoprim, cimetidine lower tubular Cr
urine collection?
Creatinine Excretion
The amount of creatinine excreted per day is
creatinine index
Use
SCr
Follow GFR
Cr
Clearance Estimate GFR
Cr Index
Determine
adequacy of
collection
Effect of
GFR muscle
mass
Cystatin C
Cystatin C is a 13 KD protein produced by all
eGFR
Increasing requirements for dialysis and
eGFR
eGFR
Problem
Need an easy test to screen for early
eGFR
eGFR calculation has been recommended by
Proteinuria
In health:
High molecular weight proteins are retained
Proteinuria
Glomerular:
Mostly albumin, because of its high
concentration and therefore high filtered load
Tubular:
Overflow:
Excessive filtration of one protein exceeds
reabsorbtive capacity (Bence-Jones,
myoglobin)
the urine
Most dip sticks report albumin at greater than
150 mg/L
Urinary Albumin
Detection of low levels of albumin (even if
Creatinine Standardization in
British Columbia
Based on Isotope dilution /mass spectrometry
Importance of Standardization
Low bias creatinine:
Total Error
TE = % bias + 1.96 CV
Goal is <10% (requires bias 4% and CV
3%)
Kidney Functions
Selectively secretes into or re-absorbs from
Water Balance
Retention of nutrients
Kidney Functions
Selectively secretes into or re-absorbs from
Salt Balance
Kidney Functions
Target organ
Production
Erythropoietin
1, 25 dihydroxycholecalciferol
Urinalysis
Dipstick
Protein
Urinalysis
Dipstick contd
Hemoglobin
Urinalysis
Dipstick contd
Glucose
Specific Gravity
Approximate only
Measurement of osmolarity preferred when
pH
pH changes with time in a collected urine
Calculations to determine urine ammonium
Microscopic Urinalysis
Epithelial Cells
Red Cells
May originate in any part of the urinary tract
Small numbers may be normal
There is provincial protocol for the
Casts
Hyaline and granular casts not always
RTA
If NH4 + is not present (or if HCO3 - is
RTA
Ammonium Chloride Loading
weight hourly)
Collect urine hourly from 0600 for osmolarity
Baseline serum osmolarity, Na+, ADH
When osmolarity plateaus repeat above tests
and administer ADH
Interpretation
If urine concentrates (osmolarity >600 and
No Urine Concentration
No Response to ADH
Nephrogenic diabetes insipidus
No Urine Concentration
Positive response to ADH
To summarize:
1. Use the Creatinine Clearance as the best estimate
of GFR
2. Use the Serum Creatinine to follow renal function
over time
3. Use the Creatinine Index to check the adequacy of
a urine collection
4. Use the BUN to help assess GFR, volume status,
and protein intake