Biochemistry Flashcards
What two functions of the kidneys are assessed using biochemical measurements in renal disease?
- Glomerular function
- Tubular function
What do…
- Glomerular function
- Tubular function
… actually mean?
- Glomerular function: the ability of the glomeruli to filter the blood
- Tubular function: the ability of the renal tubules to reabsorb the filtered blood from the glomeruli
Glomerular function can be assessed by investigating which two factors?
- Glomerular filtration rate (GFR)
- Proteinuria
What is the single best test for assessing kidney function?
GFR
Describe some properties that the ‘ideal marker’ for assessing glomerular filtration rate (GFR) would have
- Endogenous (produced by the body)
- Easy to measure (e.g., in urine)
- Appears at a constant rate
- Freely filtered at the glomerulus
- Not reabsorbed from the renal tubule
- Not secreted into the renal tubule
- Doesn’t undergo extra-renal elimination
Name the plant carbohydrate which gives an almost perfect indication of GFR
Inulin
Why is measuring inulin clearance not gold standard for assessing GFR?
Inulin is not endogenous - it needs to be injected into the body before being measured which makes it impractical
Clearance of which two substances can be used as a marker for GFR instead of inulin?
Creatinine (main one)
Urea
What is urea?
The final breakdown product of amino acids found in proteins and the main component of urine
What properties make urea a…
-Good
-Bad
… marker for assessing GFR?
Good:
- Endogenous
- Easy to measure
- Freely filtered by the glomerulus
- Not secreted into the renal tubule
Bad:
- Levels fluctuate post-prandially (not present at a constant rate)
- Reabsorbed from the renal tubules
- Extra-renal elimination by the gut so GFR will be underestimated
What is the most significant limitation for use of urea as a marker of GFR?
It’s extra-renal elimination by the gut (~25% of total urea)
What is creatinine?
A waste product of muscle metabolism
What properties make creatinine a good marker for assessing GFR?
- Endogenous
- Easy to measure
- Appears at a constant rate
- Freely filtered by the glomerulus
- Not reabsorbed from the renal tubule
- Doesn’t undergo extra-renal elimination
What is the limitation of using creatinine as a marker of GFR?
~5-10% of creatinine is secreted into the renal tubule so GFR is overestimated
What is the problem with measuring serum creatinine and what is the solution?
Problem: serum creatinine isn’t sensitive to changes in GFR until the GFR is significantly lowered (i.e., serum creatinine stays within the reference interval even when GFR has nearly halved)
Solution: urine creatinine clearance is sensitive to changes in GFR at these higher GFR levels (60-120 mL/min)
What is urinary creatinine clearance?
The volume of blood that’s cleared of creatinine per minute by glomerular filtration
What 3 measurements are required to calculate urinary creatinine clearance?
Serum creatinine
24-hour urine collection creatinine
Urine volume
What equation is used to calculate urinary creatinine clearance?
(urine creatinine conc. x urine volume) / (serum creatinine conc. x duration of collection*)
- duration of collection in minutes so 24 hours = 1440 mins
Calculate the urinary creatinine clearance:
- Serum creatinine: 100 micromols
- Urine creatinine: 6800 micromols
- Urine volume: 2500 ml
(6800 x 2500) / (100 x 1440) = 118 ml/min
Serum creatinine is affected by the amount of creatinine produced per day. With this in mind, what are the confounding variables in serum creatinine measurement?
Muscle mass and diet
Muscle mass and diet cannot reasonably be measured for each patient. What ‘proxies’ are used to take into account the confounding variables?
Age, sex and ethnicity
Due to the presence of confounding variables and the use of proxies, what are the results of these methods of calculating GFR called?
Estimated glomerular filtration rate (eGFR)
Clearance of what substance may be used instead of creatinine to get a more accurate eGFR (e.g., in oncology)?
51Cr-EDTA clearance
Chronic kidney disease is classified from stage 1-5 based on eGFR. What values of eGFR are the range for each stage of CKF?
Stage 1: >90 mL/min (may not = KD)
Stage 2: 60-89 mL/min (very mild renal dysfunction)
Stage 3: 30-59 mL/min (decline in renal function, can be due to normal aging)
Stage 4: 15-29 mL/min (needs renal replacement)
Stage 5: <15 mL/min (end-stage renal failure)
Why is a eGFR of >=60 mL/min just reported as ‘>=60 mL/min’?
eGFR is still not accurate at higher GFR values
So only values <60 mL/min are reported
What aspects of glomerular function does measuring proteinuria specifically investigate?
The ability of the glomerulus to act as a filter
How is proteinuria estimated?
By measuring plasma protein content in a 24-hour collection of urine
Why does plasma protein content in urine give an indication of glomerular function?
Plasma proteins are normally retained by the glomeruli because they are large molecules
‘Leaky’, damaged glomeruli will filter through more plasma proteins than they should
What conc. of protein in the urine suggests significant glomerular damage?
> 150 mg/day
Urine dilution will also affect the protein content of the urine. How is this taken into account?
By working out the protein/creatinine ratio in a spot sample of urine
Suggest two conditions which can cause proteinuria
Multiple myeloma can cause overflow proteinuria (overproduction of Ig’s leak into the urine)
Nephrotic syndrome can cause glomerular proteinuria (the glomeruli are unable to retain protein and so excess protein spills into the urine)
What is meant by the term ‘microalbuminuria’?
Excretion of albumin in abnormal quantities but still not enough to be detected by a urine dipstick
Why is it important to assess for microalbuminuria in patients with diabetes?
Microalbuminuria is the earliest expression of diabetic nephropathy
This can be detected and treated early (w/ an ACEI)
What is the function of the renal tubules?
To reabsorb important substances from the filtrate from the glomeruli e.g., water, electrolytes, amino acids, glucose etc
What % of filtrate is reabsorbed?
~99%
Tubular pathology can be classified as pre-renal, renal or post-renal
Suggest a cause of pre-renal tubular pathology
Blood loss/hypovolaemia (reduced renal perfusion)
Tubular pathology can be classified as pre-renal, renal or post-renal
Suggest a cause of renal tubular pathology
Glomerulonephritis, nephrotoxins (intrinsic kidney tissue damage)
Tubular pathology can be classified as pre-renal, renal or post-renal
Suggest a cause of post-renal tubular pathology
Stones/malignancy (ureteric/urethral obstruction)
What 2 measurements can be used to assess tubular function?
Urine osmolality
Serum osmolality
How are urine and serum osmolalities used to assess tubular function?
Comparing serum and urine osmolalities can help assess tubular function
If the renal tubules are functioning, the values should be different
If the renal tubules are damaged, serum and urine osmolalities will be almost identical as there will be little altering of the filtrate
Urine osmolality is most useful if it is either exactly the same as, or very different from serum osmolality. T/F
True
