GFR and Renal Clearance Flashcards
What is GFR?
It is the amount of fluid filtered from the glomeruli into the Bowman’s capsule per unit time (mL/min). Sum of filtration rate of all functioning nephrons.
What is freely filtered substance?
For substance X,
ConcentrationX (Plasma) = ConcentrationX (Glomerular filtrate)
How do you calculate GFR?
What are properties of inulin which make it an ideal marker for GFR calculation?
Freely filtered
No reabsorption
No secretion
Non-toxic
Can be measured in plasma & urine
What conclusion can you draw about a substance whose renal clearance is higher than that of inulin?
Secretion of that substance occurs
If the renal clearance of a substance X is lower than that of inulin, does this rule out the possibility of X being secreted into the tubular fluid?
No, it could be secreted, but possibly more is being reabsorbed.
Explain the reasoning behind clearance of PAH being able to give an estimate of the rate of renal plasma flow.
If PAH clearance = 625 ml/min and the inulin clearance = 125ml/min, what proportion of the plasma entering the glomeruli is filtered?
PAH clearance = RPF = 625 ml/min = rate of plasma entering kidney
Inulin clearance = GFR = 125ml/min = rate plasma filtered
Proportion filtered = 125/625 = 20% (the filtration fraction)
Why is measurement of PAH clearance rarely performed clinically when renal disease is suspected?
Abnormal PAH clearance could be due to:
- Issues with renal plasma flow
- Incomplete secretion
Therefore, reliability of test is affected.
What are the 3 main methods of estimating GFR clearance?
(a) Inulin Clearance.
(b) Creatinine clearance (C creatinine)
- 24h urine collection
- a single plasma sample taken at some time during the clearance period
Creatinine shares most of the properties of inulin. It is freely filtered and neither reabsorbed nor metabolised by the kidneys. However, since a small amount of creatinine enters the urine by secretion into the proximal tubule, the amount excreted slightly exceeds the amount filtered. In addition, the method used to measure creatinine concentrations is not sufficiently specific: in addition to creatinine it measures the concentrations of so-called “non-creatinine chromogens” present in plasma but not usually in urine. However, these two errors tend to cancel out and because of its simplicity Ccreatinine is widely used as an estimate of GFR.
What are the issues with inulin clinically?
Inulin does not occur naturally in the body, so, in order to measure its renal clearance, it has to be infused intravenously.
The requirement for intravenous infusion causes several problems, which mean that measurement of inulin clearance is rarely used clinically.
In particular, it is time consuming and tedious, requires several blood samples, and, because of the short duration over which measurements are usually made, bladder catheterisation (since voluntary bladder emptying may be incomplete).
Why is creatinine advantageous over inulin?
Creatinine has a major advantage over inulin in that it is an endogenous substance, produced from the metabolism of muscle creatine.
Moreover, it is released into the blood at a relatively constant rate, so the plasma concentration of creatinine remains fairly stable in a given individual.
What are similarities between inulin and C creatinine?
It is freely filtered and neither reabsorbed nor metabolised by the kidneys.
What are the issues with creatinine?
However, since a small amount of creatinine enters the urine by secretion into the proximal tubule, the amount excreted slightly exceeds the amount filtered.
In addition, the method used to measure creatinine concentrations is not sufficiently specific: in addition to creatinine it measures the concentrations of so-called “non-creatinine chromogens” present in plasma but not usually in urine.
However, these two errors tend to cancel out and because of its simplicity C creatinine is widely used as an estimate of GFR.
What is the normal value for GFR?
90-150 mL/min
When does GFR start to fall, and by how much?
at the age of 40 and it falls by about 10 mL/min per decade
What is inulin?
a polysaccharide with a molecular weight of approximately 5000 daltons
How is PAH secreted?
para aminohippuric acid is secreted avidly into the proximal tubules
- provided the plasma concentrations aren’t too high, the combination of filtration and secretion ensures that practically all the PAH arriving at the kidneys in the plasma appears in the urine (and virtually none leaves the renal vein)
Why is inulin not given orally when measuring inulin clearance?
insulin is a starchy substance, bacteria of gut can use it as its own food so less is left as it is metabolised
Why is bladder catheterisation not usually considered necessary when creatinine clearance is measured although it is required for measurement of inulin clearance?
Inulin is added externally and has a particular time frame in body and will be eventually removed from the body, but creatinine is always in the body.
What can be used intsead of inulin and creatinine?
EDTA/ 51Cr EDTA (a gamma emitter)
Why is EDTA preferred?
From the foregoing we can say that in the measurement of GFR, C inulin is accurate but inconvenient, whilst C creatinine is convenient but not so accurate.
Because of these problems, many clinical laboratories now use substances with the same properties as inulin, but which can be measured more easily, by virtue of the fact that they emit radiation.
This allows them to be readily and accurately quantified in plasma.
The clearance of such substances can be determined by monitoring their disappearance from the plasma after administering a given dose, thus eliminating the need to collect urine.
How would EDTA be administered and how would it be measured?
one injection, then measure plasma activity of 51Cr at subsequent intervals
How is the slope of a EDTA log graph linked to clearance?
The greater the slope the greater the clearance
What is the advantage of EDTA?
1) injection of a single dose of 51Cr EDTA.
2) collection of 2-3 plasma samples taken at appropriate times after the injection (i.e. on the straight line portion of the curve; far fewer samples are necessary than are shown).
Given the fact that 51Cr EDTA is free to permeate the whole of the extracellular fluid, how do you explain the initial steep phase of the plasma disappearance curve (log plasma 51Cr EDTA vs Time) following a single IV injection of 51Cr EDTA.
Because it quickly diffuses (quick diffusion rate) initially in the extracellular fluid down concentration gradient
At that point it is removed from the plasma at a consistent rate
How would the plasma disappearance curve (log plasma 51Cr EDTA vs Time) be affected in someone suffering from severe renal failure?
less steep line, gradient because of slower clearance
renal failure is a lower glomerular filtration rate
