Thursday, February 17, 2011

Creatinine, BUN and GFR: part one

Question: What is the most basic concept in clinical nephrology?

Answer: As renal function falls, the creatinine and BUN rise.

For the purpose of this post the renal function is synonymous with glomerular filtration rate.

Think about every lab measurment in clinical medicine and think about how the normal range changes as the GFR falls from 100 mL/min to 10 mL/min, a 90% reduction of renal function.
  • How much does sodium change? 
    • Not at all.
  • How much does potassium change? 
    • In the absence of ACEi or other drugs which alter normal renal handling or an extreme change in diet, it doesn't change at all.
  • Phosphorous? 
    • Maybe a 25% bump from the low 4s to the mid 5s.
  • White blood cell count? 
    • Not at all.
  • Albumin? 
    • Not at all.
  • Lipase? 
    • Not at all.
  • SGPT? 
    • Not at all.
In the broad world of clinically relevant biochemical tests, essentially none are readily affected by changes in glomerular filtration rate. BUN and creatinine (and cystatin C) stand alone in their exquisite sensitivity to changes in GFR. Of course this is not a weird coincidence, those labs are clincially relevent precisely due to their sensitivity to changes in GFR. But why is it, that as GFR falls, the creatinine rises?

Imagine a 70 kg male. Men, on average, generate 20 mg of creatinine per Kg body weight, so our patient will generate 1400 mg of creatinine and, if the renal function is stable, all of that creatinine is excreted by the kidneys every day. It makes no difference if the GFR is 10 or the GFR is 100, all of the creatinine generated is excreted.

None of it lingers.

None of it accumulates in some creatinine depot in the subcutaneous fat or lateral horn of the cerebral ventricles.

This has to be true because if some of creatinine hung around and accumulated, the serum creatinine would rise. By definition, stable renal function means the creatinine doesn't rise. So our 70 kg man generates 1,400 mg of creatinine and excretes 1,400 mg of creatinine.

Once you know the amount of a substance excreted we cane solve for the plasma concentration using the standard clearance formula.

Using the 1,400 mg of creatinine, assuming a modest urine output of 1 liter and assuming a GFR of 100 the equation looks like this:
We can rearrange the equation to solve for the plasma creatinine:

and if you do the calculation you get a creatinine of 0.97 mg/dL. The neat part of the equation is that it is totally independent of the urine volume. If the patient excretes the 1400 mg of creatinine in 2 liters rather than 1 as we claculated above, the urine creatinine concentration falls by half (same amount of total creatine dissolved in twice as much urine), the urine volume doubles and the serum creatinine remains the same.
On the other end of the renal function spectrum, the poor patient with a GFR of 10, looks like this:
This gives him a serum creatinine of 9.7 mg/dL. The creatinine went from 0.97 to 9.7 with a change in GFR from 100 to 10. Imagine if any other electrolyte had a ten-fold change associated with a drop in the GFR? Raise your hand if you have seen a potassium of 40.

President Bush is 5'11"
You can use this spreadsheet below to predict the serum creatinine based on different GFRs, urine volumes and creatinine production. Try different urine volumes and see how that doesn't affect the serum creatinine (the reason is that the numerator in the clearance formula is simply solving for the mass of creatinine excreted. Concentration of X multiplied by the volume gives amount of X dissolved in the solution.) . Use the spreadsheet to discover what Shaquile O'Neal's serum creatinine is. Assume 20 mg/kg body weight, a weight of 147 kg, and a GFR of 120.

If you want to edit and use the equation image files download this Word file. Double click the equations to launch the equation editor.
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