Answer this renal question -

[Kaustikos]

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I want to know what equation to use in figuring out the answer. Assuming a 125 GFR being reduced to 20% (25) doesn't begin to explain the excreted creatinine. Or my professor never explained chronic renal failure's influence on excreted creatinine. I understand the levels of plasma creatinine increasing but not the levels of creatinine in the urine remaining the same and not substantially reducing. Is there a formula I'm missing here?

 

[CaptainSSO]

This is my Intuitive reasoning, we didnt specifically learn this, but:

The kidney failure results in some nephrons shutting down.

So less plasma is filtered, thus more creatinine building up in plasma.

Well, the nephrons that are still functioning are still filtering plasma normally, so the snGFR is not changing. Thus the urine creatinine concentration is not going to necessarily be changed, as the functional nephrons are still secreting as normally. The nephrons that are not working are not filtering anything, so they're not altering urine concentrations of creatinine.

 

[normtheniner]

The kidney failure results in some nephrons shutting down.

So less plasma is filtered, thus more creatinine building up in plasma.

Well, the nephrons that are still functioning are still filtering plasma normally, so the snGFR is not changing. Thus the urine creatinine concentration is not going to necessarily be changed, as the functional nephrons are still secreting as normally. The nephrons that are not working are not filtering anything, so they're not altering urine concentrations of creatinine.

Would nephron hypertrophy also play a factor in this as well?

 

[CaptainSSO]

Would nephron hypertrophy also play a factor in this as well?

Yea, I'm guessing it would start compensating for the kidney failure and start normalizing the creatinine levels.

Take what I'm saying with many grains of salt though, we never learned all this, I'm just making intuitive assumptions.

I just looked in my phsyiogy notes and we actually discussed one case where plasma creatinine was elevated and urine creatinine was down, which would suggest the OP was correct in his reasoning. I was just thinking of an explanation to account for the apparent discrepancy between elevated plasma creatinine and normal urine creatinine, but yea, I'm sure you're right, the hypertrophy would cause this as well, and perhaps hypertrophy is the primary reason behind this.

 

[armybound]

I don't see an image in the OP.

 

[Charles_Carmichael]

i don't see an image in the op.

+1

 

[Kaustikos]

Sorry, I was afraid that would happen.

 

[FIREitUP]

Forgive this nonsensical answer (i'm tired), hopefully you can make sense of it:

20% GFR means 5 times the amount of plasma creatinine because the GFR is lowered, creatinine cannot be excreted from the body so it builds up in the plasma. Since the concentration is 5 times more, the same amount per day will be excreted since the concentration is 5x while GFR is 1/5 means filtered load (GFR x Plasma concentration) will be roughly the same: filtered load is roughly equal to the excretion rate with creatinine.

 

[ushush]

Sorry, I was afraid that would happen.

The formula is Filtered Load of Cr in mg/min= GFR*PlasmaCr. GFR is down because of kidney damage. That means that PlasmaCR increases (accumulates proportionately). It is not choice C, because elderly people have less muscle mass and so they produce slightly less creatinine.

 

[Kaustikos]

Forgive this nonsensical answer (i'm tired), hopefully you can make sense of it:

20% GFR means 5 times the amount of plasma creatinine because the GFR is lowered, creatinine cannot be excreted from the body so it builds up in the plasma. Since the concentration is 5 times more, the same amount per day will be excreted since the concentration is 5x while GFR is 1/5 means filtered load (GFR x Plasma concentration) will be roughly the same: filtered load is roughly equal to the excretion rate with creatinine.

The decreased GFR means more creatinine accumulates in the body. This increased creatinine is not being filtered at all because of the decreased GFR. Which is also why you see increased Sodium with decreased GFR (Adenosine stimulates afferent constriction to reduce sodium filtration to reduce urinary sodium concentrations).

The formula is Filtered Load of Cr in mg/min= GFR*PlasmaCr. GFR is down because of kidney damage. That means that PlasmaCR increases (accumulates proportionately). It is not choice C, because elderly people have less muscle mass and so they produce slightly less creatinine.

Like I said; I understand the accumulation of creatinine being substantially higher due to GFR decrease. I don't understand the physiology/explanation for why urinary creatinine would not change.

 

[loveoforganic]

Forgive this nonsensical answer (i'm tired), hopefully you can make sense of it:

20% GFR means 5 times the amount of plasma creatinine because the GFR is lowered, creatinine cannot be excreted from the body so it builds up in the plasma. Since the concentration is 5 times more, the same amount per day will be excreted since the concentration is 5x while GFR is 1/5 means filtered load (GFR x Plasma concentration) will be roughly the same: filtered load is roughly equal to the excretion rate with creatinine.

This is correct. You only have transient changes in plasma concentrations - you will eventually hit steady state again. For creatinine, you can assume you have free filtration and no reabsorption or secretion (there actually is some secretion, but it's a relatively small percent of urine composition). As nephrons drop out, filtration fraction will decrease. With the decrease in FF, you'll have a corresponding decrease in GFR (with a corresponding rise in plasma creatinine concentration). As plasma creatinine levels increase, you have a corresponding rise in creatinine excretion. This is because creatinine is freely filtered (and because creatinine is not reabsorbed or secreted, this will lead to a corresponding directly proportional increase in creatinine excretion). Plasma levels of creatinine will still be elevated - you will just be at your new steady state

 

[CaptainSSO]

OK, so this is amount excreted and not the concentration in the urine.

^But if you're excreting the same amount you're producing, that would imply you're producing more, and not filtering less. She has to be excreting less, otherwise their wouldn't be a rise in plasma concentration.

So the amount excreted would have to drop, and it did, to 950 mg-- I think he's just wondering how to pick between answer choices A and B.

 

[Kaustikos]

So the amount excreted would have to drop, and it did, to 950 mg-- I think he's just wondering how to pick between answer choices A and B.

B is correct, but I wanna know why. To me, I feel like A would be correct, but given loveoforganic's explanation, I can see why it would be B. I was just never taught about creatinine levels returning to steady state in chronic renal failure. I assumed that decreased GFR meant decreased clearance/excretion of creatinine. Since creatinine levels are high, you wouldn't see any stimulation of creatinine production and so it'd just cause a decrease in excreted creatinine.

 

[loveoforganic]

I was just never taught about creatinine levels returning to steady state in chronic renal failure.

Disclaimer - I'm a first year in traditional curriculum renal phys now, so my pathophys is... absent, essentially. However, what we were taught was that in anything short of a severe, acute kidney failure, you will have a temporary fluctuation followed by a return to steady state (due to the rise in plasma concentration leading to an increased filtered load)

ince creatinine levels are high, you wouldn't see any stimulation of creatinine production and so it'd just cause a decrease in excreted creatinine.

I also remember being told that creatinine production is constant barring changes in muscle mass

 

[loveoforganic]

OK, so this is amount excreted and not the concentration in the urine.

^But if you're excreting the same amount you're producing, that would imply you're producing more, and not filtering less. She has to be excreting less, otherwise their wouldn't be a rise in plasma concentration.

So the amount excreted would have to drop, and it did, to 950 mg-- I think he's just wondering how to pick between answer choices A and B.

I would say that I think a big hint in the question stem is "slowly progressive chronic renal failure." As nephrons slowly lose function, the filtered load of creatinine is going to increase directly following the decrease in GFR (and if GFR is significantly slow, as I think was deliberately hinted, you're not going to be significantly deviating from normal excretion)

Edit: To play devil's advocate against myself here though, and as I think about it a little more, the response to decreased GFR and increased plasma creatinine concentration should be essentially immediate - there are no cellular or nuclear mechanisms at play, it's a physical response to increased concentration. The importance of it being "slow chronic failure" may be to hint that a normal water balance is maintained (i.e. the body's going to have accommodated to decreased kidney function to allow normal fluid excretion/filtration through altering afferent arteriole constriction, systemic blood pressure, etc.)

Does this make sense?

 

[Morsetlis]

If the answer were A, where would the extra ~800mg of creatinine created per day go?

What goes in, must come out.

Since GFR goes down, but creatinine excretion must remain roughly equal, then the plasma concentration steadily rise from 1x normal to 5x normal (production > excretion), at which point there is steady state between production and excretion.

So, the answer comes down to B, or C. Creatinine is form from Creatine/Creatine phosphate breakdown produced by muscles, and she's older now, so she has less muscle mass.

And because I like graphs:

 

[FIREitUP]

The decreased GFR means more creatinine accumulates in the body. This increased creatinine is not being filtered at all because of the decreased GFR. Which is also why you see increased Sodium with decreased GFR (Adenosine stimulates afferent constriction to reduce sodium filtration to reduce urinary sodium concentrations).



Like I said; I understand the accumulation of creatinine being substantially higher due to GFR decrease. I don't understand the physiology/explanation for why urinary creatinine would not change.

That's not true. It is being filtered, however it is being filtered at 1/5th the rate. Since the creatinine has built up 5x, they balance each other out: Filtered load=GFR (1/5) x serum concentration (5). Filtered=excreted with creatinine (very little is secreted).

 

[Kaustikos]

If the answer were A, where would the extra ~800mg of creatinine created per day go?

What goes in, must come out.

Since GFR goes down, but creatinine excretion must remain roughly equal, then the plasma concentration steadily rise from 1x normal to 5x normal (production > excretion), at which point there is steady state between production and excretion.

So, the answer comes down to B, or C. Creatinine is form from Creatine/Creatine phosphate breakdown produced by muscles, and she's older now, so she has less muscle mass.

And because I like graphs:

Thank you!

My issue from the beginning was having someone explain/show what happens to creatinine levels and why it occurred. I never meant to refute this answer, but just to understand what the hell was going on. We were never taught/explained this steady-state return in chronic renal failure (Hell, we were never taught about chronic renal failure at all) but this question pops up and I'm confused.

So, thanks for the clarification.

 

[CaptainSSO]

I would say that I think a big hint in the question stem is "slowly progressive chronic renal failure." As nephrons slowly lose function, the filtered load of creatinine is going to increase directly following the decrease in GFR (and if GFR is significantly slow, as I think was deliberately hinted, you're not going to be significantly deviating from normal excretion)

Edit: To play devil's advocate against myself here though, and as I think about it a little more, the response to decreased GFR and increased plasma creatinine concentration should be essentially immediate - there are no cellular or nuclear mechanisms at play, it's a physical response to increased concentration. The importance of it being "slow chronic failure" may be to hint that a normal water balance is maintained (i.e. the body's going to have accommodated to decreased kidney function to allow normal fluid excretion/filtration through altering afferent arteriole constriction, systemic blood pressure, etc.)

Does this make sense?

Yea, that makes sense. The "slow chronic failure" implies that homeostasis must be at work, and you couldn't be holding on to the extra creatinine.

Like the OP, we didn't learn about these mechanisms with regard to the kidney. We just learned, kidney disease---> nephrons shut down ---> plasma creatinine up. It's the increased plasma creatinine concentration that is driving it's increased filtration. Still having a bit of trouble figuring out why this subsequent increase in filtration would not lead to a decreased plasma [creatinine], but I guess I'm taking it a step too far, a la PTH.


And thanks for the graph, Morsetlis.

 

[Kaustikos]

Yea, that makes sense. The "slow chronic failure" implies that homeostasis must be at work, and you couldn't be holding on to the extra creatinine.

Like the OP, we didn't learn about these mechanisms with regard to the kidney. We just learned, kidney disease---> nephrons shut down ---> plasma creatinine up. It's the increased plasma creatinine concentration that is driving it's increased filtration. Still having a bit of trouble figuring out why this subsequent increase in filtration would not lead to a decreased plasma [creatinine], but I guess I'm taking it a step too far, a la PTH.


And thanks for the graph, Morsetlis.

I guess I'm thinking too much about it. It just pissed me off that this was a practice question and no verifiable source to prove that creatinine clearance remains the same. Thanks for the help, guys. 🙂

 

[FIREitUP]

I guess I'm thinking too much about it. It just pissed me off that this was a practice question and no verifiable source to prove that creatinine clearance remains the same. Thanks for the help, guys. 🙂

Creatinine excretion remains the same, clearance decreases since creatinine clearance is ~= to GFR, and her GFR is 20% of what it was.

 

[loveoforganic]

Still having a bit of trouble figuring out why this subsequent increase in filtration would not lead to a decreased plasma [creatinine], but I guess I'm taking it a step too far, a la PTH.

What would be causing the decreased concentration? The only thing causing increased filtered load is increased plasma concentration - once they meet at equilibrium there isn't a driving force in either direction