Help: question about kidney disease

[ero87]

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I've struggled with an important concept regarding renal failure for a while now, and I'd love some help understanding this. When the glomerulus/kidney is damaged, protein spills into the urine (proteinuria). However, urine creatinine levels decrease as renal function continues to decline.

So why do protein and creatinine urine levels move in opposite directions? Why is one spilling into the urine and the other can no longer pass through the glomerulus?

Thanks!

 

[armybound]

I think you just have to think about the mechanism behind each component, then realize that the two don't always go together.

Obviously protein isn't usually filtered. You can take a disease like minimal change disease where the GBM loses its filtration capacity, but the kidney itself is not damaged and GFR is preserved. This would cause "normal" creatinine levels but you'd lose protein in the urine.

Creatinine is usually fully filtered and secreted a little. Imagine a disease where GFR drops, but the GBM is still intact (a lot of diseases). In this case you'd have an increased creatinine and BUN but wouldn't lose protein in your urine.

I'm not sure about this part, but I would imagine a disorder where proteinuria and an increase in serum creatinine coexist is demonstrating that some glomeruli are "functional" but have lost their filtration barrier capacity (= proteinuria) but other glomeruli have shut down and aren't filtering anything (= azotemia). The same glomerulus in this case wouldn't be responsible for both the azotemia and proteinuria.

The other case I could imagine is that GFR has significantly decreased (= azotemia) but still preserved enough that protein is spilling due to its structural defects. You get a little of both due to decreased GFR and an inability to keep albumin in.

Not sure how right these are...

 

[jdh71]

I've struggled with an important concept regarding renal failure for a while now, and I'd love some help understanding this. When the glomerulus/kidney is damaged, protein spills into the urine (proteinuria). However, urine creatinine levels decrease as renal function continues to decline.

So why do protein and creatinine urine levels move in opposite directions? Why is one spilling into the urine and the other can no longer pass through the glomerulus?

Thanks!

You might see a small window with a decrease in Cr following the beginning of a GN, but the creatinine soon heads upwards as the glomeruli get destroyed by the process causing the GN, and then they can't filter crap, let alone Cr, and the creatinine goes up. Don't expect "real life" GN to have a decrease in Cr.

 

[Yope]

Kidneys that do not eliminate creatinine properly will remove less from the blood, causing an increase in blood [creatinine] and lowering the concentration of urine [creatinine]. If one goes up the other has to go down.

As for the proteinuria the glomerular basement membrane is probably messed up, so there's no negative charge repulsion against anionic albumin and other proteins, hence the increase in urine [protein] despite an overall decrease in urine [creatinine].

 

[ero87]

So in (most) renal disease the glomerulus becomes leaky, allowing proteins to spill into the urine. I get that. So if this membrane is so leaky, why does the urine creatinine level drop?

Is renal blood flow decreasing, causing urine creatinine to drop? That would make sense to me - the kidneys are failing, so the afferent & efferent arterioles constrict, so less blood is sent to the kidneys to be filtered. At the glomerular level, 100% of creatinine is still being filtered, but less creatinine is getting to the glomerulus in the first place. Is that right?

Sorry, but I'm still struggling with this contradiction; the diseased glomerulus filters more protein and less creatinine, and I still don't really get how that can be.

 

[armybound]

Yes, blood flow decreases. Just remember that oliguria is one of the main symptoms of renal failure.

Proteinuria shows that the glomeruli are damaged but blood flow is preserved. Azotemia shows that blood flow is not preserved, or not effectively reaching the glomeruli to be filtered.

 

[Hoju]

decreased GFR --> increased blood creatinine

screwed up glomerulus --> allows protein to leak into urine even with decreased GFR

 

[Rokitansky]

decreased GFR --> increased blood creatinine

screwed up glomerulus --> allows protein to leak into urine even with decreased GFR

Everyone keeps repeating this, which I think the OP already knows/gets.

The way I'm reading the OP's question is this: If the GBM is leaky why isn't creatinine spilling out like protein?

The quick answer is that creatinine is an alkaloid derivative, which has very different chemical properties than proteins such as albumin. Don't just think of the damaged glomeruli as busted pipes through which anything can leak out, there is still a lot of chemistry at play. Loss of negatively charged GAGs, as someone mentioned above, helps albumin get through the GBM and leak out, but likely hinders creatine movement.

 

[armybound]

Everyone keeps repeating this, which I think the OP already knows/gets.

The way I'm reading the OP's question is this: If the GBM is leaky why isn't creatinine spilling out like protein?

The quick answer is that creatinine is an alkaloid derivative, which has very different chemical properties than proteins such as albumin. Don't just think of the damaged glomeruli as busted pipes through which anything can leak out, there is still a lot of chemistry at play. Loss of negatively charged GAGs, as someone mentioned above, helps albumin get through the GBM and leak out, but likely hinders creatine movement.

Serum creatinine is usually normal in minimal change disease

 

[Hoju]

You may be overly complicating it. Creatinine is already freely filtered in the normal state, and the GBM becoming more permeable to larger protein molecules probably doesn't significantly mess with the filtration fraction of creatinine.

Everyone keeps repeating this, which I think the OP already knows/gets.

The way I'm reading the OP's question is this: If the GBM is leaky why isn't creatinine spilling out like protein?

The quick answer is that creatinine is an alkaloid derivative, which has very different chemical properties than proteins such as albumin. Don't just think of the damaged glomeruli as busted pipes through which anything can leak out, there is still a lot of chemistry at play. Loss of negatively charged GAGs, as someone mentioned above, helps albumin get through the GBM and leak out, but likely hinders creatine movement.

 

[Rokitansky]

Serum creatinine is usually normal in minimal change disease

MCD is primarily a podocyte destruction issue, the GBM is not nearly as affected as in other glomerular diseases. I'm speculating of course, but without significant loss of anions creatinine (an alkaloid) can still be easily filtered.

 

[Rokitansky]

You may be overly complicating it. Creatinine is already freely filtered in the normal state, and the GBM becoming more permeable to larger protein molecules probably doesn't significantly mess with the filtration fraction of creatinine.

Like I said earlier, increased serum creatinine is not really related to the larger protein molecules. It's likely that the loss of anions from the GBM can hinder the movement of an alkaloid like creatinine (partial positive charge). For this reason in many glomerular diseases while you have tons of protein spilling into the urine you have creatinine retention, which initially seems counterintuitive and was the thing that was bugging the OP. At least that's what I got from his/her question.

I'm not always good at explaning stuff in sentences, so let me try this --

Damaged GBM or damaged podocytes --> larger slits --> larger molecules can get through
+
Loss of anions from GBM --> negatively charged large molecules (albumin) can get through (even better)

Separate issue --
Loss of anions from GBM (irrespective of how large or small the slits are) --> less movement of positively charged molecules

my $.02

 

[georgeissa7]

So in (most) renal disease the glomerulus becomes leaky, allowing proteins to spill into the urine. I get that. So if this membrane is so leaky, why does the urine creatinine level drop?

Sorry, but I'm still struggling with this contradiction; the diseased glomerulus filters more protein and less creatinine, and I still don't really get how that can be.

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acutely, proteinuria isn't really connected to creatinine levels in urine ..

however on a longer basis, proteinuria itself - for unclear reasons - causes more damage to the glomeruli, and that is when the the GFR becomes lower consequently casuing renal failure and high blood creatinine levels (low urine levels).

 

[evilbooyaa]

The reason creatinine increases is because of the decreased blood flow.

When everything is NORMAL in a kidney, creatinine is filtered and excreted without issue. Damaging the kidneys isn't going to somehow let more creatinine be filtered. On the other hand, albumin is NOT filtered in a normal kidney. The only time it spills into the urine is when there is some damage to the kidney.

 

[SpecterGT260]

The reason creatinine increases is because of the decreased blood flow.

When everything is NORMAL in a kidney, creatinine is filtered and excreted without issue. Damaging the kidneys isn't going to somehow let more creatinine be filtered. On the other hand, albumin is NOT filtered in a normal kidney. The only time it spills into the urine is when there is some damage to the kidney.

And fibrosis will result in generalized decrease in filtration with lower selectivity. Creatine will be diluted out in the urine and the overall decrease in filtration is what increases blood levels. This isn't different to what you just said. I'm only restating it another way

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