ACE-Inhibitor increasing creatinine clearance?

[WashMe]

I can't figure out why an ACE-inhibitor increases creatinine clearance in patients with renal artery stenosis. Preventing angiotensin effects-- which include efferent>afferent vasoconstriction-- seems like it would decrease glomerular filtration pressure and GFR. My only thought is that somehow the decreased perfusion pressure leads to some sort of hypoxic tubule damage, causing increased creatine secretion (thus allowing high creatinine in a low GFR state). The point was made in a cardiovascular pathophys class, but I guess I don't know enough renal pathophys to understand it. Ideas?

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[TobiasFish]

Here are my thoughts:

Its true about angiotensin II being a vasoconstrictor but it also has other effects.

ACE inhibitors block the conversion of angiotensin I to angiotensin II, and thus decrease the levels of aldosterone. Lower levels of aldosterone means more water is going to be secreted into the nephron and dilute the urine (despite stenosis). Thus GFR is going to go up and more creatinine is going to be secreted.

Hope this helps.

I posted some notes on the physiology of the kidney, maybe this will help.

 

[WashMe]

Here are my thoughts:

Its true about angiotensin II being a vasoconstrictor but it also has other effects.

ACE inhibitors block the conversion of angiotensin I to angiotensin II, and thus decrease the levels of aldosterone. Lower levels of aldosterone means more water is going to be secreted into the nephron and dilute the urine (despite stenosis). Thus GFR is going to go up and more creatinine is going to be secreted.

Hope this helps.

I posted some notes on the physiology of the kidney, maybe this will help.

Thanks for the reply. I guess the bolded portion is what confuses me. I understand that you will lose aldosterone, thus you wont have as many ENaC channels in the collecting duct and you'll be forced to put out dilute urine in higher volume. I don't see how this will increase creatinine though, because the hemodynamics at the nephron are what would determine creatinine clearance (and the loss of AngII will decrease filtration pressure). Creatinine is only mildly secreted, so my thought is that there must be some nephron pathology that leads to abnormally high creatinine clearance when you give an ACE-I to a renal artery stenosis patient. I don't know how it would work though.

It seems like since the collecting duct is the end point, it wouldn't affect creatinine clearance (i.e., you'd excrete a constant amount of creatinine, regardless of activity, or lack thereof, of aldosterone-- the creatinine would just be concentrated or diluted, respectively. The upstream GFR should not increase due to the downstream status of the collecting duct.)

 

[Ariodant]

In renal artery stenosis, blood flow to the kidney is impaired, so creatinine clearance goes down simply because not much is making its way to the glomerulus. Once you block AGII, vessels dilate and you get increased blood flow, which not only increases your GFR but also preserves renal function in the long term, delays kidney atrophy, and helps with patient survival.

 

[WashMe]

In renal artery stenosis, blood flow to the kidney is impaired, so creatinine clearance goes down simply because not much is making its way to the glomerulus. Once you block AGII, vessels dilate and you get increased blood flow, which not only increases your GFR but also preserves renal function in the long term, delays kidney atrophy, and helps with patient survival.

This sounds a lot like what they said, so you're probably right. I still don't understand how vasodilation by AngII leads to increased GFR. Since you vasodilate the efferent arteriole more than the afferent arteriole when you block AngII, you're actually decreasing the filtration pressure that will squeeze fluid and solutes into Bowman's space, so it seems like GFR would drop off. I mean, doesn't AngII normally increase filtration? Blocking AngII production seems like it would decrease filtration...

 

[TobiasFish]

Oh i see you point, but Creatinine is also secreted (albeit to a small extent) in the proximal tubule, so i guess i was just assuming that the more dilute the urine was the more creatinine that would be secreted. This is why creatinine isn't a perfect substrate to measure the GFR. Also the more dilute the urine, the more creatinine that will be absorbed from the blood.

 

[atengnr]

I can't figure out why an ACE-inhibitor increases creatinine clearance in patients with renal artery stenosis. Preventing angiotensin effects-- which include efferent>afferent vasoconstriction-- seems like it would decrease glomerular filtration pressure and GFR. My only thought is that somehow the decreased perfusion pressure leads to some sort of hypoxic tubule damage, causing increased creatine secretion (thus allowing high creatinine in a low GFR state). The point was made in a cardiovascular pathophys class, but I guess I don't know enough renal pathophys to understand it. Ideas?

I havent heard that clearance increases. Shouldnt it decrease due to decreased GFR? This is the basis of the captopril renal scan, as I understand it.

 

[WashMe]

I havent heard that clearance increases. Shouldnt it decrease due to decreased GFR? This is the basis of the captopril renal scan, as I understand it.

That's what I thought, but the points was made 3 different times in the same lecture (which I didn't attend but later read, thus I haven't asked the doc). The thing is, people make a big deal about stopping ACE-I's if a patient with kidney disease exhibits a >30% increase in creatinine clearance, so it must happen-- I just don't see how or why...

 

[WashMe]

Oh i see you point, but Creatinine is also secreted (albeit to a small extent) in the proximal tubule, so i guess i was just assuming that the more dilute the urine was the more creatinine that would be secreted. This is why creatinine isn't a perfect substrate to measure the GFR. Also the more dilute the urine, the more creatinine that will be absorbed from the blood.

That may be. To be honest, I never learned exactly where stuff gets secreted in the nephron. Your idea would make sense if the secretion occurs in the collecting duct, but not if it occurs anywhere else, because the osmolarity in other sections of the tubule doesn't really define the end urine concentration directly. Those tubular fluid milieus should be similar across most patients in the absence of loop diuretic use, thiazides, diabetes, or other such diseases.

 

[turkeyjerky]

where are you guys getting the idea that ACE inhibition leads to increased GFR in the setting of renal artery stenosis? Ang II acts to protect GFR by preferentially constricting the efferent arterioles. This maintains GFR in the setting of decreased renal perfusion (ie, in the setting of renal artery stenosis). Block ACE, and you lose that effect--the patient's creatinine will go up (gfr will go down).

That's why elevation in a patient's creatinine is suggestive of renal artery stenosis; turns out that this usually only happens when both renal arteries are stenotic.

 

[turkeyjerky]

That's what I thought, but the points was made 3 different times in the same lecture (which I didn't attend but later read, thus I haven't asked the doc). The thing is, people make a big deal about stopping ACE-I's if a patient with kidney disease exhibits a >30% increase in creatinine clearance, so it must happen-- I just don't see how or why...

Either you're misinterpreting the lecturer's notes, or he's an idiot.

You know, I think you're misinterpreting serum creatinine with "creatinine clearance".

 

[Dirt]

ACEs decrease creatinine clearance.

 

[WashMe]

where are you guys getting the idea that ACE inhibition leads to increased GFR in the setting of renal artery stenosis? Ang II acts to protect GFR by preferentially constricting the efferent arterioles. This maintains GFR in the setting of decreased renal perfusion (ie, in the setting of renal artery stenosis). Block ACE, and you lose that effect--the patient's creatinine will go up (gfr will go down).

That's why elevation in a patient's creatinine is suggestive of renal artery stenosis; turns out that this usually only happens when both renal arteries are stenotic.

Either you're misinterpreting the lecturer's notes, or he's an idiot.

You know, I think you're misinterpreting serum creatinine with "creatinine clearance".

The notes say "CrCl,", but I believe you because it doesn't make any sense otherwise. GFR has to go down, so I just couldn't see how creatinine clearance would go up. It definitely makes sense that serum creatinine would be elevated though. Thanks 🙂

ACEs decrease creatinine clearance.

That makes sense, thanks. Lecturer must have written some bad notes; if "CrCl" means creatinine clearance, the mistake was made a few times and it screwed me up.

 

[senseiturtle]

This was a STEP 2 question.

Ace inhibitors are CONTRAINDICATED in renal artery stenosis.

Taken from a random website (CVpharmacology.com), but this reflects my current understanding.

Patients with bilateral renal artery stenosis may experience renal failure if ACE inhibitors are administered. The reason is that the elevated circulating and intrarenal angiotensin II in this condition constricts the efferent arteriole more than the afferent arteriole within the kidney, which helps to maintain glomerular capillary pressure and filtration. Removing this constriction by blocking circulating and intrarenal angiotensin II formation can cause an abrupt fall in glomerular filtration rate. This is not generally a problem with unilateral renal artery stenosis because the unaffected kidney can usually maintain sufficient filtration after ACE inhibition; however, with bilateral renal artery stenosis it is especially important to ensure that renal function is not compromised.

If I'm wrong, then we could all probably use the education anyway.

 

[Ariodant]

I think turtle was right, I was confusing ACEi with something else, sorry. NSAIDs are also contraindicated in renal artery stenosis. I'm only 6 months removed from medschool and everything is a blur already, oh no...🙁

That said, I don't see why increased creatine clearance would be bad regardless, had to be a typo.

 

[da8s0859q]

ACEs decrease creatinine clearance.

This, for the same efferent > afferent constriction reasoning.

Creatinine goes up, and potassium goes up.

 

[WashMe]

This, for the same efferent > afferent constriction reasoning.

Creatinine goes up, and potassium goes up.

Because you've blocked the Aldo effect at then end of RAAS with the ACEi? Sorry, I'm a renal noob.

 

[da8s0859q]

Because you've blocked the Aldo effect at then end of RAAS with the ACEi? Sorry, I'm a renal noob.

Yep!

 

[TobiasFish]

This was a STEP 2 question.

Ace inhibitors are CONTRAINDICATED in renal artery stenosis.

Taken from a random website (CVpharmacology.com), but this reflects my current understanding.




If I'm wrong, then we could all probably use the education anyway.

Actually ACE inhibitors are used in treating refractory renal artery stenosis, but they are not first line. It is important to monitor creatinine clearance when the patient is on it, but they are accepted in clinical practice.

Check the literature: http://www.google.com/url?sa=t&sour...wJn7HQhew&sig2=egTcawOytqcJ68Yv5f6dLQ&cad=rja

 

[Dirt]

Actually ACE inhibitors are used in treating refractory renal artery stenosis, but they are not first line. It is important to monitor creatinine clearance when the patient is on it, but they are accepted in clinical practice.

Check the literature: http://www.google.com/url?sa=t&source=web&cd=1&ved=0CBUQFjAA&url=http%3A%2F%2Fwww.nejm.org%2Fdoi%2Fpdf%2F10.1056%2FNEJMoa0905368&rct=j&q=renal%20artery%20stenosis%20astral%20&ei=n2icTPGuF8-TjAfjxIGCDQ&usg=AFQjCNECqDX0ALF3pyI35dwwpwJn7HQhew&sig2=egTcawOytqcJ68Yv5f6dLQ&cad=rja

That article merely illustrates that medical management may be superior to revascularization with equal survival and less adverse effects but it does not speak directly towards the use of ACEs in renal artery stenosis.


For those reading this, if you ever get a question on any test ever ACEs are contraindicated in renal artery stenosis.

 

[turkeyjerky]

That article merely illustrates that medical management may be superior to revascularization with equal survival and less adverse effects but it does not speak directly towards the use of ACEs in renal artery stenosis.


For those reading this, if you ever get a question on any test ever ACEs are contraindicated in renal artery stenosis.

No, I agree with the above poster. Medical management of renal artery stenosis involves ACE-inhibitors. In fact, other anti-hypertensives are unlikely to be effective in this condition. You just have to monitor Cr carefully and balance the dosage to avoid acute renal failure.

 

[TobiasFish]

That article merely illustrates that medical management may be superior to revascularization with equal survival and less adverse effects but it does not speak directly towards the use of ACEs in renal artery stenosis.


For those reading this, if you ever get a question on any test ever ACEs are contraindicated in renal artery stenosis.

Part of the 'superior medical treatment' includes ACE inhibitors--as would be true for many treatment regimens for renal artery stenosis. But I will grant you most USMLE books will probably (incorrectly) list it as contraindicated.