Hi, I am currently studying for step2 and am a bit confused about how ACE-I are contraindicated in renal failure, but are used to treat proteinuria which is one of the first signs of renal failure...

Are ACE-I contraindicated simply because they decrease GFR i.e. renal function by blocking the efferent constriction and when a kidney is in failure it's GFR is already low and thus decreasing it even lower will cause uremia and increase in Creatinine faster?

But because the efferent vessel is not constricted in a patient with minor kidney damage or someone who's just beginning to have kidney damage this will cause a decrease in intrarenal hypertension and thus prevent more kidney damage to occur, sure the GFR will drop in this patient and Creatinine will increase but because the GFR was normal to begin with that drop won't be as significant as the reduction of intrarenal hypertension and further renal destruction?

am I think through this correctly??

Thank you in advance for your help.

Just graduated, so I'm going to give you the pre-intern, I don't remember anything from medical school answer.

First off, lose the renal physiology, you won't need it on step 2.

Ace-I's are contraindicated in acute renal failure because they can exacerbate ACUTE renal failure. They are used for proteinuria and chronic renal disease as a long term solution to slow the progression of the disease.

thank you for the quick and dirty answer.. i know that quick and drity as all we need but it helps me remember the answer if i know how it works that way i don't have to memorize but can think it through, and that way it will stick in my head better.

Also attendings pimp physio and pathophys and don't just want the quick and drity answers so it will help with that too.

so was my thinking way off then?

Hi, I am currently studying for step2 and am a bit confused about how ACE-I are contraindicated in renal failure, but are used to treat proteinuria which is one of the first signs of renal failure...

Are ACE-I contraindicated simply because they decrease GFR i.e. renal function by blocking the efferent constriction and when a kidney is in failure it's GFR is already low and thus decreasing it even lower will cause uremia and increase in Creatinine faster?

But because the efferent vessel is not constricted in a patient with minor kidney damage or someone who's just beginning to have kidney damage this will cause a decrease in intrarenal hypertension and thus prevent more kidney damage to occur, sure the GFR will drop in this patient and Creatinine will increase but because the GFR was normal to begin with that drop won't be as significant as the reduction of intrarenal hypertension and further renal destruction?

am I think through this correctly??

Thank you in advance for your help.


ACE-I dilate the efferent arteriole-->decreasing blood supply to the glomerulus-->contributing to worsening renal fxn.

this is mine 2 cents (mind you I am a 2 year medical student)

In renal failure you have a decrease in Renal blood flow -> this causes decrease in Na absorption in macula densa ->increase in the Renin-Ang system -> this increase the GRF by constricting the eff more the afferent. Thus by inhibiting this system you have killed the only chance the kidney have to try and maintain GFR.

once again you are way higher up than me, so take my logic with a grain of salt.

no you're correct on the basic science part and how ACE-I would exacerbate renal failure..

my question is then why are they used to prevent progression of renal failure? I mean one of the clues to development of renal failure is proteinurea and ACE-I are used to treat that and prevent it's progression to chronic renal failure...

ACE-I dilate the efferent arteriole-->decreasing blood supply to the glomerulus-->contributing to worsening renal fxn.


then why are they given to patients with microalbuminurea and proteinurea to prevent it's progression? wouldn't they thus speed up progression?

Often what we know about a medication in pathophys and pharmocologic mechanisms doesn't always pan-out in large randomized controlled trials. often people with CKD have multiple medical problems and ACEIs don't act within a vacuum in the body.

Having said that, the two most common reasons for starting an ACEI is in patient's with Diabetes and patients with HTN.

Diabetes: The glomerular membrane becomes glycated and loses it charge barrier, therefore negatively charged molecules (i.e. albumin and other proteins) are freely filtered across the membrane. This further damages the glomerular membrane (like throwing rocks through a piece of SaranWrap). So, giving an ACEI decreases the glomerular pressure, eases the workload, and theoretically prevents further damage to the glomerular membrane.

HTN: The rational is similar to the above, except that the major pathophysiologic force in this example is hydrostatic pressure (increased arterial pressure) causing hyperfiltration across the glomerular membrane and, over time, chronic kidney disease for the reasons listed above.

Often HTN and DM occurs simultaneously with other medical problems, so the pathophysiology is not as cut and dry. What we do know is that ACEIs are effective in reducing the progression of kidney disease in patients with microalbumiuria AND/OR those with a GFR < 60.

There is a nice review in the current issue of Annals examining this particular question in those over 70.

RussianJoo, the pathophys in your first post is spot on. I believe it's cited in Rose's text on renal physiology. That explains why ACE-I could hurt in the setting of ARF. My crack-idea about ACE-I in diabetics is that long-term gradual reduction of GFR places less stress on the glomeruli, thus preserving its structural integrity, which prevents further leakage of protein. Don't take that as THE answer, just an idea. The literature is not clear on how or why it helps in this scenario. I believe the phrase I would run into is "mechanism not completely elucidated." The kidneys are very complex, and sometimes it's hard to establish a direct connection between pathophys and management logic. A nephrologist I worked with told me that sometimes trial results defy physiologic logic, but we have to go with what works on a macroscopic scale, even if it doesn't compute from what we know on a microscopic level.

Good luck with Step 2! Don't sweat too much of the details.

thanks for the help guys.. I guess I just have to look at ARF and CRF as two separate diseases with different etiologies. thus the same med in one can damage the kidney and it can protect it in the other.

thanks for the help guys.. I guess I just have to look at ARF and CRF as two separate diseases with different etiologies. thus the same med in one can damage the kidney and it can protect it in the other.

This is true. Acute kidney injury from moderate to severe dehydration or nephrotoxic insults is not going to have the same pathophys as diabetic nephropathy. For Step 2 and renal mechanisms, think classic textbook broad strokes. Like why do NSAIDs lead to renal failure, why does a marathon runner develop ARF, etc.

Often what we know about a medication in pathophys and pharmocologic mechanisms doesn't always pan-out in large randomized controlled trials. often people with CKD have multiple medical problems and ACEIs don't act within a vacuum in the body.

Having said that, the two most common reasons for starting an ACEI is in patient's with Diabetes and patients with HTN.

Diabetes: The glomerular membrane becomes glycated and loses it charge barrier, therefore negatively charged molecules (i.e. albumin and other proteins) are freely filtered across the membrane. This further damages the glomerular membrane (like throwing rocks through a piece of SaranWrap). So, giving an ACEI decreases the glomerular pressure, eases the workload, and theoretically prevents further damage to the glomerular membrane.

HTN: The rational is similar to the above, except that the major pathophysiologic force in this example is hydrostatic pressure (increased arterial pressure) causing hyperfiltration across the glomerular membrane and, over time, chronic kidney disease for the reasons listed above.

Often HTN and DM occurs simultaneously with other medical problems, so the pathophysiology is not as cut and dry. What we do know is that ACEIs are effective in reducing the progression of kidney disease in patients with microalbumiuria AND/OR those with a GFR < 60.

There is a nice review in the current issue of Annals examining this particular question in those over 70.

I agree with this...and explained better than I ever could.
Russianjoo,
your explanation/ideas in original post are correct as well.

I agree with this...and explained better than I ever could.
Russianjoo,
your explanation/ideas in original post are correct as well.

Here is the link I was referring to:
http://www.annals.org/cgi/content/abstract/150/10/717

Also in this issue is the cursed article on the "Demise of primary care" that will no doubt cause more med students to jump ship and further exacerbate the problem.:scared:

I was always taught that ACE inhibitors modulate chronic renal failure through their effects on glomerular hyperfiltration. Depending on the disease process, there is often a glomerular hyperfiltration which ultimately leads to glomerular failure and progression of the the chronic renal failure. In diabetes, this is thought to be 2/2 alterations in the RAS system, whereas in HTN, this can be directly 2/2 to the high blood pressure and loss of renal parenchyma (via fibrosis and shunting of blood to "good" glomeruli--worsening the hyperfiltration). This reduction in GFR assoc with ACEs is thus helpful in chronic renal failure, but deleterious in acute renal failure.

Google hyperfiltration and ACE and lots of articles will come up.

It's starting to get redundant in here.

seems renal docs try to push the ACEi to the limit for people in CRF; treat the high K with Na polystyrene and hope for the best; also treat the HTN agressively; as long as K is less then 6.5!