ACE-Inhibitor dose and renal protection

[shroomysoup]

Is the renal protection with ACE-Inhibitors dose dependent? In other words, does increasing the dose provide better renal protection? Thanks for responses!

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[patmcd]

Is the renal protection with ACE-Inhibitors dose dependent? In other words, does increasing the dose provide better renal protection? Thanks for responses!

There is plenty of info out there on this question. Fire up pubmed or OVID.

 

[Requiem]

pubmed is only good, to quote our DI pharmacist, once you have the studies you need to look up.

to find general info try uptodate or pharmacist's letter(is this a canadian ref? you guys never talk about it)

 

[shroomysoup]

pubmed is only good, to quote our DI pharmacist, once you have the studies you need to look up.

to find general info try uptodate or pharmacist's letter(is this a canadian ref? you guys never talk about it)

What is uptodate? And is pharmacist's letter free?

 

[stevephhs016]

Never really heard about that. I actually would even think it would be the opposite way around? Since it does increase Cr slightly with higher doses?

 

[Praziquantel86]

Never really heard about that. I actually would even think it would be the opposite way around? Since it does increase Cr slightly with higher doses?

It does seem somewhat counterintuitive, especially given the initial increase in serum creatinine. However, there are many studies showing the renal-protective effect, especially in diabetics. ACE inhibitors are now the standard of care in diabetics, regardless of their baseline blood pressure standing.

 

[PumpkinSmasher]

ARB me matey... in case they get a little coughy cough works too.

 

[mdx2x]

The only ones that are approved for renal protection:

ACE: 25 mg tid, captopril
ARBS: Irbesartan 300mg/day, losartan 50mg/day

Remember ACE2** can raise BP, and constricts the arteriole causing pressure on the glomerulus -> causing injury.

ACE-I lowers GFR pressure and slows injuy.

NB: All ACE can be given with food! except for Cap, Moex

Edit:
**I meant Angiotensin-2

 

[Praziquantel86]

The only ones that are approved for renal protection:

ACE: 25 mg tid, captopril
ARBS: Irbesartan 300mg/day, losartan 50mg/day

Remember ACE2 can raise BP, and constricts the arteriole causing pressure on the glomerulus -> causing injury.

ACE-I lowers GFR pressure and slows injuy.

NB: All ACE can be given with food! except for Cap, Moex

I agree for the most part, except for a few points (more semantics, really). It's Angiotensin II that causes the BP rise, not ACE2. Also, ACE-I's don't lower GFR pressure; they lower filling pressure within the glomerulus, thereby causing a decrease in GFR.

Keep in mind that this is considered a class effect among ACE-Is and ARBs, regardless of whether they carry FDA approval for that specific indication.

 

[PumpkinSmasher]

The only ones that are approved for renal protection:

ACE: 25 mg tid, captopril
ARBS: Irbesartan 300mg/day, losartan 50mg/day

Remember ACE2 can raise BP, and constricts the arteriole causing pressure on the glomerulus -> causing injury.

ACE-I lowers GFR pressure and slows injuy.

NB: All ACE can be given with food! except for Cap, Moex

That's nice.

 

[mdx2x]

I agree for the most part, except for a few points (more semantics, really). It's Angiotensin II that causes the BP rise, not ACE2. Also, ACE-I's don't lower GFR pressure; they lower filling pressure within the glomerulus, thereby causing a decrease in GFR.

Keep in mind that this is considered a class effect among ACE-Is and ARBs, regardless of whether they carry FDA approval for that specific indication.

Sorry Yes, you are correct. I meant Angiotensin II.

When you give an ACE-I there's a reduction of
Angiotensin II, therefore lowers GFR pressure via
decreasing arterial bp and dilation of efferent arterioles.

Yes it is class effect, but wasn't sure if he wanted the approved ones.

 

[acetyl]

If you're concerned with diabetic patients:
Ramipril, Enalapril, Captopril, Lisinopril have all shown benefit in kidney disease.

 

[acetyl]

Sorry Yes, you are correct. I meant Angiotensin II.

When you give an ACE-I there's a reduction of
Angiotensin II, therefore lowers GFR pressure via
decreasing arterial bp and dilation of efferent arterioles.

Angiotensin II inhibition mostly dilates the efferent arteriole, causing reduced tubular pressure..not really "GFR pressure". Reduced tubular pressure results in a decreased rate of filtration, as said above.

It's all about preventing the hypertrophy. The body tries to fix the problem, but it's no good in the long-term!

 

[DrCbass]

Is the renal protection with ACE-Inhibitors dose dependent? In other words, does increasing the dose provide better renal protection? Thanks for responses!

I would suggest looking over the K/DOQI guidelines... good place to start by looking at the studies they have referenced.

 

[mdx2x]

Sorry maybe I'm just not saying it... in the right way:
Don't want to give the wrong information to the OP's question so I'm quoting now:

Goodman And Gilman's
"Several mechanisms participate in the renal protection afforded by ACE inhibitors. Increased glomerular capillary pressure induces glomerular injury, and ACE inhibitors reduce this parameter both by decreasing arterial blood pressure and by dilating renal efferent arterioles."

Harrison's:
"Since angiotensin II increases efferent arteriolar resistance and, hence, glomerular capillary pressure, one key mechanism for the efficacy of ACE inhibitors or angiotensin receptor blockers (ARBs) is reducing glomerular hypertension. Patients with Type 1 diabetes for 5 years who develop albuminuria or declining renal function should be treated with ACE inhibitors. Patients with Type 2 diabetes and microalbuminuria or proteinuria may be treated with ACE inhibitors or ARBs."

Heptinstall's
"The effects of these agents are complex but include alterations in glomerular hemodynamics resulting in decrease of hyperfiltration, inhibition of glomerular and tubular hypertrophy, and lowering of systemic blood pressure"

Lehne's
"The principal protective mechanism appears to be reduction of glomerular filtration pressure, ACE inhibitors lower filtration pressure by reducing levels of angiotensin II, a compound that can raise the filtration pressure by two mechanisms. First angiotensin II raises systemic blood pressure, which raisses pressure in the afferent arteriole of the glomerulus. Second it constricts the efferent arteriole, thereby generating backpressure in the glomerulus. The resultant increase in filtration pressure promotes injury. By reducing levels of angiotensin II, ACE inhibitor lower glomerular filtration pressure, and thereby slow development of renal injury.

At this time, the only ACE inhibitor actually approved for nephropathy is captopril. However, the American Diabetes Association considers benefits in diabetic nephropathy to be a class effect, and hence recommends choosing an ACE inhibitor based on its cost and likelihood of patient compliance."

 

[Pharmavixen]

Question for the hospital folks: the guidelines and monographs universally tell us ACEIs are contraindicated in renal artery stenosis. How commonplace is it to determine the condition of patients' renal arteries?

 

[Requiem]

Question for the hospital folks: the guidelines and monographs universally tell us ACEIs are contraindicated in renal artery stenosis. How commonplace is it to determine the condition of patients' renal arteries?

"Diagnosis/pt. having bilateral renal artery stenosis is extremely rare"

 

[28657]

Question for the hospital folks: the guidelines and monographs universally tell us ACEIs are contraindicated in renal artery stenosis. How commonplace is it to determine the condition of patients' renal arteries?

It's actually very common to hold ACE Inhibitors, ARBs and NSAIDs for patients who experience acute renal failure. Pre-renal azotemia, the most common cause of acute renal failure for hospitalized patients, is a result of reduced blood flow to the kidneys. As said before (in more esoteric terms ) ACEI, ARBS, and NSAIDs can decrease blood flow through the kidney.

Most patients in the ICU have these meds held after 'damage' has been done. A patient can have RAS 'before' any damage occurs.... Therefore, we as pharmacists, don't determine the condition of patients' renal arteries - that's what the doctors do. But we can help in recommending D/C once the SCr starts climbing.

 

[Glycerin]

It's actually very common to hold ACE Inhibitors, ARBs and NSAIDs for patients who experience acute renal failure. Pre-renal azotemia, the most common cause of acute renal failure for hospitalized patients, is a result of reduced blood flow to the kidneys. As said before (in more esoteric terms ) ACEI, ARBS, and NSAIDs can decrease blood flow through the kidney.

Most patients in the ICU have these meds held after 'damage' has been done. A patient can have RAS 'before' any damage occurs.... Therefore, we as pharmacists, don't determine the condition of patients' renal arteries - that's what the doctors do. But we can help in recommending D/C once the SCr starts climbing.

Ditto. This was a very common thing to see on my IM rotation.

By the way, not to derail the thread, but long time, no see, Amanda. It's FutureRxGal, from back in the day.

 

[meister]

ACE-Is lower GFR and increase RPF/RBF by dilating efferent arterioles and decreasing renal vascular resistance, therefore they lower FF. That's all I know.*


*seriously, that's everything. I don't even know how to typ

 

[MdBrndPhrmcst]

Lehne's
"The principal protective mechanism appears to be reduction of glomerular filtration pressure, ACE inhibitors lower filtration pressure by reducing levels of angiotensin II, a compound that can raise the filtration pressure by two mechanisms. First angiotensin II raises systemic blood pressure, which raisses pressure in the afferent arteriole of the glomerulus. Second it constricts the efferent arteriole, thereby generating backpressure in the glomerulus. The resultant increase in filtration pressure promotes injury. By reducing levels of angiotensin II, ACE inhibitor lower glomerular filtration pressure, and thereby slow development of renal injury."


this is the best explanation i've seen so far