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Discussion Starter · #1 ·
In Goljan it is given,

that ACE inhibitors are beneficial in diabetic nephropathy cause they maintain renal perfusion beyond efferent arteriole and thereby supplying blood to kidney parenchyma.

but in UW its given ACE mediated nephrotoxity is due to :

"RENAL HYPOPERFUSION"

??????????????
:notsure::notsure::notsure::notsure::confused::confused::confused::confused:
 

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Discussion Starter · #3 ·
sorry

sorry but can u plz stress on their mechanism???

i mean to say that how they cause hypoperfusion even if they are causing efferent arteriolar dilation???
 

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In case of renal artery sclerosis we have only one regulatory mechanism - ATII constrict the efferent arteriole (see FA, p.458). In the other words "we" can't dilate afferent arteriole (because it sclerotic). So we can increase GFR/perfussion ONLY by constricting efferent arteriole by Angiotensin II.
If we will use ACE inhibitors we just block to conversion of AT to ATII and we will have lost control to renal perfusion.

Actually in some causes (may be in most) renal artery sclerosis is not well recognised. :(
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1113401/
 
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sorry but can u plz stress on their mechanism???

i mean to say that how they cause hypoperfusion even if they are causing efferent arteriolar dilation???
According to Raymon, the mechanism is not very well known.

It's thought that ACE inhibitors reduce the progress of diabetic nephropathy independently from their blood pressure-lowering effect.http://en.wikipedia.org/wiki/ACE_inhibitor#cite_note-2This action of ACE inhibitors is utilised in the prevention of diabetic renal failure.
 

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yes vasodilation of efferent arteriole will lead to decreased GFR and decreased renal function and may give rise to high BUN and creatinine but on the short term basis and providing long term beneficial effect in reducing microalbuminuria and hypertension in case of diabetics , so its good to be used in diabetic nephropathy but alone not in combination with ARBS because both can worsen the function to a high level

in case of renal artery stenosis , renal ischemia leads to activation of renin angiotensin , AGT2 vasoconstricts and incrases the perfusion using the ace inhibitors will compromise the renal function specially when the aldosterone is extremely high in stenosis
 

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what you are confusing is agt2 vasocontriction with ace mediated vasodilation

agt2 vaasoconstriction ll increase renal perfusion meaning less blood in peripheries and more in central organs , lungs , kidneys , brain , heart

ace mediated vasodilation ll meaning more blood in peripheries and less load on heart so there u go
 

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this ll help u understand

ACE inhibitors block the conversion of angiotensin I to angiotensin II. They, therefore, lower arteriolar resistance and increase venous capacity; increase cardiac output, cardiac index, stroke work, and volume; lower renovascular resistance; and lead to increased natriuresis (excretion of sodium in the urine). Renin will increase in concentration in the blood due to negative feedback of conversion of AI to AII. Angiotenson I will increase for the same reason. AII will decrease. Aldosterone will decrease. Bradykinin will increase due to less inactivation that is done by ACE enzyme.
Under normal conditions, angiotensin II will have the following effects:

  • vasoconstriction (narrowing of blood vessels), which may lead to increased blood pressure and hypertension
- constriction of the efferent arterioles of the kidney, leading to increased perfusion pressure in the glomeruli.
  • Contribute to ventricular remodeling and ventricular hypertrophy of the heart.
  • stimulation of the adrenal cortex to release aldosterone, a hormone that acts on kidney tubules to retain sodium and chloride ions and excrete potassium. Sodium is a "water-holding" molecule, so water is also retained, which leads to increased blood volume, hence an increase in blood pressure.
  • stimulation of the posterior pituitary to release vasopressin (also known as anti-diuretic hormone (ADH)), which also acts on the kidneys to increase water retention.
  • decrease renal protein kinase C.
With ACE inhibitor use, the effects of angiotensin II are prevented, leading to decreased blood pressure.
 

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As far as I know, AT II constricts both the afferent and efferent arteriole. However, it contracts efferent more than afferent. This leads to less perfusion with increased plasma filtration fraction, and, therefore, increased Glomerular Filtration Rate.

So, in a diabetic that still does not have renal impairment, ACE inhibitors increase perfusion, but would decrease GFR if there were no compensatory mechanisms... But, as the exist, ACE inhibitors increase perfusion and don't change GFR, what is perfect to diabetic because its nephropathy is due to microvascular insufficiency.

Actually, a patient that donated its kidney is not insufficient because its other kidney nephrons have compensatory mechanisms that improves his renal function up to 80% of the original.

However, if your patient already has renal insufficiency, due to any cause, he lost nephrons and the remaining ones, althought they are working at maximum rate, are not able to compensate. If you give ACE inhibitors to this patient, you will increase perfusion and decrease GFR because, remember, - ATII contracts both arterioles, but efferent more - and - these nephrons are working at maximum capacity and, therefore, have no compensatory mechanisms to use. This leads to a best perfusion, but a decrease in renal function.

Because of this, ACE inhibitors are indicated to Hypertension and Diabetes coexistence, but contraindicated when there is Renal Insufficiency.

I'm sorry for english mistakes I hope I was clear.
 

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I am really sorry but i still fail to understand the exact reasoning of ACEi cointraindication in Renal Artery Stenosis.

If ACEi increase the overall perfusion of kidney which is what is decreased in the Renal Artery Stenosis, why would it be contraindicated? I mean, wouldn't you want ATII to be decreased? This would lead to dilated efferent arteriole so even if its less blood coming from the afferent, at least we will send it more in the later part or something. I hope i am able to convey my confusion here and hopefully get a better explanation.
 

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Because even though ACE inhibitors increase overall kidney perfusion, they decrease glomerular perfusion. That's great in something like diabetic nephropathy where glomerular hypertension is accelerating the glomerulosclerosis - but it could be dangerous in something like bilateral renal artery stenosis, where the atII-constricted efferent arteriole is the only thing maintaining the glomerular pressure that is needed to maintain renal function.
 

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Because even though ACE inhibitors increase overall kidney perfusion, they decrease glomerular perfusion. That's great in something like diabetic nephropathy where glomerular hypertension is accelerating the glomerulosclerosis - but it could be dangerous in something like bilateral renal artery stenosis, where the atII-constricted efferent arteriole is the only thing maintaining the glomerular pressure that is needed to maintain renal function.
None could have cleared my doubts any better. Thanks a lot dude!
 

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That definitely clears up why Ace inhibitors are contraindicated in renal artery stenosis. Thanks!
One more question tho.
How do Ace Inhibitors increase nateuresis if they decrease GFR??
 

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That definitely clears up why Ace inhibitors are contraindicated in renal artery stenosis. Thanks!
One more question tho.
How do Ace Inhibitors increase nateuresis if they decrease GFR??
ACE Inhibitors reduce Aldosterone, thereby reducing the channels for sodium and water reabsorption in collecting duct... Hence they cause natriuresis.
 

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Ace inhibitors

In diabetics - it has a reno protective effect. It delays renal damage . Delays not block.There is a difference . It will slow down the galloping effect of chronic DM on creatinine rise.Eventually , the DM will push up the creatinine values even though you have ace in place.

Separate from the above is that Ace inhibitors cause renal damage. A small rise in creatinine is tolerated.Hence after 1 week check creatinine level . If damage is not tolerable stop it and move on to another class of medications. If its tolerable and check over the next 2-3 weeks doing renal funtion weekly.
- if it is so. If after the first check a week later cretinine not affected - then no need to do follow up the following week.

In bilat renal artery stenosis - do NOT use ace at all . It will shut down the kidneys via decreased GFR .
 
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