Two questions on diuretics

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1) Why is mannitol contraindicated in anuria?

2) Given that spironolactone increases plasma K+ and H+, it is contraindicated in renal failure. Therefore, what about the ACE-inhibitors / ATII-receptor blockers?

1. Mannitol does not influence urine production, only enhances existing urine output. If there is no production (as in ARF) you would have hyperosmotic plasma due to mannitol since it would be trapped in that compartment (and thus be of no benefit and possible harm).

Plus I think I remember something where mannitol can contribute to renal failure by saturating some pathway for excretion of acids or what not in the kidney, not sure about this one though.

2. "Renal impairment is a significant adverse effect of all ACE inhibitors, but the reason is still unknown. Some suggest it is associated with their effect on angiotensin II-mediated homeostatic functions, such as renal blood flow. Renal blood flow may be affected by angiotensin II because it vasoconstricts the efferent arterioles of the glomeruli of the kidney, thereby increasing glomerular filtration rate (GFR). Hence, by reducing angiotensin II levels, ACE inhibitors may reduce GFR, a marker of renal function. To be specific, they can induce or exacerbate renal impairment in patients with renal artery stenosis. This is especially a problem if the patient is concomitantly taking an NSAID and a diuretic. When the three drugs are taken together, there is a very high risk of developing renal failure" - Wikipedia
Reference quoted: Thomas (2000). "Diuretics, ACE inhibitors and NSAIDs--the triple whammy". The Medical journal of Australia 172 (4): 184–5. PMID 10772593.

So it seems ACE-I and ARBs do impair renal function especially if combined with other nephrotoxic drugs. However, this is probably weighted with possible benefits. ACE-I haven proven effect of cardiac remodeling for example. Much in the same way why you administer fluoroquinolones to kids with meningitis. In all other scenarios fluoroquinolones are strongly contraindicated for use by children except in acute bacterial meningitis because the benefits outweigh the complications.


EDIT: My hunch was correct regarding mannitol
https://www.medify.com/insights/art...oning-anuria-caused-by-a-diuretic?ref=related

It can cause renal failure in patients with impaired renal function.
 
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ACE Inhibitors and ARBs can precipitate acute renal failure. You need to use ACEI with caution in the following:

1. bilateral renal artery stenosis
2. decompensated heart failure
3. chronic kidney disease
4. volume depletion

ACEI are great to prevent the heart remodeling associated with CHF and the remodeling in diabetic renal disease. But you can only stop the progression to diabetic nephropathy if you start the patient on ACEI early enough. I believe for diabetics it's when they first have microalbuminemia in the urine.

There's no absolute contraindication to using ACEI in renal failure but that is a decision made clinically based on the patient. No specific protocol/cuttoff creatinine levels to go off. If the physician thinks the patient will benefit from ACEI despite the risks then patient gets ACEI, if not patient will get something else.
 
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