Thanks, right now I'm investigating other options for my symptoms.
Glad to see you seem to be back on here, in any case.
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BP Meds possibly linked to kidney damage
- Thread starter Bodyofwork365
- Start date
Glad to see you seem to be back on here, in any case.
as an aside, my concerns are mostly based on the fact that I suffered at least one verified AKI in the past (three days in the ER, aided fluid ressuscitation,...), then had two more ER episodes, both from acute hypertensive urgencies,
might make me more prone to kidney issues down the line, although I obviously cannot prove it.
That's why the kidney health issue is often at the back of my mind these days.
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The safety of ARBs is an important topic, especially considering the ever increasing number of bodybuilders who take these drugs without proper medical supervision.
User 'Type-IIx' has already pointed out the two main areas of concern: (1) Acute kidney failure in those who have certain underlying conditions and (2) Hyperkalemia.
Let's first explore the cause of (1). Below you see an illustration of a glomerulus, of which each kidney has about a million and which together do all the filtering.
As you can see, the blood flows in through the 'afferent' arteriole and flows out through the 'efferent' arteriole. Angiotensin II is a hormone that leads to constriction (narrowing) of the efferent arteriole (and more so than for the afferent arteriole), which in turn increases pressure within the glomerulus, which leads to more filtration. ARBs (angiotensin receptor blockers) prevent Angiotensin II from attaching to its receptors and thereby lead to vasodilation (widening) of the efferent arteriole. As a result, pressure in the glomerulus decreases, which in turn lowers the filtration rate. So when you start to take an ARB, your (estimated and actual) glomerular filtration rate (GFR) will decrease, which will be reflected by a higher Creatinine serum level. This is perfectly normal and does not indicate any damage to the kidneys.
However, when the reduction in eGFR, or equivalently, the increase in serum Creatinine is too high, then this could indicate an underlying health issue such as Renal artery stenosis (RAS).
RAS is most often caused by atherosclerosis, so the usual risk factors for atherosclerosis will also increase your likelihood of RAS. In people with RAS, blood flow through the afferent arteriole is reduced (generally due to plaque higher up in the renal artery). In that situation, the Angiotensin II mediated vasoconstriction in the efferent arteriole (outflow) is essential to maintaining sufficient pressure in the glomerulus.
If you take an ARB in that situation, the pressure in the glomerulus can decrease by so much that "renal ischemic nephropathy develops and renal failure ensues" [1].
Hence, everybody, but especially those with risk factors for atherosclerosis (male, age>50, smoking, high saturated fat intake, bad lipids on bloodwork, family history of CVD), should do bloodwork before and 10-14 days after their first dose of an ARB or ACEi. If there is a greater than ~20 per cent increase in serum creatinine, then you have to immediately stop taking the ARB and consult a doctor to figure out your underlying conditions. In addition, you should start with a low dose (such as 40mg Telmisartan) and only increase the dosage if necessary. As I will discuss in my next post, there may be good reasons to stick to moderate dosages and to combine ARBs with other BP meds if necessary to achieve optimal blood pressure.
It is worth noting that ARBs are generally very well tolerated. It is very very rare for them to cause serious side effects such as acute kidney failure. But a small risk remains and so I highly recommend everyone to do the bloodwork to be on the safe side.
Speaking of blood work, it should also include potassium levels. As noted in (2) hyperkalemia (excess potassium levels in the blood) is another potential side effect of ARBs. Hyperkalemia occurs in up to 6% of users [2]. Severe hyperkalemia can cause cardiac arrhythmias, which is particularly concerning for enhanced bodybuilders with their high risk of undiagnosed cardiomyopathy.
The risk of hyperkalemia is increased by taking potassium supplements, using salt substitutes, taking beta-blockers, and taking potassium‐sparing diuretics. So avoid all that and regularly get blood work to check on your potassium levels.
OK, now we covered the common short-term side effects of ARBs and what to do about them. In the next post I will discuss the actual topic of this thread, namely potential long-term detrimental effects of ARB on kidney function.
[1] https://www.gponline.com/ace-inhibitors-renal-artery-stenosis/cardiovascular-system/article/914629
[2]https://onlinelibrary.wiley.com/doi/full/10.1111/j.1755-5922.2010.00258.x
User 'Type-IIx' has already pointed out the two main areas of concern: (1) Acute kidney failure in those who have certain underlying conditions and (2) Hyperkalemia.
Let's first explore the cause of (1). Below you see an illustration of a glomerulus, of which each kidney has about a million and which together do all the filtering.
As you can see, the blood flows in through the 'afferent' arteriole and flows out through the 'efferent' arteriole. Angiotensin II is a hormone that leads to constriction (narrowing) of the efferent arteriole (and more so than for the afferent arteriole), which in turn increases pressure within the glomerulus, which leads to more filtration. ARBs (angiotensin receptor blockers) prevent Angiotensin II from attaching to its receptors and thereby lead to vasodilation (widening) of the efferent arteriole. As a result, pressure in the glomerulus decreases, which in turn lowers the filtration rate. So when you start to take an ARB, your (estimated and actual) glomerular filtration rate (GFR) will decrease, which will be reflected by a higher Creatinine serum level. This is perfectly normal and does not indicate any damage to the kidneys.
However, when the reduction in eGFR, or equivalently, the increase in serum Creatinine is too high, then this could indicate an underlying health issue such as Renal artery stenosis (RAS).
RAS is most often caused by atherosclerosis, so the usual risk factors for atherosclerosis will also increase your likelihood of RAS. In people with RAS, blood flow through the afferent arteriole is reduced (generally due to plaque higher up in the renal artery). In that situation, the Angiotensin II mediated vasoconstriction in the efferent arteriole (outflow) is essential to maintaining sufficient pressure in the glomerulus.
If you take an ARB in that situation, the pressure in the glomerulus can decrease by so much that "renal ischemic nephropathy develops and renal failure ensues" [1].
Hence, everybody, but especially those with risk factors for atherosclerosis (male, age>50, smoking, high saturated fat intake, bad lipids on bloodwork, family history of CVD), should do bloodwork before and 10-14 days after their first dose of an ARB or ACEi. If there is a greater than ~20 per cent increase in serum creatinine, then you have to immediately stop taking the ARB and consult a doctor to figure out your underlying conditions. In addition, you should start with a low dose (such as 40mg Telmisartan) and only increase the dosage if necessary. As I will discuss in my next post, there may be good reasons to stick to moderate dosages and to combine ARBs with other BP meds if necessary to achieve optimal blood pressure.
It is worth noting that ARBs are generally very well tolerated. It is very very rare for them to cause serious side effects such as acute kidney failure. But a small risk remains and so I highly recommend everyone to do the bloodwork to be on the safe side.
Speaking of blood work, it should also include potassium levels. As noted in (2) hyperkalemia (excess potassium levels in the blood) is another potential side effect of ARBs. Hyperkalemia occurs in up to 6% of users [2]. Severe hyperkalemia can cause cardiac arrhythmias, which is particularly concerning for enhanced bodybuilders with their high risk of undiagnosed cardiomyopathy.
The risk of hyperkalemia is increased by taking potassium supplements, using salt substitutes, taking beta-blockers, and taking potassium‐sparing diuretics. So avoid all that and regularly get blood work to check on your potassium levels.
OK, now we covered the common short-term side effects of ARBs and what to do about them. In the next post I will discuss the actual topic of this thread, namely potential long-term detrimental effects of ARB on kidney function.
[1] https://www.gponline.com/ace-inhibitors-renal-artery-stenosis/cardiovascular-system/article/914629
[2]https://onlinelibrary.wiley.com/doi/full/10.1111/j.1755-5922.2010.00258.x
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Onto the potential long-term side effects of ARBs. Let's first recap the main points from Watanabe et al. (2021):
To summarize, they present a good amount of evidence that the long-term administration of ARBs or ACEis leads to afferent arteriolar hypertrophy. Specifically, the smooth muscle cells in the arteriolar walls thicken.
The "contractile state of vascular smooth muscle cells establishes the diameter of [blood] vessels and thus resistance to flow"[3]. In principal, the thickening of the arteriolar walls could cause them to stiffen.
As illustrated in the figure below, the diameter of blood vessels fluctuates with the beating of the heart. During systole, the diameter increases, and during diastole it shrinks.
This dynamic movement of the arterial walls turns the pulsatile flow of the heart into a steadier flow[4]. In case the arteriolar walls stiffen due to excessive hypertrophy of the smooth muscles,
the diameter would not increase during systole, thereby reducing blood flow to the kidneys and increasing variability in the glomerular pressure.
However, it is not clear that wall thickening will automatically lead to stiffening [5]. And even if there is stiffening, is it enough to cause renal damage? As Watanabe et al. (2021) note, there is insufficient evidence to conclude that concentric hypertrophy of renal arterioles in humans in pathological. But it may well be. And if it is, then we should be able to find some empirical evidence that there is a causal relationship long-term use of RASi and renal failure.
Unfortunately, there is one such study by Mann et al. (2008) [6]. They study people older than 55 with cardiovascular disease and/or diabetes. Total sample size is 29,000. The subjects are randomly assigned to one of three treatment arms: i) 80mg Telmisartan (an ARB), or ii) 10mg Ramipril (an ACEi), or iii) 80mg Telmisartan AND 10mg Ramipril. The primary endpoint is the proportion of patients who either die, go on dialysis, or see their creatinine double. The figure below shows the proportion of patients who reached this unfortunate end point.
To the surprise of everyone, including the authors, the ARB+ACEi treatment group did the worst. They note that "The observation that combination therapy was associated with more renal outcomes and a faster decrease in GFR than on ramipril alone is of concern." Why is this finding so surprising? Well, all prior studies showed that combination therapy was superior for maintaining kidney function. Why did this study find the opposite? It's a bit of a mystery, but the most plausible explanation is that the study population differed. In most of the other studies, the patients had preexisting kidney damage and were leaking protein (microalbuminuria or macroalbuminuria).
In contrast, most participants in Mann et al. (2008) did not have microalbuminuria or macroalbuminuria. In fact, when the authors restrict their analysis to only those patients who had diabetic nephropathy, they find that the combination therapy is no worse than monotherapy. But your typical bodybuilder who wants to use ARBs for preventative purposes is much more similar to the patients in Mann et al. (2008) than to the patients in most of the other studies. In other words, the one study whose patients are somewhat close to bodybuilders is the one that shows negative effects of high levels of RAS inhibition.
Another factor could be the follow-up. Most of the other studies only look at the first couple of weeks and assess the efficacy of the drugs in terms of their ability to reduce proteinuria and to reduce hypertension.
There is solid theoretical evidence that proteinuria itself causes progressive renal damage [7]. So if a drug corrects both hypertension and proteinuria after a couple of weeks, it is often concluded that the drug is reno-protective. But what this approach is missing is that there may also be other factors that impact disease progression in chronic kidney disease. And one of those factors may be concentric hypertrophy of renal arterioles. So while ARBs may help the kidneys by lowering BP and by reducing proteinuria, it may also damage them in the long-term by another mechanism. If the positive effects occur in the short-term, and the negative effects in the long-term, then that could explain why most of the short-term studies paint too rosy of a picture.
[3] https://www.sciencedirect.com/topics/medicine-and-dentistry/vascular-smooth-muscle
[4] https://www.sciencedirect.com/science/article/pii/S073510971406639X
[5] https://www.ahajournals.org/doi/10.1161/01.HYP.26.2.355
[6] https://www.thelancet.com/journals/lancet/article/PIIS0140673608612362/fulltext
[7] https://jasn.asnjournals.org/content/17/11/2974
To summarize, they present a good amount of evidence that the long-term administration of ARBs or ACEis leads to afferent arteriolar hypertrophy. Specifically, the smooth muscle cells in the arteriolar walls thicken.
The "contractile state of vascular smooth muscle cells establishes the diameter of [blood] vessels and thus resistance to flow"[3]. In principal, the thickening of the arteriolar walls could cause them to stiffen.
As illustrated in the figure below, the diameter of blood vessels fluctuates with the beating of the heart. During systole, the diameter increases, and during diastole it shrinks.
This dynamic movement of the arterial walls turns the pulsatile flow of the heart into a steadier flow[4]. In case the arteriolar walls stiffen due to excessive hypertrophy of the smooth muscles,
the diameter would not increase during systole, thereby reducing blood flow to the kidneys and increasing variability in the glomerular pressure.
However, it is not clear that wall thickening will automatically lead to stiffening [5]. And even if there is stiffening, is it enough to cause renal damage? As Watanabe et al. (2021) note, there is insufficient evidence to conclude that concentric hypertrophy of renal arterioles in humans in pathological. But it may well be. And if it is, then we should be able to find some empirical evidence that there is a causal relationship long-term use of RASi and renal failure.
Unfortunately, there is one such study by Mann et al. (2008) [6]. They study people older than 55 with cardiovascular disease and/or diabetes. Total sample size is 29,000. The subjects are randomly assigned to one of three treatment arms: i) 80mg Telmisartan (an ARB), or ii) 10mg Ramipril (an ACEi), or iii) 80mg Telmisartan AND 10mg Ramipril. The primary endpoint is the proportion of patients who either die, go on dialysis, or see their creatinine double. The figure below shows the proportion of patients who reached this unfortunate end point.
To the surprise of everyone, including the authors, the ARB+ACEi treatment group did the worst. They note that "The observation that combination therapy was associated with more renal outcomes and a faster decrease in GFR than on ramipril alone is of concern." Why is this finding so surprising? Well, all prior studies showed that combination therapy was superior for maintaining kidney function. Why did this study find the opposite? It's a bit of a mystery, but the most plausible explanation is that the study population differed. In most of the other studies, the patients had preexisting kidney damage and were leaking protein (microalbuminuria or macroalbuminuria).
In contrast, most participants in Mann et al. (2008) did not have microalbuminuria or macroalbuminuria. In fact, when the authors restrict their analysis to only those patients who had diabetic nephropathy, they find that the combination therapy is no worse than monotherapy. But your typical bodybuilder who wants to use ARBs for preventative purposes is much more similar to the patients in Mann et al. (2008) than to the patients in most of the other studies. In other words, the one study whose patients are somewhat close to bodybuilders is the one that shows negative effects of high levels of RAS inhibition.
Another factor could be the follow-up. Most of the other studies only look at the first couple of weeks and assess the efficacy of the drugs in terms of their ability to reduce proteinuria and to reduce hypertension.
There is solid theoretical evidence that proteinuria itself causes progressive renal damage [7]. So if a drug corrects both hypertension and proteinuria after a couple of weeks, it is often concluded that the drug is reno-protective. But what this approach is missing is that there may also be other factors that impact disease progression in chronic kidney disease. And one of those factors may be concentric hypertrophy of renal arterioles. So while ARBs may help the kidneys by lowering BP and by reducing proteinuria, it may also damage them in the long-term by another mechanism. If the positive effects occur in the short-term, and the negative effects in the long-term, then that could explain why most of the short-term studies paint too rosy of a picture.
[3] https://www.sciencedirect.com/topics/medicine-and-dentistry/vascular-smooth-muscle
[4] https://www.sciencedirect.com/science/article/pii/S073510971406639X
[5] https://www.ahajournals.org/doi/10.1161/01.HYP.26.2.355
[6] https://www.thelancet.com/journals/lancet/article/PIIS0140673608612362/fulltext
[7] https://jasn.asnjournals.org/content/17/11/2974
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Continued below due to word limit per post:
But don't throw your Telmisartan in the trash just yet. The study by Mann et al. (2008) did not have a control group that did not receive any medication. Based on similar studies, it seems likely that such a control group would have had renal failure at a higher rate than those who received medication. The only thing that the study really shows beyond a doubt is that more is not always better. It is not a good idea to completely nuke your RAS with a megadose of either ARB or ACEi or a combination of both that does not adjust each individual dose. It seems plausible that the arteriolar hypertrophy from ARBs is dose-dependent, so that the thickening of the wall only becomes pathological at complete suppression of the RAS.
My recommendation would be as follows: Continue to take your ARB or ACEi, but keep the dosages reasonable. For example, consider Telmisartan. You should only take as much as is necessary to achieve optimal blood pressure. You may also rely on combination therapy to achieve your blood pressure goal. So for example, Temisartan+Nebivolol, or alternatively Telmisartan plus some Calcium channel blocker (CCB).
That way, you can control your blood pressure and get all the many other benefits of an ARB, while minimizing the risk of long-term side effects.
But don't throw your Telmisartan in the trash just yet. The study by Mann et al. (2008) did not have a control group that did not receive any medication. Based on similar studies, it seems likely that such a control group would have had renal failure at a higher rate than those who received medication. The only thing that the study really shows beyond a doubt is that more is not always better. It is not a good idea to completely nuke your RAS with a megadose of either ARB or ACEi or a combination of both that does not adjust each individual dose. It seems plausible that the arteriolar hypertrophy from ARBs is dose-dependent, so that the thickening of the wall only becomes pathological at complete suppression of the RAS.
My recommendation would be as follows: Continue to take your ARB or ACEi, but keep the dosages reasonable. For example, consider Telmisartan. You should only take as much as is necessary to achieve optimal blood pressure. You may also rely on combination therapy to achieve your blood pressure goal. So for example, Temisartan+Nebivolol, or alternatively Telmisartan plus some Calcium channel blocker (CCB).
That way, you can control your blood pressure and get all the many other benefits of an ARB, while minimizing the risk of long-term side effects.
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Good to see you
Thank you for the insights man!Onto the potential long-term side effects of ARBs. Let's first recap the main points from Watanabe et al. (2021):
To summarize, they present a good amount of evidence that the long-term administration of ARBs or ACEis leads to afferent arteriolar hypertrophy. Specifically, the smooth muscle cells in the arteriolar walls thicken.
The "contractile state of vascular smooth muscle cells establishes the diameter of [blood] vessels and thus resistance to flow"[3]. In principal, the thickening of the arteriolar walls could cause them to stiffen.
As illustrated in the figure below, the diameter of blood vessels fluctuates with the beating of the heart. During systole, the diameter increases, and during diastole it shrinks.
This dynamic movement of the arterial walls turns the pulsatile flow of the heart into a steadier flow[4]. In case the arteriolar walls stiffen due to excessive hypertrophy of the smooth muscles,
the diameter would not increase during systole, thereby reducing blood flow to the kidneys and increasing variability in the glomerular pressure.
However, it is not clear that wall thickening will automatically lead to stiffening [5]. And even if there is stiffening, is it enough to cause renal damage? As Watanabe et al. (2021) note, there is insufficient evidence to conclude that concentric hypertrophy of renal arterioles in humans in pathological. But it may well be. And if it is, then we should be able to find some empirical evidence that there is a causal relationship long-term use of RASi and renal failure.
Unfortunately, there is one such study by Mann et al. (2008) [6]. They study people older than 55 with cardiovascular disease and/or diabetes. Total sample size is 29,000. The subjects are randomly assigned to one of three treatment arms: i) 80mg Telmisartan (an ARB), or ii) 10mg Ramipril (an ACEi), or iii) 80mg Telmisartan AND 10mg Ramipril. The primary endpoint is the proportion of patients who either die, go on dialysis, or see their creatinine double. The figure below shows the proportion of patients who reached this unfortunate end point.
To the surprise of everyone, including the authors, the ARB+ACEi treatment group did the worst. They note that "The observation that combination therapy was associated with more renal outcomes and a faster decrease in GFR than on ramipril alone is of concern." Why is this finding so surprising? Well, all prior studies showed that combination therapy was superior for maintaining kidney function. Why did this study find the opposite? It's a bit of a mystery, but the most plausible explanation is that the study population differed. In most of the other studies, the patients had preexisting kidney damage and were leaking protein (microalbuminuria or macroalbuminuria).
In contrast, most participants in Mann et al. (2008) did not have microalbuminuria or macroalbuminuria. In fact, when the authors restrict their analysis to only those patients who had diabetic nephropathy, they find that the combination therapy is no worse than monotherapy. But your typical bodybuilder who wants to use ARBs for preventative purposes is much more similar to the patients in Mann et al. (2008) than to the patients in most of the other studies. In other words, the one study whose patients are somewhat close to bodybuilders is the one that shows negative effects of high levels of RAS inhibition.
Another factor could be the follow-up. Most of the other studies only look at the first couple of weeks and assess the efficacy of the drugs in terms of their ability to reduce proteinuria and to reduce hypertension.
There is solid theoretical evidence that proteinuria itself causes progressive renal damage [7]. So if a drug corrects both hypertension and proteinuria after a couple of weeks, it is often concluded that the drug is reno-protective. But what this approach is missing is that there may also be other factors that impact disease progression in chronic kidney disease. And one of those factors may be concentric hypertrophy of renal arterioles. So while ARBs may help the kidneys by lowering BP and by reducing proteinuria, it may also damage them in the long-term by another mechanism. If the positive effects occur in the short-term, and the negative effects in the long-term, then that could explain why most of the short-term studies paint too rosy of a picture.
[3] https://www.sciencedirect.com/topics/medicine-and-dentistry/vascular-smooth-muscle
[4] https://www.sciencedirect.com/science/article/pii/S073510971406639X
[5] https://www.ahajournals.org/doi/10.1161/01.HYP.26.2.355
[6] https://www.thelancet.com/journals/lancet/article/PIIS0140673608612362/fulltext
[7] https://jasn.asnjournals.org/content/17/11/2974
Do you have plans on also updating the "Maintaining kidney health" thread that you started a few years ago?
IMO your thread is still the most informative thread about kidney health on this board.
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I just got prescribed Amlodipine/norvasc what can you tell me about it ? just had kidney dialysis
they took me off inderal . I had great experience with propranolol ill keep it on hand just incase.
but the half life is terrible and my bp would often spike using only that to manage bp
but i was actually prescribed it for PTSD
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I just read about your story. Stay strong brother, I'm praying for a full and speedy recovery.
Amlodipine is a calcium channel blocker and an excellent choice to control blood pressure in your situation. ARBs or ACEis are contraindicated given the current state of your kidneys. Don't hesitate to go for frequent follow-up at the hospital, and stick to your doctors' advice. So if they say not to take the Propanolol, I would follow that advice.
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I need the study they did. this just tells us “long term” how long is long. How many randomized selected personals had underlying diseases? HTN, previous kidney disease, diabetes, heart failure ?
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Once you’re on dialysis; your BP is very unpredictable. we usually have patient on dialysis on 3-4 BP meds and a beta blocker
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Telimisartan does cause hyperkalemia and blood work is needed to monitor potassium levels.
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To make my recommendations a bit more concrete, see the flowchart below. It is my take on what BP meds one could take if one's goal is to prevent/ameliorate chronic kidney disease as an otherwise healthy, AAS-abusing bodybuilder. It is purely from a research perspective. It is not medical advice.
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Let explore why, despite their potential side effects, ARBs/ACEis are still superior to CCBs in terms renoprotection.
jamanetwork.com
The figure below (from the same paper) nicely illustrates how CCBs (like Amlodipine) lead to an increase in proteinuria. Proteinuria is one of the strongest predictors for, and potentially causes of, worsening kidney function.
In line with this finding, we can see that at least in the medium term (3 years after initiation of medication), end-stage renal disease and death were more frequent in those who receive a CCB (like Amlodipine) instead of an ACEi (like Ramipril). We know from Mann et al. (2008) that the deleterious effects of excess RAS suppression already occur after 3 years (see the red line in the graph in post#64).
So if these negative effects of reasonably-dosed RAS suppressing drugs (like an ACEi or an ARB) are real, then they are already baked into the cake in the below graph. However, despite those negative effects of RAS suppressing drugs, they are still superior to CCBs in terms of preventing death and progression to ESRD.
It is worth noting that the size of the advantage of the ACEi over the CCB depended on the state of the patients' kidney health when they started medication. The stronger the initial level of proteinuria, the higher the benefit of using an ACEi rather than a CCB. But even at low initial levels of proteinuria, the ACEi is likely superior:
As most readers will know, ACEis and ARBs have a very similar mechanism of action, and ARBs are generally considered equally effective as ACEis, but have better tolerability. Hence why the above results also apply to ARBs and not just ACEis. And among class of ARBs, Telmisartan is considered one of the best (for reasons that have been discussed on this forum at length).
Effect of Ramipril vs Amlodipine on Renal Outcomes in Hypertensive Nephrosclerosis
Context Incidence of end-stage renal disease due to hypertension has increased in recent decades, but the optimal strategy for treatment of hypertension to prevent renal failure is unknown, especially among African Americans.Objective To compare the effects of an angiotensin-converting enzyme...
jamanetwork.com
The figure below (from the same paper) nicely illustrates how CCBs (like Amlodipine) lead to an increase in proteinuria. Proteinuria is one of the strongest predictors for, and potentially causes of, worsening kidney function.
In line with this finding, we can see that at least in the medium term (3 years after initiation of medication), end-stage renal disease and death were more frequent in those who receive a CCB (like Amlodipine) instead of an ACEi (like Ramipril). We know from Mann et al. (2008) that the deleterious effects of excess RAS suppression already occur after 3 years (see the red line in the graph in post#64).
So if these negative effects of reasonably-dosed RAS suppressing drugs (like an ACEi or an ARB) are real, then they are already baked into the cake in the below graph. However, despite those negative effects of RAS suppressing drugs, they are still superior to CCBs in terms of preventing death and progression to ESRD.
It is worth noting that the size of the advantage of the ACEi over the CCB depended on the state of the patients' kidney health when they started medication. The stronger the initial level of proteinuria, the higher the benefit of using an ACEi rather than a CCB. But even at low initial levels of proteinuria, the ACEi is likely superior:
As most readers will know, ACEis and ARBs have a very similar mechanism of action, and ARBs are generally considered equally effective as ACEis, but have better tolerability. Hence why the above results also apply to ARBs and not just ACEis. And among class of ARBs, Telmisartan is considered one of the best (for reasons that have been discussed on this forum at length).
@MyNameIsJeff you're one the great assets to this board - I appreciate the time you put into these posts.
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This is excellent. I need to bookmark this one. Great post.Let explore why, despite their potential side effects, ARBs/ACEis are still superior to CCBs in terms renoprotection.
Effect of Ramipril vs Amlodipine on Renal Outcomes in Hypertensive Nephrosclerosis
Context Incidence of end-stage renal disease due to hypertension has increased in recent decades, but the optimal strategy for treatment of hypertension to prevent renal failure is unknown, especially among African Americans.Objective To compare the effects of an angiotensin-converting enzyme...
The figure below (from the same paper) nicely illustrates how CCBs (like Amlodipine) lead to an increase in proteinuria. Proteinuria is one of the strongest predictors for, and potentially causes of, worsening kidney function.
In line with this finding, we can see that at least in the medium term (3 years after initiation of medication), end-stage renal disease and death were more frequent in those who receive a CCB (like Amlodipine) instead of an ACEi (like Ramipril). We know from Mann et al. (2008) that the deleterious effects of excess RAS suppression already occur after 3 years (see the red line in the graph in post#64).
So if these negative effects of reasonably-dosed RAS suppressing drugs (like an ACEi or an ARB) are real, then they are already baked into the cake in the below graph. However, despite those negative effects of RAS suppressing drugs, they are still superior to CCBs in terms of preventing death and progression to ESRD.
It is worth noting that the size of the advantage of the ACEi over the CCB depended on the state of the patients' kidney health when they started medication. The stronger the initial level of proteinuria, the higher the benefit of using an ACEi rather than a CCB. But even at low initial levels of proteinuria, the ACEi is likely superior:
As most readers will know, ACEis and ARBs have a very similar mechanism of action, and ARBs are generally considered equally effective as ACEis, but have better tolerability. Hence why the above results also apply to ARBs and not just ACEis. And among class of ARBs, Telmisartan is considered one of the best (for reasons that have been discussed on this forum at length).
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As a follow-up question, you might wonder whether a combination of ARB and CCB is a good idea, or if instead, the two drugs will 'cancel each other out' in terms of their effects on proteinuria and GFR. The TLDR is that these 2 classes of drugs work very well together.
We know that from a study by Brenner et al. (2001) [8]. Their study consisted of 1513 patients, with a mean follow-up of 3.4 years. Those patients are randomly assigned to either a treatment or a control group. In the control group, patients take any kind of blood pressure medication other than ARBs or ACEis. In the treatment group, patients take Losartan (an ARB) and another class of blood pressure medication if necessary. As it turns out, more than 80 percent of patients in both the control and the treatment group took a CCB during the study. So essentially, the comparison is between taking only a CCB or a combination of CCB and Losartan. This way, we can evaluate whether the combination of those 2 classes of drugs is beneficial.
In the figure below, we can see the proportion of patients that reached a primary end point of i) doubling Creatinine, ii) end-stage renal disease (ERD), or ii) death (all of them are bad things). Note that the authors call the control group the 'placebo' group, which is slightly misleading since the other patients did receive drugs to lower their BP, rather than a strict placebo.
As we can see from the graph, adding an ARB on top of a CCB confers additional benefits. That is, the 2 drugs work well together. Taking Losartan on top of a CCB means you have a much lower chance of reaching ESRD. The next graph shows the differences in proteinuria between the 2 groups:
We can see that fortunately, an ARB can significantly reduce proteinuria even in the presence of a CCB.
Segura et al (2005) [9] concur:
Hence my recommendation in post #74 to start with only a low-to-moderate dose of an ARB and to add a CCB if optimal blood pressure has not been achieved yet. This is almost certainly better than taking a large dose of ARB alone and to then risk the potential long-term adverse effects that are the topic of this thread.
[8] https://www.nejm.org/doi/full/10.1056/nejmoa011161
[9] https://jasn.asnjournals.org/content/16/3_suppl_1/S64
We know that from a study by Brenner et al. (2001) [8]. Their study consisted of 1513 patients, with a mean follow-up of 3.4 years. Those patients are randomly assigned to either a treatment or a control group. In the control group, patients take any kind of blood pressure medication other than ARBs or ACEis. In the treatment group, patients take Losartan (an ARB) and another class of blood pressure medication if necessary. As it turns out, more than 80 percent of patients in both the control and the treatment group took a CCB during the study. So essentially, the comparison is between taking only a CCB or a combination of CCB and Losartan. This way, we can evaluate whether the combination of those 2 classes of drugs is beneficial.
In the figure below, we can see the proportion of patients that reached a primary end point of i) doubling Creatinine, ii) end-stage renal disease (ERD), or ii) death (all of them are bad things). Note that the authors call the control group the 'placebo' group, which is slightly misleading since the other patients did receive drugs to lower their BP, rather than a strict placebo.
As we can see from the graph, adding an ARB on top of a CCB confers additional benefits. That is, the 2 drugs work well together. Taking Losartan on top of a CCB means you have a much lower chance of reaching ESRD. The next graph shows the differences in proteinuria between the 2 groups:
We can see that fortunately, an ARB can significantly reduce proteinuria even in the presence of a CCB.
Segura et al (2005) [9] concur:
Hence my recommendation in post #74 to start with only a low-to-moderate dose of an ARB and to add a CCB if optimal blood pressure has not been achieved yet. This is almost certainly better than taking a large dose of ARB alone and to then risk the potential long-term adverse effects that are the topic of this thread.
[8] https://www.nejm.org/doi/full/10.1056/nejmoa011161
[9] https://jasn.asnjournals.org/content/16/3_suppl_1/S64
OuchThatHurts
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Question. What about those of us who take a ARB (eg Telmisartan 40mg) and a beta blocker (eg Inderal 60mg)? I love that my blood pressure is 120/80 but I don't want to crash my kidneys doing it right?As a follow-up question, you might wonder whether a combination of ARB and CCB is a good idea, or if instead, the two drugs will 'cancel each other out' in terms of their effects on proteinuria and GFR. The TLDR is that these 2 classes of drugs work very well together.
We know that from a study by Brenner et al. (2001) [8]. Their study consisted of 1513 patients, with a mean follow-up of 3.4 years. Those patients are randomly assigned to either a treatment or a control group. In the control group, patients take any kind of blood pressure medication other than ARBs or ACEis. In the treatment group, patients take Losartan (an ARB) and another class of blood pressure medication if necessary. As it turns out, more than 80 percent of patients in both the control and the treatment group took a CCB during the study. So essentially, the comparison is between taking only a CCB or a combination of CCB and Losartan. This way, we can evaluate whether the combination of those 2 classes of drugs is beneficial.
In the figure below, we can see the proportion of patients that reached a primary end point of i) doubling Creatinine, ii) end-stage renal disease (ERD), or ii) death (all of them are bad things). Note that the authors call the control group the 'placebo' group, which is slightly misleading since the other patients did receive drugs to lower their BP, rather than a strict placebo.
As we can see from the graph, adding an ARB on top of a CCB confers additional benefits. That is, the 2 drugs work well together. Taking Losartan on top of a CCB means you have a much lower chance of reaching ESRD. The next graph shows the differences in proteinuria between the 2 groups:
We can see that fortunately, an ARB can significantly reduce proteinuria even in the presence of a CCB.
Segura et al (2005) [9] concur:
Hence my recommendation in post #74 to start with only a low-to-moderate dose of an ARB and to add a CCB if optimal blood pressure has not been achieved yet. This is almost certainly better than taking a large dose of ARB alone and to then risk the potential long-term adverse effects that are the topic of this thread.
[8] https://www.nejm.org/doi/full/10.1056/nejmoa011161
[9] https://jasn.asnjournals.org/content/16/3_suppl_1/S64
OuchThatHurts
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This stuff should go in the Definitive Health Thread for reference. 
This is good stuff. Kidneys are way overlooked IMO.
This is good stuff. Kidneys are way overlooked IMO.Similar threads
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