To NSAID or not to NSAID - Manny vs Sophie - NSAIDS part 2

In this episode, Manny and Sophie discuss NSAID use in the healthy population. What does the data support? Is Sophie's regular use of NSAIDs going to land her on dialysis? Or will Manny's NSAID aversion result in a healthy set of kidneys in exchange for some unnecessary aches and pains?

Sophia Ambruso DO @Sophia_Kidney, Sarah Young MD @kidneycritic, Judy Blaine MD, Parisa Mortaji, MD

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Kidney Essentials NSAIDs part 2

[00:00:00] So I admit I may be a little melodramatic. My wife has diagnosed me with the man flu more than once.

 Welcome to kidney essentials, a podcast for medical students, residents, and advanced practitioners at the university of Colorado and beyond. Let's start with some short introductions. Hey everybody. I'm Manny Urra I'm one of the university, Colorado chief medical residents, and a soon to be nephrology fellow privileged to work with these two folks here.

I just want to bring up that it was Manny's last podcast. It got him the spot here. Otherwise they were like, he is a no go. And then he just shined dropped the mic a couple of times. So we're glad you're with us, Manny. Glad I pulled it off. Thank you guys. Yeah, there's chief residents. We never want them.

They're kind of slackers. Yeah. I'm I'm Sophia Ambruso. I'm Sophia underscore kidney on Twitter and I am a clinical nephrologist and on [00:01:00] faculty at the university of Colorado, I'm also at the Denver VA kind of got those in reverse order, but I have no conflicts of interest. And I am Sarah Young. I am a nephrologist at the university of Colorado at the CU Anschutz campus.

And I have no conflicts of interest. And I tweet at kidney critic. So we don't really actually have a case today. We're going to sort of have instead a little debate between. And Sophie, but before we get into that, let's just remind everyone that kitty essentials it's available on apple podcasts.

And we would love a five-star review from our listeners. Sarah, do we have any reviews? Yeah, we have a review, a five star review. That's pretty funny actually. Is it you, you should read it. Yeah. Okay. It says something to the effect of, they actually make nephrology sexy, which is pretty hard, super sexy.[00:02:00] 

So if you want to start with our mission statement. Okay. So our mission statement is to make nephrology more accessible and less intimidating. We want to provide concise nephrology, pearls, and each episode and help listeners understand renal pathophysiology . Here I go again, we're here to make nephrology sexy one episode at a time.

And Manny for our legal disclaimer, make it sexy. I'll try my best. So this podcast is for educational purposes, only the views and statements expressed on this podcast are solely those of the hosts. Not that sexy Manny, I gave it a little deeper voice. I'm not sure if you guys noticed, but I'll try it.

I'll try again later. I think it's, it's hard to make LA lawyerly stuff. Don't tell my husband who's a lawyer that, but, okay. So last episode, we talked about patient populations that are [00:03:00] vulnerable to even low doses of nonsteroidal anti-inflammatories because the kidney really relies on prostoglandins to maintain renal blood flow and GFR.

And those patient populations include patients with nephrotic syndrome, heart failure, cirrhosis. And elderly patients with chronic kidney disease. And if you give them and says they can get acute kidney treat very easily. In addition, patients on diuretics, ACE inhibitors and calcineurin oh man, you guys, I learned a lot last episode.

My favorite part was still listening to you both disagree on how to pronounce cyclosporine. I'm still not sure how you actually say it and I'm not going to be picking sides, but I very much enjoyed it. Okay. I am definitely right. It is not cycles for ride or whatever. That's not, although every time I say it, I stop it.

I go

maybe it should say, make the, I say its name. So it would be [00:04:00] cyclosporine, even if that's definitely not. You know, I re I, when I look at it, I'm like, it's cyclosporine, but I feel like I should be saying cyclosporine. I don't know. Can I just say CSA?

All right. Okay. And in our last episode, Manny admitted, he never takes and sets out of fear of developing renal disease and Sophie confessed. She is a regular NSAID. So that begs the question. What is the risk to relatively healthy patient population? Is Sophie being overly flippant about the risk or is Manny being a little melodramatic?

All right. So I admit I may be a little melodramatic. My wife has diagnosed me with the man flu more than once I've memorized so many adverse associations with NSAIDs from GI bleeds to worsening edema worsening hypertension to AKI is to maybe development of [00:05:00] CKD. I just don't want to risk it.

And that's, that's my stance. Yeah. I don't know. I've taken enough NSAIDs and felt reasonably well, most of the time. I've had labs here or there, and I still have phenomenal kidney functional function. Like, I mean, phenomenal, better than most. I don't know. Maybe we'll find out today. All right. So for Europe, buddy.

Oh, it's my turn. So I will, so, okay. I have to say this. My support of NSAIDs, at least for myself and my healthy body, my phenomenal kidney function is set and NSAIDs are widely used in the United States. I think it's like greater than 70 million prescriptions are written annually by the way, who writes prescriptions for NSAIDs most of the time, I don't not anymore.

At least. Anyhow, what do you have to say about that? Yeah. I mean, to your point, [00:06:00] that doesn't even account for the number of patients taking over the counter nsaids. So a study in which patients self reported their ibuprofen use revealed 90% of patients take it regularly. And then 37% take more than one end said, and 11% go above the recommended daily limit, which I found to be wild.

So you're saying more than one and said meaning more than one type of nsaids. So they're like on naproxen and ibuprofen. Correct. Correct? Yeah. Okay. So the question is, is ibuprofen safe in a young and relatively healthy population? And I'm going to have you guys take two sides of this debate. So Sophie, you're going to argue.

Yes. And Manny, you're going to argue no for our first ever kidney essentials debate. This is for educational purposes only. There's no money on the line. No it's high stakes, super high stakes and point out the power dynamic too. I'm I'm very much intimidated, but I will be [00:07:00] trying my best. It's all right.

I'm still an assistant professor, Manny. It won't take long for you to surpass me. No worries. Three days into your fellowship, you will no longer be intimidated by us. All right. So I get to start and I've already. Put out there that I think probably for most healthy populations and nsaids are safe. So prob one of the earlier studies that was done, it was in 2003 published in ajkd and it was analgesia accused and change in kidney function and apparently healthy men.

I like that. They put apparently healthy men in there. Yeah. And this is often referred to as a physician health study. And this was a prospective cohort study of approximately 5,000 U S male. I highlight male physicians. Where are the female physicians? I asked you they right here. So anyways, I digress.

[00:08:00] They had their blood drawn at time points of 1982 and 1996. And they looked at for creating an increase of greater than 0.3 or a decline of GFR of 29, 29 mils per men or more, this is by the MDRD method. And that was within that 14 year, time period. And basically they divided patients into never use or patients who were on aspirin, Tylenol or nsaids.

And so the never use was less than 12 pills and it was compared to those who took that combination of medicines. Again, aspirin, Tylenol, and . And the first group was 12 pills to 1,499 pills. And the next group was 1500 to 2,499 pills. And the final group was greater than [00:09:00] 2,500 pills. So we're just looking at.

Doses. So what they found is that 242 had a rise in creatinine greater than 0.3 and 224 had a decrease in the GFR of greater than 29%. And this is out of 5,000, approximately patients. They did find that the men with higher creatinine levels and a lower GFR were older, had hypertension had more cardiovascular disease.

And they were more likely to be smokers, but overall, the use of combined aspirin, acetaminophen and other nsaids was not significantly associated with a decline in kidney function. However, what was a risk factor for abnormally elevated creatinine was one or more cardiovascular risk factors. Yeah.

Thank you so much for reviewing. But I think you'd agree with me that there are several limitations to this study. I mean, the most glaring was that this was all men and almost [00:10:00] entirely white. So I'm not sure that this is representative of the nation at large. You have any, you make a good point. So if you're a white man, your risks are low and you might be reassured by the study.

But I'm always bothered by the retrospective assessment of any, you know, analgesic use. I mean, who remembers how much ibuprofen they took over a 14 year period of time. Yeah. I don't, I think it's probably higher than nanny. I, I can't argue with your comments, Sarah. I mean, most studies relying on recollection are definitely less reliable.

So, you know, you have to take it all with a grain of salt. It's the information we have. Unfortunately. Yeah. The other thing is that they looked at several analgesics, including Tylenol, aspirin, nsaids. So I just think this is a little bit tough to interpret. Definitely very good point. So I would add that there is a similar study that was done in nurses, and that was looking at the lifetime non narcotic analgesic use [00:11:00] and looking at the decline in renal function in women.

And it was published in archives of internal medicine in 2004. This was the nurses' health study. There we go. So we've done our physician's health study. Now we're doing our nurses health study. The only way we can get healthy subjects and studies. So anyways, they identified high analgesic users, meaning greater than five, 15 days per month and low users in their population who had, yeah.

So hi, I analgesic users for greater than 15 days a month of analgesic use versus low users.

So in this study, they identified high analgesic users, meaning they were, they took greater than they took analgesics greater than 15 days a month, and then low users, which was less than 15 days per month and their population. And they also had their blood drawn and ended up with a 1,697 [00:12:00] patients and their analysis.

And they comply and compared the creatinine and GFR using the MDRD again from 18 excuse me, 19 from 1989 and 2000. So in this case they found no substantial differences in creatinine level or GFR among the categories of lifetime intake or incidents or. However, they did find women who consumed greater than 100 grams of acetaminophen had a higher risk of losing kidney function.

Yeah. I mean, overall it suggests peers to be pretty safe, whether it's Tylenol or non-steroidal anti-inflammatories, but again, it has the same problems that prior study had, which is self-reporting. Well, you guys are in luck. We do have a study looking at end set prescription use specifically in us army soldiers.

And this is a good population to look at because they're young, healthy, and they engage in [00:13:00] regular vigorous exercise, which may actually put them at higher risk for renal disease. When compared to the general relatively sedentary us population. So many is now referring to a JAMA network open study by Belson.

In 2019 looking at and said you and kidney disease in us army soldiers. So dig into the study a little bit. This was a retrospective cohort study. They looked backwards and examine exposure to nsaid use. They identify to exposure to nsaid based on prescription of nsaid by providers. Yeah. So there's no, self-reporting here.

They're looking simply at the prescription. So, I mean, it's possibly theoretical that people could have. Filled the prescription and not taking the pill. And it's also theoretical that they could have been in addition, taking over the counter nsaids in addition to what was being prescribed. Right? So these were prescribed and said doses and the, and the study evaluated, whether patients eventually [00:14:00] went on to receive an ICD code of AKI or K.

So in the study, they looked at 764,228 active duty army soldiers serving between January, 2011 and December, 2014. And then they divided them into three groups based on defined daily doses of prescribed nsaids per month. So two thirds of patients actually took no nsaids of the one-third that did receive nsaids

they were divided into two groups, one to seven defined daily doses and greater than seven defined daily dose. Most of the nsaid prescriptions were ibuprofen and Naproxen. And the ibuprofen prescription was mostly 800 milligrams and allowed for three or more daily doses ranging up to 2400 3200 milligrams per day, which has a lot of ibuprofen.

They found a higher risk of AKI in CKD. If you took greater than seven defined daily doses, which conferred about an increased risk of 20%, this is significantly higher. If they had hypertension where African-American, or. If [00:15:00] the patients who are greater than 50 years old, they had seven times the risk, actually.

Yeah. So overall the individual risk is still pretty low, but it appears to be there and it doesn't make you feel better if you're one of those people who actually got the CKD from the nsaid use. Exactly. So the risk may be small, but it is when you can control. You might not be able to control whether, whether you develop hypertension or other diseases, but you can control your nsaid consumption.

All right. Well, I just got a pipe up here because I conceded earlier. So I feel like I get to have a little word here on this, this study isn't without its own number of confounders number one it has dramatically different covariates between. Those that take nsaid and those that do not take nsaids meaning that maybe there is an underlying issue.

That's predisposing someone to requiring an nsaids versus those that aren't. So maybe there's something else contributing to the actual need for [00:16:00] the nsaid or the perceived need for the nsaid. And then what does seven defined daily doses truly mean? The, a single dose and this is 200 milligrams. So seven daily doses could be.

Seven doses of 200 milligrams of ibuprofen per month, or it could be as high as 800 milligrams, three times daily per month. So it's a really wide range of doses of nsaids. And then the last thing is we don't know if the patients who are prescribed these actually took them. We're making a really big assumption there.

Yeah. I think answering the question of how much ibuprofen is too much ibuprofen largely depends on. Who the patient is and emphasizes the importance of patient centered care and the fundamental characteristics of patient centered care is first involving your patient in making the decision and individualizing your care to that [00:17:00] specific patient.

So for Manny, he's willing to endorse some pain or maybe even a lot of pain that I now found out. He played football in high school and didn't ever take nsaids, but You know, he's willing to endure some pain to avoid a potential small risk of renal disease. In contrast, Sophie, her quality of life is more important.

So she's willing to, you know, take some daily nonsteroidal so that she could do her Peloton bike in the morning. And then so in the end, both of you are right. All right. Yeah. How about that for being. Equitable. It feels pretty good. Good. Anything else you get? Go ahead. I will try a small end, said the next time I'm having some acute pain, but if I have a bump in my creatinine, I will come find you guys to talk about it.

So you're going to check your labs prior. You're then going to take your ibuprofen. You're going to check your labs afterwards, and then you're going to punch a stamp. I [00:18:00] think that's the only way to really figure this thing. That's very funny. Fair enough. But we're going to have to standardize what your volume status is and all sorts of other things in that timeframe.

All right. Well, our learning objectives for this podcast where the risk of acute kidney injury with incense is real. We see it on a daily basis in the hospital and clinic in particular, patients are at risk, which we have outlined in our prior. The risk of CKD to the general healthy population, however, appears to be quite low.

It's not, it doesn't appear to be zero given the few studies that we have, but it's pretty low. But the risk is greatest in what appears to be the patients who consume very large amounts of nonsteroidals. So how much ibuprofen is too much? ibuprofen really depends on the patient's tolerance for.

The severity of the pain and how it's affecting their quality of life and what alternative options for pain are, or are not available to the patient. And obviously we don't have a lot of good pain control options that [00:19:00] don't have significant side effects. All right. Well, our next podcast is going to be our annual articles that changed our practice in the past year, sometime, hopefully in early February.

So we hope you all will tune in. Thanks everybody. So if you want to take us out with our credits, thank you to me for editing just strong for graphics and to the university of Colorado division of, of nephrology for giving us a job. I will say to the Denver VA for giving me a job and to the university of Colorado school of medicine for training Manny.

So he will become a nephrology fellow with us.