Prescribing in CKD: What to Stop, What to Use & What to Avoid

The For Kidneys Sake podcast series is brought to you by Imperial College Healthcare NHS Trust and North West London Integrated Care Board (NWL NHS)

In this refreshed re-release episode, Professor Jeremy Levy and Dr Andrew Frankel revisit one of the most common and challenging areas in chronic kidney disease (CKD) management: medication reviews and safe prescribing. 

They discuss how to approach prescribing decisions as kidney function declines, including the practical use of eGFR over creatinine clearance, how to identify medications that need dose adjustment or review, and the importance of “Sick Day” guidance during intercurrent illness. The episode also tackles common misconceptions around so-called “nephrotoxic” drugs and explains why many beneficial medications can often be continued safely with careful monitoring.

The second half of the episode focuses on pain management in CKD — a topic that frequently causes uncertainty in primary care. Jeremy and Andrew outline which analgesics can be used safely, which should generally be avoided, and how to prescribe cautiously using the principle of “start low and go slow.” They cover the safe use of paracetamol, tramadol, oxycodone, fentanyl and neuropathic pain agents, while reinforcing why regular NSAIDs and morphine are usually poor choices in patients with impaired kidney function. A highly practical refresher packed with prescribing tips for clinicians managing CKD in everyday practice.

5 Key Takeaways

• Use eGFR pragmatically for prescribing decisions in CKD rather than worrying excessively about creatinine clearance calculations.
• Regular NSAID use should generally be avoided in CKD, although very short courses may be acceptable in selected patients.
• Metformin is usually safe down to an eGFR of 30, with dose reduction recommended below 45 and good Sick Day guidance essential.
• Safe analgesic options in CKD include paracetamol, low-dose tramadol, oxycodone and fentanyl — but morphine should usually be avoided.
• “Start low and go slow” is the key principle when prescribing many medications, especially analgesics, in people with CKD.

Resource Links:
NICE GUIDELINES [NG203] chronic kidney disease: assessment and management Overview | Chronic kidney disease: assessment and management | Guidance | NICE

Northwest London CKD guidelines for primary care Chronic kidney disease (nwlondonicb.nhs.uk)

The purpose of this podcast is to inform and educate health care professionals working in the primary care and community setting. The content is evidence based and consistent with NICE guidelines and North West Guidelines available at the time of publication.

The content of this podcast does not constitute medical advice and it is not intended to function as a substitute for a healthcare practitioner’s judgement.

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Transcript

Jeremy Levy 

Hello, Professor Jeremy Levy from Imperial Healthcare NHS Trust. And we're busy preparing our next set of podcasts for kidney sake. We've produced 30 so far. 15,000 listeners have heard these episodes. Hopefully you're one of them. And we hope people have found them useful. And just while we're getting our act together for this next series, we thought we'd re-release some of our older episodes and update them. So this week, it's all about managing pain in patients with chronic kidney disease and the other medicines and drugs to review in patients with a GFR that's falling. 

Very sadly, there hasn't been a rush of brand new analgesics since the last year, so our messages really haven't changed, but they're really important ones because this is managed so badly. To remind you very briefly, paracetamol is safe. Short courses of non-steroidal anti-inflammatories are likely to be found in early chronic kidney disease and especially if patients are not overtly sick with volume depletion and if they haven't got severe chronic kidney disease. And tramadol as a slightly stronger painkiller in low doses is generally fine as well. If more potent opiates are needed, oxycodone is not renally excreted, so one of the easier opiates to use. And actually in our episode,

We didn't talk about Nephropam which is being used a little bit more and can also be used in chronic kidney disease and can be useful in some people. It's also not renally excreted and not nephrotoxic. But you'll have to listen to the rest of this to remind yourself which painkillers you can and can't use, how to use them best and all the other medicines that you should think about modifying as the GFR falls. I hope you enjoy it.

Andrew Frankel 

In this podcast episode, we want to cover two broad issues that we think are going to be useful to you in primary care.

Firstly, to think about what to look for when you are undertaking a medication review for people with CKD, and then secondly, to consider issues around prescribing painkillers in people with CKD. These are important aspects of managing people with CKD because they will result in a minimisation of risk, but they often cause great anxiety in doctors and pharmacists.

And Jeremy, can I start with this first broad issue? And with a particular question that I often get asked, which is about measures of kidney function when checking drugs in CKD. I often still see statements about creatinine clearance when determining when drugs need dose modification or reduction. But we are all now used to using estimated GFR. Help me here?

Jeremy Levy

Andrew, that’s a great place to start! And also we're so lucky, particularly here in Northwest London, but actually across primary care in the UK, we have lots of pharmacists working with us who are fantastic colleagues, aren't they? But they also look very carefully at this, and I think they've also got a historical desire to be wedded to clearances, and this has caused huge amounts of debate. And in the end, there's a difference almost, for being very precise and actually being pragmatic. So historically, almost all drugs when the companies produce the details of pharmacokinetic studies, and the drug information leaflets and then what's written in the BNF and MIMS and all the other guides those studies were done when they look about dosing with reference to measured creatinine clearances often on 24 hour urines, or using that old formula, the Cockcroft-Gault formula. And when they published their guidance about dosing, that was how the dosing was defined, and that was before EGFR estimated GFR was being widely reported. But now, of course, we see this all the time on all the blood tests, don't we?

Now, these two measures are broadly similar, but not exactly the same, and aren't quite measuring the same thing, but in practical terms, we can consider that they really are pretty similar. And just by the fact that somebody's creatinine clearance might be 25 and their EGFR 31, in reality, that isn't very different. Even that sort of might breach a particular classification. So the bottom line really would be, actually, it's fine to use EGFR when you're thinking about kidney function and dose modification, whatever it says in the BNF or the drugs, very specific product characteristics, but always remember, the EGFR is an estimated GFR, and that it is still affected by the person's body size, if they've got a lot of muscle.

So EGFR, based on the Creatinine in a sort of large muscled man, might look slightly low when they've got very good kidney function, normal kidney function, and on the other hand, a very, very slight, 40 kilogram older person might have poor kidneys and no muscle mass, and the GFR looks pretty good. So EGFR, you can use it. It is what we should be using. But just think about the patient in front of you and that it is just an estimate.

Andrew Frankel

Jeremy, thank you so much for that, because that is clear and I think helpful to primary care. So let's now move on to medication reviews. If I was in primary care and reviewing a patient's drug list, and know they have CKD, can you give me some messages for what I should especially look out for?

Jeremy Levy

Yes of course. And I'm not going to go through the whole of the BNF and tell you about every drug, and none of us know about all the drugs - the bottom line, of course is, if we're not sure, we look it up. I look up drugs all the time, and there are loads of sources for this. The BNF actually has very good statements about almost every drug, but there are lots of others. And we're very lucky in North West London, the guidelines that we produce often have fantastic tips about many drugs, for example, antibiotics. But some things are very straightforward, and some big groups of drugs.

No one with chronic kidney disease, CKD should really ever be using regular, non steroidal anti inflammatories, the NSAIDs, really never. Now, that's not the same as somebody needing the odd dose or two, but regular use of anti inflammatories in people with chronic kidney disease. But if somebody sprains their ankle and they've got a GFR of 45 and they need ibuprofen for three days, almost certainly that's going to be absolutely fine, but not the person who needs regular use of analgesics and have got known chronic kidney disease. There are some people, we all know this, and they've got chronic arthritis, for example, who say that the enzyme is the only drug which keeps them active, keeps them moving, keeps them pain free. And then it's a discussion with them minimising the amount of drug they can use and telling them that there is a risk this might cause progressive kidney damage, but actually, much more importantly, rather than that, is the acute episode. If somebody gets diarrhea or vomiting or a fever, then they shouldn't keep using their non-steroidal, if they were having to use it occasionally. And gels. Gels are not, you don't absorb much drug from topical gels, as in rubbing gels people use, but you can absorb some. And if you've got chronic kidney disease, regular use of the gels should be avoided. 

So that's long steroidals, and that's an easy thing to look out for, and not news to any of us. Two or three other drugs to mention at this point. Metformin causes some anxiety. We know it's a fantastic drug to be using in type two diabetes, and we now know really convincingly, it is very safe to use down to a GFR of about 30. When the GFR is between about 30 and 45 you certainly shouldn't be on the highest dose one gram TDs. So a dose reduction when the GFR is dropping from 45 down to about 30, and then once the GFR drops below 30, you do need to stop Metformin. But again, this isn't because it's damaging the kidneys. It's not nephrotoxic, but what we get concerned about is it just accumulates, and then in the setting of another illness, diarrhea, vomiting, fevers, it can potentially be associated with a problem where people get a bit more acidic. So it's not causing problems to the kidney. We're worried about it being accumulated, and we should be giving people very good Sick Day guidance, exactly like the SGLT2 inhibitors and the RAASis, if people get acutely unwell on Metformin, stop it for a few days and then restart it.

Andrew Frankel

So Jeremy, just to summarise that, for Metformin, and I think this is described in our guidelines very clearly, and indeed is consistent with NICE.The dose should really be down to 500 BD once their GFR drops below 45, and you should really be thinking about stopping it when the GFR is below 30, but always use good Sick Day guidance, which is reiterated at every medication review. And if you do that, you'll never see any problem with Metformin.

Jeremy Levy

Yes that's exactly right Andrew, and it's an old drug, but it's a very good drug with some of the best data for cardiovascular protection, isn't it, in type two diabetes? Other medicines we should talk about, there was historically a sort of story that proton pump inhibitors such as omeprazole and soprazole, might be associated with chronic kidney disease, but much better studies using, often the UK sort of primary care data, suggests this is almost certainly not true. Of course, all drugs can cause acute kidney injury, but for PPIs do check whether people still need to be on them, because if they don't need them, often started in hospital years ago, they shouldn't be on them, especially if they've got chronic kidney disease.

So blood pressure and cardiovascular drugs, now most blood pressure drugs really don't need dose reduction, even in severe chronic kidney disease, because we're usually titrating the drug to blood pressure. So actually reducing doses with falling GFRs isn't usually necessary. The thing that we get more worried about with fooling GFR and drugs such as the RASSIs, is worsening risk of hyperkalemia, high blood potassium, and that we talk about in another podcast, because that's a very important topic. These drugs, the RAASis, are not nephrotoxic. It's just other problems they can cause in advanced CKD. And diuretics as well. Diuretics are not nephrotoxic in most people, but they can, as you've got advancing chronic kidney disease, just cause slightly more problems, but again, mostly in people who've got an intercurrent illness when they drop their blood pressure, and we're worried about other drugs that are just in the mix. So just routinely, these drugs don't need stopping just because you've got CKD. 

And the last cardiovascular drug to touch on briefly, high dose and atorvastatin, 80 milligrams. Quite a lot of people are on that, particularly where they've had previous ischemic heart disease, and that's too high a dose, once you've got a low GFR, less than about 30, where the maximum dose really is 40 milligrams of the atorvastatin. So that's the cardiovascular drugs, relatively straightforward.

Antibiotics for all of us, if you're not sure, just check it against the drug guide about the dosing in chronic kidney disease, but in fact, in primary care, most antibiotics don't need much dose modification at all. The one really just to highlight now would be trimethoprim. Again, it's not nephrotoxic, but it does push your creatinine up and your potassium up if you've got CKD, so that can cause concern, but it's not doing that by damaging the kidneys. It's doing it by a different mechanism, but it does cause a sort of anxiety concern, and people get very worried, so avoid trimethoprim in chronic kidney disease.

And again, I think on all of the guidelines, Andrew, they've actually got quite a lot to say about antibiotics. There's some detailed guidance about using them in CKD.

And gout. Gout’s a big problem, isn't it? Some gout, quite easy, avoid non-steroidal if at all possible. And colchicines are very effective. Some people get worried about Colchicine in chronic kidney disease, but actually it's fine to use, for example, 500 micrograms, two or three times a day for five days, or seven days. The challenge is, if people get bad diarrhoea, then they get volume depleted, and it's a problem. So careful use of Colchicine can be very good in chronic kidney disease, and an alternative is a very short course, 7 to 10 days of steroids, oral prednisolone, if there's bad gout pain.

Andrew Frankel

Gosh Jeremy, there was so much really useful information there. I like the way you are clear that what is often labeled as nephrotoxic, isn't nephrotoxic, that there are drugs which can result in changing in kidney function, in certain situations, but if you've got CKD, they are not necessarily nephrotoxic. And primary care, I know need to understand that difference, because they often stop beneficial drugs because they feel they are nephrotoxic when the GFR drops below 30 say.

Understanding that difference, avoiding trimethoprim, reviewing PPI prescription, using Sick Day rules for those drugs, such as cardiovascular drugs and Metformin, and avoiding the highest dose of atorvastatin, those are really helpful pieces of advice.

So let's now talk about analgesics, since this is such a cause of anxiety and uncertainty, especially because we want to manage pain in our patients. What can primary care use for people with CKD Jeremy?

Jeremy Levy

Yes so you are absolutely right Andrew, and of the emails and the questions that we get through all the other routes, analgesia is a really common question. So first of all, paracetamol, clearly not a very strong painkiller, but often very effective in mild, moderate pain, and sometimes in combination, is generally very safe in chronic kidney disease and can be used in normal doses. So paracetamol is actually fine, and you can use full dose, one gram, four times a day.

We've talked about avoiding regular, non-steroidal, anti-inflammatory drugs, and that's really important, but occasional use of the odd dose, particularly in earlier CKD, CKD stage two and three, is going to be okay, but not regular use.

So the next step up, probably for stronger painkillers, will be Tramadol. Now Tramadol is partly renally excreted, but not predominantly, and it can be safely used in chronic kidney disease, but not at very large doses. So generally, starting at sort of 50 milligrams, twice a day, and a maximum dose of Tramadol probably 100 milligrams, twice a day. So this isn't as much as you might use in other circumstances. And of course, we really don't want to use Tramadol long term, if at all possible, but Tramadol is safe to be used.

If you need stronger painkillers, which of course, we're then talking about opiates. The one to avoid, almost always, is morphine. Morphine itself has metabolites that accumulate, can cause fitting, and neurotoxicity, sedation, respiratory depressions, so morphine, and no, under almost all circumstances in chronic kidney disease, and the alternative is either oxycodone or fentanyl. Both of those are safe to use in chronic kidney disease. There's wide experience - fentanyl is not really excreted at all. Oxycodone, some bit of it is, but both can be used, and the advice is always start low doses and increase slowly. But oxycodone and fentanyl for severe pain in chronic kidney disease.

And in primary care, you're used to using patches, aren't you for chronic pain, and the two patches that are safe to use in chronic kidney disease are buprenorphine and fentanyl patches, both of which can be used in chronic kidney disease. But again, start low, just because we don't want them to accumulate if there is some renal excretion, which does occur with fentanyl, but will a bit with buprenorphine. So start low, but they can be used. As always. The combination with paracetamol is fine, and that can work very well together.

And really the last thing about painkillers would be sort of neurological pain, which is a big issue, isn't it, where Gabapentin and Pregabalin are often used, and again, they can be used in chronic kidney disease, but start low doses and increase slowly, and the maximum doses are not as high, as in people without chronic kidney disease, but titrate to pain. There is a small increased risk of the side effects of both of these in chronic kidney disease, but they can be used.

Andrew Frankel

So thank you so much Jeremy, incredibly helpful, as I would have expected. So just to summarise, analgesia, paracetamol, tramadol, oxycodone and fentanyl are all okay. No morphine, but remember that key rule, always start low and increase very cautiously. But also in addition, buprenorphine and fentanyl patches are okay in CKD.

Avoid regular or long term non-steroidals, and watch out for gels, particularly the high potency gels. And when reviewing drug cards, remember, Metformin stops when the GFR is less than 30, but doesn't need to be stopped before. Review the need for PPIs, review cardiovascular drugs, and remember to use good Sick Day guidance or rules, and reiterate those at every medication review.

And finally, that beautiful piece of advice that we can no longer worry about all these creatinine clearances, and other pieces of information and just stick to GFR to guide kidney function, whatever the SPAC says. So we are looking pragmatically at how we adjust drug dosages. So thank you very much Jeremy.

Jeremy Levy

Andrew, that was a great summary, great summary. I'm going to come back to one thing you mentioned there - Sick Day guidance. We've talked about this a lot. It's really important, isn't it, but the issue of people restarting these medicines as soon as they've got over their illness. It's so easy for people to stop them, and they don't restart drugs that are so important for them. And there's a great leaflet on the North West London website about sick day guidance, and reminding people to restart these medicines when they're better, so they don't then, long term, lose them. But between us, I think we've covered everything.

Andrew Frankel

Thank you very much. Jeremy, absolutely. And I'll just put one other little comment there. Never say when you're doing Sick Day guidance, stop. Always use the word ‘miss out’ or ‘emit’, because you're quite right. It's the restarting that's the issue. Thanks again, Jeremy

Jeremy Levy

Bye, Andrew.