Gout Management in Patients with Chronic Kidney Disease
Transcription
Well, thanks everybody for listening today. I'm Lisa Stamp. I'm a rheumatologist and professor of medicine in Christchurch, New Zealand. Although it looks like I'm in the middle of the sky at night, it's actually winter here, freezing cold outside, but no snow. I'm going to talk to you today about managing gout in people with chronic kidney disease.
We know that gout is very common in people with CKD and it has implications for how we manage gout — that's mainly around the dosing of medications that we use to treat gout and also interactions with medications used for their other comorbidities.
When we think about managing the gout flare in people with chronic kidney disease, we have our standard three options: that is colchicine, non-steroidal anti-inflammatories, or steroids. Now non-steroidal anti-inflammatories as we all know are contraindicated in those with CKD. So that option is off the cards.
Colchicine we can use — typically we would use a dose of 0.5 to 0.6 milligrams once or twice a day in people with a GFR above 45 mls per minute, but reduce the dose in those who have a GFR of less than 30 mls per minute.
For some patients, it may be that steroids are considered the safest option. And certainly if there's one or two joints involved that are amenable to injection in people with CKD, then intraarticular steroid can be a very effective therapy. The other alternative is oral steroids. Short courses for flares may be appropriate. This can be problematic obviously for people who also have concomitant diabetes. One of the tricks with steroids for flare management is not to reduce them too quickly, otherwise you might see a gout flare rebound.
It's important to also just be aware of potential drug interactions. As I'm sure you're all aware, colchicine does interact with P-glycoprotein and CYP3A4 inhibitors, and so the dose does need to be reduced or potentially colchicine avoided in patients on these therapies. Although there's concern around the interaction between a statin and colchicine, this is not something that we commonly see and I have no concerns about using colchicine in those on a statin.
Now as we all know, urate lowering therapy is the cornerstone of the long-term management of gout and there has been a lot of concern about the use of urate lowering therapy in people with CKD. This particularly is in relation to allopurinol, which is the recommended first-line agent for most people. I think it's fair to say that we do know that CKD is a risk factor for the hypersensitivity syndrome, and that is what most people fear because this is a very severe adverse effect and has a high mortality rate.
Our own research would suggest that you can use allopurinol safely in people with CKD but there are two factors to consider. The first one, and most importantly I think, is the starting dose. We have evidence that the starting dose is an important risk factor for the hypersensitivity syndrome. And based on this we would recommend that no one starts on more than 100 milligrams daily. For people with a GFR between 30 and 60, I would start on 50 milligrams daily. And for those with a GFR of less than 30, I'd probably start at a low dose of 50 milligrams every alternate day.
The second issue is then the maintenance dose. And by that I mean that dose that's required to achieve target urate. As you'll all be aware, the ACR/EULAR criteria said we needed to restrict the allopurinol dose based on renal function. I think we now have good evidence that that is not the case. And the most important thing is to titrate the allopurinol dose in a systematic approach to achieve the target urate of less than 0.36 millimoles per liter.
If you start allopurinol and don't increase the dose, you're potentially exposing the patient to the risk without giving them the potential benefit of getting to target. So we would typically increase the dose monthly. Some people do this two to four weekly — that's absolutely fine — just a systematic approach, increasing by either 50 or 100 milligrams with each increment until you reach target urate.
Although most people consider that you need very high doses of allopurinol, for some people the mean dose of allopurinol to achieve target is generally around 300 to 400 milligrams. So it's not that much higher, and in people with CKD we can see that they do need lower doses.
The other urate lowering therapies that are available — obviously febuxostat — we have less data on the use of febuxostat in people with CKD, but certainly it's a reasonable option. Again I would start at a lowish dose and dose titrate up. Other options such as probenecid, the uricosuric agent — we know that this becomes less effective as the GFR drops and generally I expect it to be ineffective when the GFR is less than 50. We don't need to worry about renal function with pegloticase because it is not renally cleared. So when you're
thinking about managing gout with people in CKD, think about the medication, think about the potential effects on the kidney and think about the drugs that the patient is already on that may interact with the medications that you're using.
More information about gout can be found on RheumNow. And there's a wealth of resources available there. Thank you very much.
We know that gout is very common in people with CKD and it has implications for how we manage gout — that's mainly around the dosing of medications that we use to treat gout and also interactions with medications used for their other comorbidities.
When we think about managing the gout flare in people with chronic kidney disease, we have our standard three options: that is colchicine, non-steroidal anti-inflammatories, or steroids. Now non-steroidal anti-inflammatories as we all know are contraindicated in those with CKD. So that option is off the cards.
Colchicine we can use — typically we would use a dose of 0.5 to 0.6 milligrams once or twice a day in people with a GFR above 45 mls per minute, but reduce the dose in those who have a GFR of less than 30 mls per minute.
For some patients, it may be that steroids are considered the safest option. And certainly if there's one or two joints involved that are amenable to injection in people with CKD, then intraarticular steroid can be a very effective therapy. The other alternative is oral steroids. Short courses for flares may be appropriate. This can be problematic obviously for people who also have concomitant diabetes. One of the tricks with steroids for flare management is not to reduce them too quickly, otherwise you might see a gout flare rebound.
It's important to also just be aware of potential drug interactions. As I'm sure you're all aware, colchicine does interact with P-glycoprotein and CYP3A4 inhibitors, and so the dose does need to be reduced or potentially colchicine avoided in patients on these therapies. Although there's concern around the interaction between a statin and colchicine, this is not something that we commonly see and I have no concerns about using colchicine in those on a statin.
Now as we all know, urate lowering therapy is the cornerstone of the long-term management of gout and there has been a lot of concern about the use of urate lowering therapy in people with CKD. This particularly is in relation to allopurinol, which is the recommended first-line agent for most people. I think it's fair to say that we do know that CKD is a risk factor for the hypersensitivity syndrome, and that is what most people fear because this is a very severe adverse effect and has a high mortality rate.
Our own research would suggest that you can use allopurinol safely in people with CKD but there are two factors to consider. The first one, and most importantly I think, is the starting dose. We have evidence that the starting dose is an important risk factor for the hypersensitivity syndrome. And based on this we would recommend that no one starts on more than 100 milligrams daily. For people with a GFR between 30 and 60, I would start on 50 milligrams daily. And for those with a GFR of less than 30, I'd probably start at a low dose of 50 milligrams every alternate day.
The second issue is then the maintenance dose. And by that I mean that dose that's required to achieve target urate. As you'll all be aware, the ACR/EULAR criteria said we needed to restrict the allopurinol dose based on renal function. I think we now have good evidence that that is not the case. And the most important thing is to titrate the allopurinol dose in a systematic approach to achieve the target urate of less than 0.36 millimoles per liter.
If you start allopurinol and don't increase the dose, you're potentially exposing the patient to the risk without giving them the potential benefit of getting to target. So we would typically increase the dose monthly. Some people do this two to four weekly — that's absolutely fine — just a systematic approach, increasing by either 50 or 100 milligrams with each increment until you reach target urate.
Although most people consider that you need very high doses of allopurinol, for some people the mean dose of allopurinol to achieve target is generally around 300 to 400 milligrams. So it's not that much higher, and in people with CKD we can see that they do need lower doses.
The other urate lowering therapies that are available — obviously febuxostat — we have less data on the use of febuxostat in people with CKD, but certainly it's a reasonable option. Again I would start at a lowish dose and dose titrate up. Other options such as probenecid, the uricosuric agent — we know that this becomes less effective as the GFR drops and generally I expect it to be ineffective when the GFR is less than 50. We don't need to worry about renal function with pegloticase because it is not renally cleared. So when you're
thinking about managing gout with people in CKD, think about the medication, think about the potential effects on the kidney and think about the drugs that the patient is already on that may interact with the medications that you're using.
More information about gout can be found on RheumNow. And there's a wealth of resources available there. Thank you very much.
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