In these circumstances, Professor Bardin recommended the use of febuxostat. He explained, “You can use febuxostat in chronic kidney disease (CKD) if the estimated glomerular filtration rate (eGFR) is greater than 30 mL/min/1.73m2 [because] it’s mainly metabolized by the liver.”
Febuxostat isn’t approved for patients with an eGFR less than 30 mL/min/1.73m2 because these patients were excluded from pivotal trials. However, data from small series have shown febuxostat can be well tolerated and efficacious in these patients.9 Professor Bardin shared, “I must say that I do use febuxostat in patients with severe renal failure. I start with a very low dose and slowly increase to target, while closely monitoring the patient.”
Professor Bardin noted that the recommendations for gout management in CKD differ between professional organizations (e.g., ACR and EULAR). “But in general, there are ways to deal with this problem, and we can get most of them to an appropriate [SU] target,” he said.
When it comes to end-stage renal disease, Professor Bardin reminded us that we’ve known since the 1960s that “hemodialysis is a good way to manage gout.”10 In addition, renal transplantation used to be a frequent cause of refractory gout due to calcineurin inhibitors causing hyperuricemia, and azathioprine barring the concomitant use of xanthine oxidase inhibitors. “But that problem has now been solved by mycophenolate mofetil, [which is safe to use in combination with allopurinol],” he added.11
Flare Prophylaxis
Flare prophylaxis is a crucial and oft-overlooked component of gout care. However, comorbidities like CKD and type 2 diabetes mellitus can complicate drug selection. Colchicine, non-steroidal anti-inflammatory drugs and prednisone may all be contraindicated or undesirable options for certain patients.
Professor Bardin offered, “In patients who cannot be prescribed typical medications for flare prophylaxis, consider canakinumab. It’s not approved for [this indication], but has a long duration of action. ULT could be introduced and optimized after one canakinumab dose, which can remain effective up to one year.”12 Additional options might include other interleukin (IL) 11 inhibitors (e.g., anakinra) or tocilizumab in the instance of IL-1 blockade failure.13,14
‘I really believe that refractory gout is neglected gout & shouldn’t be seen anymore.’ —Thomas Bardin, MD
Comorbidities
Last, Professor Bardin pointed out that most gout patients have comorbidities, and we can use several of their other medications to help reduce hyperuricemia. In hypertension, losartan and calcium channel blockers are uricosuric.15 In hyperlipidemia, fenofibrate lowers SU and may reduce gout attacks.16 Sodiumglucose co-transporter 2 (SGLT2) inhibitors have been shown to significantly decrease SU levels, and many drugs in this class have multiple indications (e.g., type 2 diabetes mellitus, CKD with albuminuria, heart failure).17
