DESTIN, Fla. — Patients with gout in chronic kidney disease are undertreated, and health care providers need to do more to help patients with both diseases reach serum urate targets by using existing drugs, but starting slowly, according to Kenneth Saag, MD, MSc, of the University of Alabama at Birmingham.
“The big problem is that we — and not ‘us’ necessarily, but us physicians in general and health care providers — do a really lousy job of managing people with chronic kidney disease with gout,” Saag, a Healio Rheumatology Peer Perspective Board member, told attendees. “We are very, very worried — our colleagues in particular — about these drugs in that setting, and most are just not using even the recommended dose.”
Even among patients who are receiving the recommended dose of allopurinol, just under 20% are achieving serum urate levels of 6 mg/dL or less, and just under 40% achieve that target when given more than the recommended dose, he added.
Figure 1. Patients with gout in chronic kidney disease are undertreated, and health care providers need to do more to help patients with both diseases reach serum urate targets, according to Saag.
According to Saag, gout in chronic kidney disease often represents a therapeutic “conundrum” for physicians, as many clinicians consider renally-adjusted allopurinol necessary and protective in patients with chronic kidney disease, specifically due to the perceived risk for allopurinol severe cutaneous adverse reactions. These reactions, although rare, can be “horrific,” with skin rash, fever, hepatitis, eosinophilia, worsening renal function and a 30% mortality rate, Saag said.
“This is what we’re worried about, because any physician who has seen this in a patient knows it’s absolutely horrific,” Saag said. “This is an issue because the majority of the people I see have chronic kidney with gout. The kidneys are responsible for much of the management of urate, and most of the people with gout have problems with urate excretion. By the time people get to dialysis, half are hyperuricemic.”
These concerns were codified in 1986 with the Hande Guidelines, which were based on the understanding that the byproduct of allopurinol, oxypurinol, had prolonged retention and, in the setting of chronic kidney disease, may lead to more negative outcomes. It suggested allopurinol dosing amounts based on creatinine clearance.
However, according to Saag, the database used to establish these guidelines was “weak.”
“There are pretty much just as many studies suggesting that total allopurinol dose is not important as there are suggesting that it is,” he said.
Noting multiple studies, Saag said the recency of allopurinol initiation, renal impairment, diuretic therapy and, in Han Chinese and African American populations, HLA-B*5801 allele are all more important risk factors for patients developing a hypersensitivity reaction.
With this in mind, Saag recommended that physicians “start low and go slow,” gradually increasing the dose of allopurinol in patients with chronic kidney disease, and “not necessarily worry about where you end up.”
According to Saag, a New Zealand-based study published in 2017 in Annals of the Rheumatic Diseases recommended initiating allopurinol at 100 mg daily in patients with normal renal function, and increasing the dose by 100 mg every month until target serum urate is reached. In patients with an eGFR of less than 60, they recommended a starting dose of 50 mg, with 50-mg increases every month until reaching the serum urate target.
“This seems very conservative to me and I have a bunch of people, I would say between 45 and 60 eGFR, where I would go a little faster than that,” Saag said. “However, this is their recommendation, and they have just as much experience in this as anybody. Certainly, cautioning patients about the side effects and what to look out for is really important.” – by Jason Laday
Saag Kenneth. Comorbidity conundrums and therapeutic controversies in gout. Presented at: Congress of Clinical Rheumatology; May 2-5, 2019; Destin, Fla.
Disclosure: Saag reports research funding from Ardea/AstraZeneca, Horizon and Takeda, as well as consulting fees from AstraZeneca,/Ironwood, Horizon, Sobi and Takeda.