In the JournalsPerspective

Allopurinol reduces risk of kidney function decline in gout patients

Among patients with gout, treatment with at least 300 mg allopurinol daily was associated with a 13% reduced risk for kidney function decline, according to data published in JAMA Internal Medicine.

“There are no clear data to suggest that allopurinol is detrimental to renal function in patients with gout,” Ana Beatriz Vargas-Santos, MD, from the State University of Rio de Janeiro, and colleagues wrote. “Despite this, clinicians commonly hold or lower the dose of allopurinol or even discontinue allopurinol entirely when a patient with gout exhibits kidney function decline, leading to worse gout outcomes.”

Additionally, the researchers noted that “Although [chronic kidney disease (CKD)] is common in gout, most people with gout have normal kidney function, particularly early in the course of disease, yet there are limited data regarding renal effects of allopurinol among those with gout and normal kidney function.”

 
Among patients with gout, treatment with at least 300 mg allopurinol daily was associated with a 13% reduced risk for kidney function decline, according to data.
Source: Shutterstock

To evaluate the link between allopurinol use in gout and the risk for stage 3 or higher CKD, the researchers conducted a time-stratified propensity score–matched, population-based, prospective cohort study of patients with newly diagnosed gout who started allopurinol ( 300 mg daily) vs. patients who did not start allopurinol. Resulting data were analyzed using Cox proportional hazards regression.

Following screening, the researchers determined that 71% of all patients exhibited stage 2 CKD, while 29% exhibited stage 1 CKD or standard kidney function. Additionally, the use of medications was comparable among allopurinol users and nonusers, with 31% using diuretics and 73% using NSAIDs.

Vargas-Santos and colleagues then propensity score-matched 4,760 allopurinol users with 4,760 nonusers, excluding patients with stage 3 or higher CKD or urate-lowering therapy use prior to their gout diagnosis.

According to study findings, 579 allopurinol users developed stage 3 of higher CKD vs. 623 patients who did not use allopurinol, indicating that use of allopurinol of 300 mg or more daily was linked to lower risk for stage 3 or higher CKD compared with nonusers, with an HR of 0.87 (95% CI, 0.77-0.97). In addition, allopurinol initiation at less than 300 mg daily was not linked to renal function decline (HR = 1; 95% CI, 0.91-1.09).

“Allopurinol use, initiated at a dose of at least 300 mg/d, was associated with a 13% reduction in the risk of developing CKD stage 3 or higher,” Vargas-Santos and colleagues wrote. “In contrast, initiation of allopurinol at a dose of less than 300 mg/d had no association with developing CKD stage 3 or higher, consistent with current thinking that most patients need doses higher than 300 mg/d to achieve clinically meaningful outcomes.”

The researchers added, “Because allopurinol did not appear to be associated with renal function decline, clinicians should consider evaluating other factors when faced with renal function decline in their patients with gout rather than lowering the dose of or discontinuing allopurinol, a strategy that has contributed to the ongoing suboptimal treatment of gout.” – by Robert Stott

Disclosure: Vargas-Santos reports receiving speaker fees and international medical event support from Grünenthal. Please see the study for all other authors’ relevant financial disclosures.

Among patients with gout, treatment with at least 300 mg allopurinol daily was associated with a 13% reduced risk for kidney function decline, according to data published in JAMA Internal Medicine.

“There are no clear data to suggest that allopurinol is detrimental to renal function in patients with gout,” Ana Beatriz Vargas-Santos, MD, from the State University of Rio de Janeiro, and colleagues wrote. “Despite this, clinicians commonly hold or lower the dose of allopurinol or even discontinue allopurinol entirely when a patient with gout exhibits kidney function decline, leading to worse gout outcomes.”

Additionally, the researchers noted that “Although [chronic kidney disease (CKD)] is common in gout, most people with gout have normal kidney function, particularly early in the course of disease, yet there are limited data regarding renal effects of allopurinol among those with gout and normal kidney function.”

 
Among patients with gout, treatment with at least 300 mg allopurinol daily was associated with a 13% reduced risk for kidney function decline, according to data.
Source: Shutterstock

To evaluate the link between allopurinol use in gout and the risk for stage 3 or higher CKD, the researchers conducted a time-stratified propensity score–matched, population-based, prospective cohort study of patients with newly diagnosed gout who started allopurinol ( 300 mg daily) vs. patients who did not start allopurinol. Resulting data were analyzed using Cox proportional hazards regression.

Following screening, the researchers determined that 71% of all patients exhibited stage 2 CKD, while 29% exhibited stage 1 CKD or standard kidney function. Additionally, the use of medications was comparable among allopurinol users and nonusers, with 31% using diuretics and 73% using NSAIDs.

Vargas-Santos and colleagues then propensity score-matched 4,760 allopurinol users with 4,760 nonusers, excluding patients with stage 3 or higher CKD or urate-lowering therapy use prior to their gout diagnosis.

According to study findings, 579 allopurinol users developed stage 3 of higher CKD vs. 623 patients who did not use allopurinol, indicating that use of allopurinol of 300 mg or more daily was linked to lower risk for stage 3 or higher CKD compared with nonusers, with an HR of 0.87 (95% CI, 0.77-0.97). In addition, allopurinol initiation at less than 300 mg daily was not linked to renal function decline (HR = 1; 95% CI, 0.91-1.09).

“Allopurinol use, initiated at a dose of at least 300 mg/d, was associated with a 13% reduction in the risk of developing CKD stage 3 or higher,” Vargas-Santos and colleagues wrote. “In contrast, initiation of allopurinol at a dose of less than 300 mg/d had no association with developing CKD stage 3 or higher, consistent with current thinking that most patients need doses higher than 300 mg/d to achieve clinically meaningful outcomes.”

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The researchers added, “Because allopurinol did not appear to be associated with renal function decline, clinicians should consider evaluating other factors when faced with renal function decline in their patients with gout rather than lowering the dose of or discontinuing allopurinol, a strategy that has contributed to the ongoing suboptimal treatment of gout.” – by Robert Stott

Disclosure: Vargas-Santos reports receiving speaker fees and international medical event support from Grünenthal. Please see the study for all other authors’ relevant financial disclosures.

    Perspective
    Iris Zink

    Iris Zink

    In 2017, at age 47, I considered myself a healthy adult in excellent physical shape. I did not fit the typical characteristics associated with gout for which I had been diagnosed: I rarely drank alcohol, adhered to a Mediterranean-based diet, had a normal BMI, and was perimenopausal. Gout was a condition that I diagnosed others with, not a disease that I associated with my own personal health.

    What I did not take into consideration was genetics. My father walked with a cane most of my childhood due to polyarticular gout, which predisposed me to this ancient rheumatic disease that currently affects 4% of the population. Recently, during a detailed discussion with my nephrologist during screening for an upcoming kidney surgery, I was relieved to learn that tight disease control with continued dosing of allopurinol, was the best plan for my future and the health of my remaining kidney.

    The current guidelines from the American College of Physicians recommend against initiating long-term uric acid-lowering therapy in most patients after an initial gout attack or in patients with infrequent attacks. However, current evidence supports the use of these medications in the management of gout.

    In the study from Vargas-Santos and colleagues, patients who were started on at least allopurinol 300 mg per day showed less progression to stage 3 CKD than those who did not take allopurinol; this indicates that allopurinol does not cause worsening renal function and may have protective affects for the kidney. Additionally, a study from Kapetanovic and colleagues in Arthritis Research & Therapy showed a marginally higher incidence of women evolving from hyperuricemia to gout than men — specifically, 10-20% of those with hyperuricemia will turn into clinically meaningful gout.

    Numerous studies have shown that poor gout control contributes to comorbidities down the road, yet so many patients remain untreated or undertreated for their gout due to ongoing ignorance in the medical community. It is our duty to keep our patients well, not just treat their illnesses. In doing this, we must take an aggressive stance when it comes to the treatment of gout. As providers and educators, we must advocate for our patients, as well as remain up to date on new evidence.

    • Iris Zink, MSN, RN, ANP-BC, RN-BC
    • Healio Rheumatology Peer Perspective Board member
      Past president, Rheumatology Nurses Society
      Rheumatology nurse practitioner
      Owner, Lansing Rheumatology
      East Lansing, Mich.

    Disclosures: Zink reports no relevant financial disclosures.