Inpatient Management of Gout: Serum Urate Testing and Allopurinol Dose Adjustment

DISCUSSION

Despite clear local guidelines, most people receiving allopurinol who are admitted to hospital did not have SU measured during admission. The majority of admissions (83.15%) also did not result in a change in allopurinol therapy. Despite patients being above target SU, we found that allopurinol was discontinued or decreased during admission, especially in those with CKD stages 4 and 5. Given the difficulty of accessing general practitioner appointments, both due to scarce appointment availability and cost, hospital admission is an opportunity to optimize gout therapy—whether or not gout is the primary reason for admission—similar to that undertaken in other chronic diseases such as hypertension or diabetes.

Although we did not collect data on reason for admission, gout flare is not an uncommon reason for admission and there is an increased risk of gout flares during hospital admissions for other medical conditions.⁴ People who experience a gout flare during a hospital admission are reported to have an increased length of stay. For example, a retrospective review of 77 individuals who developed a gout flare during hospital admission experienced a 6-day increase in length of stay compared to matched controls who had the same principal diagnosis and demographics but without a gout flare (9 days vs 3 days; P < 0.0005).¹² Our study also reported that the length of stay was significantly longer in admissions where SU was measured. Thus, it is possible gout was a primary or secondary reason for admissions where SU was measured and, in those admissions where SU was not measured, gout was in an intercritical period. Given the high healthcare costs associated with prolonged admissions for gout flares, the ability to predict whether a gout flare will occur would be of use. Factors reported to help predict gout flares during an admission include preadmission SU > 0.36 mmol/L, tophus, acute kidney injury, surgery, alteration in ULT, and adjustment of diuretics.¹³

CKD and gout often coexist, and underdosing of allopurinol due to concerns about its use in renal impairment is common. Acute deteriorations in renal function may precipitate cessation or reduction in dose, which may explain why more admissions in our study with CKD stage 4 or 5 discontinued allopurinol or reduced their dose. However, discontinuation of allopurinol may also be associated with increased risk of gout flare. The majority of admissions in our study had eGFR consistent with CKD stages 2 and 3, with comparatively small numbers of those in CKD stages 1, 4 and 5. Those with CKD stage 1-2 had the most patient admissions at target SU, compared to CKD stage 3-5. This likely reflects multiple factors that may include the smaller allopurinol dose adjustment increments during dose titration recommended for reduced renal function; overcautious prescribing in patients with reduced renal function; comorbidity causing reduced attention to gout management in lieu of other illnesses; or disease that is more difficult to treat. Unfortunately, there remain relatively few admissions where allopurinol was increased despite SU being above target.

Cessation of gout flares and resolution of tophi occur with sustained reduction in SU to the target of < 0.36 mmol/L,¹⁴ and ULT should generally be continued indefinitely.⁹ It is unclear why allopurinol was often discontinued despite SU being at target, although there may have been valid reasons for discontinuation that we we cannot confirm.

There are several limitations to this study. First, we cannot be sure that allopurinol was being prescribed for gout. However, we excluded admissions to urology, where allopurinol may be used for urate stones; hematology and oncology, where it may be used for prevention of tumor lysis syndrome; and those coprescribed a thiopurine, wherein allopurinol may be used to increase thiopurine metabolite concentrations. Treatment of asymptomatic hyperuricemia is not recommended in Aotearoa NZ, making it likely that allopurinol was being prescribed for gout. Many admissions were not included in allopurinol dosing analysis as they did not have SU testing completed during the admission period, although it is possible that patients received SU testing prior to admission. However, this highlights a group that is also unlikely to have had their gout management reviewed during admission. A major limitation of the data is that the reason for admission was unknown, so some changes may have been made appropriately in the context of an acute illness, recent titration of dose in the community, palliative care setting, or allergy. Additionally, patients may have discontinued or reduced their allopurinol dose in response to a change in renal function. There are no guidelines on the management of ULT in the setting of significant change in renal function. However, SU increases as renal function declines and, for individuals with gout, discontinuation of ULT may result in a return of this painful condition. Clinicians need to be mindful to reconsider the need for allopurinol and the dosage once any acute illness has settled. Alternatively, if the reason for admission was a gout flare, the recommendation would be to continue ULT, not discontinue allopurinol. Further, SU can fall well into the normal range or below target SU during gout flares, leading to diagnostic uncertainty as well as resulting in a missed opportunity to identify a group of individuals who would benefit from further allopurinol dose titration. Finally, the upper limit of the normal range for SU is 0.42 mmol/L, which is well above our therapeutic target SU for patients with gout. This represents another point in the care pathway where there is a lost opportunity for good management if the SU is not recognized by the healthcare provider who views the result as being above treatment target but within the so-called normal range.

Despite the availability of local management pathways, gout remains suboptimally treated during hospital admissions. Whereas other chronic conditions (eg, hypertension and diabetes) are routinely reviewed during hospital admissions, the same does not appear to be the case for gout. Education to consider gout in the same way as hypertension and diabetes could result in an increase in the frequency of gout management review. The electronic prescribing system does enable prompts to be added to remind doctors to review gout management when prescribing allopurinol. In addition, prompts could be added to admission proformas, which may also help remind doctors to consider completing an SU test and to review a patient’s current gout management.

In conclusion, our study found that in those prescribed allopurinol, SU was measured in only 16% of hospital admissions. When measured, 43% were above target SU and only 7% of these admissions received an increase to their allopurinol dose. This reflects a missed opportunity to review and optimize management of this common, painful, yet treatable condition.