Background/Purpose: untreated or undertreated gout is characterized by recurrent episodes of acute inflammation of joint structures, called gout flares, and flares are commonly treated with non-steroidal anti-inflammatory drugs (NSAIDs). To evaluate risk factors associated with acute kidney injury (AKI) attributed to NSAIDs in a cohort of patients who were exposed to NSAIDs to treat gout flares gout prior to urate-lowering therapy.

Methods: retrospective analysis of a nested prospective cohort of 983 gout patients in whom general variables (age, gender, renal function, ethanol intake, hypertension, hyperlipidemia, diabetes, vascular events, diuretic use) and also variables related to gout and severity of gout (serum urate levels, number for flares per year, presence of tophi, joint distribution, X-ray involvement, previous prescription of urate-lowering therapy) are available for analysis. Outcomes considered were loss of renal function attributed to NSAIDs prescription following the KDIGO AKI Work Group and staging. Variables associated to increased risk in Kaplan-Meier survival analysis were tested with multivariate Cox survival analysis, using time from onset of gout to the event as time exposed to NSAIDs.

Results: 55/983 patients (5.59%, 0.82 per 100 patient-yr) experienced an episode of AKI: 31, 13, and 11 patients showed Grade 1, Grade 2, and Grade 3 AKI. Among the gout-related variables, the number of flares in the year previous to the renal event and polyarticular joint distribution were associated with higher risk of renal events. Other general variables previously described in the literature, as the presence of previous chronic renal disease, the use of diuretics, and prevalent vascular events were also independently associated to increased risk of AKI. Interestingly, patients who had been previously prescribed allopurinol (other medications were uncommonly prescribed) showed a lower risk of acute renal events (Table).

Conclusion: the number of flares and extensive joint distribution, variables related to gout clinical severity and surrogates for NSAID prescription, were associated with higher risk for renal injury in patients with gout, while previous prescription of allopurinol was associated with lower risk. We are uncertain if this finding is related to the use of allopurinol or a signal of better standard of healthcare that may reduce the risk of events indirectly.